13 Miscellaneous

SECTION 13

Miscellaneous 65.

Weight Loss – A Practical Approach SV Ramana Murty

361

66.

Sleep as Prescription Anil Bhoraskar

369

67.

Have Doctors Forgotten the Most Important Diagnostic Tool ?

Colin Robertson

377

68.

Approach to Disorder of Sweating H Basavanagowdappa

378

69.

Practical Approach to Stress Related Disorders NK Singh, Vaibhav Agnihotri, Richa Manaswita

382

70.

Alternate Medicine and Yogic Practices in Indian Scenario Hatha Yoga Chandrasekhar Valupadas

388

71.

Medical Errors in Day-To-Day Practice Raveendra KR

397

72.

Practical Approach to Pedal Edema Kumar Natarajan

401

73.

Cord Blood Ashesh Bhattacharya, Meenakshi Bhattacharya

406

74.

Routine Use of Vitamins, Minerals, Probiotics & Anti-Oxidants Vijay Garg, Raman Parashar, Aadish Kumar Jain, AK Pancholia

409

75.

Chronomedicine: A Unique Concept to Manage Human Diseases Anuj Maheshwari, Narsingh Verma

415

76.

Holistic Learning in Medical Education; Status & Future Ahead Ashutosh Ojha, Varsha Mundley

419

77.

Essential Life Saving Skills a Physician Must Know Dhruva Chaudhry, Brijesh Prajapat

423

78.

Principles of Diet Therapy Shilpa Joshi

430

79.

Drug Induced Diseases TK Suma

435

80.

An Overview of Persistent Pain Palanisamy Vijayanand, Sudhindra Dharmavaram

439

81.

Prescribing Cascades in Elderly Shohael Mahmud Arafat, Tahsin Mahmood

444

82.

From Guidelines to Rational Care - A Perspective Krishna G Seshadri

447

83.

The Science and Art of Medical Writing Shankar Subramanian

449

84. Hiccups

S Avudaiappan

452

85.

Gynecological Malignancies: Prevalence, Early Diagnosis and Preventive Strategies from a Physician’s Perspective Jayanta Chatterjee

454

86.

Contribution of India in Medical Sciences Saikat Datta, Sharmistha Bhattacherjee, Dibyayanam Sahoo

460

C H A P T E R

65

Weight Loss – A Practical Approach SV Ramana Murty

dieting, exercise, starvation or decreased nutritional intake which accompanies old age.

ABSTRACT

Weight loss is one of the common ailments encountered by the physician in medical out patient departments all over the world. India is not an exception. Many individuals may present with sarcopenia or cachexia. To quantify the weight loss, body mass index appears to be the best indicator.

Weight loss may be voluntary or involuntary / unintended.

Unintended weight loss may be associated with many diverse conditions; tuberculosis, HIV/AIDS, chronic worm infestation, cancer or collagen vascular disorders occasionally psychiatric disorder.

It will be prudent to investigate all cases with a methodical approach; which should include meticulous history, thorough clinical examination and appropriate investigations, so that it can unravel hidden cause and go a long way towards the diagnosis and management of weight loss.

INTRODUCTION

Over the past few decades there has been a dramatic increase in concern over the extremes of weight; weight loss or gain! It is evident that an individual with over weight is suspected to have hyperlipidemia and coronary artery disease and the one with underweight may be suspected to have hyperthyroidism, type 1 diabetes or to rule out slim disease (HIV/AIDS).

Clinically significant involuntary/ unintentional weight loss is defined as a loss of 4.5 kg or > 5% of the usual body weight over a period of 6 - 12 months, especially when progressive. Weight loss of > 10% of normal body weight is considered to represent protein-energy malnutrition (PEM).

Types of weight loss

Voluntary weight loss •

Loss of body weight with deliberate use of weight reducing drugs or foods, exercise, or bariatric surgery.

Involuntary / Unintentional weight loss •

Note •

Loss of body weight occurring unintentionally in individuals due to the presence of disease or ingestion of drugs or exposure to toxins or radiation.

Physiological weight loss: Weight loss due to

•

Pathological weight loss: Weight loss due to systemic disease, advanced disease of any organ system or psychiatric illness.

Epidemiology •

Involuntary weight loss (IWL) is seen in ~ 8% of adult population.

•

~ 27 % of elderly > 65 years suffer from IWL.1

•

~ 25% of individuals with IWL may not have evident cause.

•

Significant weight loss is associated with increased mortality, 9 - 38 % within 1 to 2.5 years in the absence of clinical attention.

•

Mortality rates appear to be increased when weight loss is involuntary

DEFINITION

Clinically weight loss is defined as loss of more than 5 percent of usual body weight in six to twelve months.2

PATHOPHYSIOLOGY

Weight loss results when more calories are expended than taken in (ingested and absorbed). Disorders that increase expenditure or decrease absorption tend to increase appetite. More commonly, inadequate caloric intake is the mechanism for weight loss and such patients tend to have decreased appetite. Sometimes, several mechanisms are involved. For example, cancer tends to decrease appetite but also increases basal caloric expenditure by cytokine-mediated mechanisms. Obesity / weight gain is the most common reason for deliberate decrease in food intake.

TERMINOLOGY

•

Sarcopenia is a geriatric syndrome of diminished muscle mass and function, which may or may not be accompanied by unintentional weight loss.3

•

Cachexia is a syndrome of weight loss characterized by decreased muscle mass in the presence of the metabolic effects of an underlying illness such as some types of cancer or advanced heart failure.4

Physiological considerations •

Lean body mass (fat free mass) begins to decline at a rate of 0.3 kg per year from third decade onwards.

•

The total body weight peaks in sixth decade of life

and generally remains stable until ninth decade, after which it gradually declines.

362

•

MISCELLANEOUS

•

•

•

modifications, low fat diet, and regular aerobic / anaerobic exercises or bariatric surgery.

The rate of decline in lean body mass increases further at 60 in men and at 65 in women.

Note

Loss of sex steroids at menopause in women and more gradually with aging in men also contributes.

In the healthy elderly an increase in fat tissue balances the loss in lean body mass until very old age.5

• Anorexia •

Cachexia (weight loss, loss of muscle, adipose tissue, anorexia and weakness)

Decreased hunger is a reflection of reduced physical activity and loss of lean body mass producing lower demand for calories and food intake.

•

Sarcopenia (loss of muscle mass)

At cellular level telomeres shorten and body cell mass (the fat free part of the cell) declines steadily with aging.

ETIOLOGY

Unintentional weight loss with decreased appetite

The four major manifestations of unintended weight loss • Dehydration

All elderly people are to be screened for: •

Simplified nutritional assessment,

•

Observation of eating habits,

•

Activities of daily living,

•

Dementia and depression Cancer screening

•

Chronic collagen vascular disorders

•

-

Rheumatoid arthritis, sarcoidosis, SLE, polyarteritis nodosa etc.

History of present illness

• Infections -

Tuberculosis, HIV, Viral hepatitis B, C, chronic lung abscess, empyema, chronic fungal or bacterial infections, chronic helminthic infestation, etc.

•

Questions about the amount of weight loss; whether acute or chronic.

•

Appetite, food intake, and bowel patterns should be described.

•

For repeat evaluations, patients should keep a food diary.

•

Symptoms of potential causes are noted, such as fatigue, malaise, fever, and night sweats. for which the individual may attribute to fate theory or horoscope.

Thorough evaluation of elderly is required.8

•

Gastrointestinal disorders

-

Peptic ulcer disease, malabsorption, dysphagia, inflammatory bowel disease etc.

•

Vitamin deficiency; e.g. Vitamin D def.6

•

Psychiatric disorders

•

-

Anxiety disorder, depression, bipolar II disorder7 etc.

Past medical history

• Malignancy -

Prostatic, renal or lung cancer; lymphomas, or GI malignancies etc.

•

Neurologic disorders

-

Parkinson disease, motor Alzheimers disease etc.

•

Disease of liver (cirrhosis) lungs (chronic Bronchiectasis), heart (CCF), kidneys (CKD) etc.

•

Drug abuse: opiates, alcohol, heroin, etc.

neuron

disease,

Unintentional weight loss with increased appetite •

Vigorous physical activity; like active involvement in sports and games

•

Uncontrolled type 1 diabetes

• Hyperthyroidism

CLINICAL ASSESSMENT

Voluntary weight loss •

History suggestive of deliberate dieting, lifestyle

•

May reveal a disorder capable of causing weight loss. e.g. tuberculosis, hyperthyroidism

•

Consumption of “Over the counter drugs”; drugs prescribed by doctors or recreational drugs, and Herbal products through advertisements.

•

Social history may reveal changes in living situations that could explain why food intake is decreased (e.g. loss of communal eating).

•

Individual reasons; loss of loved one, loss of independence or job.

Physical examination: Certain indicators •

Ideal body weight = 22.5 X height in meters2

•

Brocas Index: Height in cms – 100

•

Body Mass Index (BMI)

•

Skin fold thickness

•

Mid arm circumference

•

Waist hip ratio

Table 1: BMI in Different Groups

363

Table 2: Skin Fold Thickness Measurement

BMI < 18.5:

Below normal weight

Standard

80%

60%

BMI >= 18.5 and < 25:

Normal weight

Adult Male

12.5

10.0

7.5

BMI >= 25 and < 30:

Overweight

Adult Female

16.5

13.0

10.0

BMI >= 30 and < 35:

Class I Obesity

Nutritional status

Normal

Moderate

Poor

BMI >= 35 and < 40:

Class II Obesity

BMI >= 40:

Class III Obesity

Note: The 80% and 60% ranges are associated with moderate and severe nutritional depletion

“Body Mass Index” appears to be the most suitable one when we deal with weight loss BMI = Weight in kg / height in Meter2

Note1 •

•

Note2.

The term “BMI” was first invented in the 19th century by a Belgian polymath called Adolphe Quetelet, hence it is also known as “Quetelet Index”.

Interpretation of body mass index into different categories can be obtained with reference to Quetelet’s index9,10 wide Table 1.

•

Vital signs are checked for fever, tachycardia, tachypnea, and hypotension.

•

Triceps skin fold thickness wide. Figure 6, Table 2 and mid upper arm circumference can be measured to estimate lean body mass.

•

•

Examination of the heart, lungs, abdomen (liver, spleen), rectum (including prostate) and testing for occult blood), head and neck, breasts, central nervous system, lymph nodes, joints, skin.

Special attention to be drawn towards behavior, mood, and affect; since chronic psychiatric conditions are known to cause cachexia.

•

Sleep disturbance, depression

loss

•

Heat intolerance, hyperthyroidism

tremor,

•

Polyuria, polyphagia, polydipsia: type 1 diabetes mellitus

•

Headache or visual symptoms and muscle pains in an older adult: Giant cell arteritis (temporal arteritis)

•

Fever, night sweats: cancer, infections, giant cell arteritis

•

Bone pain not related to activity, especially prominent at night: cancer: multiple myeloma, bone metastases from breast, prostate, or lung cancer

•

Rectal bleeding, abdominal pain : colorectal cancer

•

Lymphadenopathy: Infections, cancer, sarcoidosis

•

Edema: hypoprotenemia, chronic kidney disease,

•

Hematuria: Renal or prostate cancer

•

Ascites: Nephrotic syndrome, alcoholism, CCF

Note

and/or

visual

•

Roth spots, Janeway lesions, Osler nodes, splinter hemorrhages, retinal artery emboli

•

Dyspnea, cough, hemoptysis

•

Bone pain

•

Inappropriate fear of weight gain in an adolescent or young woman

•

Polydipsia and polyuria

Clinical correlation with common findings •

Cough, dyspnea, hemoptysis: Lung cancer, TB, Sarcoidosis, Fungal pneumonias

•

Fatigue: Adrenal insufficiency, cancer, chronic

anxiety,

sadness, sweating:

Pathologically malnutrition can affect immune response; wound healing, muscle strength; sometimes respiratory muscles; heat regulation and water and electrolyte disturbances.

•

Clinically Serious weight loss may reduce the quality of life, impair the treatment effectiveness or recovery and worsen the disease processes and be a risk factor for high mortality rates.

Fever, night sweats, generalized lymphadenopathy

• Headache, jaw claudication, disturbances in an older adult

libido,

•

To be noted with caution!

•

of

Useful questionnaire •

How much weight have you lost? Slow or fast?

•

When did the weight loss begin?

•

Are you doing vigorous exercise?

•

Are you eating less, do you have any dental problems or mouth sores?

•

Do you have more stress or anxiety than usual?

•

Have you history of recurrent vomiting?

CHAPTER 65

How to Calculate Body Mass Index?

kidney disease, depression, infections, giant cell arteritis, nephrotic syndrome, sarcoidosis

364

Table 3: Tuberculosis; Age –BMI Correlation BMICAT AGECAT AGE <20

Normal

Over WT

Type 1 OB

0

4

0

0

4

0.0%

100.0%

0.0%

0.0%

100.0%

14

9

1

0

24

58.3%

37.5%

4.2%

0.0%

100.0%

15

9

1

0

25

60.0%

36.0%

4.0%

0.0%

100.0%

7

0

0

1

8

87.5%

0.0%

0.0%

12.5%

100.0%

36

22

2

1

61

59.0%

36.1%

3.3%

1.6%

100.0%

Count % within AGECAT

AGE 21-40

Count % within AGECAT

MISCELLANEOUS

AGE 41-60

Count % within AGECAT

AGE 61-80

Count % within AGECAT

Total

Total

Under WT

Count % within AGECAT

Table 4: Tuberculosis; Gender – BMI Correlation BMICAT Sex

F

Under WT

Normal

Over WT

Type 1 OB

10

6

0

0

16

62.5%

37.5%

0.0%

0.0%

100.0%

26

16

2

1

45

57.8%

35.6%

4.4%

2.2%

100.0%

36

22

2

1

61

59.0%

36.1%

3.3%

1.6%

100.0%

Count % within SEX

M

Count % within SEX

Total

Total

Count % within Sex

•

Do you have increased hunger, palpitations, stools and tremor?

sweating,

•

Have you diarrhea or constipation?

•

Are you drinking more water than previous?

•

Identify and treat the underlying cause.

•

Is there history of frequent micturition?

•

•

Do you feel sad or depressed?

Treat the underlying metabolic, psychiatric, infectious or other systemic disorder.

•

What medicines are you taking frequently without doctor’s prescription?

•

Then restore functional status gradually.

•

Medications causing nausea or anorexia should be avoided or changed.

•

The underlying disorder is treated. If an underlying disorder causes under nutrition and is difficult to treat, nutritional support should be considered.

•

Helpful general behavioral measures include encouraging patients to eat, assisting them with feeding, offering snacks between meals and before bedtime.

•

Providing favorite or strongly flavored foods, and offering only small portions.

•

If behavioral measures are ineffective and weight loss is extreme, enteral tube feeding can be tried if patients have a functioning GI tract.

•

Measures of lean body mass are followed serially.

•

Appetite stimulants have not been shown to prolong life.

Lab tests •

Complete blood counts

•

Serum chemistry (serum electrolytes, calcium, hepatic and renal function tests)

•

Ferritin levels

•

Thyroid function tests, Serum levels of vitamin D3

•

ESR and C- reactive protein

•

Complete urinalysis

•

HIV screening if indicated

•

Chest radiography

•

Abdominal ultra sound

•

Age, sex and risk factor- specific cancer screening tests such as mammography and colonoscopy

•

If weight loss continues and all other findings

remain normal, further testing (eg, CT, MRI) should be considered.

Management

365

Table 5: Cancer; Age – BMI Correlation BMICAT AGECAT Age Below 20

Count % within AGECAT

Age 21-40

Count % within AGECAT

Age 41 -60

Count % within AGECAT Count % within AGECAT

Total

Count % within AGECAT

•

Normal

Over WT

Class 1 OB

3

1

0

0

4

75.0%

25.0%

0.0%

0.0%

100.0%

2

10

5

2

19

10.5%

52.6%

26.3%

10.5%

100.0%

9

22

8

2

41

22.0%

53.7%

19.5%

4.9%

100.0%

5

18

6

3

32

15.6%

56.3%

18.8%

9.4%

100.0%

19

51

19

7

96

19.8%

53.1%

19.8%

7.3%

100.0%

In addition, malnutrition can lead to vitamin and other deficiencies and to inactivity, which in turn may pre-dispose to other problems, such as pressure sores.

Hemoptysis, coupled with poor living conditions.

Sputum for AFB will clinch the diagnosis; and treated with appropriate regimen of anti tuberculosis drugs.

•

Unintentional weight loss can be the characteristic leading to diagnosis of diseases such as cancer and Type 1 diabetes.

Increased appetite, loss of weight, anxiety tremor, sweating, diarrhea – T3, T4 raised and TSH decreased treated with Propylthiouracil, carbimazole or methimazole

•

Some medications e.g. metformin can cause weight loss, while others can cause weight gain.

ARE THERE ANY CONSTRAINS?

Social conditions •

•

•

Social conditions such as poverty, social isolation and inability to get or prepare preferred foods can cause unintentional weight loss, and this is most common in older people living alone.

Nutrient intake can also be affected by culture e.g.

Indian vegetarians avoid non veg. items, due to family traditions. Sometimes Ill-fitting dentures and other dental or oral health problems can also affect adequacy of nutrition.

Loss of hope, status or social contact and spiritual distress can cause depression, which may be associated with reduced nutrition.

Hyperthyroidism12

Bacterial endocarditis13

Fever, night sweats, joint pains, shortness of breath, fatigue, valvular heart disease, Musical murmurs – echocardiography, blood cultures required- treated with appropriate intravenous antibiotics for 4-6 weeks.

Sarcoidosis

A disease of unknown etiology with noncaseating granulomas, fever, fatigue, cough, SOB, night sweats, mediastinal lymphadenopathy, CVS – conduction defects; CNS- seizures, facial palsy, treated with corticosteroids.

Adrenal insufficiency

Adrenal insufficiency resulting from destruction of adrenal cortex, low glucocorticoid, mineralocorticoids, low adrenal androgens – malaise, fatigue, general weakness, nausea, vomiting, anorexia weight loss. It is treated with steroid replacement.

Treatment related

HIV / AIDS14

Surgery related

Malabsorption syndrome15

•

Medical treatment with certain drugs (cancer chemotherapy drugs, DMARDs can directly or indirectly cause weight loss, impairing the treatment effectiveness and recovery.

Fever, diarrhoea, lymphadenopathy, SOB, associated fungal infections due to reduced immune status – western blot positive and HIV viral load – treated with HAART and other suitable measures.

Some important conditions with weight loss

Diarrhoea, steatorrhea, weight loss and fatigue, flatulence and abdominal distention, anemia and edema, bleeding disorders, bone pain and pathologic fractures, - endoscopy, CT and Ultra Sound abdomen, barium studies, tests for fat, carbohydrate and protein absorption, - treated with gluten free diet if necessary, avoidance of milk and milk products, corticosteroids, low fat diet.

Pulmonary Tuberculosis11

Worm infestation16

•

Many patients will be in pain and have a loss of appetite after surgery.

•

Certain patients of TB intestines may undergo resection of large segments leading to malabsorption.

Evening rise of temperature, night sweats, cough,

Fever and abdominal pain, bloating, flatulence, diarrhoea,

CHAPTER 65

Age Above 61

Total

Under WT

MISCELLANEOUS

366

Fig. 1: M40 yr, BMI - 12.64kg/m2; Height 164cm, Weight 34 kg; Alcoholic with Malnutrition

Fig. 3: F35 yr, BMI- 13.67kg/m2 ; Height 153cm, Weight 32kg; Carcinoma Esophagus - microscopic examination of stools reveal ova.- treated with albendazloe / mebendazole.

Giant cell arteritis17

Elderly people with headache, muscle pain, Jaw claudication, fever, visual disturbances; blood counts (raised ESR), Temporal artery biopsy; Treated with corticosteroids.

Depression18

Fatigue, sadness, loss of sexual desire or pleasure, sleep disturbances â&#x20AC;&#x201C; detailed history is important. â&#x20AC;&#x201C;physical examination-normal, treated with antidepressants and behavioral therapy.

Cancer

Night sweats, fatigue, fever, bone pain, organ related

Fig. 2: M25 yr BMI - 13.72kg/m, Height 171cm, Weight40 kg; Pulmonary Tuberculosis

Fig. 4: M30 yr, BMI - 14.2kg/m2; Height 168cm, Weight 40kg; Type 1 Diabetes Mellitus complaints- dysphagia in case of carcinoma esophagus, jaundice and pain abdomen in case of Hepatocellular carcinoma, cough and Hemoptysis in case of bronchogenic carcinoma, rectal bleed in cases of colorectal cancer, breast cancer19,20 etc. Appropriate chemotherapy/ Surgery/ Radiotherapy.

Alcoholism21

History of drinking excess alcohol, features suggestive of liver cell failure, gynaecomastia, breast atrophy, bilateral parotid enlargement etc. Appropriate behavioral counseling / De-addiction therapy.

Note

Cross sectional retrospective studies with respect to patients with pulmonary tuberculosis and patients with cancer reveled following results with regard to BMI

367

CHAPTER 65

Fig. 5: M60 yr, BMI - 14.69kg/m; Height 165cm, Weight 40kg; Pulmonary Tuberculosis

Fig. 7: Algorithm

REFERENCES

1.

Alibhai SM, Greenwood C, Payette H. An approach to the management of unintentional weight loss in elderly people. CMAJ 2005; 172:773-780

2.

Wong CJ. Involuntary weight loss: Med Clin North Am 2014; 98:625.

3. Bales CW, Ritchie CS, Sarcopenia, weight loss, and nutritional frailty in the elderly. Annu Rev Nutr 2002; 22:309.

4.

Fig. 6: Skin Fold Thickness Measurement Pulmonary tuberculosis •

Cancer •

In patients with sputum positive pulmonary tuberculosis: 45 are males and 16 are females (total 61 patients, age ranging from 18 to 80 years).

36(59.0%) are under weight, 22 (36.1%) are normal weight and 3(4.9%) are over weight and obese. (P value - 0.035) wide Tables 3 and 4.

In patients with cancer 19(19.8%) are under weight, 51(53.1%) are normal weight and 26(27.1%) are over weight and obese (Total 96 patients, age ranging from 18 to 80 years ). (P value - 0.325) wide Table 5.

CONCLUSION

Involuntary or unintentional weight loss is a significant cause of morbidity and mortality, which can be either minimized or prevented depending on case scenario.

Most of the times, the cause is approachable, identifiable and manageable. Barring certain congenital diseases like cystic fibrosis, in many situations, it can be addressed to a reasonable level of satisfaction with a methodical approach, wide Figure 7.

ZamboniM, Rossi AP, Corzato F, Bambace C, Mazzali G, Fantin F. Sarcopenia, Cachexia and congestive heart failure in the elderly. Endocr Metab Immune Disord Drug Targets 2013; 13:58-67.

5. Compston, Juliet E. et al. “Increase in Fracture Risk Following Unintentional Weight Loss in Postmenopausal Women: The Global Longitudinal Study of Osteoporosis in Women.” Journal of bone and mineral research : the official Journal of the American Society for Bone and Mineral Research 2016; 31.7:1466–1472.

6.

Holick MF. Resurrection of vitamin D deficiency and rickets. The Journal of Clinical Investigation 2006; 116:20622072. doi:10.1172/JCI29449.

7.

Judd LL, Akiskal HS, Schettler PJ, et al A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen psychiatry 2003; 60:261

8. Robbins LJ. Evaluation of weight loss in the elderly.

Geriatrics 1989; 44:31 9. National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI). The practical guide: identification, evaluation, and treatment of overweight and obesity in adults. Bethesda: National Institutes of Health 2000, NIH publication 00-4084.

10. Khosla T, Lowe CR. Indices of obesity derived from body weight and height. Br J Prev Soc Med 1967; 21:122-128.

11. Schwenk A, Macallan DC. Tuberculosis, malnutrition and wasting. Curr Opin Clin Nutr Metab Care 2000; 3:285– 291. [PubMed] 12. Dutta P, Bhansali A, Walia R, Khandelwal N, Das S,

368

Masoodi SR. Weight homeostasis & its modulators in hyperthyroidism before & after treatment with carbimazole. The Indian Journal of Medical Research 2012; 136:242-248.

MISCELLANEOUS

13. Yuan S-M. Right-sided infective endocarditis: recent epidemiologic changes. International Journal of Clinical and Experimental Medicine 2014; 7:199-218.

14. Sebastian, Shibu Thomas, and Sunitha Siddanna. “Social, Psychological and Health Concerns of People Living with HIV/AIDS in Mysore District, Karnataka.”Journal of Clinical and Diagnostic Research : JCDR 10.3 (2016): LC06–LC10.

PMC. Web. 19 Aug. 2016.

15. Ghoshal UC, Mehrotra M, Kumar S, et al. Spectrum of malabsorption syndrome among adults & factors differentiating celiac disease & tropical malabsorption. The Indian Journal of Medical Research 2012; 136:451-459.

16. Acka CA, Raso G, N’Goran EK, et al. Parasitic Worms: Knowledge, Attitudes, and Practices in Western Côte d’Ivoire with Implications for Integrated Control. Diemert DJ, ed. PLoS Neglected Tropical Diseases 2010; 4:e910. doi:10.1371/journal.pntd.0000910

17. Shukla S, Hull R. Unintentional weight loss. Think of giant cell arteritis. BMJ 2011; 342:d2889 18. Grover S, Dutt A, Avasthi A. An overview of Indian research in depression. Indian Journal of Psychiatry 2010; 52(Suppl1):S178-S188. doi:10.4103/0019-5545.69231.

19. Mathew, A et al. “Anthropometric Factors and Breast Cancer Risk among Urban and Rural Women in South India: A Multicentric Case–control Study.”British Journal of Cancer 99.1 (2008): 207–213. PMC. Web. 19 Aug. 2016.

20. Davis IJ et al. unintentional weight loss as the sole indication colonoscopy is associated with colorectal cancer.

J Am Board Fam Med 2011; 24:218-19[PMID:21383224] 21. Gupta A, Priya B, Williams J, et al. Intra-household evaluations of alcohol abuse in men with depression and suicide in women: A cross-sectional community-based study in Chennai, India. BMC Public Health 2015; 15:636. doi:10.1186/s12889-015-1864-5.

Sleep as Prescription

C H A P T E R

66

Anil Bhoraskar

Sleep Physiology - Sleep is the greatest gift of God to the mankind.

and that chronic poor sleep is now associated with an increased risk for:

Normal human sleep can probably be described as “a reversible behavioural state of perceptual disengagement and unresponsiveness to the environment”. Sleep is vital for our good health. Most of us know that when we do not sleep well we feel tired and irritable.1,2 Some of the more well-recognized results of poor sleep are:

• obesity

•

impaired thinking

•

reduced learning ability

•

decreased libido1,2

Most of the complex problems get solved if we “sleep over it“, However, many of us do not realize that poor sleep also affects our cardiovascular and metabolic health,

Table 1: Stages of NREM sleep Stage

Characteristics

N1

Transitional stage from wakefulness to sleep.

Brain and body begin to relax; muscle jerking/twitching is fairly common.

Most people without sleep disorders spend just a few minutes in stage N1.

N2

As the body further relaxes, breathing and heart rate slow down and become regular.

Most adults spend about 50% of their total sleep time (TST) in this stage.

Sleep spindles (bursts of brain activity to keep sleep tranquil) and K complexes (brain responses to stimuli), are two commonly observed traits.

N3

May be referred to as deep sleep or slow wave sleep (SWS) due to the types of brain waves seen during a sleep study.

Deepest of all sleep stages, revealing the slowest breathing and heart rate of the night.

The sleeper is very difficult to arouse; there are no noticeable eye movements.

As people age, this stage decreases. Because of the restorative physiological processes that occur during N3, this may explain why older adults report a lack of the same restorative benefits during sleep as when they were younger.

•

hypertension and heart disease

•

type 2 diabetes3-7

Poor sleep may be a result of not giving yourself enough time to sleep. But if you do sleep long enough, it may be that your quality of the sleep is poor due to an undiagnosed sleep disorder. Either way, it is likely that you may have adverse health outcomes including impaired cognitive or mental processing and functioning.4-6 Conversely, a good night’s sleep allows you to awake refreshed and energized, ready to take on all the challenges of the day—both mentally and physically. In short, good sleep improves your quality of life.8-10 Sleep structure changes from night to night depending on the sleeper’s physical and psychological state and environmental conditions. For most people, sleep is composed of two very distinct types of sleep: •

non-rapid eye movement (NREM)

•

rapid eye movement (REM)11-12

At the beginning of sleep, sleepers may fluctuate between Stage W (wakefulness) and Stage N1 of NREM sleep.

During Stage W, the patient may range from full alertness through to the early stages of drowsiness.

Table 2: REM sleep Stage

Characteristics

REM

Most dreams take place during this stage.

Heart rate and breathing become more irregular.

Sleeper experiences almost total muscle paralysis except for the diaphragm.

Occurs roughly every 90 minutes and progressively increases in duration over the course of the night.

Occurs after stage N3 in the first part of the night and occasionally after stage N2 as sleep progresses.

First cycle lasts approximately 10 minutes and can progress up to 25 minutes.

Typically accounts for 20–25% of TST.

370

After Stage W, the sleeper begins NREM sleep with the following stages (Table 1):11-14 The following Table 2 describes what happens during REM sleep11,13,12,15

PHYSIOLOGICAL CHANGES DURING SLEEP

MISCELLANEOUS

During sleep, many of our biological functions undergo change. Sleep is an inactive state for most of our systems, thereby allowing our mind and body to rest and perform essential activities. For example: During sleep there is less need to be vigilant, and as a result, there is a generalized decrease in our central nervous system activity, allowing our nervous system time to rest and restore.4,11,13,16 Our heart rate and blood pressure decrease allowing for rest and repair of the heart and vascular system.6,9,11 As our metabolic needs are not as great in sleep, our breathing rate decreases giving our respiratory system a time to rest and repair.11,13,17 While most of our bodily functions undergo rest during sleep, our hormonal production system is very active. It is during sleep, particularly stage N3, that our growth hormones, essential to our good health and good metabolism, are produced. Without sufficient sleep we have an imbalance in these hormones and our metabolic health is adversely affected.4,12,14,18

SLEEP DEPRIVATION

The effects of sleep deprivation are the results of not allowing either our body or mind sufficient time to rest and to carry out the vital functions that can only occur during sleep. When we get insufficient sleep, we do not get to rest, restore or conserve energy adequately which adversely affects our cognitive, cardiovascular and metabolic health.4,10,19 The accumulation of lost sleep is like monetary debt, which needs to be paid back eventually. Consequences of sleeplessness include:12,10,6,8,17 •

deficiency in alertness and attentiveness

•

increase in irritability, lethargy and other mood problems

•

lack of concentration and judgment

•

difficulty in conducting simple tasks

•

decline in productivity

•

higher risks for developing anxiety or depression

•

increased risk of developing coronary disease

•

lack of control over sleepiness and unintentionally falling asleep

•

physical symptoms of sleep deprivation, including headaches, gastrointestinal problems and more.

SLEEP DISORDERS

There are over 80 documented sleep disorders which

affect either the quality or quantity of sleep. Many of these disorders have the potential to seriously disrupt sleep and have long-term ill-effects on our health. Therefore, it is important to diagnose and treat them quickly.10

Insomnia

Insomnia is defined as trouble falling or staying asleep. If you suffer from insomnia, it affects both your waking and sleeping hours.10 Insomnia may be: •

transient—a few nights

•

short term—two or three weeks

•

chronic—poor sleep every night or most nights.

Insomnia afflicts people of all ages and it is estimated that up 35% of adults suffer from insomnia at some time during their life.

Insomnia has many possible causes and may be a result of: •

internal factors—such as depression or a tumor

• external factors—primarily those surrounding good sleep hygiene.

factors

Many cases of insomnia can be improved with the implementation of good sleep hygiene, including developing relaxation methods for coping with stress and improving the sleeping environment.12,10,19 Sleep Deprivation as a Fashion –Many teen agers as well as young adults deliberately sleep less, as it is considered as IN THING to sleep less , many young executives who are working for American companies sitting in India work at American time and keep up whole night can never get 8 hrs of good sleep. Many teen agers keep up and sleep late not for studies but to be playing on their computers or mobiles on what’sup. Frequent fliers fly out of India at odd hrs and rarely sleep well on board.

Most flights leave India at late night to suit European and American airports which close down at nights unlike ours and it is fashionable for a dynamic CEO of a company to fly overnight and come to the work next morning before the rest of the staff just to show off his or her dedication and fitness! All these eventually has a toll on their health of both body and mind. The average sleeping time over a period of last 20 years has reduced from 8 hrs to 5 hrs or fragmented sleep of a period from 2 to 3 hrs.

Learned insomnia, a result of a period of insomnia causing an ongoing fear of the insomnia repeating itself, is often improved by cognitive behavioural therapy.1

NARCOLEPSY

Narcolepsy is a neurological disorder that causes uncontrollable daytime sleepiness. It affects the part of the brain that regulates sleep and wakefulness, resulting in the sudden onset of REM sleep. Symptoms typically begin between puberty and age 25, developing slowly over months or years.10,9,2 Narcolepsy usually goes undiagnosed for many years.

Narcolepsy is characterized by:

371

Table 3: Symptoms of Narcolepsy Description

Excessive daytime sleepiness

Episodes of falling asleep at inappropriate times.

Usually the earliest sign of narcolepsy.

Cataplexy

Abrupt loss of strength brought on by strong emotions like surprise, joy, anger or fear.

Hypnagogic hallucinations

Auditory, visual and tactile hallucinations that take place at sleep onset.

Atonia

Paralysis occurring between waking and sleeping.

Note: In this illustration, the size of the disorder indicates the relative frequency of occurrence. OSA is the largest because it is the most common SDB.

Fig. 1: Sleep Disordered Breathing •

Central sleep apnoea syndrome (CSA)

•

a frequent and irresistible need for sleep

•

Cheyne-Stokes Respiration (CSR)

•

occasional paralysis and hallucinations

•

Nocturnal hypoventilation (NH)16,17,19

•

sudden and uncontrollable attacks of deep sleep that are often brief, lasting from a few seconds to 30 minutes or more.

The Figure 1 below shows the different disorders that fall under the umbrella of SDB.

The following Table 3 lists the four primary symptoms of narcolepsy. Only 25% of people with narcolepsy have all four symptoms, though all experience excessive daytime sleepiness (EDS), with sudden episodes of sleep onset at inappropriate times.2,9,10,12,19 Narcoleptics may take anywhere from 1–6 naps/day.

Currently no cure exists, but its symptoms can be controlled through lifestyle management and medications such as stimulants and antidepressants.2,10

PARASOMNIAS

Parasomnias are a category of sleep disorders that involve abnormal movements, behaviours, emotions and perceptions that occur while: •

falling asleep

•

during sleep

•

arousal from sleep.10,12,19

Parasomnias are classified according to the sleep state in which they occur, either NREM or REM.

NREM PARASOMNIAS (TABLE 4)

The following parasomnias typically occur during NREM sleep:

REM PARASOMNIAS (TABLE 5)

The following parasomnias typically occur during REM sleep:

Sleep Disordered Breathing (SDB) (TABLE 6)

Sleep Disordered Breathing (SDB) is the general term used to describe any sleep related breathing abnormalities.

SDB describes a number of clinical disorders including: •

Obstructive sleep apnoea syndrome (OSA)

SDB describes a number of different disorders that affect breathing during sleep. The following Table 4 lists and describes these disorders:

Obstructive Sleep Apnea (OSA)

Obstructive sleep apnoea (OSA) is a sleep disorder that involves cessation or significant decrease in airflow in the presence of breathing effort. It is the most common type of sleep-disordered breathing and is characterized by recurrent episodes of upper airway collapse during sleep. These episodes are associated with recurrent oxyhaemoglobin desaturations and arousals from sleep.5,6,10,11,13,16,17

Prevelance

Various studies indicate the prevalence of OSA in India is between 4-21 percent in males and between 2.5-7.4% in females. Here is a list of studies in India which have been done on OSA (Table 7).

These figures closely match global figures – the study by Peppard et al21 in US studied 1520 participants concluded that the prevalence of OSA is 14% in males and 5% in females. Similarly, the study by Young et al22 puts the prevalence at 24% of men and 9% of women, between 30 and 60 years old with average BMI from 25 to 28.

SIGNS AND SYMPTOMS

Adults

Diurnal •

Excessive daytime sleepiness

• Hypertension •

Depression, irritability

•

Fatigue, lack of energy

•

Morning headaches

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Symptom

372

Table 4: NREM Parasomnias Disorder

Description

Restless leg syndrome (RLS)

This disorder often appears in otherwise healthy people.

RLS affects primarily the legs, but is seen in the arms as well.

People experiencing restless legs all describe it as a very unpleasant “creepy, crawly” sensation that occurs in the legs when they are sitting or lying still.

MISCELLANEOUS

Symptoms occur primarily when awake, and they may also be present during sleep.

The constant need to stretch or move the legs often prevents a person with RLS from achieving and maintaining sleep.

RLS affects 5–10% of the population, and is more common in older individuals.10,19 Disorder Description Periodic limb movement disorder (PLMD)

While the movements of RLS are a voluntary response to uncomfortable feelings, the movements of PLMD only occur when a person is asleep and are involuntary.

Periodic limb movements usually occur in the legs but can also affect the arms. The movements occur at periodic intervals, typically every 30 seconds.

The incidence of PLMD increases with age and men and women are equally at risk.

The cause of PLMD is unclear, but it is more common in people who have kidney disease or narcolepsy.

Some antidepressant medications can also increase the frequency of limb movements.10,12,19

Night terrors and sleepwalking

Both night terrors and sleepwalking arise during NREM sleep and occur mostly in children between the ages of three and five.

Treatment is rarely needed and these parasomnias usually do not indicate any underlying medical or psychological problems.

Children generally outgrow them.19

Bruxism

This is one of the most common sleep disorders.

It is characterized by the grinding of teeth and the clenching of the jaw. In its more severe form, if left untreated, it can cause major health issues.19,20

Table 5: REM Parasomnias Disorder

Description

REM behaviour disorder

This is the ability to act out your dreams.

Ordinarily all body muscles, with the exception of those used in breathing, are usually paralysed during REM sleep.

However, in some cases this paralysis is incomplete or absent, thus allowing dreams to be acted out. u such as this can be violent and result in serious injuries to the victim and bedpartner.

After awakening, the sleeper is usually able to recall vivid dreaming.2,12,19

Nightmares

Nightmares are frightening dreams that arise during REM sleep.

They can be caused by stress, anxiety, and some drugs.

When nightmares frequently interfere with sleep, treatment with cognitive behavioural interventions is sometimes undertaken.19

373

Table 6: Sleep Disordered Breathing Type

Description

Obstructive sleep apnea (OSA)

Also known as OSA or in some cases simply referred to as SDB. This syndrome is characterized by repeated episodes of the collapse and the reopening of the upper airway during sleep occurring at a rate of five or more per hour.

Some symptoms of the disease are: • snoring • witnessed apnoeas • daytime sleepiness2,15–17

Central Sleep Apnea (CSA)

CSA is characterized by no effort and no airflow for periods of 10 seconds or more.

This syndrome is characterized by CSAs occurring at a rate of five or more per hour during sleep.

In contrast to OSA, in CSA there is no snoring and the person is frequently unaware that they have SDB. However, symptoms may include: • excessive daytime sleepiness/daytime fatigue • insomnia • frequent arousals.

CSA is categorized according to the patient’s blood CO2 level: • Hypercapnic CSA: When the CSA is associated with high levels of CO2 it is referred to as hypercapnic CSA. This type of CSA is discussed in depth in the section on Nocturnal Hypoventilation.

• Non-hypercapnic CSA: When CSA is associated with normal/low levels of CO2, it is referred to as non-hypercapnic CSA. This includes Cheyne-Stokes respiration (CSR) and Complex Sleep Apnoea (CompSA).5,10,12,16

Cheyne-Stokes Respiration (CSR)

This is a type of CSA and is often seen in patients with heart failure and in some patients after a stroke.

• CSR is often under-diagnosed as it is a silent disorder.

• CSR is a breathing pattern characterized by a period of apnea lasting approximately 20 seconds followed by a gradually increasing of depth and frequency of depth, and frequency of respirations. it is also known as a waxing and waning pattern alternating with either apnoeas or hypo apnoeas.

• CSR is common in patients with congestive heart failure and is detrimental to sleep quality and the general health of these patients. Statistically it leads to increased morbidity and mortality.5,10,12,16,19

Nocturnal Hypoventilation (NH)

Nocturnal hypoventilation, or NH, is a reduced rate and depth of breathing.

• It occurs due to the loss of muscle tone during sleep, especially during REM sleep.

• Nocturnal hypoventilation often occurs in patients with: - chronic obstructive pulmonary disease (COPD) - neurological impairments - restrictive diseases (eg, scoliosis) - obesity11,19

•

Concentration and memory problems

Nocturnal

•

Mood Swings

• Snoring

• Diabetes

•

Partner-witnessed apnoeas

•

Irregular breathing during sleep

CHAPTER 66

• restless sleep

374

Table 7: Studies of Obstructive Sleep Apnea Author

Sample Size

OSA Percentage

Questionnaire

Sleep Study

Overall

Males

Females

Udwadia Et Al, 2004

658

250

NA

19.5

NA

Sharma Et Al, 2006

2150

150

13.7

19.7

7.4

Viiayan Et Al, 2006

7975

47

3,5

4.4

2.5

Reddy Et Al, 2009

2505

365

9,3

13.5

5.6

MISCELLANEOUS

• Nocturia •

Sexual dysfunction

•

Cardiac arrhythmias

•

Night sweats10,16,17,23

Children

Although this so-called “hypersomnolence” (excessive sleepiness) may also occur in children, it is not at all typical of young children with sleep apnoea. Toddlers and young children with severe OSA instead ordinarily behave as if “over-tired” or “hyperactive.” Adults and children with very severe OSA also differ in typical body habitus. Adults are generally heavy, with particularly short and heavy necks. Young children, on the other hand, are generally not only thin, but may have “failure to thrive”, where growth is reduced. Poor growth occurs for two reasons: the work of breathing is intense enough that calories are burned at high rates even at rest, and the nose and throat are so obstructed that eating is both tasteless and physically uncomfortable. OSA in children, unlike adults, is often caused by obstructive tonsils and adenoids and may sometimes be cured with tonsillectomy and adenoidectomy.

This problem can also be caused by excessive weight in children. In this case, the symptoms are more like the symptoms adults feel: restlessness, exhaustion, etc.

Children with OSA may experience learning and memory deficits and OSA has also been linked tolowered childhood IQ scores.16,17,23

COMPLICATIONS3,6,15,17,23–27

Screening and diagnosis

The screening of OSA is done based on clinical evaluation, and through the help of various standard questionnaires like the Epworth Sleepiness Score, the Berlin Questionnaire or the STOP-BANG questionnaire.15,15,23,17,24 In certain cases, overnight oximetry may also be used for screening OSA. The diagnosis is done through a sleep study, which may either be done at home, or in a hospital. There are various types of sleep studies - as follows:

Type 1 device: Full Polysomnography (PSG) In-lab study including audio-visual.

Over 24 channels, including EEG, EOG, EMG, ECG, thermistors and pressure transducer, respiratory effort, SaO2, body position, limb movement. While this is the gold

standard, it is usually expensive and should be reserved for diagnosing sleep disorders other than OSA, or for patients having OSA and significant comorbidities.15,17,20

Type 2 device: Ambulatory PSG

In-lab or in-home, with cut down version of PSG and usually without audio-visual. Indications are similar to type 1.23

Type 3 device: Polygraphy (PG)

Studies using atleast four channels at home or hospital, including pressure transducer, snore, respiratory effort and Sp02. This is usually adequate for diagnosis for OSA – unless there are significant comorbid conditions.23

Type 4 device

Screening devices - Usually one/two channels These devices measure the AHI – or the apnoea hypopnea Index – which is the diagnostic measure of OSA. The Apnoea–Hypopnea Index or Apnoea–Hypopnoea Index (AHI) is an index used to indicate the severity of sleep apnoea. It is represented by the number of apnoea and hypopnea events per hour of sleep. The apnoeas (pauses in breathing) must last for at least 10 seconds and be associated with a decrease in blood oxygenation.

Combining AHI and oxygen desaturation gives an overall sleep apnoea severity score that evaluates both the number of sleep disruptions and the degree of oxygen desaturation (low blood level).5,6,10,17,23,28 The AHI is calculated by dividing the number of apnoea events by the number of hours of sleep. The AHI values are categorized as: Normal: 0-4 Mild sleep apnoea: 5-14 Moderate sleep apnoea: 15-29 Severe sleep apnoea: 30 or more

Treatment

In mild cases, avoiding alcohol and smoking is recommended, as is avoiding medications that relax the central nervous system (for example, sedatives and muscle relaxants). Weight loss is recommended in those who are overweight. Continuous positive airway pressure and mandibular advancement devices are often used.

Physical training, even without weight loss, improves sleep apnoea.6,3,9,10,16,17,23,24,29,26 For moderate to severe cases, the most widely used current

Table 8: Complications of sleep disorders Cardiovascular

• Insulin resistance (type 2 diabetes)

• Hypertension

• Metabolic syndrome

• Rhythmic problems

• Weight gain

• Cerebrovascular events

• Nocturia

• Myocardial infarction

• Sexual dysfunction

• Heart failure

Behavioural

Others

• Cognitive and memory problems

• Excessive daytime sleepiness

• Irritability

• Fatigue-related accident

• Concentration difficulties • Headaches • Premature aging

Fig. 2: OSA Related Medical Problems therapeutic intervention is positive airway pressure whereby a breathing machine pumps a controlled stream of air through a mask worn over the nose, mouth, or both. The additional pressure holds open the relaxed muscles.6,7,10,12,16,17,20,24 There are several variants: Continuous positive airway pressure (CPAP) is effective for both moderate and severe disease.

(APAP), or automatic positive airway pressure, also known as “Auto CPAP”, is the newest form of such treatment. An APAP machine incorporates pressure sensors and a computer which continuously monitors the patient’s breathing performance.26,27 CPAP and APAP aregold standard treatment for obstructive sleep apnoea.

(VPAP), or variable positive airway pressure, also known as bilevel or BiPAP, uses an electronic circuit to monitor the patient’s breathing, and provides two different pressures, a higher one during inhalation and a lower pressure during exhalation. This system is more expensive, and is sometimes used with patients who have other coexisting respiratory problems and/or who find breathing out against an increased pressure to be uncomfortable or disruptive to their sleep.10,17,26 Oral appliances or splints may be tried in mild to moderate cases, but are not as effective as CPAP and need to be individually tailored for them to be effective.9,10,12,17,23,24,26,29 Surgical treatments to modify airway anatomy, known as sleep surgery, are varied and work only in selected patients with obvious anatomical abnormalities.6,15,17,23,24,26

REFERENCES

1. Mansel JK, Carey EC. Nonpharmacologic Approach to Sleep Disorders 2014; 20:345–51.

• Depression 2.

Ramar K, Olson EJ. Management of common sleep disorders.

Am Fam Physician [Internet]. 2013; 88:231–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23944726

3. Zhang W, Si L. Obstructive sleep apnea syndrome (OSAS) and hypertension: pathogenic mechanisms and possible therapeutic approaches. Ups J Med Sci [Internet]. 2012; 117:370–82. Available from: http://www.pubmedcentral. nih.gov/articlerender.fcgi?artid=3497224&tool=pmcentrez &rendertype=abstract 4.

Briançon-Marjollet A, Weiszenstein M, Henri M, Thomas A, Godin-Ribuot D, Polak J. The impact of sleep disorders on glucose metabolism: endocrine and molecular mechanisms.

Diabetol Metab Syndr [Internet]. 2015; 7:25. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25834642\ nhttp://www.pubmedcentral.nih.gov/articlerender. fcgi?artid=PMC4381534

5. Moon K, Punjabi NM, Aurora RN. Obstructive sleep apnea and type 2 diabetes in older adults. Clin Geriatr Med [Internet]. 2015; 31:139–47, ix. Available from: http://www. ncbi.nlm.nih.gov/pubmed/25453306 6. Jean-Louis G, Zizi F, Brown D, Ogedegbe G, Borer J, McFarlane S. Obstructive sleep apnea and cardiovascular disease: evidence and underlying mechanisms. Minerva Pneumol [Internet]. 2009; 48:277–93. Available from: /pmc/ articles/PMC3106988/?report=abstract 7. Kiran Devulapally1, Raymond Pongonis Jr.2, and Rami Khayat1 3. OSA: the new cardiovascular disease: Part II: overview of cardiovascular diseases associated with obstructive sleep apnea. Hear Fail Rev 2009; 14:155–64.

8.

Watson NF, Badr MS, Belenk G, Bliwise DL. Recommended amount of sleep for a healthy adult. Am Acad Sleep Med Sleep Res Soc 2015; 38:843–4.

9.

Pepin JL, Borel AL, Tamisier R, Baguet JP, Levy P, Dauvilliers Y. Hypertension and sleep: Overview of a tight relationship.

Sleep Med Rev [Internet]. 2014; 18:509–19. Available from: http://dx.doi.org/10.1016/j.smrv.2014.03.003

10. Khoury J, Doghramji K. Primary Sleep Disorders. Psychiatr Clin North Am [Internet]. 2015; 38:683–704. Available from: http://dx.doi.org/10.1016/j.psc.2015.08.002

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Metabolic

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11. Sowho M, Amatoury J, Kirkness JP. Sleep and Respiratory Physiology in Adults 2016; 35:469–81.

12. Gooneratne NS, Vitiello M V. Sleep in older adults: normative changes, sleep disorders, and treatment options.

Clin Geriatr Med [Internet]. 2014; 30:591–627. Available from: http://www.pubmedcentral.nih.gov/articlerender.fc gi?artid=4749027&tool=pmcentrez&rendertype=abstract

MISCELLANEOUS

13. Ross KR, Rosen CL. Sleep and respiratory physiology in children. Clin Chest Med [Internet]. 2014; 35:457–67.

Available from: http://dx.doi.org/10.1016/j.ccm.2014.06.003 14. Mesarwi O, Polak J, Jun J, Polotsky VY. Sleep disorders and the development of insulin resistance and obesity.

Endocrinol Metab Clin North Am [Internet]. 2013; 42:617– 34.

Available from: http://www.ncbi.nlm.nih.gov/ pubmed/24011890 15. Stierer TL. Obstructive Sleep Apnea, Sleep Disorders, and Perioperative Considerations. Anesthesiol Clin [Internet].

2015; 33:305–14. Available from: http://dx.doi.org/10.1016/j. anclin.2015.02.003 16. Dempsey J a, Veasey SC, Morgan BJ, O’Donnell CP. Pathophysiology of sleep apnea. Physiol Rev [Internet].

2010; 90:47–112. Available from: http://www.ncbi.nlm.nih. gov/pubmed/20086074 17. Mannarino MR, Di Filippo F, Pirro M. Obstructive sleep apnea syndrome. Eur J Intern Med [Internet]. 2012; 23:586–93. Available from: http://dx.doi.org/10.1016/j. ejim.2012.05.013 18. Botros N, Concato J, Mohsenin V, Selim B, Doctor K, Yaggi HK. Obstructive sleep apnea as a risk factor for type 2 diabetes. Am J Med [Internet]. 2009; 122:1122–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19958890 19. Sateia MJ. International Classification of Sleep Disorders.

2005;(September):687–701.

20. Kushida C a., Nichols D a., Holmes TH, Quan SF, Walsh JK, Gottlieb DJ, et al. Effects of Continuous Positive Airway Pressure on Neurocognitive Function in Obstructive Sleep Apnea Patients: The Apnea Positive Pressure Long-term Efficacy Study (APPLES). Sleep [Internet]. 2012; 35:1593– 602. Available from: http://www.pubmedcentral.nih.gov/ articlerender.fcgi?artid=3490352&tool=pmcentrez&rendert ype=abstract

21. Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol 2013; 177:1006–14.

22. Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective.

Am J Respir Crit Care Med [Internet]. 2002; 165:1217– 39.

Available from: http://www.ncbi.nlm.nih.gov/ pubmed/11991871 23. Gharibeh T, Mehra R. Obstructive sleep apnea syndrome: Natural history, diagnosis, and emerging treatment options. Nat Sci Sleep 2010; 2:233–55.

24. Rotenberg BW, Vicini C, Pang EB, Pang KP. Reconsidering first-line treatment for obstructive sleep apnea: a systematic review of the literature. J Otolaryngol Head Neck Surg [Internet]. 2016; 45:23. Available from: http://www. pubmedcentral.nih.gov/articlerender.fcgi?artid=4822285& tool=pmcentrez&rendertype=abstract 25. Koren D, O’Sullivan KL, Mokhlesi B. Metabolic and Glycemic Sequelae of Sleep Disturbances in Children and Adults. Curr Diab Rep 2014; 15:1–17.

26. Donovan LM, Boeder S, Malhotra A, Patel SR. New developments in the use of positive airway pressure for obstructive sleep apnea. J Thorac Dis 2015; 7:1323–42.

27. Pamidi S, Tasali E. Obstructive sleep apnea and type 2 diabetes: Is there a link? Front Neurol 2012; 1–13.

28. Gurubhagavatula I, Fields BG, Morales CR, Hurley S, Pien GW, Wick LC, et al. Screening for severe obstructive sleep apnea syndrome in hypertensive outpatients. J Clin Hypertens (Greenwich) [Internet]. 2013; 15:279–88. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25300886 29. Ramar K, Dort LC, Katz SG, Lettieri CJ, Harrod CG, Thomas SM, et al. Clinical Practice Guideline for the Treatment of Obstructive Sleep Apnea and Snoring with Oral Appliance Therapy: An Update for 2015. J Clin Sleep Med [Internet]. 2015; 11:773–827. Available from: http:// www.pubmedcentral.nih.gov/articlerender.fcgi?artid=448 1062&tool=pmcentrez&rendertype=abstract.

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Have Doctors Forgotten the Most Important Diagnostic Tool ?

The patient’s medical history is the single most important factor in making a correct diagnosis. There is good evidence that for the majority of diseases that the history contributes between 70-80% of the diagnosis.1-3 A careful clinical examination will add a further 10-15% and diagnostic tests the remainder. Medical teachers have repeated this mantra to their students for decades but, nowadays, doctors are increasingly investigation orientated. This is to the detriment of the diagnostic process and to the doctor-patient relationship. Repeatedly, in surveys of patient experience, communication failure heads the list of complaints. This is compounded by the introduction of computer screens into the consultation room. Comments such as: ‘The doctor looked at the screen, not at me.’; ‘The doctor talked to me, not with me.’; ‘Nobody listened to my story’ are frequently heard.

Thus it is unsurprising that ‘complementary’ therapies are popular with patients. ‘Conventional’ doctors, steeped in the importance of randomized clinical trials and evidence-based medicine, are often derogatory about these treatments, but, many patients claim benefit. Even in life-threatening conditions such as cancer up to 50% of individuals use such therapies. The common factor is that these practitioners listen, give time and have empathy. By letting the patient tell their story they restore their sense of identity and individuality.

We cannot overemphasize the importance of the patient’s story – or as we term it - the history. Stories seem to be essential to give structure to human life. They impose a framework in which we can interpret life’s central questions. A patient’s story is intrinsic and inseparable from their life, uniquely defining personality and identity. Gaining access to it enables the clinician to reach the nature of their problems, concerns and expectations.

There is a view that investigations (often complex, expensive, invasive and time-consuming) will give the diagnosis more accurately and rapidly. But this approach confuses and complicates the situation with false-positive and negative results and incidental irrelevant findings leading to diagnostic wild-goose chases.

Colin Robertson

The best clinicians seem to have an almost instinctive, even magical, ability to obtain an accurate history. Although this is central to the practice of clinical medicine many doctors simply don’t listen. Recorded doctor-patient interviews show that more than 75% of patients were not allowed to complete even their opening statement of concerns. In addition, elements of sexism intrude: Doctors (both male and female) are more likely to interrupt a female patient than a male one.4 The skills needed to recognise, absorb and interpret a patient’s story are known as ‘narrative competence.5 Narrative competence, requires a return to our early attitudes and experiences a relearning of how to listen to a story and how to give information optimally. This presentation will outline how clinicians can help their patient in this way and facilitate both the diagnostic process but also their management.6 As Sir William Osler said: ‘The good physician treats the disease; the great physician treats the patient who has the disease’.

REFERENCES

1.

Hampton JR, et al. Contributions of history-taking, physical examination and laboratory investigation to diagnosis and management of medical outpatients. British Medical Journal 1974; 2:486-489

2.

Peterson MC, et al. Contributions of the History, Physical Examination and Laboratory Investigation in Making Medical Diagnoses. Western Journal of Medicine 1992; 156:163-5.

3.

Tsukamoto T, et al. The contribution of the medical history for the diagnosis of simulated cases by medical students.

International Journal of Medical Education 2012; 3:78-82.

4. Rhoades DR, et al. Speaking and interruptions during primary care office visits. Family Medicine 2001; 33:528-32.

5. Charon R. Narrative and Medicine. New England J Medicine 2004; 350:863-4.

6. Robertson C, Clegg G. Storytelling in Medicine: How Narrative can improve Practice. ISBN 9781785231377. CRC Press, London. 2016.

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Approach to Disorder of Sweating

ABSTRACT

Physiological sweating is required for normal mechanism of thermoregulation. Hyperhidrosis is characterized by sweating in excess of physiological amount necessary for thermal homeostasis. Hyperhidrosis can be primary disorder or secondary to underlying disorders.

Though hyperhidrosis is not a fatal condition, but can have serious social, emotional & professional consequences.

It is important to be aware of this disorder because the individuals may often do not seek clinicians help because of social inhibition. Currently, wide arrays of local and systemic therapies are available for the treatment of hyperhidrosis. Awareness about availability of various treatment modalities helps in planning and customizing the therapy for the patient to have better quality of life and prevent complications.

INTRODUCTION

Sweating is a common physiological phenomenon. The sweat glands are designed to participate in compensatory thermoregulatory mechanism. Hyperhidrosis is sweating in excess of physiological amount necessary to maintain thermal homeostasis, it is also known as polyhidrosis or sudorrhoea. It is difficult to define excessive sweating; however, the level of hyperhidrosis that affects the quality of life is a good indicator of conventional definition.1 The individuals often delay in seeking help as there could be apprehension.2 We can grade the pathological sweating as mild, moderate & profuse. Several conditions can cause mild hyperhidrosis, a few conditions can produce moderate hyperhidrosis whereas a very few conditions can produce profuse sweating. Clinicians can make a sensible analysis to know the cause and select appropriate available treatment options.

Hyperhidrosis may not contribute to any mortality but, can lead to psychosocial disturbances, personal discomfort, and occupational low output. Affected individuals often are anxious and apprehensive of facing social situations and managing day to day activities. Bacterial byproducts from the excessively colonized organisms can produce bad odor (bromhydrosis) and lead to social discomfort.3,4 Individuals with primary hyperhidrosis tend to sweat from the skin surfaces and these subjects will be at distress and are ashamed to shake their hands with others.5 Excessive dampness due to hyperhidrosis can render the skin susceptible to various fungal and bacterial infections.

Hence, it is important to understand this condition and its

H Basavanagowdappa

complications for better management of the patients with this disorder

KEY WORDS

Hyperhidrosis, sweating, botulinum, Iontophoresis.

EPIDEMIOLOGY

The literature review indicates that the magnitude of primary hyperhidrosis ranges from 1% to 2.8% in general population.6,7 Only 38% of individuals with symptoms of primary hyperhidrosis had sought consultancy with health care professionals, as observed in one of the American surveys. This disorder can present at any age, with the reported prevalence of 1.6% in teenagers. It is uncommon as the age advances, suggesting spontaneous regression.8 Japanese tend to have higher prevalence of palmo-plantar hyperhidrosis (20 times more frequent) compared to other ethnic groups.9 49 out of 58 subjects had family history of hyperhidrosis in a European study, indicating that there can be influence of genetic mutation in some sub-ethnic groups.

Development of sweat glands probably influences axillary hyperhidrosis as the manifestations usually begin at puberty. The most common site of primary hyperhidrosis is axilla (73%), hands (45.9%) and feet (41.1%). The scalp region is fourth common site (22.8%), and least common region is groin (9.3%).10 There is no significant gender difference reported in the literature.

CLASSIFICATION OF HYPERHIDROSIS

1.

Primary hyperhidrosis (unidentifiable cause)

2.

Secondary hyperhidrosis: with an underlying cause

Primary hyperhidrosis: the exact reason for excessive sweating is not clearly identifiable. However, increased sympathetic activity is suspected to be the possible underlying influencing factor. Autosomal dominant pattern of inheritance has been reported in certain ethnic group in palmo-plantar hyperhidrosis.

Secondary hyperhidrosis: Secondary hyperhidrosis can occur due to numerous conditions and several drugs have also been implicated.

Generalized hyperhidrosis â&#x20AC;˘

Infective disorders: chronic infections, such as tuberculosis, malaria, brucellosis, HIV, bacterial endocarditis and few of the acute illnesses produced by viral or other bacterial infections can produce pathological sweating.

• Endocrine: Diabetes with dysautonomia, hypoglycemia, thyrotoxicosis, post-menopausal, pregnancy, Carcinoid syndrome, hyperpituitarism (acromegaly) & pheochromocytoma, •

Nervous system: Autonomic dysfunction, stroke, spinal cord injuries, extrapyramidal disorders like Parkinsonism, Riley-Day syndrome (familial dysautonomia) can be associated with excess sweating,

• Malignancies: Lymphoma myeloproliferative disorders,

other

Medication induced excess sweating: Alcohol, cocaine, heroin, ciprofloxacin, acyclovir, omeprazole, antidepressants,

• Spontaneous periodic hypothermia and hyperhidrosis: This is postulated to be a rare cerebral neurotransmitter disorder, •

Others: congestive heart failure, anxiety, obesity & gout,

Gustatory sweating: sweating around the nose, lips & forehead, commonly occurs after consumption of hot, spicy food. It can also be due to sympathetic nerve damage by diabetic neuropathy.

Chromhidrosis: Coloured sweat is an uncommon idiopathic non-hyperhidrotic condition. Apocrine glands secrete coloured sweat-yellow, blue, green or black. This can occur over face, axilla, groin or areola. The pigment is due to lipofuscin granules.

Emotionally induced hyperhidrosis: It is triggered by fear or anxiety. It mainly affects the palms, soles, and axillae.

Night sweats: It is defined as drenching sweats that require changing bed cloths at night. Benign increased sweat due to overheated room or too many bed coverings needs to be ruled out. Common causes could be-malignancies like lymphoma, solid tumors like prostatic cancer, renal cell carcinoma & insulinoma. Common infections like tuberculosis, HIV, brucellosis & SBE are other possibilities in those with predominant night sweats.

PATHOPHYSIOLOGY

Consensus criteria for diagnosing primary hyperhidrosis11

Localized hyperhidrosis: 1. Abnormal regeneration of sympathetic nerves 2. Peripheral neuropathy 3. Chronic alcoholism (Palmoplantar hyperhidrosis).

Pathophysiology is not clearly known in primary hyperhidrosis. Sweat glands can be of normal density but are found to produce excess sebum. Triggering factors like anxiety, stress, heat, exercise, tobacco, alcohol, and hot spices can contribute to primary hyperhidrosis.

Focal, visible, excessive sweating of at least six months’ duration without apparent cause with at least any two of the six characteristics: 1.

Bilateral and relatively symmetrical

Sweating is important in assisting thermoregulation, skin hydration and electrolyte balance. The sweat glands are of three types- eccrine, apocrine & apoeccrine glands, with variable distribution in various regions of the body.

Eccrine glands are maximally located in palms and soles. Sweating from these glands is linked to emotional stimuli, which stops during sleep and controlled by cerebral cortex. Apoeccrine glands are responsible for hyperhidrosis in axillae. Sweating in face, scalp, chest and back are linked to heat stimuli and can persist throughout the day. Hypothalamus controls thermal sweating via thermosensitive pre-optic sweat centre. All the types of sweat glands are present in axillae; hence there can be odour and staining on cloths. Though the sweat glands are histologically normal, they respond abnormally to emotional stress.

2.

Impairs daily activities

3.

At least one episode a week

4.

Age of onset less than 25 years

5.

Positive family history

6.

Cessation of focal sweating during sleep.

CLINICAL PRESENTATION

Hyperhidrosis is associated with increased incidence of other cutaneous disorders, common ones being dermatophytosis, pitted keratolysis and viral warts.

Atopic eczematous dermatitis may have frequent association with hyperhidrosis.

Onset of Primary hyperhidrosis is common in childhood or adolescence & it can persist throughout life. Patients will have focal sweating most often in palms, soles & axillae and less often in scalp, face and groin. Environmental humidity and psychological stress can worsen primary hyperhidrosis. It is not considered as psychological disorder.

Physical examination: Focal or generalized sweating is usually clearly notable. For direct visualization of the affected areas by hyperhidrosis, the iodine starch test may be used. This test requires spraying of the affected area with a mixture of 0.5-1 g of iodine crystals and 500 g of soluble starch. Areas that produce sweat turn black.

Evidence of any diseases that can produce hyperhidrosis such as Thyrotoxicosis, malignancy, pheochromocytoma, tuberculosis etc must be looked for.

:

Investigations There is no standard definition for excessive sweating. Normal sweating can be considered as less than 1 ml/m2 /min to the production of less than

379

CHAPTER 68

•

and

Patients note excessive sweating in affected areas. The most commonly affected sites are axillae, palms & soles, rarely other sites of the body are affected. Palmar hyperhidrosis can cause problems and fear of shaking hands, soiling of papers. Patients may have difficulty in performing tasks that require dry grip, these may result in social problems hyperhidrosis beginning later in life and generalized sweating & persisting during sleep should prompt a search for secondary causes.

MISCELLANEOUS

380

100 mg of sweat in one axilla within 5 min, or less than 50 mg within 1 min.

Disadvantages include staining, contact sensitization, irritancy, and limited effectiveness.

Following investigations are done based on clinical clue

Iontophoresis: the principle is that, the charged ions are introduced into the skin by low intensity electrical current which inhibits the functions of the sweat glands.16 It may also block the sweat glands temporarily. This is commonly done using tap water and anticholinergics, the latter being more effective. This technique merits consideration prior to systemic or aggressive surgical intervention and is more useful for palmo-plantar hyperhidrosis. More than 75% of patients notice a reduction in their symptoms within a month when iontophoresis is done on alternate days. The procedure is safe and simply but it can produce dry & cracked hands, skin erythema and transient vesiculation.

1.

Thyroid function tests- to confirm hyperthyroidism,

2.

Blood glucose levels- to confirm hypoglycemic episodes and diagnosis of diabetes mellitus (as diabetic dysautonomia can contribute to gustatory sweating),

3.

Urinary metanephrine and vanillyl mandelic acidto confirm pheochromocytoma,

4.

Uric acid levels- to detect gout,

5.

Tests to screen for infections such as tuberculosis, HIV, endocarditis and brucellosis,

6.

Chest radiography and ultra-sound abdomen to evaluate tuberculosis or neoplasms.

Treatment of hyperhidrosis: Treatment of hyperhidrosis is not very rewarding in nearly 50% of the patients. However, satisfactory therapeutic response can be achieved in 40% of the patients. The selection of therapy depends on patientâ&#x20AC;&#x2122;s acceptability and clinicianâ&#x20AC;&#x2122;s confidence. The investigations can give a clue to the underlying cause which may be treatable.

Certain general guidelines are to be given to all the subjects suffering from hyperhidrosis:12 1.

Avoid alcohol & spicy food as much as possible.

2.

Stress management- identify and manage emotional triggers.

3.

Use antiperspirant sprays instead of deodorants.

4.

Wear clothes made of natural fibers, which are not tight fitting.

First line therapy: the topical anti-perspirants are the most useful initial therapy for axillary hyperhidrosis. These are economical and easily available with least side-effects.

Anti-perspirants: Aluminium chloride preparations are the commonly used first line agents (topical antiperspirants) and have been found to be quite effective in trials.13 The low dose metal salt preparations are used in the treatment of milder cases. Those with moderate to severe disease may require 20% aluminium chloride hexahydrate in ethanol or 6.25% aluminium chloride hexahydrate. Lifestyle modification and topical therapy for at least six weeks should be tried prior to switching over to other measures. Treatment with string antiperspirants can produce skin irritation more so in the Axillary area which can be overcome by using lowpotency corticosteroid creams.

Topical anticholinergics: They reduce perspiration by denaturing keratin and occluding the pores of the sweat glands. Commonly used agents are glycopyrrolate,14,15 boric acid, 2-5% tannic acid solutions, resorcinol, potassium permanganate, glutaraldehyde, and methylamine. They need to be used more frequently as they are short acting.

Botulinum toxin injections: Temporary reduction in sweat production occurs as the toxin blocks the release of acetylcholine at neuromuscular junctions. They are found to be effective for axillary hyperhidrosis.17,18 Onabotulinum toxinA has been approved by US-FDA for axillary hyperhidrosis. The response to treatment is usually evident within two to four days and persists for four to nine months or longer. It is injected intradermally or subcutaneously using a 30 gauge needle. 10 to 20 injections spaced 1-2 cm apart are given in each axilla.

This therapy is found o efficacious but expensive.

Microwave thermolysis: Microwave energy can be used to destroy eccrine glands and relieve hyperhidrosis in axilla.

A commercial device design is available and approved by FDA. Microwave thermolysis is typically administered for 20 to 30 minute treatment sessions separated by three months. The overall reduction of sweat production by 50 to 75% has been observed by several studies.

Systemic agents: several agents have been tried for the treatment of primary hyperhidrosis but their potential adverse effects limit their usage. Commonly used agents are clonidine, glycopyrrolate, benztropine, oxybutynin.

The common side effects include blurring of vision due to mydriasis, difficulty in defecation and micturition.

Surgical treatment: is the last resort considered when other measures have failed to give satisfactory outcome.

Endoscopic thoracic sympathectomy, radiofrequency ablation, excision of the affected areas and subcutaneous liposuction are some of the modalities in use. Reports of operative success is more than 90%.19 Sympathectomy involves the surgical destruction of the ganglia responsible for hyperhidrosis. The second (T2) and third (T3) thoracic ganglia are responsible for palmar hyperhidrosis, the fourth (T4) thoracic ganglia controls axillary hyperhidrosis, and the first (T1) thoracic ganglia controls facial hyperhidrosis. Endoscopic thoracic sympathectomy (ETS) procedure for upper extremity or cervicofacial involves the interruption of the upper sympathetic chain through cauterization, cutting, or clipping. The ideal patients for ETS, are young adults, BMI less than 28, absence of sweating during sleep, absence of significant co-morbidoities and resting heart rate of more than 55. ETS has been shown to give relief for variable

length of time in 66 to 95% of patients with upper limb hyperhidrosis. Excision of the affected area is particularly useful in axillary hyperhidrosis.20 Subcutaneous liposuction and curettage is another means of removing the eccrine sweat glands responsible for axillary hyperhidrosis. Compared with classic surgical excision, this modality results in less disruption to the overlying skin, resulting in smaller surgical scars and a diminished area of hair loss.

9.

Cloward RB. Treatment of hyperhidrosis palmaris (sweaty hands); a familial disease in Japanese. Hawaii Med J 1957; 16:381-7.

10. Lear W, Kessler E, Solish N, Glaser DA. An epidemiological study of hyperhidrosis. DermatolSurg 2007; 33:S69-75.

11. Hornberger J, Grimes K, Naumann M, Glaser DA, Lowe NJ, Naver H, et al. Recognition,diagnosis, and treatment of primary focal hyperhidrosis. J Am AcadDermatol 2004; 51:274-86.

COMPLICATIONS OF HYPERHIDROSIS

12. National Institute for Health and Care Excellence.

Hyperhidrosis. Clinical knowledge summary. http://cks. nice.org.uk/hyperhidrosis#!scenario.

CONCLUSION

13. Streker M, Reuther T, Hagen L, Kerscher M. Hyperhidrosis plantarisâ&#x20AC;&#x201D;a randomized, half-side trial for efficacy and safety of an antiperspirant containing different concentrations of aluminium chloride. J DtschDermatolGes 2012; 10:115-9..

Common complications are: psycho-social disturbances, anxiety neurosis and depressive illness. There can be increased incidences of fungal and bacterial infections.

Although hyperhidrosis is difficult to treat, variety of treatment modalities are now available. Though the condition is not associated with mortality, it may adversely affect the patientâ&#x20AC;&#x2122;s personal and professional life. Effective counseling, suppression of sweating by combination of treatment strategies can go a long way in giving effective relief to this challenging disorder.

REFERENCES

1.

Shams K, Rzany BJ, Prescott LE, Musekiwa A. Interventions for excessive sweating of unknown cause (Protocol). John Wiley & Sons, 2011.

2.

Strutton DR, Kowalski JW, Glaser DA, Stang PE. US prevalence of hyperhidrosis and impact on individuals with axillary hyperhidrosis: results from a national survey.

J Am AcadDermatol 2004;51:241-8.

3. Huang Y-H, Yang C-H, Chen Y-H, Chen C-H, Lee S-H. Reduction in osmidrosis using a suction-assisted cartilage shaver improves the quality of life. DermatolSurg 2010;36:1573-7.

4.

Lee D, Cho S, Kim YC, Park JH, Lee SS, Park SW. Tumescent liposuction with dermal curettage for treatment of axillary osmidrosis and hyperhidrosis. DermatolSurg 2006;32:50511; discussion 511.

5. Cheshire WP, Freeman R. Disorders of aweating.

SeminNeurol 2003; 23: 399-402.

6.

Strutton DR, Kowalski JW, Glaser DA, Stang PE. US prevalence of hyperhidrosis and impact on individuals with axillary hyperhidrosis: results from a national survey.

J Am AcadDermatol 2004;51:241-8.

7. Adar R, Kurchin A, Zweig A, Mozes M. Palmar hyperhidrosis and its surgical treatment: a report of 100 cases. Ann Surg 1977; 186:34-41.

381

14. Kim WO, Kil HK, Yoon KB, Yoon DM. Topical glycopyrrolate for patients with facial hyperhidrosis. Br J Dermatol 2008; 158:1094-7.

15. Mackenzie A, Burns C, Kavanagh G. Topical glycopyrrolate for axillary hyperhidrosis. BrJDermatol 2013; 169:483-4.

16. Solish N, Bertucci V, Dansereau A, Chih-Ho Hong H, Lynde C, Lupin M, et al. A comprehensive approach to the recognition, diagnosis, and severity-based treatment of focal hyperhidrosis: recommendations of the Canadian Hyperhidrosis Advisory Committee. DermatolSurg 2007; 33:908-23.

17. Naumann MK, Hamm H, Lowe NJ; Botox Hyperhidrosis Clinical Study Group. Effect of botulinum toxin type A on quality of life measures in patients with excessive axillary sweating: a randomized controlled trial. Br J Dermatol 2002; 8:247-52.

18. Naumann M, Lowe NJ. Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis: randomised, parallel group, double blind, placebo controlled trial. BMJ 2001; 323:596-9.

19. Solish N, Bertucci V, Dansereau A, Chih-Ho Hong H, Lynde C, Lupin M, et al. A comprehensive approach to the recognition, diagnosis, and severity-based treatment of focal hyperhidrosis: recommendations of the Canadian Hyperhidrosis Advisory Committee. DermatolSurg 2007; 33:908-23 20. Li Y, Li W, Lv X, Li X. A refined minimally invasive procedure for radical treatment of axillary osmidrosis: combined tumescent liposuction with subcutaneous pruning through a small incision. J PlastReconstrAesthetSurg 2012; 65:e320-1.

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Sweat gland suction is a new surgical technique in which local anesthesia is applied and the sweat glands are carefully removed. This process is similar to liposuction.

8. Lonsdale-Eccles A, Leonard N, Lawrence C. Axillary hyperhidrosis: eccrine or apocrine? ClinExpDermatol 2003; 28:2-7.

Practical Approach to Stress Related Disorders

C H A P T E R

69

NK Singh, Vaibhav Agnihotri, Richa Manaswita

ABSTRACT

The high prevalence of stress related disorders and the magnitude of disability and distress have focused the efforts on managing them within the context of primary care physicians. Numerous studies from India have documented significant number of depression, anxiety, and common mental disorders cases in general hospital settings. Research has shown that there is robust neurotrophical basis of stress related disorders. The DSM5 system of classification and the ICD-10 are supposedly a theoretical and not in same tuning. Physicians need a more practical classification which is at present lacking.

At primary care level it will be sufficient to look for the following disorders: [1] Acute stress disorders (ASD) [2] Post-traumatic stress disorder(PTSD) [3] Anxiety disorders : Generalized anxiety disorder (GAD), Phobic anxiety, Panic disorders and some other similar disorders.

Successful treatment approaches generally involve medication combined with psychotherapy. Cognitivebehavioural therapy (CBT) has been proven superior.

Combining CBT with medications is extremely helpful in resistant cases.

Stress (stressors and stress responses) plays a major role in immunological diseases and immune-related disease processes. There is a clear link between persistent stress and development of many diseases like cardiovascular, diabetes, hypertension,asthma, headache, gastrointestinal disorders,obesity and dementia.

Stress related disorders are now posing heavy burden to a physician clinic. It has been estimated that 5 to 15 percent of consultations are sometimes due to continued stress related life situations in India. In busy clinic it is not easy to level the exact nature of such disorders according to criteria led in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), or International classification of diseases (ICD 10). Many physicians find the numerous case finding instruments and screening questionnaires to diagnose stress related disorders too cumbersome and time consuming for routine use. The many diagnostic criteria are elaborate and difficult to apply in routine medical practice. Studies have shown that focus on clinical presentations without diagnosis and the symptomatic management of people with emotional distress who present to primary care are complimentary and treatment guidelines do not seem to improve the situation.1-2 The high prevalence of these disorders and the magnitude of disability and distress have focused the

efforts on managing them within the context of primary care.

MAGNITUDE OF THE PROBLEM

Status of stress disorder research from India in relation to epidemiology, phenomenology, course, outcome and management are lacking. A meta-analysis of 15 epidemiological studies (on psychiatric disorders), by Ganguli in India, found the prevalence rate of anxiety neurosis to be 16.5/1000 population.3 A meta-analysis

by Reddy and Chandrashekhar yielded an estimated prevalence rate of 20.7% for all neurotic disorders, which was reported to be highest among all psychiatric disorders. The weighted prevalence rates of different anxiety disorders were 4.2% (Phobia), 5.8% (GAD), 3.1% (Obsession) and 4.5% (Hysteria).4 Madhav in an analysis of ten Indian studies on psychiatric morbidity, concluded that prevalence rates for anxiety neurosis and hysteria were 18.5 and 4.1 per 1000 population respectively.5 These are not the real picture as such studies were done in tertiary centers with limited sample size.6

WHAT IS STRESS

The concept of stress was developed by Hans Selye in th 1930s. Currently,stress usually refers to the consequence of the failure to respond appropriately to emotional or physical threats, whether actual signs of stress can be defined at a cognitive,emotional,physical or behavioral level. Although the stress response of the body functions to maintain stability or allostasis (process of achieving stability, or homeostasis), a long term activation of stress system can have serious negative consequences for the body.7

WHAT HAPPENS AT BIOCHEMICAL & NEUROTROPHIC LEVEL [FIGURE 1 AND FIGURE 2]

Latest studies have shown that stress decreases the expression of brain-derived neurotrophic factor (BDNF) in limbic structures that control mood and that antidepressant treatment reverses or blocks the effects of stress. Decreased levels of BDNF, as well as other neruotrophic factors, contribute to the atrophy of certain limbic structures, including the hippocampus and prefrontal cortex that has been observed in depressed subjects. Conversely, the neurotrophic actions of antidepressants could reverse neuronal atrophy and cell loss and thereby contribute to the therapeutic actions of these treatments.8 Corticotropin-releasing hormone (CRH) initiates the cascade. One neural site linked to a sense of adversity is the amygdale. Glucocorticoids

Differentiating Acute Stress Disorders (ASD) with PTSD Criteria Duration

ASD Within 2 days to 4 weeks

383

PTSD Usually within 3 weeks

Symptoms Mainly dissociative

Not a focus dissociative cluster

Resolution Within 1 month

Persisting longer than 1 month

Fig. 3: Differentiating Acute Stress Disorders (ASD) with PTSD

Fig. 1: What happens at Biochemical & Neurotrophic level

•

Autonomic signs of panic anxiety (tachycardia, sweating, flushing) are commonly present. The symptoms usually appear within minutes of the impact of the stressful stimulus or event, and disappear within two to three days (often within hours). Partial or complete amnesia for the episode may be present. If the symptoms persist, a change in diagnosis should be considered.

2.

Post-traumatic stress disorder (PTSD)

•

The DSM construct of PTSD, while legitimizing the longterm impact of trauma, does not clearly implicate the external event in causation.10 Nowadays, the label PTSD seems to be employed in clinical psychiatric practice for patients who present with symptoms after a traumatic event.10

•

The Indian Council of Medical Research collected data on psychiatric morbidity from clinics and from community surveys in Bhopal after Union Carbide disaster and described anxiety, depression, and adjustment reaction after the disaster, but made no mention of PTSD.11-12 In Gujarat which was engulfed in communal riots in February 2002, the cardinal symptoms of PTSD (i.e., reexperience, avoidance, and arousal) and their relation to the trauma was documented.13 Similarly, reports of PTSD have been described among Kashmiri Pundits forced to leave their homes and livelihoods.14

•

PTSD is a diagnosis employed in clinical practice in India for people who present with the “classical” symptoms of the syndrome after a traumatic event (i.e., reexperience, avoidance, and arousal).

PTSD arises as a delayed or protracted response to a stressful event or situation (of either brief or long duration) of an exceptionally threatening or catastrophic nature, which is likely to cause pervasive distress in almost anyone.

•

Typical features include episodes of repeated reliving of the trauma in intrusive memories (“flashbacks”), dreams or nightmares, occurring against the persisting background of a sense of “numbness” and emotional blunting, detachment from other people, unresponsiveness

Fig. 2: What happens at Biochemical & Neurotrophic level enhance the production of CRH in this region of the brain, resulting in increased attention to external events and, when sustained for longer periods of time, perhaps contributing to anxious depression.9

PRACTICAL APPROACHES

At first we need to know what are stress related disorders and how to differentiate them?

Worldwide DSM- 5 or ICD-10 are used by psychiatrists to pinpoint the diagnosis of stress related disorders. But it is not uniform in both guidelines. The DSM-5 chapter on anxiety disorder no longer includes obsessive-compulsive disorder. PTSD (Post-traumatic stress disorders) was also removed from anxiety disorders in DSM-5. In a simplified approach ICD -10 will be easy to follow. At primary care level it will be sufficient to look for the following disorders: [1] Acute stress disorder(ASD) [2] Post-traumatic stress disorder (PTSD) [3] Anxiety disorders : Generalized anxiety disorder (GAD),Phobic anxiety, Panic disorders.5 Others like, Agoraphobia, Adjustment disorders, Dhat syndrome etc.

ANALYZING STRESS DISORDERS

1.

Acute stress disorder (ASD) [Figure 3]

•

A transient disorder (only between 2 days to 4 weeks) that develops in an individual without any other apparent mental disorder in response

CHAPTER 69

to exceptional physical and mental stress and that usually subsides within hours or days.

to surroundings, anhedonia, and avoidance of activities and situations reminiscent of the trauma.

384

MISCELLANEOUS

•

There is usually a state of autonomic hyperarousal with hypervigilance, an enhanced startle reaction, and insomnia. The onset follows the trauma with a latency period that may range from a few weeks to months. The course is fluctuating but recovery can be expected in the majority of cases.

3.

Adjustment disorders

•

Adjustment disorder is a stress-related, short-term, nonpsychotic disturbance. The symptoms develop when the person is responding to a particular event or situation, for example a loss, a problem in a close relationship, an unwanted move, a disappointment, or a failure. No specific physical findings correlate with adjustment disorder, but people may consult a healthcare provider for poor sleep, aches and pains, indigestion, fatigue, and other typical symptoms.

4.

Panic disorders

•

An abrupt surge of intense fear or intense discomfort occurs that reaches a peak within minutes, and during which time four (or more) of the following symptoms occur: 1. Palpitations, pounding heart, or accelerated heart rate. 2. Sweating. 3. Trembling or shaking. 4. Sensations of shortness of breath or smothering. 5. Feelings of choking. 6. Chest pain or discomfort. 7. Nausea or abdominal distress. 8.

Feeling dizzy, unsteady, light-headed, or faint. 9.

Chilis or heat sensations. 10. Paresthesias (numbness or tingling sensations). 11. Derealization (feelings of unreality) or depersonalization (being detached from oneself). 12. Fear of losing. Diagnosis of panic attack needs to be considered after ruling out specific medical conditions.

5.

Agoraphobia

•

Patients having fearful and anxious about two or more of the following situations: using public transportation; being in open spaces; being in enclosed places; standing in line or being in a crowd; or being outside of the home alone in other situations can be diagnosed as agoraphobia.

6.

Generalized anxiety disorder. (GAD)

•

Patients having persistent and excessive anxiety and worry about various domains, including work and school performance, that the individual finds difficult to control should be leveled as GAD. Such persons also experience physical symptoms, including restlessness or feeling keyed up or on edge; being easily fatigued; difficulty concentrating or mind going blank; irritability; muscle tension; and sleep disturbance. Two main elements of the mental status examination should be assessed in generalized anxiety disorder, first involves asking about suicidal/homicidal ideation or plan and second involves formal testing of orientation/recall.

7.

Specific phobias

•

Individuals with specific phobias may fear embarrassment or humiliation (e.g., embarrassment about fainting when they have their blood drawn), but they do not generally fear negative evaluation in other social situations.

8.

Situations which can mimic like stress induced disorders

•

These have been not categorized. Dissociative [conversion] disorders have previously been classified as various types of “conversion hysteria”.

They are presumed to be psychogenic in origin, being associated closely in time with traumatic events, insoluble and intolerable problems, or disturbed relationships. The symptoms often represent the patient’s concept of how a physical illness would be manifest. Medical examination and investigation do not reveal the presence of any known physical or neurological disorder.

9.

Dhat syndrome

•

Patients are diagnosed as Dhat syndrome if the physician is aware of the label and the explanation and the content is carefully focused. These patients could also receive a label of anxiety, depression, somatization, or neurasthenia if the physician emphasizes the form of the presentation. The patient perspective of “loss of semen” as cause of the symptoms is the hallmark of his illness.15-17 Patients, relatives, and health workers often provide nonmedical explanations for the cause of illness.

Many patients (and their relatives) simultaneously seek biomedical and nonbiomedical interventions.18

Essential to rule out medical disorders as they can mimic symptoms of stress disorders

Exampleshyperthyroidism, hyperparathyroidism, pheochromocytoma, vestibular dysfunctions, seizure disorders, and cardiopulmonary conditions (e.g., arrhythmias, supraventricular tachycardia, asthma, chronic obstructive pulmonary disease. Appropriate laboratory tests (e.g., serum calcium levels for hyperparathyroidism; Holter monitor for arrhythmias) or physical examinations (e.g., for cardiac conditions) are helpful in diagnosis. We should rule out CNS disorder by EEG, lumber puncture, CT scan,MRI or PET scan.

Monitoring and referral

Physicians should closely monitor physical and psychological symptoms of all patients who have experienced trauma. Physicians should refer patients who have prolonged reactions that cause distress or affect interpersonal relationships and daily functioning.

Re-assessment

The difficulty in reaching a diagnosis at the time of the initial presentation is because it is often difficult to recognize the classic syndromes at the onset of the

are helpful for generalized anxiety disorder, panic disorder, and social phobia. All SSRIs may be equal in the treatment of anxiety disorders.Paroxetine represents a partially sedating SSRI option that is also available in a controlled-release preparation which may improve tolerability.

Mirtazapine has a much more sedating effect, generally reducing its potential to aggravate initial anxiety. Mirtazapine acts distinctly as an alpha-2 antagonist, consequently increasing synaptic norepinephrine and serotonin, while also blocking some postsynaptic serotonergic receptors that conceptually mediate excessive anxiety when stimulated with serotonin.

3.

Benzodiazepines act quickly but carry the liability of physiologic and psychologic dependence. They can be reasonably used as an initial adjunct while SSRIs are titrated to an effective dose, and they can then be tapered over 4-12 weeks while the SSRI is continued. This approach can improve short-term tolerability, although it may increase the risk of sedation.Â

4.

Alprazolam has been widely used for panic disorder, but it is currently discouraged because of its higher dependence potential; alprazolam has a short half-life, which makes it particularly prone to rebound anxiety and psychological dependence. Clonazepam has become a favored replacement because it has a longer half-life and empirically elicits fewer withdrawal reactions upon discontinuation.

4.

Buspirone is a nonsedating antipsychotic drug unrelated to benzodiazepines. It has been found to be comparable with benzodiazepines in reducing symptoms of anxiety and has fewer sedative or withdrawal adverse effects than benzodiazepines.

Buspirone also has fewer cognitive and psychomotor adverse effects, which makes its use preferable in elderly patients. Buspirone is a novel antianxiety agent.

5.

Trazodone is useful in the treatment of panic disorders. It is antagonist at the 5-HT2 receptor and inhibits the reuptake of 5-HT.

6.

Serotonin And Norepinephrine Reuptake Inhibitors such as venlafaxine and duloxetine may be helpful in a variety of mood and anxiety disorder

7.

The tricyclic antidepressants (TCAs) are a complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects.

They include imipramine and clomipramine.

Caution is warranted in the use of TCAs because of their higher toxicity and potential lethality in overdose. Their use should be limited to cases in which SSRIs are ineffective or cannot be afforded.Â

8.

Beta blockers such as propranolol are used to

illness. However, these can be identified over time as they develop the syndrome later.

OTHER COIN OF STRESS : STRESS-RELATED DISEASES

Stress (stressors and stress responses) plays a major role in immunological diseases and immune-related disease processes. Inflammation, infection, autoimmune processes, and perhaps even the onset and development of malignant tumors may occasionally be associated with the stress phenomenon. Stress has been shown to be important in vascular hypertension. It may serve as a risk factor,induce blood pressure spikes, or increase an already elevated blood pressure.

A stress-specific coronary syndrome, known as transient left ventricular apical ballooning cardiomyopathy or stress (Takotsubo) cardiomyopathy, also exists. Among patients with coronary heart disease, acute psychological stress has been shown to induce transient myocardial ischemia.19 Different forms of emotional stress are associated with an increased risk of development of type 2 diabetes, particularly depression, general emotional stress, anxiety, anger/hostility and sleeping problems.20 Exposure to stress (especially chronic stress) is a major risk factor in the pathogenesis of different diseases of gastrointestinal tract including gastroesophageal reflux disease (GERD), peptic ulcer, functional dyspepsia, inflammatory bowel disease (IBD), irritable bowel disease (IBS), and other functional disorders of GI tract.21 Development of psychological distress has been associated with asthma that is more difficult to manage, requiring higher doses of steroids,more frequent and prolonged admissions to hospital, and greater functional disability.22

TREATMENT PEARLS (FIGURES 4 & 5)

Which drugs to choose?

1.

Selective serotonin reuptake inhibitors (SSRIs) are generally used as first-line agents, followed remotely by tricyclic antidepressants (TCAs). The SSRIs include paroxetine, escitalopram, sertraline, fluoxetine, fluvoxamine, and citalopram. SSRIs

CHAPTER 69

Fig. 4: Treatment of Stress Disorders

2.

385

substance abuse, a benzodiazepine can be considered until the SSRI takes effect.

386

MISCELLANEOUS

PTSD treatment is often best accomplished with a combination of pharmacologic and non-pharmacologic therapies. Medications may be required to control the physiological symptoms, which can enable the patient to tolerate and work through the highly emotional material in psychotherapy. A meta-analysis of studies in adults with PTSD indicated that trauma-focused cognitive-behavior treatment (CBT) and Eye Movement Desensitization and Reprocessing (EMDR) should be first-line non-pharmacologic therapies for PTSD.25 Social phobia typically responds to either an SSRI or a monoamine oxidase inhibitor (MAOI). Initiate treatment with an SSRI and titrate to the minimum effective dose.

SSRIs approved for social phobia include paroxetin including SR form and sertraline, but other SSRIs have also been shown to be effective (eg, fluvoxamine).

Fig. 5: Algorithm for Management of Stress Disroders control autonomic symptoms (eg. Tachycardia) in anxiety disorders.

DRUGS AND OTHER INTERVENTIONS IN SPECIFIC SITUATIONS

Treatment usually consists of a combination of pharmacotherapy and/or psychotherapy.Deciding which treatment or combination of treatments to prescribe depends on a careful interview and assessment of the patient’s goals and level of pathology.

For Generalised Anxiety Disorders successful treatment approaches generally involve medication combined with psychotherapy. However, cognitive-behavioral therapy (CBT) has been proven superior in placebo-controlled trials. CBT generally includes self-reward as well as problem solving and can be as effective as medications, especially for children with mild generalized anxiety disorder. Combining CBT with medications is extremely helpful in resistant cases Other psychotherapies, such as relaxation therapy, supportive psychotherapy, or mindfulness therapy, have been used if CBT is not appropriate.23-24 For panic attacks pharmacotherapy, cognitive and behavioral psychotherapy, and other psychological treatment modalities are all used to treat panic disorder.

Untreated panic attacks can subside spontaneously within 20-30 minutes, especially with reassurance and a calming environment.25 Agoraphobia (specifically, the panic symptoms) most often responds to treatment with an SSRI. Benzodiazepines can be used either as an adjunct or as primary treatment; however, benzodiazepines are usually not chosen as a first-line treatment because of the potential for abuse. If the patient has frequent panic attacks and no history of

Non-western psychological interventions like yoga and meditation, which are employed across diverse clinical problems and are popular across cultures. These are useful in the management of a range of contents in dissimilar contexts, regions, and cultures.15 Interpersonal Psychotherapy (IPT) may also be effective in the treatment of eating disorders and anxiety disorders.26

FINAL POINT

All physicians working in general medical settings find difficulty in separating anxiety, depression, and somatic presentations because of milder, less distinct syndromes and overlapping symptoms. It is difficult to employ the more complex classification. It would be time consuming and impractical in primary care. The psychiatric classifications for use in primary care should consider the different context. There should be increased efforts to assess and manage issues related to context and cultures, meaning and idioms of distress, and coping and stress. Do not ignore the patient version of illness and never say he or she has hysteria. Psychological factors present before exposure to stress also have an impact on responses to stress and its assessment is equally important.

REFERENCES

1.

Jacob KS. The diagnosis and management of depression and anxiety in primary care: The need for a different framework. Postgrad Med J 2006; 82:836.

2.

Fritzsche K et al. Symptom presentation, interventions, and outcome of emotionally-distressed patients in primary care. Psychosomatics 2010; 51:386-94.

3.

Ganguli HC. Epidemiological findings on prevalence of mental disorders in India. Indian J Psychiatry 2000; 42:14–20.

4. Math SB, Chandrashekar CR, Bhugra D. Psychiatric epidemiology in India. Indian J Med Res 2007; 126:183–92.

5.

Madhav M. Epidemiological study of prevalence of mental disorders in India. Indian J Community Med 2001; 26:10-2.

6.

Trivedi JK, Gupta PK. An overview of Indian research in anxiety disorders. Indian J Psychiatry 2010; 52:S210.

7. Bao AM,Meynen G,Swab DF. The stress system in

depression and neuro-degeneration:focus on human hypothalamus. Brain Res Rev 2008; 57:531-553.

18. Jacob KS. Mental disorders and systems of medicine. Indian J Psychiatry 2002; 44:397-8.

8. Ronald S.Dumanand Lisa,M Monteggggi.Neurotrophic Models for Stress Related Mood Disorders. Biol Psychiatry 2006; 59:1116-1127.

19. Andrew Steptoe and Mika Kivimäki Steptoe, A. & Kivimäki, M. Stress and cardiovascular disease. Nat Rev Cardiol 2012; 9:360–370.

Jay Schulkin,PhD, Angst and the amygdala. Dialogues Clin Neurosci 2006; 8:407-416.

20. Frans Pouwer et al. Does emotional stress cause Type 2 Diabetes Mellitus?.A review from the European depression in diabetes (EDID), Research Consortium. Discovery Medicine 2010; 9:112-118.

9.

10. Jacob KS. PTSD, DSM and India: A critique. In: Zachariah A, Srivats R, Tharu S, editors. Towards a Critical Medical Practice: Reflections on the dilemmas of medical culture today. New Delhi: Orient Blackswan; 2010; 57-68

12. Murthy RS, Isaac MK. Mental needs of Bhopal disaster victims and training of medical officers in mental health aspects. Indian J Med Res 1987; 86:51-8.

13. Mehta K, Vankar G,Patel V.Validity of construct of post traumatic stress disorder in a low income country.

Interview study of women in Gujrat, India. Br J Psychiatry 2005; 187:586-6.

14. Bansal R, Thappa J, Shah HU, Hussain A, Chowhan A, Kaur H et al. Psychiatric morbidity in adult Kashmiri migrant camp at Jammu. Indian J Psychiatry 2010; 52:154-8.

15. Jacob KS, Kuruvilla A. Psychotherapy across cultures: The formcontent dichotomy. Clin Psychol Psychother 2012; 19:915.

16. International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10)-2014WHO Version for; 2014.Chapter V. Mental and behavioural disorders (F00-F99).

17. Jacob KS, Kallivayalil RA, Mallik AK, Gupta N, Trivedi JK, Gangadhar BN, et al. Diagnostic and statistical manual 5 – Position paper of the Indian psychiatric society. Indian J Psychiatry 2013; 55:12-30.

22. Rosalind J Wright, Mario Rodriguez, Sheldon Cohen.

Review of psychosocial stress and asthma: an integrated biopsychosocial approach. Thorax 1998; 53:1066–1074.

23. Hunot V, Churchill R, Silva de Lima M, Teixeira V. Psychological therapies for generalised anxiety disorder.

Cochrane Database Syst Rev 2007; (1):CD001848.

24. Ipser JC, Carey P, Dhansay Y, Fakier N, Seedat S, Stein DJ. Pharmacotherapy augmentation strategies in treatmentresistant anxiety disorders. Cochrane Database Syst Rev 2006; 18:CD005473.

25. Hogberg G, Pagani M, Sundin O, Soares J, Aberg-Wistedt A, Tarnell B, et al. Treatment of post-traumatic stress disorder with eye movement desensitization and reprocessing: outcome is stable in 35-month follow-up. Psychiatry Res 2008; 1-2:101-8.

26. Cuijpers P, Donker T, Weissman MM, Ravitz P, Cristea IA. Interpersonal Psychotherapy for Mental Health Problems: A Comprehensive Meta-Analysis. Am J Psychiatry 2016; 173:680-7.

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11.

Sethi BB,Sharma M,Trivedi JK,SinghH.Psychiatric morbidity in patients attending clinic in gas affected areas in Bhopal. Indian J Med Res 1987; 86:45-50.

21. PC Kontureki, T. Brozozowski et al. Stress and the gut. Pathophysiology,clinical consequences,diagnostic approach and treatment options. Journal of physiology and pharmacology 2011; 6:591-99.

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Alternate Medicine and Yogic Practices in Indian Scenario

C H A P T E R

70

KEY WORDS

Complementary Nutraceuticals

and

Chandrasekhar Valupadas

alternative

medicine,

•

Traditional Chinese medicine with the use of Acupuncture, Qi gong, Tai Chi etc.

•

Alternative medicine of USA with the use of chiropractic, osteopathy for manipulation of spine, joints using hand pressing.

•

Alternative medicine of Europe with Homeopathy, Naturopathy and exercise.

Yoga,

INTRODUCTION

Health is a state of complete physical, mental, social and spiritual well being, not merely absence of disease. Quality health is the right of every human being but it relies on individual, social and environmental factors. Health is a positive concept and does not just mean freedom from disease. Unfortunately, the current system of Medicine worldwide, concentrates on treating symptoms and diseases, leaving the mission of health unaccomplished and giving scope for alternate means for restoration of health. Despite many scientific and technological advances in modern medicine, there are many number of illnesses which remain incurable, or not completely treatable, Fortunately, alternative medicinal systems are readily available from ages, and are now being reinvented and rediscovered to fill those gaps and all of them need a critical appraisal, scientific evaluation and test of time. The search for health includes many beliefs and practices that are outside conventional medicine, sources being family, role of family priests, culture and traditions. Current day physicians should be aware of patient’s attitude for self treating using alternatives and warn the potential harm involved in such activities.

CLASSIFICATION OF HEALTH CARE SYSTEMS

1. Conventional Medicine: Synonyms include dominant, orthodox, western, allopathic, modern, scientific or technologic medicine. Conventional medicine is the medicine prescribed with the use of diagnostic techniques and pharmaceutical/ surgical interventions. It is the major healthcare system adopted across the globe which has got strengthened since a few decades by clinical research trials and evidence based medicine.

2. Alternative medicine: Synonyms include traditional, unconventional, uncommon, natural or native medicine. Alternative medicine is the main stream medicinal system characteristic to societies, cultures and nations. It has been practiced in their respective areas to fill the gap or to replace the modern medicine. Examples include: •

Indian Ayurvedic Medicine with use of herbs, yoga, meditation etc.

Diet,

3. Complementary or adjunctive medicine: Independent from the above two major healthcare systems, complementary medicine synergizes benefit and outcome of an individual health.

Mind-body practices like physiotherapy, massage therapy, reflexology, hypnosis, meditation, yoga are few examples.

4.

Adjuvant therapy: Adjuvant therapy is an addition to the primary (initial) medicine designed to help reach the ultimate goal. In cancer, adjuvant therapy usually refers to surgery followed by chemotherapy or radiotherapy to help reduce the risk of the recurring cancer. Other examples include nutraceuticals/pharmaconutrients or dietary integrators.

5.

Integrative or holistic medicine: This is a new trend to respect belief and reject harm of any of the above systems to focus more on patient and less on technology [Figure 1]. This approach seems attractive as it is less interventional and more natural but lack of evidence is a cause of concern and controversy. Example 1.Veterans Administration and Department of Defence (VADD) & American Pain Society of USA utilizing integration of chiropractic osteopathy to treat low backache & other musculoskeletal disorders and 2.Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homeopathy (AYUSH) of India.

II. BACKGROUND

Complementary and Alternative Medicine (CAM) has been used in various countries like India, China, Latin America, Europe and USA much before the development of present day medical science which became global in chronological order. In India, Ayurveda and yoga are two major CAM systems. In Sanskrit, Ayurveda means “knowledge of life”. Ayurvedic knowledge was born from the wisdom of the ancient rishis (sages and healers) and yogis (ascetics practicing yoga) of India, and was first passed on from healer to healer as an oral tradition

389

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Fig. 1: Health Care System

Fig. 2: Popularity of traditional medicines and complementary alternative medicines worldwide for untold generations before the earliest known texts were written around 5000 BC. Yoga, a system envisaged

by Maharshi Patanjali also exists in India since ages but is now recognised worldwide and being absorbed into main stream of medicine and World health organization (WHO) observed International Yoga Day on June, 21st of every year. Unani, another old methodology of East Indian medicinal system originated from Persian medicine, is practiced primarily in the Muslim community along with ‘Tibbe’; it is also called as ‘hikmat’, a science which deals with prevention and treatment of health problems. Siddha is also an oldest system of medicine in India, prevalent among Tamil speaking people1. Homeopathy, discovered

by Samuel Hahnemann, a German physician treats illness by going with, rather than against symptoms that are seen as the body’s natural defence. Other older traditional practices of India include Dhara (Oil massage therapy/

Kerala Ayurveda), Mud therapy, Magnetic therapy, Agnikarma, Magic/Mantra therapy etc. Figure 2 shows the popularity of traditional and CAM worldwide2.

In the Western countries, there are many existing traditional practices struggling with dominant system.

At present only six fields are educationally accredited, they are osteopathy, chiropractic, acupressure, massage, naturopathy & homeopathy. Though widely practiced, Indian yoga and ayurveda are neither accredited nor licensed in US. In Latin America and Africa many primitive practices are existing but few are mentioned theoretically in currently available literature. In the Far East, Tibetan medicine and Traditional Chinese Medicine are existing from ages. In US, chiropractic is offered as two year UG course followed by 4years of internship in many accredited medical schools, offering PG courses in osteopathy. It is estimated that in US 52000 licensed

MISCELLANEOUS

390

Fig. 3: Domain of Complementary and Alternative Medicine chiropractors3, 3000 naturopathics, 155000 massage therapists and 70% family practitioners are being carried out by osteopathy. In India, courses like BAMS, BHMS, BNYS & BUMS and their respective PG courses are taught in many government & private medical colleges recognized by many health universities & UGC. In 1993, David Eisenberg and colleagues surprised by showing the utilization of complementary or alternative health approach is more than 30% of Americans. According to Centres for Disease Control and Prevention’s National Centre for Health Statistics National survey in 2007, 42% of hospices in USA had integrated CAMs in mainstream medicine. In Veterans Administration and Department of Defence, utilising of complementary approaches for management of various pain syndromes (headache, low back ache etc.) and post-traumatic stress disorder is common. A survey on complementary and alternative health approaches estimated that approximately 18% of overall population used non-vitamin, non-mineral dietary supplements in 2002, 2007 and 2012 respective studies. This states that Americans are willing to pay about $34 billion out-of-pocket expenditure amounting 1.5% of total USA health expenditures3. Globally, herbalbased products accounts for $120 billion annual market of which half of the share is by Ayurvedic products4.

In India, by 1998 there are 2,860 hospitals with 45720 beds, 22100 dispensaries with estimated 587536 registered traditional medicine practitioners4, both institutionally and non-institutionally qualified, to provide traditional medicine particularly in rural areas which accounts 70% of total population. More than 75% of beds are occupied by patients receiving ayurvedic treatment.

Allopathic resident doctors have little knowledge about ayurveda and ayurvedic medicine use but engaged in prescribing ayurvedic medicine compared to other alternative medicine5.

IV. ALTERNATIVE MEDICINE

A.

Definition

“Alternative medicine” or “complementary medicine” is interchangeable terms with traditional medicine in some countries. National Centre for Complementary and Alternative Medicine (NCCAM) defines Complementary and Alternative Medicine as a group of diverse medical and health care systems, products and practices that are not presently considered part of conventional medical care6.

B.

Types of Alternative medicine

Alternative medicines mainly fall into five major domains 6 [Figure 3]

The common alternative medicines used globally are listed in table 1.

C.

Significance of Alternative medicine

Alternative medicine has been in vogue for a long time, but it was discarded in pursuance of the energetic science of allopathy. Decades later, ancient alternative medicine has again come to light. Reasons for this is two-fold; 1. Drawbacks of modern medicine like increasing side effects, dramatic rise in the cost of allopathic medicine despite failure in achieving desired cures of their ailment, 2. Inherent advantages of alternative medicine like its simplicity & cost-effectiveness, its cultural links to tradition and religion, hatred to certain western practices.

D.

Indian Alternative Medicine:

There are many Indian traditional therapies [Table 2] practiced by many Indian tribes and rural people4, some of them are proved beneficial in many incurable diseases like migraine, insomnia, sinusitis, asthma, spondylitis, sciatica, indigestion,

391

Table 1: List of various Alternative Medicines Alternative medicine Acupunture & acupressure: Stimulation on defined anatomic points with insertion & manipulation with thin metallic needles.

2

Alexander technique: Movement of body therapy to improve posture & efficient use of muscles for improvement of overall body function.

3

Anthroposophic: A spiritual based medicine involving herbs, homeopathy, and movement therapy called ‘eurhythmy’.

4

Aromatherapy: Treatment with extracted natural oil to enliance psychological and physical well-being

5

Ayurveda: Treatment regimen include diet, exercise, complex herbs

6

Chiropractic: Spine & joints adjustment to reduce pain & improve backache, headache, musculo skeletal disorders.

7

Curanderismo: Spiritual healing of Latin America with ritual cleansing, herbs, incantations, smudging (cleaning room with smoke of sacred plant)

8

Electric Therapy: Use of electric devices like deep brain stimulator, muscle stimulation

9

Energy medicine: Energetic or informational interaction with a biological system to bring back homeostasis in the organism is energy medicine

10

Faith healing: Ritualistic practice of prayer and gestures for spiritual and physical healing.

11

Guided imagery: Use of relaxation technique followed by visualization of images, usually calm & peaceful in nature, to invoke specific images to alter neurological function & physiological state.

12

Greeva Basil Soaking the neck in pool of herbal oils to alleviate pain, stiffness and cervical compression

13

Herbal medicine: Also called Phytomedicine/Botanical, use of plants for medicinal purpose

14

Homeopathy: Originated in German, based on the belief in the theory of’like cures likes’, compoiuids that produce symptoms in very dilute solution will be curative.

15

Heat Therapy: Use of hot cloth, container/heating pad etc for pain relief

16

Hypnosis: Induction of altered state of consciousness characterized by increased responsiveness to suggestions.

17

Magic Therapy: Religious worships as therapy for diseases assumed as a result of wrath of God 18 Magnetic Therapy: Use of magnetic devices for treatmg diseases.

19

Massage: Manual therapies that manipulate muscles & connective tissues to promote muscle relaxation, healing & sense of well being.

20

Meditation Practices based on spiritual traditions intended to focus I control attention & obtain greater awareness/mindfulness of present moment

21

Mud Therapy: Use of mud (rich in minerals) on body as well as houses to prevent germs and related diseases

22

Music Therapy: Use of music as therapeutic intervention to reduce anxiety, improve cognitive functioning, promote physical rehabilitation

23

Native American medicine: Treatment with awareness of self spirit, rest, connection with nature, herbs, social support and spiritual healing

24

Naturopathy Clinical medicine with holistic approach involving herbs, exercises, diet.

25

Netradhara: Special cleansing technique of pouring herbal decoction over the eyes for 20 min m a continuous stream

26

Oil massage Kerala Ayurveda: Use of vegetable oil, essential oils etc for mental and physical health

27

Osteopathy: Spinal manipulative methods to reduce pains.

28

Physical medicine & rehabilitation: Treating physical impairments or disabilities by counselling

29

Qi gong: Traditional Chinese gentle and slow exercise for health maintenance, healing and increasing vitality Contd.

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1

MISCELLANEOUS

392

Table 1: List of various Alternative Medicines 30

Reflexology: Manual stimulation of point- on hands feet that are believed to affect organ function

31

Reiki Japanese technique for stress reduction and relaxation that also promotes healing

32

Rolfing: Manual therapy attempting to realign the body by manipulating deep tissue & fascia.

33 Sekkotsu: Traditional Japanese technique of bone setting.

34

Siddha: Medicinal system prevalent in Tamil speaking people.

35

Spinal Manipulation: Manual techniques by chiropractic/osteopaths for adjusting spine lo affect neuromuscular functions

36

Tai Chi: A mind body practice achieving slow, gentle movements, a kind of moving meditation.

37

Tau-dam Agnikarma Treatment using burn red hot iron rod touching the affected area of skin.

38

Touch therapy: A version of lying on hands, a kind of healing meditation.

39

Tibetan medicine: Diagnose by examining pulse & urine, treatment by diet, herbs & massage.

40

Traditional Chinese Medicine: Involving acupuncture, herbal mixtures, massages, exercise & diet.

41

Unani: Medicine originated from Persian, prevalent in Muslim community, also called as â&#x20AC;&#x2DC;hikmatâ&#x20AC;&#x2122;.

42

Yoga: An exercise based practice, combines physical postures, breathing exercises & meditation.

Table 2: Indian Alternative Medicine 1

Kerala Ayurveda

3000 years old, originated in Kerala, spread world wide Also called as Dhara/Panchkarma Fivefold purification revives equilibrium of Tridosha

2

Mud therapy

1000 years old, practiced in rural / tribal communities Mud paste smeared on walls of house to maintain temperature & keeps germs away Mild from north is good for nervous system disorders

3

Herbal therapy

Prehistoric, tree worship of Indus Valley civilization Herbs in the form of powder, decoction, tonic & mixtures Rigveda mentioned plants like Semal, Pithvam, Palash, Pippal Kalpasutra of Atharwaveda explain 579 plants list.

4

Megnetic therapy

Sand and stone are spelled as SIKATA & ASHMAN in Atharvaveda Used to treat bleeding disorders and infertility in woman because iron is an important ingredient in blood.

Low powered magnets used to treat sensitive organs

5

Agnikarma (TauDam)

Traditional Himalayan Therapy Tau is an iron rod, burned till red hot and touches the affected skin for few seconds and massaged with oil.

Dam, burnt seeds of Terminalia chebulta or Anaphalis araneso used as same as Tau Mostly used for liver and gastrointestinal disorders

6

Magic therapy

Also called as Zadu, Tantra, Mantra Practiced in Central Himalaya, elsewhere in rural India Diseases are result of wrath of God, to invoke the God of ceremonial worship during night performed and sacrifice of goat, pig, cock or coconut is offered.

50% are cured, psychosomatic in nature.

substance abuse and general ill health. Some of them are very barbarous, unscientific, self harming than curative.

E. Ayurveda:

Principles of ayurveda are made up of 5 basic

elements viz., Akasa (ether), Vayu (air), Tejas (fire, minerals, acids, alkalis), Jala (water) and Prithvi (organic substances & earthy matter). Combination of all these elements classifies into 3 types of basic diagnoses viz., Vata (ether & air); responsible for movement in the body & mind, Pittha (fire

hyper function of Vata elements in the body which cause various forms of anxiety, phobias, neurotic & psychotic ailments. Any changes in circadian rhythm, a biological cycle of 24 hours duration, and results in physiological changes because of excess or under production of bodily secretions is the fundamental cause. Ayurvedic remedies to cure this malady include

& water); functions associated with digestive processes, metabolic activity & body temperature, Kapha (earth & water); corresponds to anabolism of body tissues & stored substances. Final diagnosis can be defects in any one or more of these defects in different permutations, e.g. Tridosha is defect in all three principle which are not balanced, may be excess (hyper function) or deficiency (hypo function) of each component which needs to be corrected by adopting ayurvedic principles of treatment. Figure 4 depicts principles of Ayurveda.

SIGNIFICANCE OF AYURVEDIC MEDICINE

Ayurvedic methods can be applied to any disease of present day human life; few scientifically proven examples are outlined below:

1.

Guidelines of Swasthavritta in ayurveda are remedies for obesity, which addresses & advocates that

a.

the obsession & compulsion for food intake should be strictly controlled; avoid sweet, salt & oily food in regular diet; avoid curd and take butter milk; boil and drink warm water;

b.

avoid day time sleep,

c.

walking, swimming, cycling etc;

d.

ayurvedic medicines like Triphala churna or guduchi churna at bedtime with honey/ Brihat Pancha Moola or amla powder can be used.

2.

According to ayurveda, sleep disorders are caused by tridosha, which result in impaired psychological tendencies. Lifestyle changes in accordance with nature cause enthusiastic, vivacious, regular, excitable & quick-change in individual mood, hence mind body practices have to be adopted for good sleep, like regular exercise, yoga & meditation; limiting toxins containing tobacco, alcohol, tea & coffee; and taking right food at right time in right amount.

3.

Generalized Anxiety Disorder (GAD) is because of

Massage therapy: abhyanga with sesame oil daily, warm oil for feet & marma therapy (vital junction point’s treatment),

b.

Aroma therapy with mixture of warm, sweet & sour aromatic oils of basil, orange & rose for Vata purification,

c.

Regular exercise, yoga & meditation for at least 30 minutes daily between 6 am to 7 am,

d.

Consume all 6 types of tasting foods (sweet, sour, salt, bitter, pungent & astringent) and

e.

Facilitate well ventilated bed room without direct blow of the air.

4.

Ayurvedic medicine with its natural & traditional base has the potential to provide remedies to the many challenging health issues like drug withdrawals2, adverse drug reactions and economic disparities without many side effects. Traditional, Complementary and Alternative Medicine (TCAM) delays in seeking help from the allopathic practitioners and related health facilities by healing or slowing the progression of disease7.

IV. ADJUVANT THERAPY

Adjuvant therapy may involve addition of medicine or treatment to the primary therapy e.g. in cancer (surgery with radiotherapy/chemotherapy), ophthalmology (surgery with spectacles), orthopedics (surgery with physiotherapy/rehabilitation) and in psychiatry (medication with cognitive behavior therapy). It is common in treating chronic illnesses in addition to primary treatment, as many patients suffer from loss of appetite & general weakness resulting in malnutrition and/or malabsorption are vice versa, apart from druginduced nutrient deficiency and socio-economic factors contributing to development of incurable & perpetuating diseases. Many nutraceuticals are claiming to be adjuvant therapy; hence there is a need for FDAs of every nation to look for genuine claims, as many compounds escape from clinical trials to establish therapeutic benefits but many fraudulent lies in claim “maintaining” the integrity of tissue & health.

V. NUTRACEUTICALS

A nutraceutical is any non toxic food supplement which is scientifically proven for health benefits8 and used for non-specific therapy to control symptoms and upgrade wellness. They range from nutrients; dietary supplements and special diet prepared by herbs and of late, genetic engineering technology. There are traditional

CHAPTER 70

Fig. 4: Principles of Ayurveda

a.

393

394

Bhakti Yoga

is the path of love and devotion

Karma Yoga

MISCELLANEOUS

is the path of work, and service

Jnana Yoga

is the path of knowledge

Raja Yoga

is the path of meditation

Crown-chakra (Sahasrara-Chakra) Brow-Chakra (Agya-Chakra)

Violet Indigo Blue

Throat-Chakra (Vishuddha-Chakra)

Green

Heart-Chakra (Anahal-Chakra)

Yellow

Solar Plexus-Chakra (Manipurak-Chakra) Sacral-Chakra (Svadhishtan-Chakra) Base-Chakra (Muladhar-Chakra)

Orange Red

Hatha Yoga

Kundalini Yoga

Fig. 5: Types of Yoga nutraceuticals from fruits, vegetables, grains, fish and dairy products e.g.: lycopene of tomatoes, omega 3 fatty acid in Salmon, and saponins of soy; and non-traditional nutraceuticals from agriculture breeding or nutrient fortification of juices, e.g.: Calcium fortified with orange juice and folic acid in wheat flour9.

VI. YOGA

Yoga is defined as the application of yogic principles to a person with objective of achieving a physiological, psychological & spiritual goal. Sanskrit meaning of yoga is ‘union’ indicating integration of body, mind & soul. It is one step ahead of WHO’s definition of health by adding 4th dimension to the health i.e., concept of soul.

Yoga is divided into eight types viz., Bhakthi, Jnana, Karma, Raja, Hatha, Kundalini, Manthra & Purna yogas 10 with specific purpose it serves [Figure 5] and involves eight principles viz., yuktha sikshana, bheda, desha, deha, kaala, vritti, shakthi & marga and methods involved are also eight types viz., asana, pranayama, bandha, yama, niyama, prathyahara, dharana & dhyana. Many a times it’s quoted as ‘astanga yoga’11.

This ancient art derived its principles from ‘Pathanjali’ shastra, named after its founder sage; focuses on spiritual enlightenment by physiological, physical, psychological fitness of human being. Terminology of various yoga practices are shown in T able 3.

Yoga practices are found effective for development of various dimensions of personality. Its ‘physical dimension’ addresses many current diseases being treated from their root cause, particularly chronic ailments like obesity, metabolic syndrome, cardiac diseases and psychosomatic disorders. It improves general health, strength; rejuvenates recreational and sexual health; it alters central

pain processing by unknown mechanisms so as to cure many chronic painful syndromes like sciatica, migraine & cancer pain. ‘Emotional dimension’ relates to feelings, attitudes and takes care of negative emotions like fear, anger, and anxiety and improves positive emotions like peace, kindness & love. In its ‘intellectual dimension’ it improves mental abilities like critical thinking, judgment, decision making & memory. In ‘social domain’ it brings harmony in community by improving interpersonal relations between human beings. Finally it helps in developing values, morality and discovers individual’s purpose of birth and ultimate enlightenment of moksha12.

SIGNIFICANCE OF YOGA

Yoga not only limited to physical posture, breathing exercise or meditation but gives direction to food & eating habits; rejuvenation & recreational means; thinking & conduct. Yoga is a way of life, with its 5 components viz., Ahara (food),Vihara (relaxation), Achara (conduct), Vichara (thinking) & Vyavahara (behavior/action) should be adopted to promote overall championship of health.

The following are currently available Research Evidences on Yoga for its usefulness in health: 1.

Tapas das et al from Kolkata proved that yoga therapy is beneficial in maintaining good health by regulating BMI, to overcome the complications of obesity & metabolic syndrome13.

2.

Anand Balayogi et al from Pondicherry, reported that there is a healthy reduction in heart rate, blood pressure and other cardiovascular indices following a single yoga session14, magnitude of this benefit depends on pre-existing medical condition & yoga protocol adopted, benefits achieved are attributed to enhanced cardiac autonomic function

395

Table 3: terminology of various yoga practices Yama and niyama are the principles that concern with personal conduct and social life.

Five principles of Yama

Five principles of Niyama

1. Ahimsa (non-violence)

1. Shaucha (cleanliness)

2. Satya (truthfulness)

2. Santosha (satisfaction)

3. Asteya (non-stealing)

3. Tapas (austerity)

4. Brahmacharya (abstinence)

4. Swadhyaya (Good literature, knowing about self)

5. Aparigraha (non-collectiveness)

5. Ishwarpranidhana (dedication to supreme God)

Pranayama is a breathing exercise to control breathe or respiratory process Pratyahara is yogic practice which means withdrawal of senses from sense organs and withdrawal of external surrounding in order to control mind. Observation, studying good books are some practices which improves for control of mind.

Bandha and Mudra involves manipulation of certain semi-voluntary and involuntary muscles in the body which results in voluntary control and toning up of internal organs.

Shatkarma/Kriya is cleansing or purification process which cleanse the specific organs in the body by detoxifying them using six actions namely Neti (neighter this nor that), Dhauti (purification of oesophagus and stomach), Basti (cleansing of lower abdomen, esp., colon), Trataka (fixing eyes on some object), nauli (cleansing of abdomen by turning abdominal muscles) and Kapalabhati (forehead and all other organs under skull to brighten by breathe exercise) as result of coordinated breath-body work & mindbody relaxation.

3.

Kerstin et al proved that the relaxation by yoga is associated with significant increase in cardiac vagal modulation15.

4.

Williams KA et al demonstrated that a 16-week yoga therapy13 caused significance reduction in self reported disability & pain & educed use pain medication compared to a control group.

5.

David Shapiro et al support the therapeutic potential of yoga in generalized anxiety disorder (GAD), with reduction in perceived stress & related anxiety/depressed symptoms13.

was a failure. Nonetheless, alternative medicine has survived from ages till date and is growing stronger in certain areas where dominant system failed to yield good results. Undoubtedly it improves chronic ailments, preventive aspects of health and is holistic in nature of physical, psychological, social and spiritual health of human kind. Over all health is the ultimate goal, not the way which we achieve it. Accordingly, all the systems of health care should be integrated in a synergistic manner by understanding the deficiencies of oneâ&#x20AC;&#x2122;s own and by appreciating strengths of others. In the endeavor of achieving integrating system, much more research has to be conducted with well designed and unbiased trials.

REFERENCES

1.

A World Health Organization resource- Legal Status of Traditional Medicine and Complementary/Alternative Medicine - A Worldwide Review, 2001. Information available from URL: http://apps.who.int/medicinedocs/ en/d/Jh2943e/8.4.html.

Bijoya Chatterjee, Jigisha Pancholi. Prakriti-based medicine: A step towards personalized medicine-A review article.

AYU 2011; 32:141-146.

6.

Cohen et al, in large randomized trials claims efficacy of restorative yoga for treatment of menopausal symptoms in women15.

7.

Oken et al in his randomized trial showed significant improvement in fatigue but not in cognitive function in patients with multiple sclerosis versus control group16.

2.

Kolansinski et al suggests that yoga may provide a feasible treatment option for yoga in obese and old patients with osteoarthritis17.

3. Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo. Harrisonâ&#x20AC;&#x2122;s Principles of Internal Medicine. 19th ed. United States of America: McGraw-Hill;2015.

8.

CONCLUSION

Despite significant expenditure spent on testing alternative medicine, many studies have failed to prove its effectiveness as claimed and could not provide proper explanation regarding mechanisms of healing, which remain hypothetical. Other point of view is that, because of allopathic research bias (a defect in their study designs and scientific tools) alternative medicine

4. Lalit Tiwari. Alternative Medical Therapies of India: an Introduction. The infinity foundation. Information available from URL: http://www.infinityfoundation.com/ mandala/t_es/t_es_tiwar_therapies_frameset.html 5.

Suchita R. Gawde, Yashashri C. Shetty, and Dattatray B. Pawar. Knowledge, attitude, and practices toward ayurvedic medicine use among allopathic resident doctors:

CHAPTER 70

Asana is a sitting yoga practice in a particular posture steadily to improve stability and comfort at physical and mental health

396 6.

A crosssectional study at a tertiary care hospital in India.

Perspect Clin Res. 2013; 4:175–180.

13. Tapas Das, Dr. Sutapa Roy. Effect of Yoga on Metabolic Syndrome. Inter J of Sci and Res Publ 2015; 5:1-5.

World health organization. Global status report on noncommunicable diseases (NCDs) launched- 2011.

14. Ananda Balayogi Bhavanani, Meena Ramanathan and Madanmohan. Immediate Cardiovascular Effects of a Single Yoga Session in Different Conditions. Altern & Integra Med 2013; 2:1-4.

7. Alex Broom, KR Nayar, Philip Tovey, Rashmi Shirali, Rakesh Thakur, Tulika Seth, Prem Chhetri. Cancer Patients’ use of Traditional, Complementary and Alternative Medicine (TCAM) and delays in presentation to Hospital.

OMJ 2009; 24:103-107.

MISCELLANEOUS

8.

Dillard CJ and German JB. Phytochemicals: nutraceuticals and human health. J Sci Food Agric 2000; 80:1744-1756.

9. North Carolina Association for Biomedical Research, Nutraceuticals, WWW. About bioscience. Org; July 2007.

10. Information available from URL: http://yoga.iloveindia. com/yoga-types/index.html 11. Scientific Evidence on the Therapeutic Efficacy of Iyengar Yoga- A Compilation of Research Papers, Mumbai research conference.

12. Yoga-A healthy way of living. Secondary stage. 1st ed.

Publication Division by the Secretary, National Council of Educational Research and Training; 2015.

15. Cohen B E, Kanaya AM, Macer J L, Shen H, Chang A A, Grady D. Feasibility and acceptability of restorative yoga for treatment of hot flushes: A pilot trial. Mauritas 2004 E-Pubmed.

16. B.S. Oken, S. Kishiyama, D. Zajdel, D. Bourdette, J. Carlsen, M. Haas, DCC. Hugos, D.F. Kraemer, J. Lawrence, BS. Randomized controlled trial of yoga and exercise in multiple sclerosis. Neurology 2004; 62:2058-2064.

17. S Kolansinski, M Garfinkel, A Singhal, AG Tsai, W Matz, A V Dyke, R Schumacher. Iyengar Yoga for Treating Symptoms of Osteoarthritis of the Knees: A Pilot Study. J Altern Comp Med 2005; 11:689-693.

C H A P T E R

71

Medical Errors in Day-To-Day Practice Raveendra KR

“There are men and classes of men that stand above the common, herd; the soldier, the sailor and the shepherd not frequently; the artist rarely; rarer still the clergyman; the physician almost as a rule, he is the flower of our civilisation” Robert Louis Stevens, 1887

INTRODUCTION

Medical profession, the noblest profession is suddenly facing threats and challenges on daily basis. Violence at work place has become a routine affair in our country.

Today’s aggressive journalism doing “public trials” in electronic media has done more harm than good to this profession. The Indian society off late has become intolerant to the doctors and hospitals and expect miracles to happen every day. Unfortunately doctors do not find any support from any corner. All are eager to find fault in the working pattern of doctors. Medical profession considered once as divine next to God often finds itself in bad reputation in recent times due to multiple factors including medical errors. Outcome of patient -physician encounter may be good but may go worse at times. Bad outcomes in medical practice are caught,dramatized and celebrated by lay press worldwide, especially in India worsening patient perceptions about physicians.

Medical error or injury has been known since the time of Hippocrates as principle of primum non nocere the popular axiomwhich translates to “First, do no harm.”In a pioneering work by Schimmel on “Hazards of hospitalization,” medical errors were presumed as “noxious episodes” in patient care and stressed on documentation of such episodes to determine its total incidence and impact.1

Definition

Medical error is defined by Institute of medicine as the failure of a planned action to be completed as intended or the use of a wrong plan to achieve an aim.

The problem

In the landmark institute of medicine report, which triggered widespread discussion in 1999, estimated that least 44,000 people and perhaps as many as 98,000 people, die in hospitals each year as a result of medical errors that could have been prevented.2 Makary Martin et al in 2016 examined medical errors as the 3rd leading cause of mortality in United States just behind cardiovascular disease and cancer mortality leading to 2,51,454 deaths. They relied on four studies to

find the mortality related medical errors which involved more than 37 million patients. Medical error is not included on death certificates or in rankings of cause of death. Hence often not accounted properly.3 Patient may suffer injury or will be put to high risk of injury which may range from trivial to life threatening damage. Damage may result in prolonged hospital stay or disability or long lasting psychologic distress. Society also bears the brunt of medical error like loss of productive work, escalating health care costs, school absenteeism, creating lacunae in physician-patient relationship, physician mistrust and doctor shopping. For the health care provider it may lead to frustration, feeling of inability to treat, fear of shaming or losing the practice.

Adverse event is a close term. An adverse event is an unintended injury to patients caused by medical management (rather than the underlying condition of the patient).4 Medical negligence is the failure to meet the standard of practice of an average qualified physician practicing in the specialty in question. It occurs not merely when there is an error, but when the degree of error exceeds the accepted norm.

CLASSIFICATION OF MEDICAL ERRORS

Medical error may be classified as errors in diagnosis, treatment, prevention, follow up and miscellaneous.5

Diagnostic errors 1.

Error or delay in diagnosis.

eg- considering and treating anemia as a disease; anemia is a sign of an underlying condition but not a diagnosis by itself.6

2.

Failure to employ indicated tests.

eg- failure to do ECG for diagnosing acute myocardial infarction.

3.

Use of outmoded tests or therapy.

eg- applying tourniquet, cryotherapy electrocautery to snake bitten limb.

4.

Failure to act on results of monitoring or testing.

eg- Not reducing insulin dosage in diabetic patient with low blood sugars.

Treatment errors 1.

and

Error in the performance of an operation, procedure, or test.

398

eg- not accounting for false positive rates of test like RA factor or Widal test.

2.

Error in administering the treatment

eg- Administration of a drug that has expired.

3.

Error in the dose or method of using a drug

MISCELLANEOUS

eg- Giving IV drug where subcutaneous route is indicated.

4.

Avoidable delay in treatment or in responding to an abnormal test

eg- Not acting quickly in the golden hours of ischemic stroke even though when thrombolytic facility is available.

5.

Inappropriate (not indicated) care

eg- Using anticoagulation when not indicated

Preventive errors 1.

Failure to provide prophylactic treatment

eg- Not following ABCD in diabetic patient management- A1c, blood pressure, cholesterol and diabetic education.7

2.

Inadequate monitoring or follow-up of treatment

eg- Failure to screen for complications like acute kidney injury in snakebite, renal dysfunction in a long standing hypertensive patient.

Others 1.

Failure of communication

eg- misinterpretation of Amlopress-AT to Amlopress-80 resulting in hypotension in a hypertensive patient or mistaking 60 units for 6 units of Insulin in a prescription â&#x20AC;&#x201C; inj plain insulin 6u sc in a hand written format.

for diagnosis in the absence of emergency investigations, eg-Bronchial asthma v/s Cardiac Asthma, Ischemic stroke v/s Hemorrhagic stroke in the absence of CT brain, treating acute fever & chills with anti-malarials in the absence of blood tests.

In IATROREF Study, the five most common adverse events were errors in administering medications (vasoactive drugs and insulin) and events related to mechanical ventilation (unplanned extubation, overinflation of intubation catheter balloon, and failure to place the patient in the semi recumbent position).This study also showed having more than two adverse events was an independent risk factor for ICU mortality.8

PREGNANCY

Pregnancy is regarded as a part of healthy life and not disease process. Maternal deaths are audited by governments and it is considered as an yardstick of progression of health care of the society. Errors in maternal care should be assessed and self evaluated for betterment of maternal and child care and safe pregnancy.9

POLYPHARMACY

Technically more than one drug can attract drug interaction and itâ&#x20AC;&#x2122;s risky to prescribe multiple drugs to a single patient.

Unfortunately the number of drugs prescribed increases especially in the elderly patients due to multiple comorbid conditions. The Bostop collaborative surveillance study has reported 6% of adverse drug reaction (ADR) in its 9,900 patients of its 83,000 exposures. As medication errors are a part of measure source of medical errors and it is practically impossible to remember all significant drug interactions, it is advised to have special care in prescribing certain drugs like anti-coagulants , anti epileptics, antibiotics, anti cancer drugs etc.,

RESEARCH

2.

Equipment failure

eg- Poor performance or lack of calibration of machines resulting in wrong reports.

Various errors may occur in different phases of medical research. Mistakes are usually made during the design phase; but may also be made during the data collection, analysis or manuscript preparation phases.10

3.

Other system failure

CAUSES OF MEDICAL ERRORS

eg- Lack of proper referral system for adequate and Human factors comprehensive care.

SPECIAL SITUATIONS

Intensive care setting

Medical errors in intensive care units will have a greater impact on mortality. Multiple underlying co-morbidities, multi organ dysfunctions, life sustaining treatments, use of narrow therapeutic window drugs and usage of high end technologies make critically ill patients more susceptible for error. Hence there are higher chances of medical sentences of medical error or judgements in the ICU set up. Medical errors should not be considered as medical negligence in the emergency situations as life saving procedure and treatment is more important than detailed history or detailed clinical examination. Lot of confusion prevail in the emergency room treatment even

Cause for human error, is due to a failure of achieving the intended outcome in a planned sequence of mental or physical activities when that failure is not due to a chance.

According to Reason, human errors are divided into two major categories: (A) slips that result from the incorrect execution of a correct action sequence and (B) mistakes that result from the correct execution of an incorrect action sequence.11 Ergonomics: Night shift and extended work duration may affect performance.Being awake for over 24 hours caused interns to double or triple the number of preventable medical errors, including those that resulted in injury or death.12 Advancing complexity of health care system Knowledge,training and competency issues.13

Table 1: Some common errors and preventive tools Prevention

Sponge /instrument left off in surgical site

Regular sponge/ instrument count

Drug reactions

Allergic testing, documenting,labelling records and patient arm bracelet

Bed sores

Adequate nursing care and nutrition

Misspelling error

Using computerized prescription,bold capital letters

Multiple prescriptions from various specialities

To be approved by the primary consultant

Wrong side limb amputation

Marking surgical site involving patient ,double cross checking

Polypharmacy with drug interactions

Common drug interaction charts to be displayed

Errors in critical care

Protocol based management

Equipment errors Communication failures Overexpectation by the patient and attendants or expecting from treating doctor which some other person has promised.

Preventing errors (Table 1) 1.

National level agenda and focus to enhance safe medical practice through leadership, research, tools and protocols.

2.

Developing an integrated system for reporting of errors which includes voluntary as well as mandatory reporting system through health care delivery system both public and private.

3.

Implementing safe practices at the delivery level.

4.

Raising performance standards and expectations for improvements in safety.

5. Avoiding blame shaming voluntary reporting.

Disclosure of medical error

Disclosure of medical error to patient is often considered as a double edged sword. Sharing of trust is prime in disclosing errors. But in a study by Mazor et al 88.8% wanted full disclosure, 83% favoured financial compensation and even then, upto 47% of patients would still seek legal advice with a view of filing a lawsuit.14

Practice of defensive medicine

Defensive medicine is departing from normal medical practice to safeguard health care provider from litigation.

Save your skin before you save others has become todayâ&#x20AC;&#x2122;s mantra. Asking for battery of investigations even for small

for

encouraging

6.

Adequate legal protection for the profession to avoid defensive medicine practice.

7.

Reporting near misses (i.e., an event/occurrence where harm to the patient was avoided), which can occur 300 times more frequently than adverse events, can provide invaluable information for proactively reducing errors.

8.

Inclusion of ethics of reporting medical error in medical curriculum.

9.

Anonymous reporting and a feedback system for medical errors will be useful without risk of career compromise or litigation fear.

PROBLEMS OF SPECIALIZATION

Specialist consultations came into existence after 1960s from general practice. New technologies, inventions, procedures, diagnostic techniques, better understanding of pathophysiology of disease processes, newer drugs, hospital facilities have led pathway for sub specialization and super specialization. Many hospitals are opened for organ based management than patient centric approach.

Patients often get confused where to go in the middle of plenty of options for eg; pregnant female visiting an ENT clinic for labor pains just because it is near to her home or to a question of who should admit a patient with hypertension, diabetes, ischemic heart disease, atrial fibrillation now with stroke and acute kidney injury?

399

10. Periodic medical, surgical audits and intra departmental mortality meetings maintaining anonymity and professionalism, should be encouraged.

11.

All hospitals and institutions should form a special enquiry committee to decide on the medical errors and rectify within such environment.

12.

Consultants or treating doctors should not be given responsibility of day to day affairs of hospital administration(drug procurement, bed availability etc).

13. Professionals mainly non doctor administrators should look after non clinical part of patient management issues like getting investigations done/ arranging blood for transfusions, arrangement to transfer a patient to ICU, providing an ambulance to shift the patient to other hospitals etc.

14. Multidisciplinary team meeting to decide and

CHAPTER 71

Error

problem has become a routine affair so that a physician do not want to miss the rare possibility-eg; asking for CT Brain for all headaches. It not only increases health care costs but also pose health risks to the patient and spoil doctor-patient relationship.15 Unfortunately doctors are clubbed under service providers along with traders, barbers, bankers and building contractors under consumer protection act in India. The consequence of loss related to medical negligence, medical errors and consumer court have led to the practice of defensive medicine.

plan in patient care for multi organ diseases/ emergencies/multiple co-morbid conditions.

400

15. Active participation in patient safety education programs by physicians.16,17

MISCELLANEOUS

CONCLUSION

Patient centric management is very important. Patient’s wellbeing is more important than mere diagnosis and treatment, especially in an emergency situation. At every step patient and his/herrelatives should be given all options (both diagnostic and therapeutic) to decide the plan for most appropriate management and this increases the participation of all. Efforts should be made for smooth management as physicians have a responsibility for the patient in particular and to the society in general.

Up to 95 % of physicians have reported being witnessed to a medical error. And 61 % of health care professionals actually believe that errors are routine part of medical practice.18 “To err is Human “ but to maintain the honour and noble traditions of medical profession continous efforts are needed to minimize medical error. All doctors are encouraged to accept, discuss and learn from the past medical errors. In my opinion, establishment of department of Trauma & Emergency at every major Hospital/Institution will help to manage the emergency cases more urgently, efficiently, especially in the golden time.

REFERENCES

1.

Schimmelem .The hazards of hospitalization. Ann Intern Med 1964; 60:100-10

2.

Institute of Medicine. To Err is Human: Building a Safer Health System. LT Kohn, JM Corrigan, MS Donaldson, eds.

Washington, DC: National Academy Press, 1999.

3. Makary Martin A, Daniel Michael. Medical error—the third leading cause of death in the US. BMJ 2016; 353:i2139 4.

Brennan TA et al Incidence of adverse events and negligence in hospitalized patients. Results of the Harvard Medical Practice Study I. Engl J Med 1991; 324:370-6.

5.

Leape, Lucian; Lawthers, Ann G.; Brennan, Troyen A., et al.

Preventing Medical Injury. Qual Rev Bull 1993; 19:144–149.

6. Smith A,PepperellD.Evaluation and recommended treatment of anemia. Prescriber 2010; 21:17-29.

7. Abbate SL;Expanded ABCs of diabetes. Clinical Diabetes 2003; 21:128-33.

8.

MaitéGarrouste-Orgeas et al.Selected Medical Errors in the Intensive Care Unit”. American Journal of Respiratory and Critical Care Medicine 2010; 181:134-142.

9.

Gaskin IM. Maternal Death in the United States: A Problem Solved or a Problem Ignored? The Journal of Perinatal Education 2008; 17:9-13. doi:10.1624/105812408X298336.

10. Glenn T. Clark, Roseann Mulligan, Fifteen common mistakes encountered in clinical research. Journal of Prosthodontic Research, 2011; 55:1-6, ISSN 1883-1958 11. J Reason, Human error, Cambridge University Press, Cambridge, UK (1992) 12. Barger, L. K.; et al. “Impact of Extended-Duration Shifts on Medical Errors, Adverse Events, and Attentional Failures”.

PLoS Med. 2006; 3:e487.

13. Phillips DP; Barker GE. “A July Spike in Fatal Medication Errors: A Possible Effect of New Medical Residents”. J Gen Intern Med 2010; 25:774–779.

14. Mazor KM, Simon SR et al: Health plan members view about disclosure of medical errors. Ann Int Med 2004; 140:409-418.

15. Sekhar MS, Vyas N. Defensive Medicine: A Bane to Healthcare. Annals of Medical and Health Sciences Research.

2013; 3:295-296. doi:10.4103/2141-9248.113688.

16. Leape et al Promoting Patient Safety by Preventing Medical Error. JAMA 1998; 280:16.

17. Barach P, Small SD. Reporting and preventing medical mishaps: lessons from non-medical near-miss reporting system. BMJ 2000; 320:759–63.

18. Rajendran PR. Ethical issues involved in disclosing Medical errors JAMA 2001; 286:1078.

C H A P T E R

72

Practical Approach to Pedal Edema

DEFINITION

Edema is defined as the abnormal fluid accumulation in the interstitial space that exceeds the capacity of physiological lymphatic drainage.

Pedal edema is a common presentation of various systemic and non-systemic diseases among Indian population which is always an enigma. A proper understanding of the pathophysiological basis of pedal edema and a systematic approach towards a patient can help a physician to narrow down to the right cause.

Kumar Natarajan

Systemic Causes – congestive cardiac failure, renal failure, anemia, pregnancy and also pulmonary hypertension secondary to Obstructive sleep apnea syndrome15-17.

Decreased oncotic pressure

Systemic Causes – Protein deficient states like chronic liver diseases, nephrotic syndrome, protein losing enteropathy, malabsorption syndrome can result in pedal edema.

Miscellaneous causes

Lymphatic obstruction – poor drainage of the interstitial fluid also results in pedal edema5,6. It may be due to -

MECHANISM

a.

Primary – Congenital lymphedema which is seen at birth or before 2 years, lymphedema precox, which is common in females, before 35 years of age and lymphedema tarda which is seen after 35 years of age.

a.

Capillary permeability

b.

b.

Capillary hydrostatic pressure

c.

Capillary oncotic pressure

Secondary – Obstruction of lymphatic drainage due to tumour, trauma, radiation and infections like filariasis.

d.

Lymphatic drainage

Interstitial fluid space is dependent on the hydrostatic and oncotic pressure gradient across the capillaries and also the lymphatic drainage1-3. So they are dependent on four main factors, namely-

Any derangement of one or more of these four factors which are involved in the regulation of interstitial fluid results in pedal edema.

CAUSES

Generally, causes of pedal edema can be identified on the basis of their pathophysiological mechanism.

A. Lipidema7 – deposition of fluid in adipose tissue.

B.

Idiopathic edema8 – In females of menstruating age idiopathic or cyclical edema is seen throughout the menstruating period. It has to be differentiated from premenstrual edema which often occurs few days prior to menstraution.

4 – Algorithm approach pedal edema The Causes ofFigure Edema are for given intoFigure 2.

PEDAL EDEMA

Increased capillary permeability –

Local Causes – cellulitis (Figure 1)

UNILATERAL

BILATERAL

Systemic Causes – allergic reactions

Increased hydrostatic pressure–

Local Causes – compartment syndrome, chronic venous insufficiency

ACUTE

CHRONIC

DEEP VEIN THROMBOSIS

VENOUS INSUFFIENCY

CELLULITIS

LYMPHEDEMA

COMPARTMENT SYNDROME

ACUTE

DRUGS

CHRONIC

SYSTEMIC

NON SYSTEMIC

HEART FAILURE

DRUGS

LIVER DISEASE

VENOUS INSUFFICIENCY

RENAL DISEASE

LYMPHADEMA

OBSTRUCTIVE SLEEP APNOEA

PELVIC TUMOUR IDIOPATHIC EDEMA

Fig. 1: Right leg Cellulitis with edema

Fig. 2: Algorithm for approach to pedal edema

Fig 5 – Pedal edema - History RHD in India along with a decline in the incidence of Heart failure due to RHD.26

402

Chronic Liver Disease

SITE

MISCELLANEOUS

DRUG INTAKE

DURATION

HISTORY

SYSTEMIC ILLNESS

PAIN

In India, Hepatitis B and Hepatitis C Virus infections were the leading cause of Chronic Liver Disease (CLD) in the past. But, alcohol has fast caught up, especially after 2007 and it is the leading cause of CLD related morbidity and mortality burden at present. A recent publication highlighting the “alcohol situation in India” strongly supports the above statement. This article highlighted that about 21% of adult men and 2% of adult women drink alcohol, of them 20% are “problem” drinkers. The number of drinkers in young age has increased from 2 to 14% in past 15 years. From1979 to 2005 CLD mortality has doubled and two-third of which is due to alcohol.27

Chronic Kidney Disease VARIABILITY

Fig. 3: History taking in Pedal Edema

PEDAL EDEMA: INDIAN SCENARIO

Coronary Artery Heart Disease and Heart Failure

Heart failure is a major public health issue globally with a current prevalence of over 23 million worldwide. From the 1970s to 1990s, a dramatic increase in the prevalence of Heart failure and number of Heart failure hospitalizations was observed in USA. The growing prevalence of HF might reflect an aging population and improvements in the treatment of Cardiovascular diseases and Heart failure or a combination of these factors.22 India is going through an epidemiologic transition whereby the burden of communicable diseases have declined slowly, but that of non-communicable diseases (NCD) has risen rapidly, thus leading to a dual burden.

Reliable estimates of heart failure are lacking in India because of the absence of a surveillance programme to track incidence, prevalence, outcomes and key causes of heart failure. Based on disease-specific estimates, the prevalence of heart failure in India due to coronary heart disease, hypertension, obesity, diabetes and rheumatic heart disease ranges from 1.3 to 4.6 million, with an annual incidence of around 0.5 to 1.8 million.23

Rheumatic Heart Disease and Heart Failure

Hospital based data between 1945 and 1963 indicate that anywhere between 20% and 50% of all hospital admissions for cardiac patients were for RHD. ICMR has conducted three school-based surveys on prevelance of RHD among children aged between 5 to 14 years over a 40-year period between 1970 and 2010. In the first study (1972-1975), the prevalence of RHD was found to be 5.3/1000. In the second study (1984-1987), the overall prevalence of RHD was ranged 2.9/1000. In the third study which was the largest one, the overall prevalence was 0.9/1000. This data clearly shows that there is a steady decline in the prevalence of

With increasing life expectancy and prevalence of life style diseases, US has seen a 30% increase in prevalence of chronic kidney disease (CKD) in the last decade.

Unfortunately, there is no longitudinal study and limited data is available in India on the prevalence of CKD. In India, diabetes and hypertension today account for 40– 60% cases of CKD.28

Chronic Venous Insufficiency

On a global perspective 1 out of 5 people suffer from Chronic Venous Insufficiency (CVI). This can be mainly attributed to occupation, lifestyle changes, environmental factors, a familial tendency and post-partum period. In India, incidence of CVI remains an iceberg phenomenon, since patients with CVI seek treatment very late.29,30

Filariasis

In India, the incidence of microfilarial infection has decreased from 1.24% to 0.26% over a period of 11 years from 2004 to 2015 along with a decrease in the incidence of lymphedema (Elephantiasis).31 The above data clearly shows that there is changing pattern in the etiology of pedal edema from communicable diseases like HBV, HCV and Filariasis to non-communicable diseases like CHD, Alcoholic Liver Disease, CKD due to Diabetes Mellitus, Systemic Hypertension etc..

EVALUATION OF PEDAL EDEMA

History

A detailed history is the most important component in the evaluation of pedal edema as it often gives a clear perspective which can pin point the underlying cause (Figure 3).

I.

SITE AND DISTRIBUTION – Whether the pedal edema is unilateral or bilateral. Unilateral edema results mainly due to local causes like Deep vein thrombosis (DVT), cellulitis, compartment syndrome and filarial lymphatic obstruction.

Bilateral pedal edema is mainly due to systemic causes like congestive cardiac failure, anemia, chronic kidney disease and chronic liver disease.11,12

II.

DURATION OF ILLNESS – Short duration of

Table 1: Drugs Causing Pedal Edema Drug classification

Drug

Anti – hypertensives

Calcium channel blockers

403

Beta blockers Methyl dopa Hormones

Corticosteroids Estrogen Progesterone Testosterone MAO inhibitors

NSAIDs

Ibuprofen Diclofenac

Oral hypoglycemics

Fig. 4: Bilateral pitting pedal edema the illness indicates an acute cause like Cellulitis, DVT, Compartment syndrome etc.. which usually occurs in 72 hours.9,10 III.

ASSOCIATION WITH PAIN – Conditions like Deep Vein thrombosis and cellulitis are generally painful whereas edema due to Heart failure, hypoproteinemia and lymphedema are painless. A dull aching type of pain is seen in chronic venous insufficiency.4

IV. VARIABILITY OF EDEMA – Venous edema due to congestive cardiac failure and venous insufficiency is aggravated by standing and improves with overnight limb elevation during sleep. Idiopathic edema which is seen in females increases throughout the day during upright posture.

V. HISTORY OF SYSTEMIC ILLNESS – Symptoms of systemic diseases like exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea and chest pain point to cardiac failure; history of oliguria and puffiness of face suggest renal etiology; long term alcohol consumption, yellowish discoloration of eyes and urine and abdominal distension points to cirrhosis of liver; symptoms of endocrine disorders like hypothyroidism are often missed. Similar history about all other systemic causes of pedal edema should be elicited in detail.

Patients who are bed ridden for a prolonged period of time have dependent edema over the sacral area.

VI. HISTORY OF DRUG INTAKE – Drugs like calcium channel blockers, NSAIDs and steroids can cause pedal edema. Around 50% of patients taking calcium channel blockers and 5% of patients taking NSAIDs complain of pedal edema.13,14 (Table 1) VII. HISTORY OF TRAUMA AND RADIATION – Trauma and radiation can cause cellulitis and compartment syndrome leading to pedal edema which may be unilateral or bilateral. Long term radiation can also cause lymphedema in some patients.

Rosiglitazone Pioglitazone

VIII. MISCELLANEOUS CAUSES- Obstructive sleep apnea can also cause pedal edema due to right ventricular failure. However it is always a diagnosis of exclusion.

CLINICAL EXAMINATION: A thorough and meticulous physical examination should be carried out in all the patients with pedal edema which along with a detailed history helps the physician to make a fairly accurate diagnosis.

i..

Local examination –

I.

Distribution - Identify whether it is unilateral (usually local causes) or bilateral (predominantly systemic causes, sometimes local).

II.

Site – Bony prominences like medial malleolus and medial surface of tibia along with the dorsum of foot has to be examined thoroughly. Dorsum of foot is not involved in lipidema which usually involves the medial malleolus area of foot.

III. Tenderness – Deep vein thrombosis, cellulitis, lipidema and compartment syndrome are generally tender. However, lymphedema and edema due to systemic diseases are painless.

IV..

Pitting edema – Except in cases of edema due to lymphatic obstruction and myxedema, most of the other diseases cause pitting pedal edema. However, in early stages of lymphedema, it is usually pitting13 (Figure 4).

V.

Skin changes

a.

Myxedema – Dry , coarse and thick skin is noted

b.

Chronic venous insufficiency – Hemosiderin deposition causes brawny skin commonly over the medial malleolus. Often varicose veins are seen on the medial side of the leg8,13.

c.

Chronic lymphedema – hyperkeratotic and papillamatous skin with induration which is known as lymphostatic verrucosis (elephantiasis)4

CHAPTER 72

Anti - depressants

detected by these tests.

MISCELLANEOUS

404

d.

Serum lipid profile –Nephrotic syndrome is associated with hyperlipidemia. Dyslipidemia is also a risk factor for coronary heart disease.

e.

Chest X ray, ECG and Brain natriuretic peptide – These tests are used for identifying heart failure.

Brain natriuretic peptide has sensitivity of 90% and specificity of 76% in predicting heart failure.

f.

D-dimer estimation – In acute cases of pedal edema, it can be used to identify deep vein thrombosis.

However, in patients with elevated D-dimer levels, additional imaging investigations like Doppler study have to be carried out for the definitive diagnosis of DVT18-17.

g.

Imaging studies –

1.

Doppler study – it is the imaging study of choice with a high specificity and sensitivity for diagnosing Deep vein thrombosis and chronic venous insufficiency.

2.

`Lympho scintigraphy – Lymphedema can be identified using a radio-nucleotide tracer which is injected into the first web space and the flow of the lymph is monitored using a gamma camera.

This gives an indirect evidence of lymphatic obstruction5,21.

3.

Echocardiography – It is used for the assessment of left ventricular function in patients with congestive heart failure. It can also measure the pulmonary artery pressure and helps in diagnosing pulmonary hypertension in conditions like cor pulmonale and Obstructive sleep apnea syndrome20.

Fig. 5: Bilateral chronic lymphedema (elephantiasis) (Figure 5). Kaposi-stemmer sign5 - It is the inability to pinch the skin on the dorsum of the foot near the second toe. ii.

Systemic examination –

I.

Congestive cardiac failure – Elevated jugular venous pressure, third heart sound and crepitations over the lung bases.

II.

Decompensated liver disease – Jaundice, ascites, splenomegaly gynaecomastia and spider naevi.

III.

Chronic kidney disease – Anemia, dry skin, uremic breath.

IV.

Hypothyroidism – Bradycardia, skin changes like dry skin and sparse hair, hoarseness of voice.

MANAGEMENT OF PEDAL EDEMA

Treatment of pedal edema widely differs across the spectrum of etiology.

A.

Venous insufficiency – Initial stages of venous insufficiency resolve easily with limb elevation.

However in chronic states it needs high knee compression stockings. Before using stockings peripheral vascular disease has to be ruled out by ankle brachial index or arterial doppler as they may aggravate the underlying condition. Patients who are refractory to treatment with stockings and who are contraindicated for stockings need pneumatic compression devices. Diuretics are of no use and often avoided as they can cause metabolic dearrangements. Skin care with topical steroids and emollients should be used to avoid excoriation and ulceration.

B.

Congestive heart failure and chronic liver disease – Respond to fluid restriction, salt restriction and limb elevation in the early stages and diuretics like frusemide and spironolactone can be used for patients who do not respond to the above measures.

Albumin infusion can also be used to correct the

INVESTIGATIONS

A set of baseline investigations has to be done to pin point the underlying diagnosis in a cases of pedal edema along with special investigations if indicated. a.

Complete blood count – helps to diagnose anemia and also gives some clues regarding the cause anemia.

b.

Urine analysis, renal function test & USG KUB – Help to diagnose chronic kidney disease & nephrotic syndrome.

c.

Liver function test including serum protein – Diseases like cirrhosis, nephrotic syndrome, protein losing enteropathy and malnutrition can be

hypoalbuminemia in liver failure which provides temporary relief.

C.

D.

F.

Obstructive sleep apnea – Weight reduction and continuous positive pressure ventilation helps in reducing pulmonary hypertension and improving edema.

Lymphedema – Initially treated with manual massaging. Compressive bandage and stockings can also be used. Later, Intermittent pneumatic compression devices are used. In refractory cases of lymphedema, surgical procedures like bypass surgery and debulking can be done. Diuretics are of no use in these patients.

Deep vein thrombosis – In chronic bed ridden patients, compression devices like bandages and stockings can prevent DVT. DVT is treated with early initiation anticoagulant therapy using low molecular weight heparin which is followed by oral anticoagulants.

G.

Lipidema – No effective treatment is available.

Weight loss is also of little use.

H.

Idiopathic edema – Responds to treatment with aldosterone antagonist like spironolactone.

REFERENCES

1.

Braunwald E, Loscalzo J. Edema. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds.

Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill; 2011. http://www. accessmedicine.com/ content.aspx?aid=9097476. Accessed January 7, 2012.

2.

O’Brien JG, Chennubhotla SA, Chennubhotla RV. Treatment of edema. Am Fam Physician 2005; 71:2111-2117.

3.

Cho S, Atwood JE. Peripheral edema. Am J Med 2002; 113:580-586.

4.

Ciocon JO, Fernandez BB, Ciocon DG. Leg edema:clinical clues to the differential diagnosis. Geriatrics 1993; 48:34–40, 45.

5.

SzubaA, Rockson SG. Lymphedema: classification,diagnosis, and therapy. Vasc Med 1998; 3:145– 6.

6.

Mortimer PS. Swollen lower limb-2: lymphoedema. BMJ 2000; 320:1527–9.

7.

Rudkin GH, Miller TA. Lipidema: a clinical entitydistinct from lymphedema. Plast Reconstr Surg 1994; 94:841–7.

8.

Streeten DH. Idiopathic edema. Curr Ther Endocrinol Metab 1997; 6:203– 6.

9.

Yale SH, Mazza JJ. Approach to diagnosing lower extremity edema. Compr Ther 2001; 27:242-252.

10. Ely JW, Osheroff JA, Chambliss ML, Ebell MH. Approach to leg edema of unclear etiology. J Am Board Fam Med 2006; 19:148-160.

11. Merli GJ, Spandorfer J. The outpatient with unilateralleg

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12. Young JR. The swollen leg. Clinical significance and differential diagnosis. Cardiol Clin 1991; 9:443–56.

13. Cho S, Atwood JE. Peripheral edema. Am J Med 2002; 113:580–6.

14. Topham EJ, Mortimer PS. Chronic lower limb oedema. Clin Med 2002; 2:28 –31.

15. Padberg F Jr, Cerveira JJ, Lal BK, Pappas PJ, Varma S, Hobson RW 2nd. Does severe venous insufficiency have a different etiology in the morbidly obese? Is it venous? J Vasc Surg 2003; 37:79–85.

16. L’Hermitte F, Behar A, Paries J, Cohen-Boulakia F, Attali JR, Valensi P. Impairment of lymphatic function in women with gynoid adiposity and swelling syndrome. Metabolism 2003; 52:805–9.

17. Ageno W, Piantanida E, Dentali F, et al. Body mass index is associated with the development of the postthrombotic syndrome. Thromb Haemost 2003; 89:305–9.

18. Stein PD, Hull RD, Patel KC, et al. D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review. Ann Intern Med 2004; 140:589–602.

19. 17. Palareti G, Legnani C, Cosmi B, et al. Predictive value of D-dimer test for recurrent venous thromboembolism after anticoagulation withdrawal in subjects with a previous idiopathic event and in carriers of congenital thrombophilia.

Circulation 2003; 108:313–8.

20. Blankfield RP, Finkelhor RS, Alexander JJ, et al. Etiology and diagnosis of bilateral leg edema in primary care. Am J Med 1998; 105:192–7 21. Studdiford J, Lamb K, Stonehouse A. Evaluating edema of the hands. J Musculoskel Med 2009; 26:30-36.

22. Anh LB, Tamara BH, Gregg CF. Epidemiology and risk profile of heart failure. Nat Rev Cardiol 2011; 8:30–41.

23. Huffman MD1, Prabhakaran D. Heart failure: epidemiology and prevention in India. Natl Med J India 2010; 23:283-8 24. Gupta R, Gupta VP. Meta-analysis of coronary heart disease prevalence in India. Indian Heart J 1996; 48:241–5. [PubMed] 25. Krishnan MN. Coronary heart disease and risk factors in India – On the brink of an epidemic? Indian Heart J 2012; 64: 364–367.

26. Shah B, Sharma M, Kumar R, Brahmadathan KN, Abraham VJ, Tandon R. Rheumatic heart disease: Progress and challenges in India. Indian J Pediatr 2013; 80(Suppl 1):77–86.

[PubMed] 27. Ray G. Trends of chronic liver disease in a tertiary care referral hospital in Eastern India. Indian J Public Health 2014; 58:186-94 28. Varma PP. Prevalence of chronic kidney disease in India Where are we heading? Indian J Nephrol 2015; 25:133–135.

29. Mukunda NK. Clinical evaluation and management of lower limb varicose veins: A study at KIMS. Unpublished doctoral dissertation submitted to Rajiv Gandhi University of Health Sciences; 2006.

30. Pinjala RK, Abraham TK, Chadha SK, et al. Long-term treatment of chronic venous insufficiency of the leg with micronized purified flavonoid fraction in the primary care setting of India. Phlebology 2004; 19:179-184.

31. Sabesan S, Vanamail P, Raju K, Jambulingam P. Lymphatic filariasis in India: Epidemiology and control measures. J Postgrad Med 2010; 56:232-8.

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E.

Chronic renal failure – Fluid restriction and salt restriction are the initial line of management of renal failure. In refractory cases, loop diuretics like frusemide or torsemide can be given. Aldosterone antagonist are contraindicated because of risk of developing life threatening hyperkalemia.

swelling. Med Clin North Am 1995; 79:435–47.

Cord Blood

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73

Ashesh Bhattacharya, Meenakshi Bhattacharya

INTRODUCTION

Cord blood is the blood from the new born baby that is left in the umbilical cord and placenta after birth. It contains special cells called hematopoietic stem cells. Cord blood collection begins at the start of the third stage of labor, immediately after delivery of the infant irrespective of vaginal or caesarean section delivery. It is collected by inserting a sterile needle into the umbilical vein and allowing gravity to drain the blood into a collection bag (FDA approved and heparin free). The collection bag is a closed system which minimizes the risk of bacterial and fungal contamination. The entire collection process takes approximately 5 to 10 minutes and on and average 75ml of blood is collected. A small segment is placed into the provided collection jar after cleaning the umbilical cord.

Three tubes of maternal blood are also collected. Cord blood and cord tissue can be kept at room temperature.

They are safe to remain in the collection kit for up to 72 hours prior to arriving for processing. Before the cord blood is stored it undergoes viral testing, including tests for HIV and Hepatitis B and C, and tissue typing to determine Human Leukocyte Antigen type, nucleated cell count, cell viability, blood group antigen ABO & Rh blood group system, molecule cluster, and bacterial and fungal growth. After processing the cord blood is cryopreserved.

Cord blood can be saved indefinitely.

Cord blood may not be collected if mother has known hereditary diseases, specifically involving hematopoiesis in the family or if severe disabilities or diseases are identified in the donor foetus before birth, presence of infectious diseases e.g., HIV, hepatitis in the mother, severe pregnancy related complications or premature delivery with birth weight less than 1,500 g or if perinatal asphyxia is present.

HISTORICAL ASPECT

Dr. Hal Broxmeyer discovered the presence of hematopoietic stem and progenitor cells in human cord blood in 1985. First successful related cord blood transplant was conducted in Paris, France, on a sixyear-old male patient from Duke suffering from a blood disorder called Fanconi’s Anemia in 1988. First public bank for umbilical cord blood was established by Dr. Pablo Rubinstein at the New York Blood Center through funding provided by the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) in 1992. First unrelated cord blood transplant in the world was performed by Dr. Joanne Kurtzberg at Duke University’s pediatric Blood and Marrow Program in

1993. FDA launched an Investigational New Drug (IND) for cord blood under the Cord Blood Transplantation Study (COBLT). The study was sponsored by the National Heart Lung and Blood Institute (NHLBI) in 1996. National Marrow Donor Program (NMDP) launched cord blood program in 1998. U.S. Congress passed national cord blood legislation, The Stem Cell Research and Therapeutic Act of 2005 (H.R. 2520), to create a national inventory of 150,000 diverse, high-quality cord blood samples in 2005.

A total of 31 UCBTs were performed, mainly in paediatric and adolescent patients; only four UCBTs were performed in adults by the end of 2008. Over 30,000 unrelated cord blood transplants performed by 2012.

BENEFITS OF SAVING CORD BLOOD

Umbilical cord blood (UCB) contain hematopoietic stem cells (HSC) and it is recognised as an alternative source of HSC after bone marrow. UCB HSC have greater proliferative and colony forming capacity, and are more responsive to some growth factors. Because they are more ‘naïve’ than proliferative cells from bone marrow, they seem to produce fewer complications associated with HSC transplantation. The major clinical use of cord blood has been for haematological malignancy mostly in children. In a survey from the International Bone Marrow Transplantation.

Registry (IBMTR) estimated that since 1998, one-fifth of stem cell transplants performed for patients less than 20 years old are cord blood transplants, mostly for acute lymphoblastic leukaemia or acute myelobastic leukaemia.

For treating cancer, as per studies, the transplant dose should be at least 25 million TNC per kilogram of patient body weight (1 kilogram equals 2.2 pounds). The average cord blood collection holds 8.6 million TNC per ml.

To overcome the low cell content of single UCB units, various alternatives have been used. Multidonor UCBTs of up to 12 units have shown that crossed immunological reaction between the units does not occur.

The simultaneous transplantation of 2 partially HLAmatched umbilical cord blood units (double umbilical cord blood transplantation, dUCBT) has also been used to overcome cell dose limitations. The first dUCBT was performed in Europe in 1999 on 2 adults with acute lymphoid and chronic myeologenous leukemia. From 1999 to March 2010, 1,152 dUCBTs, combined with conditioning of various intensities, have been performed in patients with hematologic malignancies who could not find suitable unrelated donors. There is little published evidence is currently available on the long-term immune

reconstitution and clinical benefit of dUCBT. A reasonable limitation of dUCBT is the cost of 2 umbilical cord blood units, especially from unrelated donors, and the costs of hospitalization due to the low engraftment rate.

stem cells and/or lymphocytes from the graft donor in graft failure or disease relapse.

•

Own cells may be inappropriate in genetic conditions including some leukaemia’s, because they may carry leukaemogenic mutations.

• It is a readily available source of hematopoietic stem cells.

•

• It is an alternative to bone marrow or peripheral stem cell transplantation to treat malignant and nonmalignant conditions in children and adults.

Only half to a third of samples yield mesenchymal stem cells and clinical uses for mesenchymal cells are speculative.

•

Child may never need it and possible benefits are too remote to justify the costs.

ADVANTAGES OF CORD BLOOD

• Lower incidence of viral transmission: in particular, cytomegalovirus and Epstein-Barr virus.

• Faster availability- patients on average receive cord blood transplantation earlier than those receiving conventional bone marrow grafts.

• It is harder to collect bone marrow than it is to collect cord blood. Collecting bone marrow poses some risks and can be painful for the donor.

• Cord blood transplantation tolerates a mismatch of tissue types between donor and the recipient greater than is acceptable with bone marrow or peripheral blood.

• Because of the ethnic diversity of donors of cord blood, there is a higher frequency of non-Caucasoid HLA haplotypes available compared with bone marrow registries • Bone marrow donors may change their mind over time or may no longer be available.

• In case of related donors, HLA-identical sibling cord blood transplantation has been performed almost exclusively in children. The lower risk of both treatment-related mortality and chronic graft versus host disease makes cord blood transplantation a particularly successful option for children with haemaglobinopathies.

• Cord blood transplants from unrelated donors for children has been associated with sustained engraftment, a low incidence of graft versus host disease and no higher risk of leukemic relapse.

• There is a theoretical hope that stem cells will be a crucial part of future treatments for diabetes, Alzheimers, spinal cord injuries, heart failure, stroke etc.

DISADVANTAGES OF CORD BLOOD

•

Low numbers of haemopoietin progenitor cells and stem cells in each cord blood donation, may cause delayed engraftment.

•

Cord blood has a limited number of stem cells, not enough to treat most adults.

•

Lack of availability of subsequent donations of

CORD BLOOD BANKING

Cord blood banking is a personal decision of parents.

Some people feel that the potential benefits are too few to justify the money. Others believe that it’s a worthwhile investment. Cord blood stored in private banks are used for either autologous or allogeneic transplants for the infant donor or related family member. Cord blood is considered a treatment option in pediatric and adult patients with hematologic malignancies and disorders (leukemia, thalassemia, sickle cell disease, etc.) bone marrow failures, inherited metabolic disorders, immunological defects and other genetic diseases. More than 25,000 allogeneic cord blood transplantations have been performed worldwide since the first cord blood transplantation in 1988. In an autologous transplant, the cord blood collected at birth is used by the same child. This type of transplant is rare because a child’s stem cells cannot be used to treat genetic diseases in that child as all of the stem cells have the same genes that cause the disease. In an allogenic transplant, the donor can be a relative or be unrelated to the child.

For an allogenic transplant to work, there has to be a good match between donor and recipient.

Two types of cord blood banks are available-public and private and accreditation of FDA, ISO is mandatory.

Public cord blood banks accept donations to be used for anyone in need and use national registries to find recipients for their samples. Private cord blood banks store cord blood solely for potential use by the donor or donor’s family. Cord blood transplantation doesn’t require an exact genetic match, which makes it easier to provide patients samples form unrelated donors. Private banks, in USA e.g. Viacord, CBR, and Americord, charge around $2,000 for the collection and around $200 a year for storage which is not covered by insurance. But private storage of one’s own cord blood is unlawful in Italy and France, and it is also discouraged in some other European countries.

Public and private both cord blood banks takes care of the costs involved in the collection, transport, processing and storage. As public banks accepts donations of cord blood it is done at free of cost but private banks charges vary from 70,000/- to 90,000/- per year and EMI,s are available just as insurance companies. Private cord blood banks are available in Ahmedabad, Bengaluru, Chandigarh, Chennai, Hyderabad, Jaipur, Kolkata, Lucknow, Mumbai, New Delhi and Pune in India. A free e-book of list of these banks is made available on www.superbabyonline.com.

CHAPTER 73

• Lower incidence and severity of graft versus host disease.

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408

The most important debatable question is “Is it worth spending on cord blood storage which might never be used?” Considering all the above facts donations of cord blood to public cord blood banks for the purpose of treatment and research should be promoted.

REFERENCES

MISCELLANEOUS

1. B. Anthony Armson,, Halifax NS, David S. Allan, MD, Toronto ON, Robert F. et al. Umbilical Cord Blood: Counselling, Collection, and Banking. SOGC clinical practice guideline. J Obstet Gynaecol Can 2015; 37:832–844.

2. David McKenna & Jayesh Sheth. Umbilical cord blood: Current status & promise for the future. Indian J Med Res 2011; 134:261-269.

3. Hamad Ali, and Hussain Bahbahani. Umbilical cord blood stem cells – potential therapeutic tool for neural injuries and disorders. Acta Neurobiol Exp 2010; 70:316–324.

4. FAQ 72 pregnancy. American college of Obstretitians and Gynecologists. Womens Healthcare Physicians.

5. www.superbabyonline.com.

6. Sideri A, Neokleous N, De La Grange PB, Guerton B, Le Bousse Kerdilles M-C, Uzan G, Peste et al. An overview of the progress on double umbilical cord blood transplantation. Haematologica 2011; 96:1213-1220. doi:10.3324/haematol.2010.038836.

Routine Use of Vitamins, Minerals, Probiotics & Anti-Oxidants

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74

Vijay Garg, Raman Parashar, Aadish Kumar Jain, AK Pancholia

hemodialysis), abnormal metabolism (e.g., genetic polymorphisms, alcoholism, conditions that impair fat absorption), and/or inadequate synthesis (e.g., insufficient sunlight exposure to allow vitamin D synthesis).

INTRODUCTION

India is the most potential market for nutriceutical products. Nutritional supplements by definition are concentrated sources of nutrients intend to supplement the diet but not replace it. It includes vitamins, minerals, protein, mineral complexes, enzymes etc. Improved standard of living, increasing health consciousness, education, easy availability and better income have compelled us to think of the fine line between use and indiscriminate use of these supplements.

Vitamins and minerals has shifted from trying to prevent deficiencies to taking higher amounts of them in an effort to enhance health.The need of hour is to answer a question whether daily use of vitamin, mineral, anti-oxidants and probiotics are helping or causing detrimental effects.

INDIAN SCENARIO

Accounts for 1.5% of global pharmaceutical market.

One-Fifth of Indian population lack purchasing power to consume a diet which is rich in calories and sufficient to meet RDA causing a burden of Malnutrition.Sports nutrition is gaining importance in India. Various fitness centers are contributing to increase demand of vitamins and minerals. Federation of Indian Chambers of Commerce and Industry (FICCI) stated nutrition related risk factors contribute to more than 40% deaths in developing countries including India.

SPECIFIC STRATA OF POPULATION LIKELY TO BE BENEFITED ARE

•

Women of childbearing age (need extra calcium and iron)

•

Pregnant or lactating women

•

Children and teenagers with irregular eating habits

Inadequate micronutrient intake, sometimes even at borderline levels of deficiency, has been linked to stunted growth and neurocognitive deficits, as well as increased risks of various symptoms and conditions. Most nutrients act in all tissues, and all tissues need all nutrients; therefore, inadequate intakes may adversely affect every body system, but with more pronounced effects in some than others.

APPROPRIATE USE

•

• Vitamin B12 can reverse anemia.

•

Vitamins B1, B6, B12 affect formation of serotonin, neurotransmitter involved in relaxation.

•

Vitamin D is recommended for breastfeeding babies and elderly. Low vitamin D is associated with so many diseases like heart diseases, diabetes, osteoporosis etc.

•

Vitamin K injections in newborns prevent bleeding events. Vitamin K2 has recently been revealed as an important nutrient in protecting against heart disease. It does this by putting calcium in the bones and teeth where it belongs, and not in the arteries and soft tissue.

•

Choline involved in acetylcholine synthesis which is a neurotransmitter whose reduction causes fatigue.

•

Antioxidants – Vitamin C, E, beta-carotene and coenzyme Q10 have shown to improve exercise performance and prevent exercise-induced muscle damage but in individuals deficient of them.

• Seniors •

Vegetarians or vegans (may be deficient in key nutrients)

•

Dieters or people avoiding certain food groups (may be deficient in key nutrients)

•

People with eating disorders or medical conditions (deficiency diseases, absorption problems, lactose intolerance, etc.)

•

People who often eat processed and fast food

•

Some people are at risk of micronutrient deficiencies due to excessive losses (e.g., through

B-Complex is involved in processing fats & carbohydrates for energy production and formation of hemoglobin in red blood cells.

USE OF MICRONUTRIENTS

Zinc

Zinc is a metal. It is called an “essential trace element” because very small amounts of zinc are necessary for human health. Zinc is used for treatment and prevention of zinc deficiency and its consequences, including stunted growth and

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acute diarrhoea in children, and slow wound healing.

It is also used for boosting the immune system, treating the common cold and recurrent ear infections, and preventing lower respiratory infections. It is also used for malaria and other diseases caused by parasites.

Some people use zinc for an eye disease called macular degeneration, for night blindness, and for cataracts. It is also used for asthma; diabetes; high blood pressure; acquired immunodeficiency syndrome (AIDS); and skin conditions such as psoriasis, eczema, and acne.

Side Effect of Zinc

Zinc is likely safe for most adults when applied to the skin, or when taken by mouth in amounts not larger than 40 mg daily. Routine zinc supplementation is not recommended.

Zinc is possibly safe when taking by mouth in doses greater than 40 mg daily. There is some concern that taking doses higher than 40 mg daily might decrease how much copper the body absorbs.

Decreased copper absorption may cause anemia.

Taking more than 100 mg of supplemental zinc daily or taking supplemental zinc for 10 or more years doubles the risk of developing prostate cancer.

Pregnancy and breast-feeding: Zinc is likely safe for most pregnant and breast-feeding women when used in the recommended daily amounts (RDA). However, zinc is possibly unsafe when used in high doses by breastfeeding women and likely unsafe when used in high doses by pregnant women. Pregnant women over 18 should not take more than 40 mg of zinc per day; pregnant women age 14 to 18 should not take more than 34 mg per day.

Breast-feeding women over 18 should not take more than 40 mg of zinc per day; breast-feeding women age 14 to 18 should not take more than 34 mg per day.

Alcoholism: Long-term, excessive alcohol drinking is linked to poor zinc absorption in the body.

Diabetes: Large doses of zinc can lower blood sugar in people with diabetes. People with diabetes should use zinc products cautiously.

Hemodialysis: People receiving hemodialysis treatments seem to be at risk for zinc deficiency and might require zinc supplements.

HIV (human immunodeficiency virus)/AIDS: Use zinc cautiously if you have HIV/AIDS. Zinc use has been linked to shorter survival time in people with HIV/AIDs.

Chromium

Chromium is a mineral. It is called an “essential trace element” because very small amounts of chromium are necessary for human health. There are two forms of chromium: trivalent chromium and hexavalent chromium.

The first is found in foods and supplements and is safe for humans. The second is a known toxin that can cause skin problems and lung cancer.

Chromium is used for improving blood sugar control in people with prediabetes, type 1 and type 2 diabetes,

and high blood sugar due to taking steroids and HIV treatments. It is also used for depression, Turner’s syndrome, polycystic ovary syndrome (PCOS), lowering “bad” cholesterol, raising “good” cholesterol in people taking heart medications called beta blockers, metabolic syndrome, heart attack,schizophrenia, bipolar disorder, and binge eating disorder.

Diabetes. Some evidence shows that taking chromium picolinate (a chemical compound that contains chromium) by mouth, either alone or along with biotin, can lower fasting blood sugar, lower insulin levels, and help insulin work in people with type 2 diabetes. Also, chromium picolinate might decrease weight gain and fat accumulation in people with type 2 diabetes who are taking a class of antidiabetes medications called sulfonylureas.

Some research shows that taking 15-200 mcg of chromium daily for 6-12 weeks lowers low-density lipoprotein (LDL or “bad”) cholesterol and total cholesterol levels in people with slightly high or high cholesterol levels.

Copper

Copper is a mineral. It is found in many foods, particularly in organ meats, seafood, nuts, seeds, wheat bran cereals, grain products, and cocoa products. The body stores copper mostly in the bones and muscles.

The liver regulates the amount of copper that is in the blood. Copper is used as medicine. Copper is used for treating copper deficiency and the anemia it may cause.

Having too little copper (copper deficiency) is rare. It sometimes occurs in people who get too much zinc from diet or supplements, have intestinal bypass surgery, or are fed by feeding tubes. Malnourished infants can also have copper deficiency. Copper is also used for improving wound healing, and treating osteoarthritis and brittle bones (osteoporosis). There is no evidence that people who eat a normal diet need copper supplements. Not even athletes need extra copper if they have a good diet.

Copper is necessary for producing and storing iron.

Taking copper in combination with zinc, manganese, and calcium might slow bone loss in older women.

5 MICRONUTRIENTS THAT MAY HELP REDUCE BLOOD SUGAR

Overwhelming scientific evidence confirms that vitamin, mineral and antioxidant deficiencies suppress immune function and contribute to chronic inflammatory degenerative processes, such as arthritis, cancer, Alzheimer’s, cardiovascular disease and type 2 diabetes.

We have seen over and over the myriad of scientific studies that demonstrate the ability to prevent, treat and even reverse type 2 diabetes through diet and lifestyle.

Unfortunately, however, serious nutritional deficiencies can occur even with a healthy eating plan due to many possible factors, including inadequate absorption of nutrients due to co-morbidities, toxins in our environment that may interfere with transport of nutrients, or nutrientdrug interactions as a result of the use of both prescription and over-the-counter medications. Metformin, for

example, used by many people with type 2 diabetes and pre-diabetes, has been shown to lower vitamin B12 and folic acid, which can then lead to an increase in homocysteine levels, a major risk factor for cardiovascular disease. A folate deficiency has also been associated with diabetes co-morbidities of retinopathy and renal failure. Many other pharmaceutical medications and over-the-counter treatments have been implicated in causing micronutrient deficiencies.

Alpha-Lipoic Acid

This is an antioxidant that has been shown to regenerate other antioxidants, such as glutathione, vitamin E and vitamin C, and to prevent protein glycosylation. Alphalipoic acid has been shown to enhance glucose uptake in skeletal muscle tissue, thus improving glucose regulation in people with diabetes mellitus. It has also been shown to be effective in the treatment of peripheral neuropathy, a common complication in diabetes.

Chromium

This trace mineral is fundamental in proper insulin function and is believed to facilitate the attachment of insulin to the cell’s insulin receptors. A lack of chromium can result in insulin resistance, which leads to elevated blood levels of insulin and glucose, resulting in diabetes and cardiovascular complications.

Vitamin D

Children who received 2000 IU vitamin D during the first year of life were found to have a reduced risk of developing type 1 diabetes, compared with children who were not supplemented with vitamin D. Because vitamin D modulates calcium, people with diabetes (both type 1 and type 2) have a higher risk for bone fractures, and vitamin D deficiency has clearly been associated with lower bone density. People with a low vitamin D are also at a higher risk of insulin resistance and metabolic syndrome. Vitamin D is essential for normal insulin release by increasing transmembrane calcium movement in islet cells. Vitamin D-dependent calcium binding protein has been detected in pancreatic tissue and vitamin D receptors have been identified in pancreatic islet cells. Sixty- to 65% of the time, when tested, vitamin D is deficient.

Riboflavin

Many people with diabetes have abnormal riboflavin metabolism, which is often overlooked. Even people taking over-the-counter supplements containing riboflavin, may not be getting adequate dosing because these over-the-counter supplements usually do not contain the proper form of riboflavin, which should be riboflavin 5—phosphate. Riboflavin is important for antioxidant function, working through the pathway of making more glutathione.

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Niacin acts by protecting pancreatic beta cells from autoimmune destruction. Keep in mind that this is not the nicotinic acid form of niacin used for lowering cholesterol and triglycerides, but instead the amide form of niacin (nicotinamide), which does not cause flushing. Niacin may also act as a weak antioxidant of nitric oxide radicals, but its most significant function related to diabetes is its involvement with the glucose tolerance factor (GTF).

Niacin may also retard the development of nephropathy, therefore supplementation in persons with diabetes may be appropriate.

SENSIBLE SUPPLEMENTATION

When using any nutritional supplementation, you must take a sensible approach to avoid risks and side effects: •

Start low and go slow but give it a honest try for at least one month

•

Try one new supplement at a time (every 3-4 weeks)

•

Only take what you need (not every potential supplement)

•

Test your blood sugar often to monitor effects

•

Don’t take at the same time as your other medications

•

Purchase only quality products and avoid supplements with artificial sweeteners, artificial colors, and binders.

PROBIOTICS: HEALTH BENEFITS, FACTS, RESEARCH

Probiotics are microorganisms that offer some form of health benefit to the host - they can be found in various different foods. Probiotics are believed to play very important roles in regulating proper intestinal function and digestion - by balancing intestinal microflora.

These ‘good bacteria’ are considered to be “live microorganisms which when administered in adequate amounts confer a health benefit on the host”, according to the WHO. Probiotics are normally consumed in fermented foods with active live cultures such as yogurt. There are many different strains of probiotics, but the most common strains available today in are Lactobacillus and Bifidobacterium.

WHAT ARE THE HEALTH BENEFITS OF PROBIOTICS?

It should be noted that many of the possible health benefits of probiotics still require more scientific research to be proven.

1.

Diarrhoea: Certain strains of probiotics have demonstrated positive results in treating diarrhoea and gastroenteritis. According to a report published in the Journal of Pediatric Gastroenterology and Nutrition, probiotics are “useful in the prevention or treatment of several gastrointestinal disorders”, such as infectious diarrhea, antibiotic diarrhoea, and traveler’s diarrhoea.

One study published in the Journal of Pediatrics,

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Let’s take a look at just a few of the micronutrients that are often inappropriately balanced in our diets and in inappropriate amounts or forms in over-the-counter multi-vitamin/mineral supplements, which may have an effect on glucose metabolism and its consequences.

Niacin

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Bifidobacterium infantis 35624 is a probiotic available in the USA for fortifying the digestive system.

8.

The evidence showed probiotics may be effective towards prevention and management of T1D and T2D.

RECENT DEVELOPMENTS ON PROBIOTICS FROM MNT NEWS

Probiotic formula may hold key to cow’s milk allergy.

MISCELLANEOUS

Fig. 1: Yogurt is a popular source of probiotics concluded that Lactobacillus species are a safe and effective form of treatment for children with infectious diarrhea. The researchers concluded that “Prophylactic use of Lactobacillus significantly reduced the risk of nosocomial diarrhea in infants, particularly nosocomial rotavirus gastroenteritis.”

2.

Brain function: Probiotics may be beneficial for brain function. Researchers at UCLA found that brain function improved among healthy women who regularly consumed probiotic-containing yogurt (Figure 1).

In addition, probiotic bacteria might have the potential to change brain neurochemistry and treat anxiety and depression-related disorders, according to a study published in the journal Proceedings of the National Academy of Sciences (PNAS).

Food allergies are growing in prevalence in developed countries, and 3% of children globally are allergic to cow’s milk. New research carried out on children with cow’s milk allergy has shown that structural differences in gut bacteria may be the reason why some children do not acquire tolerance.

COMMON MYTH

•

Supplements are natural, safe and better.

•

Good at a dose so better at a larger dosage.

•

Desire to improve overall health.

•

Filling gaps of our diet.

•

Taking a multivitamin make us live longer or perform better

•

Has been used for thousands of years, so must work

MISCONCEPTIONS

Cholesterol: Research presented at the American Heart Association’s Scientific Sessions in 2012 revealed that a formulation of Lactobacillus reuteri NCIMB 30242, is able to reduce blood levels of LDL or “bad” cholesterol.

•

Multivitamin reduces heart problems

•

Lowers cancer risk

•

They replace healthy diet

•

Prevent strokes

4.

Blood pressure: Some studies have found that milk fermented with strains of LAB may help lower blood pressure.

5.

Irritable bowel syndrome: There is growing evidence that probiotics can help treat IBS (irritable bowel syndrome). Two review articles, published in Nutrition in Clinical Practice, examined the therapeutic approaches to irritable bowel syndrome and found that probiotics, specifically Bifidobacterium infantis 35624 (Bifantis®), are very effective at managing IBS.

Various studies have shown no difference in rates of another heart attack, the need for hospitalization or rates of stroke and early death between vitamin-takers and placebo-takers.

3.

6.

Infection: A study published in the prestigious scientific journal PNAS (Proceedings of the National Academy of Sciences), found that probiotic bacteria can protect against bacterial infection.

The research was the first of its kind to demonstrate that Lactobacillus salivarius offered significant protection against Listeria infection.

7.

Psoriasis and Chronic Fatigue Syndrome: Scientists at University College Cork, Ireland, reported in the journal Gut Microbes that Bifidobacterium infantis 35624 may also have benefits for patients with psoriasis and chronic fatigue syndrome.

VARIOUS STUDIES

The U.S. Preventive Services Task Force (USPSTF) Systematic Review

They studied “Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force”.They intended to examine the evidence for vitamin and mineral supplementation in community-dwelling, nutrient-sufficient adults. They studied the effect of supplementation on two major killers: cardiovascular disease (CVD) and cancer.

Overall, multivitamins were found to have no effect on cardiovascular disease or cancer risk. If there is an actual effect, it’s too small to measure in these trials, and too small to be meaningful.

The French Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) RCT evaluated a supplement containing ascorbic acid 120 mg, vitamin E 30 mg,

β-carotene 6 mg, selenium 100 µg, and zinc 20 mg. This supplement was associated with a 31% reduction in overall cancer incidence and a 37% reduction in overall mortality in men (ages 45–60 years), but not in women (ages 35–60 years), after a median intake of about 7.5 years.

The double-blind, randomized, placebo-controlled Heart Outcomes Prevention Evaluation (HOPE) and 7-year open-label HOPE-The Ongoing Outcomes extension found significant increases in risk of heart failure and related hospitalization associated with vitamin E supplementation (400 IU/d) in high-risk people ≥55 years of age.

Conclusion

Supplementation with a multivitamin in a healthy group of older males appears to have no benefit. If multivitamins have any effect on cognition, then it was too small to be detectable.

VITAMIN E RAISES PROSTATE CANCER RISK: THE SELECT TRIAL 2008

The SELECT trial (the Selenium and Vitamin E Cancer Prevention Trial) was designed to determine the long range effect of selenium and vitamin E supplements on prostate cancer. Previous studies had hinted that both of these substances might offer protection against prostate cancer.

17 percent increase in the risk of developing prostate cancer in men who took 400 units of vitamin E daily, and no protection against developing prostate cancer from selenium.

HARMFUL EFFECTS

MVM supplements were associated with cardiovascular benefits in the Stockholm Heart Epidemiology Program (SHEEP), a large Swedish population-based case–control study. SHEEP compared adults aged 45 to 70 years who had no previous history of MI with those who had experienced a first MI and survived >28 days. Regular use of dietary supplements, 80% of which were MVM supplements, was associated with a significant 22% reduction in risk of MI in men and a significant 33% reduction in risk of MI in women compared with nonuse after controlling for consumption of fruit, vegetables, and fiber.

•

Excess amount of Vitamin A consumed by pregnant women may cause birth defects. In others causes painful hyperostosis, hypercalcemia, increased ICT, headaches, occ. progressing to cirrhosis.

•

Excessive amount of Niacin may cause liver damage.

•

Excess Vitamin C – Gastric irritation, faltulence, diarrhoea. Even oxalate kidney stones.

•

Excess Vitamin K – reduce ability of blood thinning drug to prevent blood from clotting.

In the randomized Age-Related Eye Disease Study (AREDS), over a median of 6.3 years, high doses of 3 vitamins with antioxidant properties (500 mg/d vitamin C, 400 IU/d vitamin E, and 15 mg/d β-carotene) with zinc (80 mg zinc oxide) significantly reduced the risk of progression to advanced age-related macular degeneration (AMD) by 28% and reduced the risk of any lens opacity by 16% and of nuclear cataract by 25%.

•

Excess Vitamin E – Increase in all- cause mortality with high doses(>400IU/day), also increase Vitamin K requirement.

•

Excess iron – cause nausea, vomiting and damage liver and other organs.

•

Ingesting too much zinc interferes with copper and iron absorption.

A meta-analysis of 10 RCTs (N = 3,200) concluded that daily MVM supplement use by cognitively intact adults significantly improved immediate free recall memory, with the strongest effect seen for MVM supplements with more constituents, but that MVM supplements had no significant effects on delayed free recall memory or verbal fluency.

•

Economical burden increased.

•

Pill burden increased.

The Physicians’ Health Study II (PHS II) Feb 2000

The PHS II was a massive study designed to study the effects of vitamins on a number of chronic diseases. This paper reported on the effects of a daily multivitamin on cognition, a secondary outcome in the study. The PHS II recruited 5947 male physicians, aged 65 or older. Patients were randomized to beta-carotene or placebo; synthetic vitamin E (400IU) on alternate days, or placebo; vitamin

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Advice •

Spend money on fruits, vegetables, nuts, beans, low fat dairy.

•

Exercising would probably be a better option.

•

Check with your doctor/ health care provider before taking unnecessary medications.

•

Do not take self prescribed remedy.

•

Follow dosage limits else overdoses can be deadly.

Whole foods are more effective than supplements in meeting nutrient needs:

•

Tomato consumption has a greater effect on human

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One of the Linxian trials, conducted in relatively healthy persons, found that supplementation with a combination of β-carotene 15 mg/d, vitamin E 30 mg/d, and selenium 50 μg/d for 5 years was associated with a trend toward a 7% lower risk of cancer and significant reductions in mortality (9% overall; 13% cancer specific). Long-term follow-up of this study indicated that the benefits of taking MVMs persisted for up to 10 years after active supplementation had ceased.

C 500mg daily, or placebo; or a multivitamin (Centrum Silver) or placebo.

prostrate tissue than an equivalent amount of lycopene.

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•

Whole pomegranates and broccoli had greater antiproliferative and in vitro chemical effects than did some of their individual constituents.

•

Free radicals were reduced by consumption of brassica vegetables, independent of micronutrient mix.

MISCELLANEOUS

CONCLUSION

Vitamins / minerals do have role when food availability, intake is restricted, in a pathological condition causing nutrient deficiency like celiac disease, malabsorption, drugs and pregnant female but to be consumed in RDA amounts. We all should remember that these cannot replace food.Supplementation of a vitamins/minerals confers health benefits Only if a person is deficient in that nutrient.

2. Guallar E, Stranges S, Mulrow C, Appel LJ, Miller ER. Enough Is Enough: Stop Wasting Money on Vitamin and Mineral Supplements, Annals of Internal Medicine 2013; 159:850-851. DOI: 10.7326/0003-4819-159-12-20131217000011.

3. Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force. Annals of Internal Medicine, 2013; 159:824-834.

DOI: 10.7326/0003-4819-159-12201312170-00729.

4. High-Dose Multivitamins and Minerals After a Heart Attack, Annals of Internal Medicine 2013; 159:I-20.

DOI: 10.7326/0003-4819-159-12-201312170-00001.

5.

Devla MN, Acharya NS, et al. Dietary supplements; a legal status In India and Foreign countries. Int J Pharm Sci 2011; 3:7-12.

6.

Draft Regulations. Food Safety and Standards Authority of India. Notification. To be published in the Gazette of India, Extraordinary, Part III, Section 4. No. 1-4/Natriceutical/ FSSAI-2013. Ministry of health and family welfare. Govt.

Of India.

7.

Omenn GS, Goodman GE, Thornquist MD, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996; 334:1150-5.

8.

Blot WJ, Li J, Taylor PR, et al. Nutrition Intervention Trials in Linxian, China: Supplementation With Specific Vitamin/ Mineral Combinations, Cancer Incidence, and DiseaseSpecific Mortality in the General Population. JNCI Journal of the National Cancer Institute 1993; 85:1483-1491.

8.

Telford RD, CatchpoleEA, Deakin V, etal.The Effect of 7 to 8 months of vitamin / mineral supplementation on athletic performance. Int J Sport Nutr 1992; 2:135-53.

Before making decision to take a supplement, it is important to consult a health care provider.

Reliable information to conclude that multivitamins offer no meaningful health benefits to the generally healthy consumer. It’s time we bring an end to the era of indiscriminate multivitamin use.

There is a urgent need to enforce strict laws to prevent misuse of supplements for concern of public health.

REFERENCES

1.

Grodstein F, O’Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, Manson JE, Glynn RJ, Buring JE, Gaziano JM. Long-Term Multivitamin Supplementation and Cognitive Function in Men. Annals of Internal Medicine 2013; 159:806814. DOI: 10.7326/0003-4819-159-12-201312170-00006.

C H A P T E R

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Chronomedicine: A Unique Concept to Manage Human Diseases

ABSTRACT

Understanding of basic rhythm of human body can enhance health unexpectedly. The science of chronomedicine explores the interaction between biological rhythms, medicine and drugs. cardiovascular variations can serve as endpoints for preventive as well as curative health care. Endogenously regulated daily cyclic rhythms of body are known as circadian rhythms.

Apart from this many biological cycles are exogenously regulated like light and dark or day and night. many a times they are organizing force for endogenous cycles.

Everyday human body experiences of being hungry, tired, active, listless or energized at regular interval. Body temperature, heartbeat, blood pressure and urine flow cycle rhythmically change throughout the day. Levels of many hormones, for example ACTH-cortisol, thyroidstimulating hormone (TSH) and growth hormone (GH), rise and fall in a daily rhythmic pattern. It is relatively predictable too and governed partially by exposure to sunlight and darkness being dependent on melatonin secretion. These daily cycles work to facilitate human body functions. We try to disrupt these cycles in many ways in our modern living and invite illnesses arising out of desynchronization from natural atmosphere.

Knowledge of these cycles helps in dispensing medicines at a time when it can be most effective or really needed by human body. Ultimately it contributes in developing effective chronopreventive and chronotherapeutic strategies.

Chronomedicine is best defined as the application of chronobiology in order to understand the pattern of disease, which can be related to disturbances of circadian rhythm. Chronobiology is derived from three different words ‘chromos’ means‘time’; ‘bio’ means‘life’; and ‘logos’ mean‘science’. Thus it can be inferred that chronobiology is the science to discover the variability in the functioning of the human body.

Time is divided into various frames known as chronomes.

Chronomes contain the major incidents in that time frame (only the deterministic events are marked) They are mapped by chronomics as the reference values for both an applied chronomedicine and a basic chronobiology.

Chronomics quantify health and helps in identifying new disease risks. They are important tool to diagnose predisease and overt illness, enabling timely and timed treatment. They are also instrumental in validating the short- and long-term efficacy of a given treatment on an inferential statistical individualized as well as population basis.

Anuj Maheshwari, Narsingh Verma If we can really understand the basic rhythms of human body, we can get our health enhanced in a way never expected before. The field of chronomedicine explores the interaction between biological rhythms, medicine and drugs. Greater extent of cardiovascular variations can also be exploited as endpoints for preventive as well as curative health care. Implementation of chronomedicine with molecular medicine is also being explored.

The founder of chronomedicine was Franz Halberg (1919–2013) he developed the technique of chronobiology which included chronomics, chronoastrobiology, and chronobioethics. He coined the term circadian, after documenting that biologic rhythms tip the scale between health and disease and even between life and death.

The daily peripheral activities of the organs are dependent on the Suprachiasmatic Nucleus (SCN) while interacting with the endocrine and autonomic nervous systems. It is reset by alternating light and dark through the retinohypothalamic tract. Feeding time and scheduled exercise can also trigger the mammalian circadian system.

WHAT IS CIRCADIAN RHYTHM?

Cyclic changes marked on a daily basis are known as the circadian rhythm. They are regulated endogenously and move through approximately 24-hours. They can be regarded as probably the best known of the natural cycles.

They can be further broken down into routine cycles of different time intervals.

Diurnal, which describes organisms active during daytime •

Diurnal which describes organisms active during daytime.

•

Nocturnal, which describes organisms active in the night.

•

Crepuscular, which describes organisms primarily active during the dawn and dusk hours like certain animals.

Many biological cycles are regulated exogenously, many external factors play an important role in regulating our body rhythms which is evident by the behavior of our body towards heat and cold weathers throughout the year.Researches show that these external forces may have greater influence on the body and may also contribute in the organizing of the body during endogenous cycles.

The name given to such external (exogenous) forces is zeitgebers (a german word meaning ‘time givers’). Rightly said, these forces which include sunlight, noise, social

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interaction and conventions such as meal times as well as man-made devices such as alarm clocks.

MISCELLANEOUS

Some of the other rhythms include: •

Infradian rhythms:They are the cycles lasting longer than a day such as the monthly cycle of mensuration in females or start or stop of hormones at a particular age.

•

Ultradian rhythms: They are the set of cycles which last less than a day such as the 90-minute REM cycle and the 3-hour cycle of growth hormone production.

•

Tidal rhythms:It is observed in tidal or aquatic life which follow the 12.4hours cycle between high and low tides.

•

Lunar rhythms:They follow the cycle of 29.4 days or the monthly e.g. lunar cycle and aquatic life and migration.

•

Gene oscillations:Some genes are expressed more during certain hours of the day than during other hours.

•

Circasemidian Rhythms: it is12 hour cycle. “Post lunch dip” is good example of its loss

•

Circaseptan rhythm: are weekly rhythms

•

Circasemiseptan: half-weekly cycles

Acrophase is the period of time when the process is most active, and bathyphase or troughphase when it is least active. The particular moment of highest activity is the peak or maximum; the lowest point is the nadir.

How high (or low) the process gets is measured by the amplitude.

The cycles can be huge such as the temperature cycle over the time of an year or small cycles of light and dark over a day. All the cycles are synchronised with other cycles to create a natural rhythm. It can be clearly observed as the body temperature cycle, cardiac cycle is in sync with our sleep-wake cycle. Some of the circadian cycles are controlled by the internal hormonal activities while some others are controlled by the exogenous stimuli.

Throughout the animal kingdom, various cycles can be observed and the result of various exogenous and endogenous cycles can be observed.

HOW DO THESE CYCLES INTERACT WITH CIRCADIAN RHYTHM?

The cycles are continuously in motion or keep revolving in order to maintain the circadian rhythm or simply to say that the cycles are the basic defining regularities. Every day we might experience change in body temperature and energy levels, the urination cycle is not exact same for two individuals nor is same for two consecutive days. Levels of many hormones, such as ACTH-cortisol, thyroid-stimulating hormone (TSH) and growth hormone (GH), also rise and fall in this relatively predictable, daily rhythmic pattern. This rhythmic pattern is initiated and

governed in part by exposure to sunlight and darkness.

These daily cycles work to our advantage.

ARE WE LOSING THIS INTERACTION?

In the modern world it is very difficult to keep in touch with the regular natural cycles and the circadian cycles are generally ignored or altered to the ease of the individual like women taking birth control pills which also alter their menstrual cycle, or staying awake during night and sleeping/wakening up late. The natural circadian cycles have also been altered due to our changing habitat; we live in era where A/Cs provide cooling during summers and we have heaters to provide warmth during winters, as such the natural cycles of temperature and weather. It can be said that we have started to command our nature and stopped being the slave of our circadian cycles. At first, it might not occur that the body is losing the synchronization but the increasing digestive problems and problems of headache and other mild disease show the impact of the imbalance created by the modern lifestyle.

TRAVELLING ACROSS TIME ZONES

‘Jet lag’ is a very commonly known desynchronisation which occurd due to imbalance caused by changing of time zones and the light and dark cycles. The symptoms of jet lag are easily evident and very common because the body also loses the synchronization with the earth’s spin. Earth spins form west to east taking a flight against this direction i.e. east to west, would lead to far severe disruption of the circadian cycle.

TIRED TEENS

Apart from travelling across time zone, many other things can leave a person out of synchronization like keeping awake up to late hours for partying, studying and working in shift job. It is very commonly seen in teenagers. Evidences suggest it has dumbing-down effect on younger generation. It is a proven fact that age has a significant effect on the number of hours required to sleep, teenagers need almost 9.5 hours while an adult requires not more than 7 hours of sleep. One of the major reasons for such behavior is that teenagers circadian cycle is longer due to higher release of hormones and more physical pressure. Due to change in lifestyles melatonin enzyme to induce sleep is delayed at night due to which loss of sleep is witnessed.

The activity level of teenagers and the daily schedule for academics or purpose of recreation put the children under a lot of pressure and therefore they might not be able to give their 100% in any of the fields. Researchers have proved that the teenagers are deprived of night’s sleep by almost three hours per day. It has also been found that change in school timings which allowed students to complete their sleep requirements was reported with higher results and lower behavioral problem.

POST-LUNCH DIP: A LOSS TO CIRCASEMIDIAN RHYTHMS

Post lunch dip (PLD)a common experience of energy dip faced by all of us at some part of the day where you might be under the urge to sleep after lunch and the situation

might be worsen by inappropriate food choices such as high glycaemic index snacks and meals. Research provides enough evidence to support that the brain signals during REM and PLD have significant similarity and it is not just a nutritional phenomenon. This also supports the fact that PLD is a 12 hourly or circasemidian fluctuation in our sleep–wake cycle.

ULTRADIAN RHYTHMS FLUCTUATIONS

Many ultadian cycles are so small that they cannot be noticed but one of such changes can be seen in skin throughout the day.

Many other ultradian rhythms simply get ignored because of the fast-paced lifestyles we like to lead. However when we are asleep they are quite pronounced. Throughout the night or whenever we sleep, our bodies go through an approximately 90-minute cycle involving REM (rapid eye movement, or dream) sleep and non-REM (deep) sleep periods. Disruption of these REM cycles can lead to insomnia, fatigue, loss of concentration and memory and mood disorders.

LONGER CYCLES (CIRCASEPTAN RHYTHM)

There exist longer and more evident rhythms called circaseptan or weekly rhythms. Though the prevalence of the circaseptan rhythms is very low, yet scientists believe that they do occur and have observed higher rate of rejection in transplant patients during seven, fourteen and twenty-one days after surgery.

Some evidences of such responses being governed by geomagnetic activity are present and thus can be related to semi-weekly or circasemiseptan cycles. Some studies show that the blood pressure shows some unknown synchronization with the time of birth and thus this phenomena is named ‘locking up’ with earth.

SOME LONGER CYCLES

•

Infradian Cycles: These are the cycles’ lasting from 28 days to a month they include the most obvious menstrual cycle with its cyclically fluctuating levels of estrogen and progesterone.

•

Circalunar Cycle: For some women their monthly menstruation also follows this lunar cycle, though opinion is divided on whether the menstrual cycle will naturally, in the absence of modern disruptions, synchronise with the normal lunar cycle.

SEASONAL CHANGES

There exist a circannual cycle which is revealed by the seasonal change in flowers or behavior of animals.

Seasonal Affective Disorder (SAD, or winter depression) is a disorder which can be related to the length of the day, similarly researchers are trying to prove that melatonin is

Annual cycles are not only difficult but expensive also to study, than the shorter circadian cycles. However research has proved seasonal fluctuations in other hormones too. Women with breast cancer have abnormal annual fluctuations in level of prolactin hormone if it is compared with healthy women. In another study of ‘cancer chromatics’, blood samples drawn at different points of year from women have shown not only it was natural annual cycle of prolactin but also thyroid stimulating hormone (TSH) lost in women who developed breast cancer.

HOW DOES IT WORK IN CHRONOMEDICINE?

Medicine dosage is very much dependent on the time during which the drug has been consumed, it has been proved by studies that non-steroidal anti-inflammatory drugs (NSAIDs) may be less dangerous to the stomach lining when taken at night rather than day. In one study of individuals with osteoarthritis the incidence of adverse effects was cut in half when NSAIDs were taken at night instead of in the morning and there is some evidence that morning pain can also be controlled by taking NSAIDs at night.

Profound cardiac rhythms can be observed in frequency and intensity of symptoms in arthritic diseases such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and gout. People suffering from rheumatoid arthritis have reported higher severity of joint pain swelling and stiffness during mornings while those with osteoarthritis reported higher pain during night.

Heartburn and ulcers get worse at night during 10 PM to 2 AM, this can be related to secretion of stomach acid which is 2–3 times higher than during the day.These night-time rises are the result of a circadian rhythm of stomach acid production so if the medicine is given at same time it is more effective.

Sychronization with the circadian rhythms is found to be far more advantageous when compared to other treatments for cardiovascular diseases or certain diseases such as asthma etc.

Most of the medical conditions show a diurnal pattern in clinical features and grave nonfatal and fatal outcomes e.g., respiratory ones of viral and allergic rhinorrhea, reversible (asthma) and non-reversible (bronchitis and emphysema) chronic obstructive pulmonary disease, cystic fibrosis, high altitude pulmonary edema, and decompression sickness; cardiac ones of atrial premature beats and tachycardia, paroxysmal atrial fibrillation, 3rd degree atrial-ventricular block, paroxysmal

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Alteration in mood can also be related to the circadian cycle and ultradian rhythm for more significant results.

Each circadian cycle consist of much shorter ultradian rhythms, ranging up to 90 minutes. We might experience many peaks and lows of during the day.

secreted exclusively at night and also the level of secretion is affected by the length of day and the season, it is found that the melatonin levels are higher during winters, when days are shorter thus reducing activity and inducing sleep or laziness. Melatonin levels usually decrease with age. But seasonal shifts are also seen in elderly. SAD may worsen with age. Natural or artificial sunlight especially in the early morning, improves mental health as it suppresses melatonin production.

MISCELLANEOUS

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supraventricular tachycardia, ventricular premature beats, ventricular tachyarrhythmia, symptomatic and non-symptomatic angina pectoris, Prinzmetal vasospastic variant angina, acute (non-fatal and fatal) incidents of myocardial infarction, sudden cardiac arrest, inbed sudden death syndrome of type-1 diabetes, acute cardiogenic pulmonary edema, and heart failure; vascular and circulatory system ones of hypertension, acute orthostatic postprandial, micturition, and defecation hypotension/syncope, intermittent claudication, venous insufficiency, standing occupation leg edema, arterial and venous branch occlusion of the eye, menopausal hot flash, sickle cell syndrome, abdominal, aortic, and thoracic dissections, pulmonary thromboembolism, and deep venous thrombosis, and cerebrovascular transient ischemic attack and hemorrhagic and ischemic stroke.

Correct knowledge of these temporal patterns not only helps guide patient care but research of their underlying endogenous mechanisms, i.e., circadian and others, and external triggers. At the same time it gives information regarding development and application of effective chronopreventive and chronotherapeutic strategies.

REFERENCES

1. Bingham, C., Corn´elissen, G. & Halberg, F. Power of “Phase 0” chronobiologic trials at different signal-to-noise ratios and sample sizes, Chronobiologia 1993; 20: 179–190.

2.

Cornelissen G, Halberg F. Chronomedicine. Encyclopedia of Biostatistics 2nd edition 2005; 2:796-812.

3. Moore RY, Speh JC, Leak RK. Suprachiasmatic nucleus organization. Cell Tissue Res 2002; 309:89e98.

4. Nelson RJ. 2005. An Introduction to Behavioral Endocrinology. Sinauer Associates, Inc.: Massachusetts.

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5. Corn´elissen, G. & Halberg, F. Impeachment of casual blood pressure measurements and the fixed limits for their interpretation and chronobiologic recommendations, in Time-dependent Structure and Control of Arterial Blood Pressure, F. Portaluppi & M.H. Smolensky, eds; Annals of the New York Academy of Sciences 1996; 783, 24–46.

6. Corn´elissen, G., Halberg, F., Breus, T., Syutkina, E.V., Baevsky, R., Weydahl, A., Watanabe, Y., Otsuka, K.,

Siegelova, J., Fiser, B. & Bakken, E.E. Nonphotic solar associations of heart rate variability and myocardial infarction, Journal of Atmospheric and Solar-Terrestrial Physics 2002; 64:707–720.

7.

Zeman, M., Corn´elissen, G., Balazova, K., Jozsa, R., Olah, A., Nagy, G., Csernus, V., Kaszaki, J., Pan, W.H., Bubenik, G. & Halberg, F. (2004). Circadian rhythm of melatonin in rat duodenum, in Proceedings, Symposium:Chronobiology in Medicine. Dedicated to the 85th Anniversary of Professor Franz Halberg, G. Corn´elissen, T. Kenner, B. Fiser, J. Siegelova, eds; Masaryk University, Brno, pp. 95–97.

8. Halberg, F. Chronobiology, Annual Review of Physiology 1969; 31:675–725.

9.

Halberg, F. Chronobiology: Methodological problems, Acta Medica Romana 1980; 18:399–440.

10. Halberg, F. Quo vadis basic and clinical chronobiology: promise for health maintenance, American Journal of Anatomy 1983; 168:543–594.

11. Touitou, Y. & Haus, E. (1992). Biological Rhythms in Clinical and Laboratory Medicine. Springer-Verlag, Berlin, p. 730 12. Halberg, F., Bakken, E., Corn´elissen, G., Halberg, J., Halberg, E., Wu, J., S´anchez de la Pe˜na, S., Delmore, P. & Tarquini, B. (1990). Chronobiologic blood pressure assessment with a cardiovascular summary, the sphygmochron, in Blood Pressure Measurements, W. Meyer-Sabellek, M. Anlauf, R. Gotzen & L. Steinfeld, eds. Steinkopff-Verlag, Darmstadt, pp. 297–326.

13. Halberg, F., Corn´elissen, G., Katinas, G., Syutkina, E.V., Sothern, R.B., Zaslavskaya, R., Halberg, F., Watanabe, Y., Schwartzkopff, O., Otsuka, K., Tarquini, R., Perfetto, F. & Siegelova, J. (2003). Transdisciplinary unifying implications of circadian findings in the 1950s. J Circadian Rhythms 1, 2. pp. 61 www.JCircadianRhythms.com/content/pdf/ 17403391/1/2.pdf.

14. Refinetti, Roberto (2006). Circadian Physiology. CRC Press/ Taylor & Francis Group.

15. Erren TC1, Koch MS, Groß JV, Kämmerer-Cruchon S, Fuchs A, Pinger A, Reiter RJ. Chronomedicine: an old concept’s fledging? A selective literature search. Neuro Endocrinol Lett 2012; 33:357-60.

16. Halberg, F., Corn´elissen, G., Otsuka, K., Schwartzkopff, O., Halberg, J. & Bakken, E.E. Chronomics, Biomedicine and Pharmacotherapy 2001; 55:153–190.

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Holistic Learning in Medical Education; Status & Future Ahead Ashutosh Ojha, Varsha Mundley

The highest function of education is to bring about an integrated individual who is capable of dealing with life as a whole.

J. Krishnamurti

INTRODUCTION

Holistic education is a philosophy of education based on the premise that each person finds identity, meaning, and purpose in life through connections to the community, to the natural world, and to humanitarian values such as compassion and peace.

Current medical education status worldwide – In Canada 40 medical schools were surveyed regarding the state of effective medical educations the observations 1 were as Table 1.

Problems of Medical Educations in India- While the graduates generally possess reasonably sound knowledge of medical science, they are often found deficient in the performance of clinical skills and problem-solving which form the core of clinical competence 2. There is growing level of mistrust among the public for the medical profession as one hears of cases of negligence, misconduct, and unethical practices leading to legal suits.

There is increasing public demand for the accountability, transparency and quality assurance among the health professionals. While the commercialisation of medical profession is cited as a common reason for the dilution of quality, doubts have been raised regarding the quality of training. Are the graduate doctors well trained to perform their clinical responsibilities? Are they aware of their ethical, moral and legal responsibilities?

Why is Holistic Education Important? When it comes to rethinking our current educational system, a holistic

Table 1: Observation by learners in survey

education offers an exciting alternative. In the past decades our knowledge regarding childhood development has expanded, and with it our teaching methodologies.

Today, parents and educators alike want more from their learners’ education. They are looking for an approach to education that is in tune with each child’s unique needs and skills, and one that prepares the child to become a well-rounded adult. As such, holistic education is based on the idea that learners can be taught in a more natural and engaging way. Rather than compartmentalizing school subjects, the holistic approach seeks to empower learners to use their academic learning as a foothold for their professional, emotional and social development.

THE BENEFITS OF A HOLISTIC APPROACH-

Education is no longer just about learning tangible and measurable skills. Our past educational paradigms relied on the “average” measurements and standardization.

Learners were prepared to memorize information and then take placement examinations. Not only is this approach not successful for learners, it may also not be psychologically healthy for some students, according to research done by Sir Ken Robinson.

Although learners should be prepped in core subjects such as mathematics, literature, or science, it is also important that they be taught how to learn. Holistic education redefines not only what a core subject is, it also redefines how learners should be taught. The biggest benefit of a holistic approach isn’t just about mental development, but it encompasses psychological, social, emotional growth and as whole an asset for community. A holistic approach motivates learners to learn about a subject. It instils curiosity and allows learners to learn naturally

Table 2: Comparison between Memorization & Holistic Learning Rote Memorization

Holistic Learning

Organizes Ideas into Boxes

Organized Ideas into Webs

Keeps Subjects and Concepts Distinct

Interrelates Subjects and Concepts

Few Neural Paths to the Same Idea

Many Neural Paths to the Same Idea

At no time did a teacher try to have students identify in detail their understanding in a given area, from which they might have built and expanded.

Views Concepts Through One Perspective

Views Concepts Through Many Unique Perspectives and Senses

None of the 40 observed teacher was constructively critical of their students’ reasoning or conclusion

Aims to Learn Through Repetition

Aims to Learn by Relating

Teachers responded to raised hands, replied direct questions and allowed critical students to have their say. Seldom did they digress from their predetermined path as a consequence of students comments All 40 instructors did allow some student questions .None, however, checked to determine if the material was effectively understood.

420

Table 3: Advantages of Holistic Approach

Resilience.

Consider your life’s greatest challenges. What did you need to know to overcome the obstacles you faced?

Consider your greatest successes. What did you need to know in order to achieve those successes? Then ask yourself, how many of those things that I needed to know did I learn in school?

To see beauty, have awe, experience transcendence, and appreciate some sense of “truths.”

PROMOTES UNIVERSALISATION THAN COMPARTMENTALISATION

About themselves.

About healthy relationships and pro-social behavior.

Social development.

Emotional development.

MISCELLANEOUS

is important for young people to learn:

and creatively. It is also attuned to each child’s individual persona and learning style, in contrast of the current mass educational system (Table 2).

Positive and Long Term Results: The result is a learner who develops better communication and social skills, and better confidence. They feel good about learning and challenging themselves with certain subjects because these things offer positive associations. Intrinsic motivation, in turn, propels them to be curious, inquisitive, and eventually be innovative adults in the workplace (Table 3).

Implementing a Successful Holistic Approach: A holistic methodology seeks to help learners develop all their skills and to build their strengths. As such, this educational approach is inclined towards play-based learning, learners’ creativity, and their imagination. For instance, a holistic curriculum could include dance and stage performance, speech, photography, or painting (to name only a few) in addition to the “traditional” subjects which answers writing only way of expression.

More importantly, a holistic approach would encourage learners to make connections between subjects–for instance, using their creative skills to solve a practical clinical or medico-social problem, or approaching a foreign language similar to the way they approach a mathematical equation.

This kind of teaching does not confine to the classroom setting. In fact, parents and educators would do well to create environments where learners can experiment and explore.

For thousands of years before schools there were social groups which taught people about the great adventure of being human; its trials and tribulations, its challenges, and its enormous possibilities for human goodness and even greatness. These groups were extended families, communities or tribes or clans, and religions. For the most part, these groups have disappeared or become compartmentalized in people’s lives.

Now, it is predominantly popular culture (the media, music) and schools from which young people can learn about what it means to be human. But culture has its own agenda (not the welfare of learners), and schools were not designed to replace extended families, communities, and religions. They were designed to prepare people for the world of work; to give them the skill sets that would help them up the ladder of material success.

WHY HOLISTIC EDUCATION?7

Parents as well as communities, in increasing numbers, are seeking alternatives to mainstream education. Few could criticize the commitment to academic excellence that most schools and teachers have and work hard to actualize. But more and more parents realize that just learning academics is not enough, and they see young people in their communities suffering from a lack of needed learning, and society suffering as well.

Parents worry about the negative social influence they see affecting their learners. Parents see themselves having less impact on their learners’ behavior, relationships, and attitudes. As a result learners’ senses of themselves and self-images are under pressure. This pressure is expressed in:

Education That Is Fun And Meaningful: Whether it’s allowing a learner to be an involved citizen after school or enrolling him or her in a extra-curricular classes such as stage speaking and reading class–the objective of holistic education is to make learning so fun and meaningful that the child seeks it even when he is out of the classroom and this continues to fuel his quest for lifelong learning and development.

•

Increased competitiveness in many aspects of a learner’s social life, such as sports, out-of-school activities, and of course, school.

•

Obsessive concern for their “look,” from their body shape to their clothes.

•

Violence in many forms, from the physical to the psychological and emotional.

Scholar Base adopts a holistic learning approach and this has successfully helped development of hundreds of learners into well-rounded and successful graduates and professionals serving the society.

Parents are also worried about negative learning attitudes they see developing in their learners. Parents saw their learners as infants eager to learn, and this eagerness dissipated as these same learners’ monotonous curriculum increased. Learning becomes a necessary chore, driven by rewards and punishments, and too often devoid of direct meaning in their learners’ lives.

Purpose of Holistic Education-The purpose of holistic education is to prepare students to meet the challenges of living as well as academics. Holistic education believes it

WHAT DO LEARNERS NEED TO LEARN?7

Learners need to develop academic capacities as these are required to live in the modern world. But much more than this is needed, and adults looking at what was required in order to meet the many challenges of their lives and the successes they have had can attest to this. The essential learning that we all need should begin in childhood.

Learners need to begin to learn about themselves. The value of “knowing thyself” is so undisputed as to be a cliché, but conveying to learners that they are worth knowing about seems fundamental to healthy self-respect and self-esteem.

Learners also need to learn about relationships.

Relationships are the greatest source of human happiness and misery, yet most learners only have the relationships they see in their immediate surroundings (e.g., family, friends, etc.) and on the media (which are usually caricatures and unreal) to learn from. Sociology and child development psychology repeatedly affirms that learning about relationships is acquired and not inherent, and yet the institutions created for learners’ learning have little to no time nor resources given to helping learners learn how to have healthy, productive relationships.

HELPING LEARNERS LEARN WHAT THEY NEED TO LEARN5

One of the tools that holistic education uses to help learners learn what they need to learn is ‘meaningfulness’.

People of all ages find it difficult to learn things which are not meaningful to them, and conversely, they find that it requires much less effort to learn things that are meaningful. This means that a holistic school will respect and work with the meaning structures that a child comes with rather than begin from a perspective of what “should” be meaningful to a child. Events and dynamics (fear, conflict, friendships, etc.) are part of every child’s life and they are interested in these things. These can be the starting point for learning any of the academic skills that every child needs to master.

Another tool that holistic education uses to help learners learn is flexible pacing. Not all learners learn at the same speed, and no child learns at the same speed all the time.

Learning is an inherently creative act, and it requires a system that can move with the individual meaning making of each child. When lessons are too slow, a child

gets bored, and when it is too fast, the child gets lost and then loses interest in the subject. If learners are seen and treated as individuals, there is no need to have groups move at some arbitrarily determined learning pace.

421

WHAT ABOUT OTHER PRESSING ISSUES?

Unfounded Notions by Teachers as well as communityMany people today feel that there are concerns which are so pressing that these concerns must be solved before any others (like developing alternative forms of education) are addressed. Such people will say that one cannot discuss philosophy with someone starving - feed the person first, and then one can give time and energy to philosophy.

Holistic education has seen the situation a bit differently, and thinks this metaphor is inadequate. Let us assume that a person is starving unnecessarily because that person has some fundamentally mistaken notions. Perhaps one needs to feed the person initially, but no amount of just feeding the person will help; simply giving them food will only mean they end up starving again later. Holistic education has long maintained that mis-education or inadequate education lies at the roots of our modern problems, and a different kind of education has a real chance of solving them.

Issue of Sustained effort by teaching community – It is a long process in which a collaborative efforts by teaching community is needed. The understanding about a learner, its need, capability and tailor made participative lessons, requires a higher teacher students ratio. Now, the whole curriculum is based upon passing on the information, to the level of affective only cognitive domain. The accumulation of resources for effective a reproducible and socially translatable knowledge in learners is a big exercise.

Slow and initially immeasurable outcome- There is an unfounded notion by community and learners that the short term goals of learning cannot be timely measured.

Such as subject wise knowledge cannot be tested and learners cannot be effectively certified in a particular subject or skills. The total development can be assessed after a long time.

CHALLENGES AND ISSUES IN MEDICAL EDUCATION IN INDIA

The Indian medical education system, one of the largest in the world, produces many physicians who emigrate to the United States, the United Kingdom, and several other countries. The quality of these physicians, therefore, has a broad global impact. Medical schools in India have rapidly proliferated in the past 25 years, doubling since 1980 for a current total of 258. Accreditation by the Medical Council of India (MCI) emphasizes documentation of infrastructure and resources and does not include selfstudy. The number of schools is determined by each state; the allocation of income-generating “payment seats” in private medical schools, coupled with the high emigration, may be motivating the increase in physician production. Student selection is almost exclusively based

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Perils of learning in isolation Many parents also look at our current society in which social problems seem to be getting worse; in which those considered successful are too often greedy, corrupt, and brutal; in which families and communities seem increasingly dysfunctional; and they ask, “Why aren’t we as humans learning what we need to know in order to live good and meaningful lives?”. Parents see the need for their learners to learn these other things as well as academics, and they look for schools that give time, attention, energy, and resources, to such learning. Parents generally do not come to holistic education from philosophical musings, but from a perceived need for their learners that they feel is not currently met.

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Table 4: Advantages of Problem Based Learning Student centered Generic competencies Integration Motivation “Deep” learning

MISCELLANEOUS

Constructivist approach on performance on an entrance examination, with a lower cut off score for underrepresented minorities.

Curriculum reforms- Curriculum reform has been advocated for over 30 years, with calls for greater relevance of the curriculum to the needs of the community. Revised guidelines from the MCI in 1997 supported these changes.

Introduction of problem based learning and inclusion of situation based questions- Many universities have started problem based integrated teaching. It promotes the better learning. Only two universities have started situation based long questions in final year examinations. The situation based Mutiple choice questions are sparingly asked in competitive examinations.

Internship Most Neglected Aspect- The internship year (the fifth year, focusing on rotating clinical experiences), under the aegis of medical schools in India, has suffered from lack of supervision and minimal assessment; it is often used predominantly as a time to study for residency entrance examinations. The college based knowledge and skill need to be integrated but lack of supervision and peer pressure of early enrolling for post graduation is a sad

scenario. There should be a mandatory provision of one year working as medical officer can solve this problem.

Way Ahead- There is well established fact that world over medical education has gone sea changed. It no more requires a teacher centric instructional model. The holistic teaching in the medical curriculum is must. The knowledge, skill and attitude all are equally expected from the doctor by community. Besides a good cut off in basic sciences and a success in competitive exams, assessment of resilience, empathy, true willingness of hard work and ethical values must be assessed. The holistic education is tried with success in some reputed medical schools. But on national level thinking need to be developed to be adopted and implemented.

REFERENCES

1.

Canadian Med Association Journal 1964; 90.

2.

Roland, C. G. Canad Med Ass J 1964; 90:887.

3.

Blakenhorn.M A.;Graduate training in Internal Medicine in a Municipal Hospital. Journal of American Medical Colleges 1940; 15:153.

4. Challenges and issues in medical education in India.Supe A1, Burdick WP. Acad Med 2006; 81:1076-80.

5. Schiro, M.S. (2008).Curriculum theory: Conflicting visions and enduring concerns. Thousand Oaks, CA:Sage Publications.

6.

Hare, JR. “Towards an Understanding of Holistic Education in the Middle Years ofEducation”. Journal of Research in Education 2006; 5:301–22.

7.

UNESCO. 1996. Learning: The Treasure Within. The Report to UNESCO of the InternationalCommission on Education for the Twenty First Century chaired by Jacques Delors.

Paris. UNESCO.Pages-77.

Essential Life Saving Skills a Physician Must Know

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77

Dhruva Chaudhry, Brijesh Prajapat

“ I would especially commend the physician who, In acute diseases, By which the bulk of mankind are cut off, Conducts the treatment better than others” HIPPOCRATES

INTRODUCTION

The field of medicine is constantly changing and evolving with new technologies, practices, evidence and innovations. The medical profession has experimented with a practice-based model of continuing education since the 1960s.1 The dynamicity of this field has led to the continuous expansion of the roles and domains of the physicians for which they need to continue their education throughout their career and hone and refine their procedural skills in order to provide the highest possible level of patient care. The role of a physician is no more limited to confinements of the outpatient department and the inpatient department or wards juggling with history taking, differential diagnosis, clinical examination, prescription writing but has expanded and evolved especially in the emergency care setting. The armamentarium of a physician must contain cutting-edge evidence based knowledge, experience and wisdom, life saving procedures and skills especially in the emergency rooms (ER). In recognition of this, a new domain- emergency medicine (EM) was launched in 1960s.2 Recent epidemiologic and demographic public health data highlight the growing need for EM, trauma, and acute care development in all countries across the socioeconomic spectrum.3 However, in countries where EM is not still well established or in developing phase, there is a huge burden on the physicians or residents working in the emergency rooms and emergency wards (EW) for which learning and perfection of the lifesaving procedures and skills is not only desired but required.

Although, the list of emergency procedures that are being performed in ER and EW routinely is long and vary in different hospital settings, knowledge of minimum set of life saving invasive procedures and interventions is mandatory (Table1).

CARDIOPULMONARY RESUSCITATION (CPR)

A report of five cases of cardio-respiratory arrest managed successfully with chest compressions, defibrillation and assisted ventilation published in 1960, paved the path or birth of cardiopulmonary resuscitation.4 In the last

Table 1: List of life saving procedures/skills in emergency room/wards Cardiopulmonary resuscitation • Basic life support (BLS) • Advanced cardiac life support (ACLS) • Defibrillation Airway management • Endotracheal intubation • Laryngeal mask airway (LMA), Combitube) • Rapid sequence intubations (RSI), • Nasotracheal intubations.

• Needle cricothyroidotomy Oxygen therapy and devices Venous access • Peripheral venous access • Central venous access (subclavian, internal jugular, femoral) • Venesection • Intraosseous route Cardiac • Cardiac pacing- transcutaneous and transvenous • Pericardiocentesis • Hemodynamic monitoring (noninvasive and invasive) Pleural procedures • Needle and tube thoracostomy (chest tube insertion) • Pleural fluid aspiration Lumbar puncture Sengstaken Blakemore tube/Minnesota tube insertion, nasogastric tube insertion Suprapubic catheterization Abdominal paracentesis Focussed assessment with sonograpghy (FAST) Peritoneal dialysis catheter insertion Hemodialysis catheter insertion Arterial blood gas (ABG) sampling and analysis Arterial line placement Others – regional anaesthetic blocks, intercostals blocks, use of sedation, suturing etc.

MISCELLANEOUS

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1

Table 2: DO’s and DONT’s for quality CPR (adapted from AHA2015 update ref 5) Rescuers Should

Rescuers Should Not

Perform chest compressions at a rate of 100-120/min

Compress at a rate slower than 100/min or faster than 120/min

Compress to a depth of at least 2 inches (5 cm)

Compress to a depth of less than 2 inches (5 cm) or greater than 2.4 inches (6 cm)

Start CPR

• Give oxygen • Attach monitor/defibrillator

Interrupt compressions for greater than 10 seconds

Ventilate adequately (2 breaths after 30 compressions, each breath delivered over 1 second, each causing chest rise)

Provide excessive ventilation (ie, too many breaths or breaths with excessive force)

3

No 9

Asystole/PEA

Shock

4

CPR 2 min

• IV/IO access

Rhythm shockable?

5

No

Yes Shock

6

10

CPR 2 min

CPR 2 min

• IV/IO access • Epinephrine every 3-5 min • Consider advanced airway, capnography

• Epinephrine every 3-5 min • Consider advanced airway, capnography

Rhythm shockable?

sixty years, CPR has become a universally mandated practice that requires certification, and is withheld only on request. Since then, various updates and guideline recommendations has added a lot of information to make ‘CPR to quality-CPR’. The recent American heart association (AHA) 2015 has recommended few changes in the steps of CPR.5 CPR training and certification need cannot be overemphasized specially for the physicians working in ER. They must know the steps of a quality CPR (Table 2) and lead the CPR team consists of doctors and paramedical staff.

The basic rationale to provide CPR is to support the circulation, maintain the airway and breathing and once patient successfully revive then provide post arrest care.

The original mnemonic for elements of basic life support (BLS) i.e ABC -Airway, Breathing, and Circulation has been rearranged to CAB- Circulation, Airway, Breathing that reflects a recent shift in emphasis from ventilation to chest compressions in the resuscitation effort.6 Time factor is an important consideration in initiating CPR and is an independent variable that predicts the survival. The most recent recommendations for chest compressions are: rate- 100-120/min, depth- at least 2 inches and avoiding excessive compression depth (Table2).5 The number of chest compressions delivered per minute during CPR is an important determinant of return of spontaneous circulation (ROSC) and survival with good neurologic function. Advanced cardiovascular life support (ACLS) includes a variety of interventions such as airway intubation, mechanical ventilation, defibrillation, and the administration of life supporting or resuscitation drugs.7 ACLS protocol is a rhythm-based approach and divides the management of cardiac arrest into 2 pathways: one for the management of ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT), and the other for the management of pulseless electrical activity (PEA) and asystole (Figure 1). The use of drugs is considered a second-line treatment in cardiac arrest because there is

Rhythm shockable?

VF/pVT

Allow full recoil after each Lean on the chest between compression compressions Minimize pauses in compressions

Yes

2

7

No

Rhythm shockable?

Yes

Yes Shock

No

8

11

CPR 2 min

CPR 2 min

• Amlodarone • Treat reversible causes

• Treat reversible causes

No 12

Rhythm shockable?

• If no signs of return of spontaneous circulation (ROSC) go to 10 or 11 • If ROSC, go to Post-Cardiac Arrest Care

Yes

Go to 5 or 7

Fig 1: Algorithm for ACLS (adapted from ref 5) no documented survival benefit.7 The cardiac arrest drugs are either vasopressors or antiarrhythmic agents. Use of vasopressin in combination of epinephrine has been removed in the recent guidelines as it offers no added advantage.5 Moreover, resuscitation monitoring and post resuscitation care is equally important and physicians must be taught about its importance.

VASCULAR ACCESS

Werner Forssmann experiment of self-insertion of plastic urethral catheter in basilic vein in 1929 marked the beginning of vascular cannulation using plastic catheters.8 Securing a vascular access is important in resuscitation protocols for the administration of resuscitation drugs and intravenous fluids. Central venous cannulations is an integral part of providing critical care support to the patients in ER and EW. The higher flow rates of large veins reduce the damaging effects of infused fluids and decrease the propensity for local thrombosis. The major indications for securing central venous access are:9 1.

When peripheral venous access is difficult to obtain specially in obese patients or intravenous drug

POSTERIOR APPROACH

Table 3: Central line bundle for reduction of CRBSI10 Recommendations

Hand Hygeine

Use an alcohol-based handrub or a soap and water handwash before and after inserting or manipulating catheters.

Barrier Precautions

Use maximal barrier precautions, including cap, mask, sterile gloves, sterile gown, and sterile full body drape, for catheter insertion and or guidewire exchange

Skin Antiseptics

Apply a chlorhexidine-based solution to the catheter insertion site and allow two minutes to air-dry

Cannulation Sites

When possible, avoid femoral vein cannulation, and cannulate the subclavian rather than the internal jugular vein

Catheter Removal

Remove cathter promptly when it is no longer needed.

A

B

Fig. 3a: IJV cannulation – anterior approach,: 3b: IJV cannulation-posterior approach hemodialysis catheters. Infection control is an essential part of vascular cannulation, and the pre-ventive measures recommended for central venous cannulation when used together as a “bundle” (Table 3) have been effective in reducing the incidence of catheter-related bloodstream infections (CRBSI).10,11 Although ultrasound guidance during central venous cannulation is desired to minimise the complication rates it is not readily available in ERs. A sound knowledge of the landmarks and the anatomy of the vein to be cannulated is required if ultrasound is not available (Figure 2). The procedure is done using seldinger technique- threading of catheter over a guidewire.

INTERNAL JUGULAR VEIN

Fig. 2: Anatomic relationships of the internal jugular vein and subclavian vein abusers or difficult to maintain (e.g., in agitated or delirious patients).

2.

For the delivery of vasoconstrictor drugs (e.g., dopamine, norepinephrine), hypertonic solutions (e.g., parenteral nutrition formulas), or multiple parenteral medications.

3.

For prolonged parenteral drug therapy requiring more than 5-7 days.

4. For specialized tasks such as hemodialysis, transvenous cardiac pacing, or hemodynamic monitoring.

The current guidelines for preventing catheter-related infections advocates that femoral vein cannulation should be avoided, and cannulating the subclavian vein is preferred to cannulating the internal jugular vein and are based on the perceived risk of catheter-related infections at each site (i.e., the highest risk from the femoral vein and the lowest risk from the subclavian vein).10 Other considerations should also take into account for site.

Subclavian vein is the least desirable site for insertion of

The internal jugular vein is located under the sternocleidomastoid muscle on either side of the neck (Figure 2). The right side of the neck is preferred for cannulation of the internal jugular vein because the vessels run a straight course to the right atrium. A headdown body tilt of 15° would distend the internal jugular vein and facilitate cannulation. The head should be turned slightly in the opposite direction to straighten the course of the vein.12 When ultrasound imaging is not available, cannulation of the internal jugular vein is guided by surface landmarks.

There are two approaches to the internal jugular vein using surface landmarks (Figure 3a & b). In the anterior approach, the operator insert the probe needle at the apex of the triangular area created by the separation of the two heads of the sternocleidomastoid muscle in which the internal jugular vein and carotid artery run. Carotid artery pulse is located in this triangle and is gently retracted toward the midline and away from the internal jugular vein. The probe needle is advanced toward the ipsilateral nipple at a 45° angle from the skin. In posterior approach, the insertion point for the probe needle is 1 cm above the point where the external jugular vein crosses over the lateral edge of the sternocleidomastoid muscle. The probe needle is inserted at this point and then advanced along the underbelly of the muscle in a direction pointing to the suprasternal notch. Complications include accidental puncture of the carotid artery, accidental puncture of the pleural space (resulting in hemothorax and/or pneumothorax), septicaemia.

SUBCLAVIAN VEIN

The subclavian vein is a continuation of the axillary vein

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Components

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Table 4: Non-invasive and invasive techniques for airway management Technique Non-invasive • Bag-and-mask • LMA and ILMA • Combitube Invasive (non-surgical)

MISCELLANEOUS

• Endotracheal intubation • Direct • laryngoscopy • Bronchoscopic • Retrograde Invasive (surgical) • Jet ventilation

Fig. 4: Anatomy of the femoral triangle and relation of femoral vein as it passes over the first rib. It runs most of its course along the underside of the clavicle. Situated just deep to the vein, on the underside of the anterior scalene muscle, is the subclavian artery and brachial plexus. The headdown body tilt distends the subclavian vein and can facilitate cannulation.13 However, other maneuvers used to facilitate cannulation, such as arching the shoulders or placing a rolled towel under the shoulder, actually cause a paradoxical decrease in the cross-sectional area of the vein.14 The vein can be located by identifying the portion of the sternocleidomastoid muscle that inserts on the clavicle (Figure 2). The subclavian vein lies just underneath the clavicle at this point, and the vein can be entered from above or below the clavicle i.e supraclavicular approach and infraclavicular approach. Complications include puncture of the subclavian artery, pneumothorax, brachial plexus injury, and phrenic nerve injury.15 Complications associated with indwelling catheters include septicemia and subclavian vein stenosis. The risk of stenosis is the principal reason to avoid cannulation of the subclavian vein in patients who might require a hemodialysis access site (e.g., arteriovenous fistula) in the ipsilateral arm.16

Femoral vein

The femoral is the main conduit for venous drainage of the legs. It is located in the femoral triangle along with the femoral artery and nerve (Figure 4). The vein is easier to locate and cannulate when the leg is placed in abduction.

For cannulation of the femoral vein, locate the femoral artery pulse and insert the probe needle 1 - 2 cm medial to the pulse. If the femoral artery pulse is not palpable, draw an imaginary line from the anterior superior iliac crest to the pubic tubercle, and divide the line into three equal segments. The femoral artery should be just underneath the junction between the middle and medial segments, and the femoral vein should be 1- 2 cm medial to this

• Cricothyroidotomy 1. Percutaneous 2. Surgical • Tracheostomy 1. Percutaneous 2. Surgical point. This method of locating the femoral vein results in successful cannulation in over 90% of cases.17 The major concerns with femoral vein cannulation include puncture of the femoral artery, femoral vein thrombosis, and septicemia. The femoral vein is a favored site for temporary hemodialysis catheters,18 and for central venous access during cardiopulmonary resuscitation as it does not disrupt resuscitation efforts in the chest.19 Other procedures which are done for assessing venous access are peripherally inserted central catheters (PICC), venous cutdown procedures, intraosseous route specially in pediatric patients and should be known to the physician.

AIRWAY MANAGEMENT

The primary objective of airway management is to secure unobstructed gas exchange and protect the lungs from aspiration. Because of the critical importance of maintaining gas exchange, compromise of upper-airway patency is a life-threatening emergency. physician must be capable of performing a variety of airway management techniques and instituting them in a logical and systematic way as there is no single airway modality that is universally applicable. Airway management techniques are generally classified as non-invasive or invasive, depending on whether instrumentation occurs above or below the glottis, surgical or non-surgical (Table 4). Bag-and mask ventilation and direct laryngoscopic tracheal intubation remain the routine methods of airway management in the emergency rooms.20 Non-invasive techniques include bag and mask ventilation, laryngeal mask airway (LMA), intubating LMA (ILMA), use of combitubes and the physician should be acclimatized with these techniques.

(induction) and neuromuscular blockade (paralysis). This is important in patients who have not fasted and are at much greater risk for vomiting and aspiration.24 Steps of RSI includes preparation, preoxygenation, pretreatment (lidocaine, fentanyl, atropine according to case), paralysis with induction, placement of tube, post intubation care and can be easily remebered as seven Ps. Tube placement must be confirmed by auscultation, using EtCo2 and imaging techniques. Other techniques include video laryngoscopy, fibreoptic bronchoscopic intubation.

427

CRICOTHYROIDOTOMY

Airway maneuvers must be instituted to maintain airway patency. The head tilt/chin lift is the basic maneuver for establishing an airway in someone without a cervical spine injury while the jaw thrust maneuver should be considered in all victims who may have sustained an injury to the cervical spine.

ENDOTRACHEAL INTUBATION

Endotracheal intubation remains the â&#x20AC;&#x2DC;gold standardâ&#x20AC;&#x2122; of definitive airway management, allowing for spontaneous and positive-pressure ventilation and protection from aspiration. Walls et al through a multicentre study determined the characteristics of intubations in the ED in terms of indications, techniques, rates of success, and unplanned events in 8,937 subjects mostly intubated using rapid-sequence intubation. The first-attempt success rate was 95%, and 99% of subjects eventually received a successful procedure.21 Indications include acute airway obstruction, facilitation of tracheal suctioning, protection of the airway in those without protective reflexes, and respiratory failure requiring ventilatory support. Preparation and checking of all relevant equipment are essential before embarking intubation. Tracheal intubation should be preceded by adequate preoxygenation. The decision to use a straight or curved laryngoscope blade depends partly on the specific anatomical features of the airway, and partly on the personal experience and preference of the operator.

The Macintoch blade is the most widely used curved laryngoscope blade,22 while the Miller blade is the most popular style of straight blade23 (Figure 5). Patient should be assessed for difficult intubation using mallampatti score, thyromental distance and examination of upper airway anatomy and if assessment is positive then difficult airway management equipment should also be accessible. Tracheal tube of optimal size should be selected according to the patient as small size tube would lead to increase resistance and work of breathing. Usually, in adult females tube size should be 7.5-8mm while in males it should be 8.5-9mm. Sometimes, use of stylet is needed inorder to facilitate the tube insertion.

Rapid sequence intubation (RSI) is the preferred method of endotracheal intubation in the emergency department (ED) because it results in rapid unconsciousness

method of choice if severe or complete upper-airway obstruction exists. The simplest method uses a horizontal incision through the cricothyroid membrane with the space held wide open by the scalpel handle or forceps.

This is followed by insertion of a small tracheostomy or endotracheal tube. If available, a small surgical hook is useful to hold down the inferior margin of the incision to facilitate cannulation. A tube with internal diameter of 3.0 mm will allow adequate gas flow for self-inflating bag ventilation provided supplemental oxygen is used.

Complications such as subglottic stenosis (1.6%), thyroid fracture, haemorrhage and pneumothorax occur during and after the procedure. Cricothyroidotomy is generally contraindicated in complete laryngotracheal disruption and age < 12 years. Other techniques include transtracheal jet ventilation, tracheostomy (percutaneous or surgical).

PLEURAL PROCEDURES- Intercostal drain insertion (ICD), needle thoracostomy, pleural aspiration Pneumothorax, hydropneumothorax, pyopneumothorax, hemothorax in the emergency rooms demand intercostal drain and a physician must be trained to put the chest tubes and provide ICD care. The most basic instruments required are a scalpel, a large (Kelly) clamp, and the thoracostomy (chest) tube. Tube sizes vary from 12 to 42 Fr, with smaller tubes being used for smaller pneumothoraces and larger (a minimum of 36 Fr) tubes for hemothorax and empyma. Tube thoracostomy can be extremely painful, so parenteral analgesics or procedural sedation to stabilize the patients before the procedure is required. Use generous local anesthesia, such as up to 5 mg/kg of locally injected 1% lidocaine with or without epinephrine. Insert the tube over the top of the rib rather than near the bottom to avoid the neurovascular structures located on the inferior aspect of the ribs. The most common location for a chest tube is the midaxillary to anterior axillary line, usually in the fourth or fifth intercostal space. After incision, blunt dissection with Kelly clamp is done and then pleural surface is punctured with the clamp. An ICD is then introduced in the pleural cavity using a curved clamp. The drain is then secured with sutures and connected to the water seal bottle. The most common complications include infection, laceration of an intercostal vessel, laceration of the lung, and intraabdominal or solid organ placement(liver,spleen) of the chest tube.26 Pleural fluid aspiration for diagnostic

CHAPTER 77

Fig. 5: Endotracheal intubation using A) Macintosh blade and B) Cricothyroidotomy is a reliable, relatively safe and easy way of providing an emergency airway.25 It is the Miller blade

428

and therapeutic (massive and recurrent pleural effusion for relief of dyspnoea) and needle thorocostomy in cases of tension pneumothorax are also being done in ERs routinely.

CARDIAC PROCEDUREScardiac pacing

Pericardiocentesis

and

MISCELLANEOUS

The purpose of cardiac pacing is to restore or ensure effective cardiac depolarization. Emergency cardiac pacing may be instituted either prophylactically or therapeutically.

Prophylactic indications include patients with a high risk for atrioventricular (AV) block. Therapeutic indications include symptomatic bradyarrhythmias and overdrive pacing. Transcutaneous and transvenous are the two techniques most commonly used in the emergency department (ED). Because it can be instituted quickly and noninvasively, transcutaneous pacing is the technique of choice in the ED . Transvenous pacing should be reserved for patients who require prolonged pacing or have a very high (>30%) risk for heart block. The transvenous method of endocardial pacing is commonly used and is both safe and effective. In skilled hands, the semifloating transvenous catheter is successfully placed under electrocardiographic (ECG) guidance in 80% of patients.27 Usually a catheter of 3-5 Fr and 100cms is used. Right IJV and subclavian is generally cannulated.

Once in the right ventricle and the position secured, the catheter is connected to the pacing generator. The procedure can be done either blind or under ultrasound guidance. Emergency pericardiocentesis is done in case of pericardial tamponade. In emergency setting, it can be done with 18 G needle,10ml syringe while monitoring ECG using subxiphoid approach. Catheter placement can also be done under ultrasound guidance using seldinger technique.

ULTRASOUND USE IN EMERGENCY ROOM

Point-of-care ultrasonography (POCUS) is a useful imaging technique for the physician working in the ED. Comprehensive training in POCUS is desired for emergency physicians. In using POCUS, the EM physician performs all image acquisition and interpretation at the point of care and uses the information immediately to address specific hypotheses and to guide ongoing therapy. The EM physician typically uses POCUS in a more extended fashion than the intensivist in the icu to include advanced abdominal, obstetric, testicular, musculoskeletal, and ocular ultrasonography. Another important assessment is the goal directed echocardiography (GDE). The GDE examination uses a limited number of standard echocardiography views in order to allow the physician to rapidly assess cardiac anatomy and function in the patient with hemodynamic failure.28 Ultrasonographic examination of the thorax allows the EM physician to rapidly assess the patient with respiratory failure for normal aeration pattern, pneumothorax, lung interstitial syndrome (LIS), consolidation, or pleural effusion.29 Focussed assessment with sonography using ultrasound

(FAST) examination allowes physician to rapidly assess the patient with thoracic and abdominal trauma.30

OTHER PROCEDURES

Other procedures that are frequently done in emergency settings for diagnostic and therapeutic indications are paracentesis (massive ascites), peritoneal dialysis catheter insertion, hemodialysis catheter insertion, lumbar puncture, arterial blood sampling for blood gases analysis, arterial line insertion for intraarterial blood pressure monitoring, analgesia(intercostals blocks, regional anaesthetic blocks, insertion of nasogastric/orogastric tube, Minnesota tube insertion etc. Use of ultrasound for focussed assessment in trauma patients (FAST) is desired in the ERs

CONCLUSION

Role of physician in acute care is not only evolving but expanding too. In the absence of well established ED, there is a huge burden on physicians working in ERs for providing critical care to the patients. For this, a sound knowledge and training of life saving skills/procedures is not only desired but mandatory. Early interventions in the form of these essential life saving interventions not only buy time but also decrease mortality.

REFERENCES

1.

Al-Azri, H., & Ratnapalan, S. Problem-based learning in continuing medical education: Review of randomized controlled trials. Canadian Family Physicia 2014; 60:157-165.

2.

Robert E. Suter. Emergency medicine in the United States: a systemic review .World J Emerg Med 2012; 3:5–10

3.

Anderson P, Hegedus A, Ohlen G, Holliman CJ, Williams D, Suter R: Worldwide growth of Emergency Medicine as a recognized medical specialty. Acad Emerg Med 2011; 18:S22-S23

4. Kouwenhoven WB, Ing, Jude JR, Knickerbocker GG. Closed-chest cardiac massage. JAMA 1960; 173:1064–1067.

5.

Neumar RW, Shuster M,Callaway CW, Gent LM, Atkins DL et al.2015 American heart association guidelines update for cardiopulmonary resuscitation and emergency cardiac care. Circulation:2015(suppl2)

6. 2010 American Heart Association Guidelines for Cardiopulmonary Resusci-tation and Emergency Cardiovascular Care Science with Treatment Recommendations. Circulation, volume 122, issue 16, supplement 2, October 16, 2010. (Available online@ http://circ. ahajournals.org/content/122/16_suppl_2.toc) 7.

Neumar RW, Otto CW, Link MS, et al. Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopul-monary Resuscitation and Emergency Cardiovascular Care.

Circulation 2010; 122 (suppl 3):S729–S767.

8. Mueller RL, Sanborn TA. The history of interventional cardiology: Cardiac catheterization, angioplasty, and related interventions. Am Heart J 1995; 129:146–172.

9. Taylor RW, Palagiri AV. Central venous catheterization.

Crit Care Med 2007; 35:1390–1396.

10. O’Grady NP, Alexander M, Burns LA, et. al. and the Healthcare Infection Con-trol Practices Advisory Committee (HICPAC). Guidelines for the Prevention of

Intravascular Catheter-related Infections. Clin Infect Dis 2011; 52:e1–e32.

center report of 8937 emergency department intubations. J Emerg Med 2011; 41:347354.

11. Furuya EY, Dick A, Perencevich EN, et al. Central line bundle implementation in U.S. intensive care units and impact on bloodstream infection. PLoS- ONE 2011; 6:e15452.

22. Scott, J; Baker, PA (2009). “How did the Macintosh laryngoscope become so popular?”. Paediatric Anaesthesia 2009: 19(Suppl 1): 24–9.

12. Feller-Kopman D. Ultrasound-guided internal jugular access. Chest 2007; 132:302–309.

23. Amornyotin, S; Prakanrattana, U; Vichitvejpaisal, P; Vallisut, T; Kunanont, N; Permpholprasert, L (2010).

“Comparison of the Clinical Use of Macintosh and Miller Laryngoscopes for Orotracheal Intubation by SecondMonth Nurse Students in Anesthesiology”. Anesthesiology Research and Practice 2010; 1–5

13. Fortune JB, Feustel. Effect of patient position on size and location of the subclavian vein for percutaneous puncture.

Arch Surg 2003; 138:996–1000.

15. Rodriguez CJ, Bolanowski A, Patel K, et al. Classic positioning decreases crosssectional area of the subclavian vein. Am J Surg 2006; 192:135–137.

16. Hernandez D, Diaz F, Rufino M, et al. Subclavian vascular access stenosis in dialysis patients: Natural history and risk factors. J Am Soc Nephrol 1998; 9:1507–1510.

17. Getzen LC, Pollack EW. Short-term femoral catheterization. Am J Surg 1979; 138:875–877.

vein

18. Parienti J-J, Thirion M, Megarbane B, et al. Femoral vs jugular venous catheterization and risk of nosocomial events in adults requiring acute renal replacement therapy.

JAMA 2008; 299:2413–2422.

19. Hilty WM, Hudson PA, Levitt MA, Hall JB. Real-time ultrasound-guided femoral vein catheterization during cardiopulmonary resuscitation. Ann Emerg Med 1997; 29:311– 316.

20. Practice Guidelines for Management of the Difficult Airway. An updated report by the American Society of Anesthesiologists Task Force on management of the difficult airway. Anesthesiology 2003; 98:1269–77.

21. Walls RM, Brown CA 3rd, Bair AE, Pallin DJ, NEAR II Investigators. Emergency airway management: a multi-

24. Sagarin MJ, Barton ED, Chng YM, et al. Airway management

by US and Canadian emergency medicine residents: a multicenter analysis of more than 6,000 endotracheal intubation attempts. Ann Emerg Med 2005; 46:328-36 25. Kress TD, Balasubramaniam S. Cricothyroidotomy. Ann Emerg Med 1982; 11:197–201.

26. Sesieme EB, Dongo A, Ezemba N, et al. Tube thoracostomy: complications and management. Pulm Med 2012; 2012:256878.

27. Francis GS, Williams SV, Achord JL, et al. Clinical competence in the insertion of a temporary transvenous ventricular pacemaker. Circulation 1994; 89:1913.

28. Walley PE, Walley KR, Goodgame B, Punjabi V, Sirounis D. A practical approach to goal-directed echocardiography in the critical care setting. Crit Care 2014; 18:1–1.

29. Volpicelli G, Elbarbary M, Blaivas M, Lichtenstein DA, Mathis G, Kirkpatrick AW, Melniker L, Gargani L, Noble VE, Via G, Dean A. International evidence-based recommendations for point-of-care lung ultrasound.

Intensive Care Med 2012; 38:577–91.

30. Holmes JF, Harris D, Battistella FD. Performance of abdominal ultrasonography in blunt trauma patients with out-of-hospital or emergency department hypotension.

Ann Emerg Med 2004; 43:354–61.

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14. Fragou M, Gravvanis A, Dimitriou V, et al. Real-time ultrasound-guided subclavian vein cannulation versus the landmark method in critical care patients: A prospective randomized study. Crit Care Med 2011; 39:1607–1612.

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Principles of Diet Therapy

C H A P T E R

78

Shilpa Joshi

Let food be thy medicine, Thy medicine be thy food Hippocrates Importance of nutrition is known to man since time immortal. In fact, before modern medicine came into being, various foods were used as medicine. Older

medical sciences like Chinese medicine and Ayurveda put in a lot of emphasis on foods and dietary restrictions as a mode of therapy.

The term “medical nutrition therapy” (MNT) was introduced in 1994 by then the American Dietetic

Table 1: MNT Provided bv RDs Application of Nutrition Care Process

MNT Provided by RD (for individual)

Nutrition screen/referral

The physician provider sends RD written referral for MNT for diabetes. The referral includes information regarding current laboratory test results, medications, and other medical diagnoses.

Nutrition assessment

The RD performs a comprehensive nutrition assessment utilizing the Diabetes Type I and2 Evidenced-Based Nutrition Practice Guideline for Adults and Toolkit, as well as the best available current knowledge and evidence, client data, medical record data, and other resources.

Nutrition diagnosis

After analyzing assessment data, the RD makes initial nutrition diagnosis(es); for example, inconsistent carbohydrate intake (diagnosis code NI-5.8.4). inconsistent timing of carbohydrate intake throughout the day. day to day, or a pattern of carbohydrate intake that is not consistent with recommended pattern based on physiological or medication needs.

Nutrition intervention

The RD provides counseling and. with the client, determines interventions using the cognitive behavioral model, including problem solving, motivational interviewing, goal setting, and self-monitoring.

Nutrition monitoring and evaluation

The RD monitors A1C. microalbuminuria. BMI. serum lipid levels, goals for food plan/intake, activity, and other behavior changes.

The RD implements changes to MNT (e.g.. patient education goals, nutrition intervention, and counseling) in future visits based on outcomes and assessments at each visit.

Nutrition documentation (supports all steps of the Nutrition Care Process)

The RD documents MNT initial assessment, nutrition diagnosis(es). and intervention(s); shares with referring physician: and keeps a copy on file.

Outcome management systems

Based on RD analysis, critical thinking, and review of data from the patient’s medical history and other health care professionals, the RD aggregates individual and population outcomes data: analyzes and shares with quality improvement department/group as indicated: and implements improvements to MNT services based on results.

Reprinted with permission from Ref. 7.

Sara F. Morris, and Judith Wylie-Rosett Clin Diabetes 2010;28:12-18; ©2010 by American Diabetes Association

431

Table 1: Summary of evidence for nutrition therapy in diabetes Type of intervention (Reference)

Study length

No. of subjects

Outcome

UKPDS Group, 19905

3 months

3,042 newly diagnosed patients with type 2 diabetes

In 2,595 patients who received intensive nutrition therapy (447 were primary diet failures), HbA1c decreased 1.9% (8.9 to 7%) during the 3 months before study randomization

Franz et al., 19956

6 months

179 persons with type 2 diabetes; 62 in comparison group; duration of diabetes: 4 years

HbA1c at 6 months decreased 0.9% (8.3 to 7.4%) with nutrition practice guidelines care; HbA1c decreased 0.7% (8.3 to 7.6%) with basic nutrition care; HbA1c was unchanged in the comparison group with no nutrition intervention (8.2 to 8.4%)

Kulkarni et al., 19987

6 months

54 patients with type 1 diabetes; newly diagnosed

HbA1c at 3 months decreased 1.0% (9.2 to 8.2%) with nutrition practice guideline care and 0.3% (9.5 to 9.2%) in usual nutrition care group

Randomized controlled trials MNT only

Glasgow et al., 19928

6 months

162 type 2 diabetic patients HbA1c decreased from 7.4 to 6.4% in over the age of 60 years control-intervention crossover group while the intervention-control crossover group had a rebound effect; intervention group had a multidisciplinary team with an RD who provided MNT

Sadur et al., 19999

6 months

185 adult patients with diabetes

97 patients received multidisciplinary care and 88 patients received usual care by primary care. MD; HbA1c decreased 1.3% in the multidisciplinary care group compared with 0.2% in the usual care group; intervention group had a multidisciplinary team with an RD who provided MNT

9 years

623 patients with type 1

Patients who reported following their meal plan >90% of the time had an average HbA1c level 0.9% lower than subjects who followed their meal plan <45% of the time

Observational studies Cross-sectional survey Delahanty and Halford, 199310

Expert opinion DCCT Research Group, 199311

DCCT group recognized the importance of the role of the RD in educating patients on nutrition and adherence to achieve A1c goals; RD is key member of the team

Franz, 199412

DCCT made apparent that RDs and RNs were extremely important members of the team in co-managing and educating patients Contd...

CHAPTER 78

MNT in combination with DSMT

432

Table 1: Summary of evidence for nutrition therapy in diabetes Type of intervention (Reference)

Study length

No. of subjects

Outcome

Johnson and Valera, 199513

6 months

19 patients with type 2 diabetes

At 6 months, blood glucose levels decreased 50% in 76 of patients receiving nutrition therapy by an RD. Mean total weight reduction was ~5 pounds

Johnson and Thomas, 200114

1 year

162 adult patients

MNT intervention decreased HbA1c levels 20%, bringing mean levels <8% compared with subjects without MNT intervention who had a 2% decrease in HbA1c levels

3 months

102 patients (15 type 1 and 85 type 2 diabetic patients with duration of diabetes >6 months

HbA1c levels decreased 1.6% (9.3 to 7.7%) after referral to an RD

Brown, 1996, 199016,17

89 studies

Educational intervention and weight loss outcomes; MNT had statistically significant positive impact on weight loss and metabolic control

Padgett et al., 198818

7,451 patients

Educational and psychosocial interventions in management of diabetes (including MNT, SMBG, exercise, and relaxation); nutrition education showed strongest effect

Norris et al., 200119

72 studies

Positive effects of self-management training on knowledge, frequency and accuracy of self-monitoring of blood glucose, self-reported dietary habits, and glycemic control were demonstrated in studies with short follow-up (<6 months)

MISCELLANEOUS

Chart audit

Retrospective chart review Christensen et al., 200015

Meta-analyses of trials

Association to better articulate the nutrition/ diet therapy process. It is defined as the use of specific nutrition therapy to treat an illness, injury, or other condition. Medical nutrition therapy involves two phases: 1) assessment of the nutritional status of the client and 2) treatment, which includes nutrition therapy, counselling, and the use of specialized nutrition supplements if required or indicated.1 MNT incorporates a process that, when implemented correctly, includes: 1) an assessment of the patient’s nutritional status and disease specific self-management knowledge and skills; 2) identification and negotiation of individually designed nutrition goals; 3) nutrition intervention involving a careful match of both a meal-planning approach and educational materials to the patient’s needs, with flexibility in mind to have the plan be implemented by the patient; and 4) evaluation of outcomes and on-going monitoring. These four steps are necessary to assist patients in acquiring and maintaining the knowledge, skills, attitudes, behaviours, and

commitment to successfully meet the challenges of daily self-management.2 In general, MNT consists of many, one-on-one sessions between an RD and a patient, in which the RD performs the nutrition assessment, diagnosis, counselling, and other therapy services according to the “MNT EvidenceBased Guide for Practice/Nutrition Protocol” or according to the best available current evidence in the nutrition science. As part of nutrition monitoring and evaluation, the RD monitors biochemical factors, as well as lifestyle factors such as dietary intake. Depending on how many sessions the RD has with the patient, these factors are used to evaluate the effectiveness of interventions in meeting goals. Diagnoses and interventions might then be revised based on nutrition-related outcomes. Therefore, MNT for nutrition-related disorders is not necessarily a linear process. Counselling in MNT is individualized and tailored to a patient’s clinical and lifestyle needs.3-4

of age and who were at increased risk of developing type 2 diabetes (i.e., having impaired glucose tolerance, being overweight, and having a family history of type 2 diabetes).

The study involved a control group (standard care plus a placebo pill) and two intervention groups: one that received a intensive lifestyle modification (healthy diet, moderate physical activity of 30 min/day for 5 days/ week) and one that received standard care plus an oral diabetes agent (metformin). The major study findings indicate that participants in the intensive lifestyle modification group reduced their risk of developing diabetes by 58% compared with the medication intervention group who reduced their risk by 31%. Even more dramatic was the finding that individuals over 60 years of age in the intensive lifestyle modification group decrease their incidence of developing type 2 diabetes by 71%.

Brown and colleagues6,7 completed a meta-analysis of 89 studies of educational interventions and outcomes specific to weight loss in diabetes care. An important highlight of the results from these findings is that nutrition therapy alone had the largest statistically significant impact on weight loss and metabolic control. The combination strategy of nutrition and behavioral therapy plus exercise had a small effect on body weight, but a very significant impact on HbA1c. These findings lend support to the effectiveness of diabetes patient education in improving patient outcomes.

MEDICAL NUTRITION THERAPY IN CARDIO VASCULAR DISEASES

Historically, a challenge to proving the benefit of MNT has been the lack of clinical and behavioral research.

In recent years, however, evidence-based outcomes research that documents the clinical effectiveness of MNT in diabetes has been reported. The evidence from randomized controlled trials, observational studies, and meta-analyses that nutrition intervention improves metabolic outcomes, such as blood glucose and HbA1c levels in individuals with diabetes, is summarized in Table 1.5 Metabolic outcomes were improved in nutrition intervention studies, both as independent MNT and as part of overall DSMT. This evidence also suggests that MNT is most beneficial at initial diagnosis, but is effective at any time during the disease process, and that on going evaluation and intervention are essential.

In a review of the effects of educational and psychosocial interventions in the management of diabetes (including education and skill training in diabetes, nutrition, selfmonitoring, exercise, and relaxation) in 7,451 patients, Padgett et al.8 found that nutrition education showed the strongest effect and relaxation training showed the weakest effect.

Medical Nutrition therapy in Prediabetes: Studies9,10 have shown that type 2 diabetes can be prevented by lifestyle interventions in subjects who are at high risk for diabetes. In the Finland Diabetes Prevention Study, published in May 2001,9 522 overweight subjects with impaired glucose tolerance were randomised in to an intervention or control group. The intervention group received individualized counseling to reduce weight (seven sessions the first year and every 3 months for the remainder of study), to decrease intake of total and saturated fat, and to increase intake of fiber and physical activity. Subjects were followed for 3.2 years and received an oral glucose tolerance test (OGTT) annually. Results at the end of 1 year showed a weight loss of 4.2 and 0.8 kg for the intervention and control groups, respectively.

The incidence of diabetes after 4 years was 11% in the intervention group and 23% in the control group. During the study, the risk of diabetes was reduced by 58% in the intervention group.

The initial results of a similar study, the Diabetes Prevention Program (DPP), a multicenter National Institutes of Health study, suggest that type 2 diabetes can be prevented and delayed.10 The DPP was a randomized trial involving more than 3,200 adults who were 25 years

Epidemiologic, experimental, and clinical trial evidence have demonstrated a relationship between diet, nutrients, and blood lipid levels; blood pressure; and coronary heart disease (CHD). Evidence from prospective studies have shown that dietary patterns are associated with risk and, specifically, that dietary patterns high in saturated fatty acids, cholesterol, and animal fat increase lowdensity lipoprotein (LDL) cholesterol levels.11 Clinical trials involving dietary interventions to reduce total fat, saturated fatty acids (SFAs), and cholesterol have further demonstrated favorable responses among dyslipidemic and normolipidemic individuals. The National Cholesterol Education Program Adult Treatment Panel III (ATP III) reviewed the evidence in 1999 and recommended the Therapeutic Lifestyle Changes diet and lifestyle.12 Since 2000 research has shifted to other dietary factors, including whole foods and favorable dietary patterns that likewise appear to affect blood lipid levels. As potential nonlipid biomarkers for CVD have also been identified (ie, blood pressure, thrombogenecity, and inflammation) research interest about how diet might influence these factors has increased.13,14 Numerous dietary factors/nutrients have been identi fied that affect CVD risk factors. Because most patients present with multiple risk factors, including the diagnosis of metabolic syndrome, an individualized dietary pattern is recommended to optimize CVD risk factor reduction while meeting nutrient needs. RDs are uniquely skilled in this process. Dietary considerations to help achieve these goals include a diet: â&#x2014;?

low in SFA (7%), TFA (1% calories), and dietary cholesterol (200 mg);

â&#x2014;?

rich in n-3 fatty acids, EPA, and DHA (500 mg/ day for primary prevention; 1 g/day for secondary prevention; and 2 to 4 g/day for TG lowering; physician supervision is indicated for patients); consume fish at least twice a week;

â&#x2014;?

ample in total dietary fiber (30 g/day) with emphasis on soluble fiber;

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MEDICAL NUTRITION THERAPY IN DIABETES

MISCELLANEOUS

434

●

that includes unsalted nuts (1 oz) as tolerated and limited by energy needs; consider other vegetable protein sources such as soy and legumes;

●

that includes skim/low-fat dairy foods and/or other calcium/vitamin D-rich sources;

7. Brown SA, Upchurch S, Anding R, Winter M, Ramirez G: Promoting weight loss in type II diabetes. Diabetes Care 1996; 19:613–624.

●

rich in vitamins, minerals, phytochemicals, and antioxidants from multiple servings of fruits and vegetables and low in sodium (2,300 mg/day);

●

rich in B vitamins and fiber from food sources such as whole grains and vegetables;

8. Padgett D, Mumford E, Hynes M, Carter R: Meta-analysis of the effects of educational and psychosocial interventions on management of diabetes mellitus. J Clin Epidemiol 1988; 41:1007–1030.

●

that may include plant sterols and stanols in high risk individuals; and

●

that achieves a healthful body weight and energy balance with the recommended dietary intervention by increasing physical activity and maintaining an adequate energy intake. MNT represents the ideal approach to treating these patients.15

CONCLUSION

Lifestyle intervention , of which medical nutrition therapy is a cornerstone is essential both in prevention and treatment of many metabolic diseases.

REFERENCES

1. American Dietetic Association: ADA’s definition for nutrition screening and nutrition assessment. J Am Diet Assoc 1994; 94:838–839, 2. Tinker LF, Heins JM, Holler HJ: Commentary and translation: 1994 nutrition recommendations for diabetes. J Am Diet Assoc 1994; 94:507–511.

3. Lacey K, Pritchett E: Nutrition care process and model: ADA adopts road map to quality care and outcomes management. J Am Diet Assoc 2003; 103:1061-1072.

4. Daly A, Michael P, Johnson EQ, Harrington CC, Patrick S, Bender T : Diabetes White Paper: Defining the delivery of nutrition services in Medicare medical nutrition therapy vs Medicare diabetes self-management training programs. J Am Diet Assoc 109:528-539, 200.

5. Jyoce Pastor, Hope Warshaw ,Anne Daly, Marion Franz, Karmeen Kulkarni: The Evidence for the Effectiveness of Medical Nutrition Therapy in Diabetes Management.

Diabetes Care 2002; 25:3.

6. Brown SA: Studies of educational interventions and outcomes in diabetic adults: a meta-analysis revisited.

Patient Educ Counsel 1990; 16:189–215.

9. Tuomilehto J, Lindstrom J, Erikksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M: Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.

N Engl J Med 2001; 344:1343–1350.

10. Availablefromhttp://www.preventdiabetes. com. Accessed January 2002.

11. Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ, Erdman JW Jr, Kris-Etherton P, Goldberg IJ, Kotchen TA, Lichtenstein AH, Mitch WE, Mullis R, Robinson K, Wylie-Rosett J, St Jeor S, Suttie J, Tribble DL, Bazzarre TL. AHA Dietary Guidelines: Revision 2000: A statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation 2000; 102:2284-2299.

12. Executive Summary of the Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001; 285:2486-2497.

13. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342:836-843. 14. Kris-Etherton PM, Pearson TA, Wan Y, Hargrove RL, Moriarty K, Fishell V, Etherton TD. High-monounsaturated fatty acid diets lower both plasma cholesterol and triacylglycerol concentrations. Am J Clin Nutr 1999; 70:1009-1015.

15. Linda Van Horn, Phd, Rd; Mikelle Mccoin, Mph, Rd; Penny M. Kris-Etherton, Phd, Rd; Frances Burke, Ms, Rd; Jo Ann S. Carson, Phd, Rd; Catherine M. Champagne, Phd, Rd; Wahida Karmally, Drph, Rd; Geeta Sikand, Ma, Rd :The Evidence for Dietary Prevention and Treatment of Cardiovascular Disease. Journal of The American Dietetic Association 2008; 108:2.

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INTRODUCTION

A drug-induced disease is the unintended effect of a drug, which results in mortality or morbidity with symptoms sufficient to prompt a patient to seek medical attention and/or require hospitalization. Drug-induced disease can result from unanticipated or anticipated drug effects.

Disease also can occur from product impurities, as was the case with deaths attributed to the use of contaminated heparin in 2008.Vigilance on the part of regulatory authorities, drug manufacturers, clinicians, and patients is necessary to minimize the potential harm that is inherent in drug use.

Drug Induced Diseases TK Suma

HISTORY

1.

Adverse Drug Reaction (ADR): The World Health Organization defines an adverse drug reaction (ADR) as any noxious, unintentional, and undesired effect of a drug, which occurs at doses used in humans for prophylaxis, diagnosis, or therapy.

Public and professional concern about drug induced diseases first arose in the late 19th century.In 1922, there was an enquiry into the jaundice associated with the use of SALVARSAN, an organic arsenical used in the treatment of Syphilis. In 1937 in the USA, 107 people died from taking an elixir of sulfanilamide that contained the solvent diethylene glycol. This led to the establishment of the Food and Drug Administration (FDA), which was given the task of enquiring into the safety of new drugs before allowing them to be marketed. The major modern catastrophe that changed professional and public opinion towards medicines was the thalidomide tragedy. The thalidomide incident led to a public outcry, to the institution all round the world of drug regulatory authorities, to the development of a much more sophisticated approach to the preclinical testing and clinical evaluation of drugs before marketing, and to a greatly increased awareness of adverse effect of drugs and methods of detecting them. With the adverse reactions some drugs have been withdrawn from use or for some the label has been changed.

2.

Adverse event (AE): Medical occurrence temporally associated with the use of a medicinal product, but not necessarily causally related. The essential difference from ADR is that AE need not be causally related to the drug in use.

It is estimated that 3-5% of hospital admissions are caused

by ADRs. The incidence of serious and fatal adverse reactions in hospital patients has been reported between 0.32% and 6.7%.

The adverse events due to drugs are extensive and is not limited to drug induced diseases. Let us first of all look in to various terminologies used to describe the untoward effects due to drugs.

3.

Unexpected adverse reaction (UAR) : Usually adverse drug reactions of a drug will be described in the product information. UAR is not consistent with applicable product information or characteristics of drug.

4.

Side effect : Unintended effect occurring at normal dose related to the pharmacological properties.

5.

Serious adverse event (SAE) : Any untoward medical occurrence that at any dose results in death, Life threatening situation, requires inpatient hospitalization or prolongation of existing hospitalization, results in deformity or incapacity.

SAE is especially important when you are doing drug trials/drug development studies.

6.

Serious Unexpected Suspected Adverse Reaction (SUSAR): It is an adverse drug rection which is suspected but unexpected and serious.

Any drug may cause an adverse drug reaction.

Undoubtedly, all drugs produce an ADR in someone who has used them.

ADVERSE DRUG REACTIONS

Adverse drug reactions is mainly devided into two groups, Type A and Type B. Type A reactions: are expected exaggerations of the drugs known effect. These are usually dose dependent and predictable and account for the majority of ADRs. Characteristics Type A reactions include: higher than normal dose administered, impaired metabolism or excretion, or very sensitive individuals. These reactions are often found in the FDA approved product labelling.

Type B reactions: are idiosyncratic and usually unrelated to the drugâ&#x20AC;&#x2122;s known pharmacology. Normally they are not related to the dose, are unpredictable, uncommon, and usually more serious than Type A. Examples are carcinogen and teratogens. These reactions are more commonly reported after a drug has been on the market for a number of years.

OTHER DRUG REACTIONS

Dose related adverse reactions: Dose related adverse reactions have led to the concept of the therapeutic

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index, or the toxic: therapeutic ratio. This indicate the margin between the therapeutic dose and the toxic dose.

Examples of drugs with a low toxic: therapeutic ratio are anticoagulants (warfarin, heparin), hypoglycemic drugs (insulin, sulfonylurea), antiarrythmic drugs (lidocaine, amiodarone), cardiac glycosides (digoxin, digitoxin), aminoglycoside antibiotics (gentamicin, netilmicin), oral contraceptives, cytotoxic and immunosuppressive drugs (cyclosporine, methotrexate, azathioprine), antihypertensive drugs ( betaadrenoceptors antagonists, ACE inhibitors) I.

Pharmaceutical Variation: ADR occur because of alterations in the systemic availability of a formulation. Examples include phenytoin intoxication, by a change in one of the excipients in the phenytoin capsules from calcium sulfate to lactose, which increase the systemic availability of phenytoin.

ADR due to presence of a contaminant: Examples are pyrogens or even bacteria in intravenous formulations.

Succinylcholine Hydrolysis: Succinylcholine is hydrolyzed by pseudocholinestrase. In some individuals pseudocholinestrase is abnormal and does not metabolize. In such cases drug persist in blood and continue to produce neuro muscular blockade for several hours. This result in respiratory paralysis called scoline apnoea.

b.

Hepatic Disease

Adverse drug reaction due to impaired hepatic metabolism are not so common. Hepatocellular dysfunction, as in several hepatitis or advanced cirrhosis, can reduce the clearance of drugs like phenytoin, theophylline and warfarin. A reduction in hepatic blood flow, as in heart failure, can reduce the hepatic clearance of drugs that have an high extraction ratio for e.g. propranolol, morphine and pethidine. Reduced production of plasma proteins (for e.g. albumin) by the liver in cirrhosis can lead to reduced protein binding of drugs.

c.

Renal Disease

If a drug or active metabolite is excreted by glomerular filtration or tubular secretion, it will accumulate in renal insufficiency and toxicity will occur.

d.

Cardiac Disease

Cardiac failure, particularly congestive cardiac failure, can alter the pharmacokinetic properties of drugs by several mechanisms:

1.

Impaired absorption, due to intestinal mucosal edema and a poor splanchnic circulation, can alter the efficacy of some oral diuretic, such as Furosemide.

2.

Hepatic congestion and reduced liver blood flow may impair the metabolism of some drugs (e.g.

Lidocaine).

3.

Poor renal perfusion may result in reduced renal elimination (e.g. Procainamide).

Out of date formulations: can sometimes cause adverse reactions, because of degradation products.

Out-dated tetracycline causing Fanconiâ&#x20AC;&#x2122;s syndrome is an example.

II.

Pharmacokinetic Variations

a.

Pharmacogenetic Effects

1.

Acetylation: Acetylation shows genetic variability.

There are fast and slow acetylators.

Several drugs are acetylated by n- acetyl transferase.

Fast acetylation is autosomal dominant and slow acetylation is autosomal recessive.

Drugs whose Acetylation is genetically determined are: Isoniazid, Hydralazine, Procainamide.

Dapsone, Some sulfonamides. Increased incidence of peripheral neuropathy is observed in slow acetylators of Isoniazid.

2.

Oxidation: Oxidation also shows genetic variability.

There are individuals with impaired oxidation and with normal oxidation. Impaired oxidation ones are called as poor metbolizers and the ones with normal are called extensive metabolizers.

4.

Reduction in the apparent volumes of distribution of some cardio active drugs, by mechanisms that are not understood cause reduced loading dose requirements (e.g. Procainamide, Lidocaine, Quinidine).

3.

hydroxylation: CYP2D6 is a cytochrome P450 enzyme and carries out Debrisoquine hydroxylation.

Impaired hydroxylation of Debrisoquine is an autosomal recessive defect of this cytochrome.

Drugs that are affected besides Debrisoquine are: Captopril, Metoprolol, Phenformin, Perhexitine, Nortryptiline

III.

Pharmacodynamic Variations

a.

Hepatic Disease:

Hepatic disease can alter pharmacodynamic responses to drugs in several ways;

1.

Reduced Blood Coagulation: In cirrhosis and acute hepatitis, production of clotting factor is impaired and patients bleed more readily. Drugs that impair blood clotting, that impair homeostasis, or that predispose to bleeding by causing gastric ulceration should be avoided or used with care for e.g. Anticoagulants and NSAIDS.

Poor hydroxilators are more likely to show dose related adverse effect of these drugs. In case of toxic metabolites risk would be greater in extensive hydroxilators.

2.

3.

Hepatic Encephalopathy: In patients with, or on the border line of, hepatic encephalopathy, the brain is more sensitive to the effects of drugs with sedative actions. If such drugs are used, coma can result. It is therefore wise to avoid Opioids & other narcotic analgesics and barbiturates.

b.

Altered Fluid And Electrolyte Balance

The pharmacodynamic effects of some drugs are altered by changes in fluid and electrolyte balance.

Example; The toxic effect of cardiac glycosides are potentiated by both Hypokalaemia and Hypercalcaemia. The Class1 of Antiarrhythmic drugs such as Quinidine, Procainamide and Disopyramide are more arrhythmogenic if there is hypokalaemia.

NON-DOSE RELATED ADVERSE DRUG REACTIONS

Include a.

Immunological and

b.

Pharmacogenetic mechanisms of adverse reactions.

IMMUNOLOGICAL REACTIONS

(Drug Allergy)

Features of allergic drug reactions

A circulating antibody of the IgG, IgM, or IgA class interact with an antigen formed by hapten. Complement is then activated and cell lysis occurs. Example: thrombocytopenia, haemolyticanaemia quinidine or quinine.

TYPE 111 REACTIONS (IMMUNE COMPLEX REACTIONS)

Antibody (IgG) combines with antigen i.e. the haptenprotein complex in circulation Complex thus formed is deposited in the tissues, complement is activated, and damage to capillary endothelium results. Serum sickness is the typical drug reaction of this type. Penicillins, Sulfonamides & Anti thyroid drugs may be responsible.

TYPE 1V REACTIONS (CELL MEDIATED)

T-lymphocytes are sensitized by a hapten-protein antigenic complex. Inflammatory response ensues when lymphocytes come in contact with the antigen. E.g.

Dermatitis caused by local anesthetic creams, topical antibiotics and antifungal creams.

PSEUDO ALLERGIC REACTIONS

Term applied to reactions that resemble allergic reactions clinically but for which no immunological basis can be found. Asthma and skin rashes caused by aspirin are the examples.

BLOOD DISORDERS

â&#x20AC;˘ Thrombocytopenia, neutropenia, hemolytic anaemia, and aplastic anaemia can all occur as adverse drug reactions.

RESPIRATORY DISORDERS

There is no relationship to the usual pharmacological effects of the drug; There is often a delay between the first exposure to the drug and the occurrence of the subsequent adverse reaction; There is no formal doseresponse curve; The illness is often recognizable as a form of immunological reaction like rash, serum sickness, urticaria etc.

â&#x20AC;˘

There are genetic factors that make some patients more likely to develop allergic reactions than others: A history of allergic disorders HLA status (antigens on human lymphocytes).

Unusual drug reaction occur in individuals whose erythrocytes are deficient in any one of three different but functionally related enzymes such as glucose-6phosphate dehydrogenase, glutathione reductase and methaemoglobin reductase.

Classified acc. to the classification of hypersensitivity reactions, i.e. into four types, types I-IV. Type 1 Reactions hypersensitivity):

(anaphylaxis;

immediate

The drug or metabolite interacts with IgE molecules fixed to cells, particularly tissue mast cells and basophiles leukocytes. This triggers a process that lead to the release of pharmacological mediators like histamine, 5-HT, kinins, and arachidonic acid derivatives, which cause allergic response. Manifest as urticaria, rhinitis, bronchial asthma, angio-oedema and anaphylactic shock. Drugs likely to cause type 1 are Penicillins, Streptomycin, local anaesthetics etc.

437

Asthma occurring as a pseudo allergic reaction to Aspirin, other NSAIDS and Tartarzine is an e.g. adverse drug reaction.

PHARMACOGENETIC VARIATION CAUSING NON DOSERELATED REACTIONS

Red cell enzyme defects

LONG TERM ADVERSE EFFECTS

a.

Adaptive Changes

Examples include development of tolerance to and physical dependence on the narcotic analgesics and the occurrence of tardive dyskinesia in some patients receiving long term neuroleptic drug therapy for schizophrenia.

b.

Rebound and Withdrawal Phenomena

During long term therapy sudden withdrawal of the drug can result in rebound reactions.

Examples are typical syndromes occurring after

CHAPTER 79

Sodium and Water Retention: In hepatic cirrhosis, sodium and water retention can be exacerbated by certain drugs. Drugs that should be avoided or used with care include NSAIDS, Corticosteroids, Carbamazepine and formulations containing large amount of sodium.

TYPE II REACTIONS (CYTOTOXIC REACTIONS)

sudden withdrawal of narcotic analgesic or of alcohol (delirium tremens), sudden withdrawal of Barbiturates result in restlessness , mental confusion and convulsions, Sudden withdrawal of β-adrenoceptors antagonists result in rebound tachycardia which can precipitate myocardial ischemia, Sudden withdrawal of corticosteroids results in syndrome of adrenal insufficiency.

438

DELAYED ADVERSE EFFECTS

MISCELLANEOUS

Carcinogenesis

There are three major mechanisms of carcinogenesis: i.

Hormonal: incidence of vaginal adenocarcinoma is increased in daughters of women who have taken stilboestrol during pregnancy for the treatment of threatened abortions.

Increased risk of breast cancers is about 50% and woman taking hormone replacement therapy (HRT) for more than five years.

ii.

Gene Toxicity: Occurs when certain molecules bind to nuclear DNA and produce changes in gene expressions. Examples: bladder cancer in patient taking long term cyclophosphamide, carcinomas of renal pelvis associated with phenacetin abuse, non lymphocytic leukemia in patients receiving alkylating agents such as melphalan, chlorambucil etc.

iii.

Suppression of immune responses: patients taking immunosuppressive drugs such as azathioprine with corticosteroids have increased risk of developing lymphomas.

EFFECTS CONCERNED WITH REPRODUCTION

A.

Impaired Fertility: Cytotoxic drugs can cause female infertility through ovarian failure with amenorrhea.

Reversible impairment can be caused by sulfasalazine, nitrofurantoin, MAO inhibitors and antimalarial drugs; Irreversible impairment, due to azospermia, can be caused by cytotoxic drugs, such as alkylating agents cyclophosphamide and chlorambucil. Male fertility can be reduced by impairment of spermatozoal production or function and can be either reversible or irreversible

B.

Teratogenesis: Teratogenesis occurs when a drug taken during early stages of pregnancy causes a developmental abnormality in a fetus.

Drugs can affect fetus at 3 stages: 1.

Fertilization and Implantation: Conception to 17 days causes failure of pregnancy which often goes unnoticed.

2.

Organogenesis: 18 to 55 days of gestation- Most vulnerable period, deformities are produced

3.

Growth and Development: 55 days onwardsdevelopment and functional abnormalities can occur.

ACE inhibitors can cause hypoplasia of organs. NSAIDs may induce premature closure of ductus arteriosus Different teratogenic drugs are: Thalidomide, Methotrexate, Warfarin, Phenytoin, Phenobarbitone, Valproate Sod. Lithium, etc.

Approach to adverse reactions: Type A reactions include medication errors. Therefore, there may be some difficultly in deciding the correct reporting procedure. If the reaction is caused by a prescribing, administering or monitoring error, a medication error has occurred and medication error report should be completed.

If the patient develops an ADR when the prescribing, administering and monitoring are appropriately carried out, an adverse drug reaction report form should be completed.

The FDA compiles information on adverse drug events. If a medicine causes a serious adverse event due to a either medication error or ADR the FDA should be notified. If a medication is commonly associated with medication errors the FDA should be notified. This feedback is essential so that the package labeling can be updated and the risk benefit ratio of the drug may be better understood.

In order for drugs to obtain FDA approval they must be proven safe and effective. The 1962 amendment to the federal food, drug, and Cosmetic Act requires manufacturers to report adverse drug events detected in postmarketing settings to the FDA. The Food and Drug Modernization act of 1997 states that substantial evidence of drug effectiveness may consist of data from one adequate and well-controlled clinical investigation plus confirmatory evidence.

Most drugs are studied in less than 4,000 patients before FDA approval. Drug reactions that occur in less than 1 in 1000 patients are difficult to detect. Premarketing trials generally excluded special populations such as children, elderly, and women of child bearing age. Most drug withdrawn from the market for serious side effects, are withdrawn within 1-2 years of FDA approval, as experience is gained in a larger population outside of the narrow confines of clinical trials.

PHARMACOVIGILANCE PROGRAM INDIA

In India, the national coordinating centre (NCC for pharmacovigilance is ALL Institute of Medical Sciences.

Medical colleges and major centres are ADR monitoring centres which will report the ADRs to the NCC. If there is a significant ADR that will be reported to WHO pharmacovigilance collaborating centre in Upsala.

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80

An Overview of Persistent Pain Palanisamy Vijayanand, Sudhindra Dharmavaram

The International Association for the Study of Pain defines pain as â&#x20AC;&#x153;an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damageâ&#x20AC;?. This implies that pain has not only physical attributes but also a strong psychological component. Keeping this in mind there has been emphasis on the biopsychosocial approach to the diagnosis and management of chronic pain conditions. It is generally agreed that any pain lasting more than three months is considered chronic pain.

As many as 15 to 25% of general adult population world over suffer from chronic pain. Although epidemiological studies of chronic pain in India are limited, there is no reason to believe that the figures for India would be any less. One study pegs the point prevalence of chronic pain in India at around 15%, i.e one in six adults. Furthermore, in India, two thirds of people with chronic pain reported their pain to be of severe nature, and a third of these patients reported to have lost at least 4 hours of work in the preceding three months due to pain1. These numbers are a good gauge of the huge economic impact of chronic pain - both at personal and societal levels.

Although it is agreed that all pains must be treated effectively, there is still a marked reluctance in using the vast armamentarium of drugs available to ease pain. This is to show a blind eye to the enormous benefits of treating pain well. Some of the physical benefits of meticulous pain management include improved sleep, better appetite, early mobilisation, faster recovery after injury/surgery, and fewer associated complications such as myocardial ischemia, pneumonia and deep vein thrombosis. Good pain relief results in faster discharge from hospital and lesser readmission rates thereby positively impacting the cost of healthcare. Well treated pain, in addition, means lesser anxiety and depression; and optimal pain reduction not only helps the sufferer but also his/her family and society. A relatively pain free person functioning well as part of the family and also providing for it, in turn, contributes to the community.

CLASSIFICATION

Appropriate treatment of pain depends on our ability to identify the type of pain that afflicts the patient. Although there are numerous ways of classifying pain, a simple method would be: 1.

Based on the duration of pain

a.

Acute pain (pain of less than 3 months duration)

b.

Chronic pan (pain lasting for more than 3 months)

On occasions, a patient with chronic pain may develop an acute exacerbation where it might be viewed as acute on chronic pain eg: acute flare up in chronic pancreatitis and pathological fracture in bony metastasis.

2.

Based on etiology

a.

Cancer pain: pain in cancer is progressive more often than not, and is of chronic nature. Acute exacerbations are not uncommon.

b.

Non cancer pain: Surgery, headaches, osteoarthritis, labour pain, burns, nerve compression/neuropathy are a few causes of non cancer pain. It can be acute, chronic or acute on chronic.

3.

Based on neural mechanism

a.

Nociceptive pain - caused by stimulation of pain receptors in injured tissue.

b.

Neuropathic pain- caused by damage to or abnormal function of nervous system.

PATHOPHYSIOLOGY OF PAIN

Here, let us describe the major characteristics of and differences between nociceptive and neuropathic pain, and the peripheral and central mechanisms driving them.

Nociceptive pain : Pain is termed such when the clinical evaluation suggests that it is sustained primarily by the nociceptive system. It is proportionate to the degree of actual tissue damage i.e. a more severe injury results in pain that is perceived to be greater than that caused by a less severe injury. Such pain serves a protective function and influences behaviours that reduce injury and promote healing e.g., pulling the hand away from a hot object.

Other examples of nociceptive pain include acute burns, bone fracture, and other somatic and visceral pains.

Neuropathic pain : Unlike nociceptive pain, neuropathic pain occurs due to peripheral nervous system (PNS) changes, such as neuroma formation, ectopic discharge from the injured axons or the somata of the dorsal root ganglion (DRG) neurons, or through central nervous system (CNS) changes that can lead to enhanced excitability of central pain networks (termed central sensitization) in patients with a prolonged exposure to noxious stimuli or nerve injury. It is disproportionate to the degree of tissue damage and can persist in the absence of continued noxious stimulation (i.e., the pathophysiologic changes become independent of the inciting event). Neuropathic pain, therefore, serves no protective function and provides no benefit to the overall

MISCELLANEOUS

440

Differences between Nociceptive Pain & Neuropathic Pain Nociceptive Pain

Neuropathic Pain

• Warns of acute or potential tissue damage

• Pain caused by nerve injury

• Has protective functions

• Could be spontaneous or evoked

• Can be differentiated from touch

• Develops in days or months

• Transient

• Associated with inflammation & neuropathy

• Well localized

• Associated with peripheral and central sensitisation

• C and Aδ fiber mediated

• Pain outlasts duration of the stimulus

• Increased activity, Wide dynamic Range Neurons

• Pain sensed in non injured areas

• Opioid sensitive

• Elicited by Aβ as well as C and Aδ fibers • Opioid insensitive

health of the person. This table compares and contrasts the salient features of nociceptive and neuropathic pain.

A BRIEF NOTE ON THE NOCICEPTIVE PATHWAY

A knowledge of the pathways that mediate nociception under normal conditions would help us better understand the pathophysiology of abnormal or neuropathic pain. The first step in nociception is the transduction of the sensory stimulus into an electrical potential by first-order afferent neurons in the DRG located external to the spinal cord.

These neurons express specialized receptors at their distal ends that respond to specific types of sensory stimuli external (e.g. the skin) or internal (e.g. visceral organ like the liver) - by opening ion channels in their membrane.

The depolarization of the sensory neuron then triggers an action potential that propagates to the dorsal horn of the spinal cord. Noxious stimulation is transmitted via small-diameter DRG neurons that give rise to either thin myelinated Aδ fibers (which conduct impulses at 2-30 m/sec) or small unmyelinated C-fibers (with conduction velocities of < 2 m/sec). Large-diameter DRG neurons possess large myelinated axons with rapid conduction velocities in the Aβ range (>30 m/sec) and generally transmit information about innocuous mechanosensation (e.g. touch, vibration).

The signals carried by all three types of sensory afferents are integrated by the synaptic network within the spinal dorsal horn, which consists of both local circuit interneurons and second-order projection neurons that transmit impulses from the spinal cord to higher brain areas (including the thalamus) predominantly via the spinothalamic tract (STT). The output of these STT neurons depends on the net balance between inhibitory and facilitatory mechanisms within the dorsal horn.

The activation of third-order neurons in the thalamus

by STT inputs allows the transmission of the noxious information to the somatosensory cortex, where nociception occurs. Numerous supraspinal control areas— including the reticular formation, midbrain, thalamus, hypothalamus, the limbic system of the amygdala and the cingulate cortex, basal ganglia, and cerebral cortex— appear to modulate the sensation of pain. It is useful to observe here that pain is a personal experience influenced by multiple factors, whereas nociception is only its neural

correlate.

PERIPHERAL AND CENTRAL MECHANISMS OF NEUROPATHIC PAIN

The mechanisms underlying neuropathic pain involve both peripheral and central components. A combination of these mechanisms results in the phenomenology of pain that could be spontaneous or evoked. The later manifests as hyperalgesia (exagerated response to a painful stimuli) or allodynia (a non-noxious stimuli resulting in a painful response).

PERIPHERAL MECHANISMS

1.

Altered expression of ion channels in axotomised neurons: There is now compelling evidence that the expression of sodium channel subtypes (e.g., Nav1.3, Nav1.7, Nav1.8, and Nav1.9) are dramatically altered by nerve injury and may account for the increased excitability of neuropathic DRG neurons in models of chronic pain. Changes in the expression of potassium and voltage gated calcium channels have also been demonstrated in chronic pain models.

2.

Sympathetic excitation of injured sensory neurones: In certain pain conditions like post herpetic neuralgia and complex regional pain syndromes (CRPS) abnormal coupling between sympathetic and the sensitised nervous system maintain what is sometimes referred to as sympathetically mediated pain. It manifests clinically as oedema, sweating, and changes in skin colour and temperature.

3.

Inflammatory cytokines and chemokines: Proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1 and IL-6, and chemokines have profound effects on neuronal activity and pain sensitivity.

CENTRAL (SPINAL AND SUPRASPINAL) MECHANISMS

1.

Long term potentiation of nociceptive inputs in dorsal horn of spinal cord: Strong activation of nociceptive sensory afferents can lead to a greater synaptic drive onto spinal projection neurons and a subsequent facilitation of pain transmission from the spinal cord to the brain.

Loss of central inhibition: Reductions in the efficacy of GABAergic and glycinergic transmission allow for greater firing in the spinothalamic tract output cells.

6.

3.

Spinal glial activation: There is now significant evidence showing that glial activation in the spinal cord appears to be important for both the initiation and the maintenance of pathologic pain. Astrocytes and microglia are activated by neuronal signals including substance P, glutamate, and fractalkine

The past medical history could be important for several reasons. Serious comorbidities may complicate or even contraindicate some pain treatment options. Particular hazards of systemic drug treatments may be posed by seriously impaired liver or kidney function, and some invasive treatments carry greater risk in patients with an increased bleeding tendency, either from a hemorrhagic disorder (e.g. thrombocytopenia, hemophilia) or anticoagulant treatment. Treatment history including both pharmacological and non pharmacological treatment, especially medications tried, dosage, duration and the reason for their discontinuation are useful. And so are details of non pharmacological treatments like surgery, acupuncture, alternative medicines, exercise therapy and electrotherapy.

4. Supraspinal pain modulation: Descending connections between higher centres of the brain and the spinal cord can either amplify or inhibit the transmission of pain related signals. Mounting evidence suggests that these descending systems are involved in the maintenance of neuropathic pain.

Peripheral nerve injury results in the strengthening of the descending facilitatory pathways from the rostral ventral medulla, producing an enhanced excitability of the dorsal horn and a subsequent increase in the sensitivity to pain2.

EVALUATION OF A PATIENT WITH CHRONIC PAIN

As in any branch of medicine the physician-patient interview is the most important part of assessment. It is useful to ask the chronic pain patient, at some point, about their expectations with the consultation. Some expect a diagnosis (or a test that will lead to diagnosis) while others might want their pain to be relieved. Some have unrealistic expectations of what is achievable and we should be alert about it early on. It is a useful exercise to allow the patient to narrate his/her story in their own words rather than providing them with leading questions. This allows the patient to talk about problems which are most important to them and to feel “listened to”. When the patient has completed telling their story of the main complaint, we can then fill in the gaps in history and explore relevant symptoms in more detail by applying a more traditional ‘‘doctor-centered’’ interviewing technique.

The following aspects could be noted in the context of establishing a diagnosis 1.

Location: It may be helpful to ask the patient to indicate the site and extent of the pain on a body line-drawing. In some conditions, the diagnosis may be made with near certainty on the basis of this alone, for example meralgia paresthetica

2. Onset 3. Intensity 4.

5.

Temporal pattern : Pain that is unremitting is often neuropathic. In addition, if there is not much variation and it is rarely influenced by physical activities it may suggest a central origin Quality: Shooting, electrical, or burning sensations are characteristic of neuropathic pains, while nociceptive pains are more likely to be described as aching, dull, cramping, or throbbing.

Exacerbating/Alleviating factors: This refers to pain modifiers noticed by the patient. Exacerbation of back pain by spinal movement or loading is a typical example

An appropriate starting point for psychosocial history are the patient’s personal circumstances (who else are at home? are you working? what is your job?). It is useful to explore the effect of the pain on activity and behavior in domains such as occupational, domestic, social, recreational, and sexual. Also important is the history of its impact on emotions (anxiety, depression, anger, frustration). On many occasions, they might have already consulted a mental health professional.

The physical examination starts with observing for painrelated behaviours such as gait, use of secondary aids and facial expression. A vast majority of chronic pains have their origin in, or influence, the musculoskeletal and the nervous system.

Key features of musculoskeletal examination include: •

Stigmata of specific rheumatological disease, e.g.osteoarthritis

•

Abnormalities of posture/gait, and fixed deformity

•

General level of fitness

•

Scars of previous surgery

•

Abnormalities of skin and subcutaneous soft tissue

•

Range of movement of affected joint or spine.

•

Antalgic movements and distress behaviour

•

Local tenderness and myofascial tender points

•

Straight leg raise: Reduced straight leg raise is generally regarded as having high sensitivity for lumbar disk herniation but poor specificity

•

Sacroiliac joint (SIJ) stressing tests for buttock pain

Key features of examination in patients with neuropathic pain3: •

abnormalities of posture or gait

•

abnormal involuntary movement

441

CHAPTER 80

2.

MISCELLANEOUS

442

•

focal wasting

•

local changes of colour or swelling

•

locally altered temperature/sweating

•

tone, power, reflexes in the motor assessment

•

light touch – deficit/allodynia

•

warm/cool – deficit/allodynia

•

pinprick – deficit/hyperalgesia

• proprioception/vibration •

movement- or pressure-evoked sensation (if appropriate to presentation) – e.g. Tinel’s test (paresthesia in the hand/fingers provoked by percussion over the median nerve at the wrist in carpal tunnel syndrome).

A psychological evaluation would help •

to determine the degree of psychological adaptation to chronic pain which includes mood state, coping skills, effect on family, and especially level of physical functioning

•

to evaluate the patient’s premorbid psychological state and personality factors and its effect on onset and etiology of pain

•

to establish the role of psychological factors in the etiology, maintenance, and exacerbation of pain

•

to devise a treatment plan in conjunction with the patient and the rest of the multidisciplinary team

•

to predict outcome of invasive medical procedures

Various questionnaires (McGill Pain Questionnaire, Beck’s Depression Inventory, Minnesota Multiphasic Personality Inventory, Coping Strategies Questionnaire) are available to assess the psychology of patients with chronic pain4.

COMMON CHRONIC PAIN CONDITIONS AND MANAGEMENT

It is beyond the scope of this article to discuss in detail all chronic pain syndromes and their treatment options.

Only an overview is provided.

HEADACHE & FACIAL PAINS

Trigeminal Neuralgia: Carbamazepine, oxcarbamazepine, phenytoin, gabapentin, pregabalin and baclofen are the drugs commonly used for pain relief. Despite excellent short-term response to carbamazepine, longterm pain relief is often not maintained. Retrogasserian percutaneous radiofrequency thermocoagulation is a technique of controlled thermal ablation of nerve fibers in the trigeminal ganglion or nerve root that relieves pain5.

Cluster headache: Sumatriptan, zolmitriptan and 100% oxygen have been used as abortive therapies.

Verapamil, prednisolone, lithum, ergotamine, methysergide and indomethacin are useful as preventive medications. Sphenopalatine ganglion radiofrequency thermocoagulation and trigeminal ganglion thermocoagulation are percutaneous interventions

that are effective in relieving pain that is resistant to medications.

Occipital neuralgia: Occipital neuralgia causes pain in the distribution of the greater or lesser occipital nerves or of the third occipital nerve, sometimes accompanied by diminished sensation or dysesthesia in the affected area.

The pain is often deep or burning, with superimposed paroxysms of shooting pain. Anesthetic blockade of the nerve temporarily reduces or abolishes the pain. Longterm peripheral neurostimulation may be a safe and relatively effective method for the treatment of intractable occipital neuralgia.

NECK PAINS

The treatment of neck pain is as varied as its etiology, with a choice of pharmacological, physical, interventional injection, and surgical techniques. Soft tissue and cervical spine disease are the most common causes of neck pain. Soft tissue structures include fascia, ligaments, tendons, and muscles. Disorders of the synovial joints and intervertebral discs of the cervical spine may contribute to neck pain as well as refer pain into the posterior head, the shoulder, and distally into the arm. Pharmacotherapy includes NSAIDs, anticonvulsants (pregabalin, gabapentin), anti depressents (amitriptyline, duloxetine), opioids (tramadol, tapentadol, buprenorphine). Interventional techniques in vogue are trapezius, rhomboid and splenius myofascial trigger point injections. Epidural steroid injections for cervical radiculopathy provides satisfactory pain relief. Facetogenic pain is treated with radiofrequency denervation of the zygapophyseal joints6.

All these interventinal treatments are followed up with aggressive rehabilitation.

LOW BACK ACHE

A majority of back pains are myofascial in nature and resolve spontaneously. However there exists a significant population where low back ache and lower limb radicular pain becomes chronic. More than a dozen pain generators have been identified in the spine and surrounding musculature. Interspinous ligaments, paraspinal muscles, quadratus lumborum, intervertebral disc, facet joints and their coverings, sacroiliac joint, piriformis muscle, nerve roots, the vertebrae could all cause pain. Thorough clinical evaluation in conjunction with appropriate imaging is needed to diagnose the pain generator. While pharmacological management is similar to neck pain, myofascial trigger point injections, caudal epidural, interlaminar epidural, transforaminal epidural, lumbar facet denervation, SIJ denervation, piriformis myofascial injection, dorsal root ganglion pulsed radiofrequency ablation are some of the interventions offered for low backache. Advanced interventions include spinal cord stimulators for post laminectomy syndrome with leg pain.

As with neck pain, subsequent rehabilitation is important to achieve better outcomes.

SHOULDER PAIN

The shoulder joint could be a common cause for pain.

Adhesive capsulitis, osteoarthritis, supraspinatus

tendinitis, biceps tendinitis, and acromio-clavicular joint afflictions are the most common. When conservative measures, including medications, physiotherapy and exercises fail, ultrasound guided glenohumeral joint injection, biceps peritendon infiltration, subdeltoid bursa infiltration, suprascapular nerve blocks and pulsed radiofrequency ablation, and acromioclavicular joint injections are common procedures to achieve pain relief. Range of movement exercises and other specific exercises for the specific condition are necessary after the procedures.

Other miscellaneous musculoskeletal issues amenable to interventions include plantar fasiitis, tennis and golfers elbow, Dequervain tenosynovitis, carpal tunnel syndrome to name a few.

CANCER PAIN

The incidence of new cancer patients in India is around 10 lakh every year. One third of these patients have pain at diagnosis. This increases to two thirds of the patients having pain in the advanced stage. Amongst the patients having pain, one third have a single pain and two thirds have two or more pains. More than 75% of pains can be treated effectively using the WHO analgesic ladder.

In reality, due to patient related, physician related and healthcare system related barriers adequate pain relief is not extended to these patients. Pharmacotherapy of cancer pain involves stepwise use of NSAIDs, weak opioids and strong opioids like morphine and fentanyl - what is commonly referred to as WHO analgesic ladder. Other adjuvants like anti emetics, anti spasmodic, sedatives, antacids, antibiotics, anti depressants, anticonvulsants are necessary to achive optimal patient comfort. Celiac plexus neurolysis (for abdominal malignancies), superior hypogastric plexus neurolysis (for pelvic malignancies), ganglion impar neurolysis (for primal malignanacies), Intrathecal morphine therapy, intrathecal neurolysis using alcohol or phenol are some of the commonly used interventions to relieve cancer pain.

NEUROPATHIC PAIN

The etiology of neuropathic pain could be traumatic (spinal cord injury), metabolic (painful diabetic neuropathy), viral (postherpetic neuralgia), surgical (post-hernia repair pains) or drug-induced (chemotherapy-induced neuropathy). The diagnosis of neuropathic pain is made when: 1.

Pain distribution is neuroanatomically plausible

2.

History is suggestive of relevant lesion or disease

3.

Sensory signs : negative or positive signs within

4.

443

Diagnostic test confirms a lesion or disease

The first line drugs in the management of neuropathic pain are gabapentinoids (gabapentin and pregabalin), serotonin and noradrenaline reuptake inhibitors (duloxetine, venlafaxine) and tricyclic antidepressants (amitriptyline). The second-line drugs include tramadol and lidocaine patches. A combination of medications is normally required to achieve the desired benefit7.

MULTI DISCIPLINARY APPROACH TO PAIN MANAGEMENT

Patients with chronic pain (especially chronic non cancer pain) often require long term care with frequent reassessment and adjustment of therapy. The biopsychosocial model of chronic pain recognises the condition as a combination of physical dysfunction, beliefs and coping strategies, distress, illness behaviour and social interactions. The multitude of factors that contribute to chronic pain often means that the condition fails to respond well to a single treatment approach. In order to achieve better outcomes in terms of analgesia and quality of life, a range of specialist treatments administered by a multi disciplinary team and tailored to the individual patient’s needs are necessary. The core members of the team vary according to local factors but typically consist of primary care physician, pain physician, psychiatrists, psychologists, physiotherapists and nurses.

Numerous studies have shown a favourable outcome with multidisciplinary pain management programs in terms of both patient satisfaction and the economics of chronic pain8.

REFERENCES

1.

Dureja G. P., Jain P. N., Shetty N., et al. Prevalence of chronic pain, impact on daily life, and treatment practices in India. Pain Practice. 2014; 14:E51–E62. doi: 10.1111/ papr.12132.

2. Jun-Ming Zhang, Mark L.Baccei. Pathophysiology of pain. Howard Smith. Current therapy in pain. 1st Ed. Philadelphia: Saunders Elsevier; 2009.

3. Paul R Nandi, Toby Newton. History taking and examination of the patient with pain. Harald Breivik.

Clincal pain management practice and procedures. 2nd Ed. London: Hodder & Stoughton Limited; 2008.

4. Allen H Lebovits. The psychological assessment of patient with chronic pain. Peter R Wilson. Clinical Pain Management Chronic pain. 2nd Ed. London: Hodder & Stoughton Limited; 2008.

5. Andrew Linn, Zahid H Bajwa. Trigeminal Neuralgia.

Howard Smith. Current therapy in pain. 1st Ed. Philadelphia: Saunders Elsevier; 2009.

6.

Susan ElizabethOpper. Neck pains. Howard Smith. Current therapy in pain. 1st Ed. Philadelphia: Saunders Elsevier; 2009.

7. Nanna Finnerup et al. Pharmacotherapy of neuropathic pain in adults: a systematic review and meta-analysis.

Lancet Neurology 2015; 14:162-173.

8. http://www.pae-eu.eu/wp-content/uploads/2013/12/ Multidisciplinary-approach-in-chronic-pain-management. pdf.

CHAPTER 80

KNEE PAIN

Osteoarthritis knee is extremely common in middle and older aged people. Rehabilitation in consultation with physiotherapy is vital. Lifestyle modification also plays a vital role in alleviating pain. Early stages of osteoarthritis can be managed with genicular nerve radiofrequency ablations. This gives meaningful benefit and can help in postponing the need for surgery.

innervations territory of lesion are present

Prescribing Cascades in Elderly

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Shohael Mahmud Arafat, Tahsin Mahmood

INTRODUCTION

The words elderly and polypharmacy go quite abreast nowadays. When elderly patients come to us with a prescription list as long as one’s arm, we do have a typical frown in our face; but at many a time, owing to obligatory circumstances, nothing much can be done. However, concerns always remain, ranging from quality of life issues to adverse drug reactions, drug interactions and prescription cascades.

DEFINITION

Prescription cascade may be described as the process, whereby the drug related side effects are mistakenly attributed as symptoms of another disease, resulting in prescription of a new medicine. This may bring forth Drug A in elderly •e.g. Flupentixol

Adverse effect of Drug-A misinterprated as new problem

Drug-B initiated to treat adverse effect of drug A causing new adverse effects

•e.g. Parkinsonism in flupentixol

•e.g. Anti Parkinson Drugs causing orthostatic hypotension and delirium

Fig. 1: Prescribing cascade in elderly1

further side effects and unanticipated drug interactions leading to further misdiagnoses and further symptoms.1 Elderly people with chronic ailments, frailty and multiple drug therapies are particularly at risk for prescribing cascades.

DISCUSSION

Over the recent years there has been a substantial rise in the incidence of chronic conditions including diabetes and hypertension; and hence the increase in use of numerous medications by the older population. As a result, correlating side-effect of each drug comes into play. If a physician ignores the detailed drug history of all the drugs that a patient is taking, there is every possibility that an adverse drug reaction (ADR) may be viewed as a new medical entity. Consequently, another drug would be prescribed to treat the new condition, which might exhibit further new side effects that could be again mistakenly diagnosed as another new medical condition. Thus the patient is put to an unnecessary risk of a bunch of unpropitious health effects.2 An example of this pharmacological feedback loop has been shown in Fig 1. Elderly people are at higher risk of prescribing cascades than young because the usual adverse drug reaction is more likely to be misinterpreted as the onset of a new

Table 1: Some common examples of prescription cascades4 Drug A

Adverse Drug Reaction caused by initially prescribed drug

Second drug to treat side effects of initial drug assuming a new symptom related or unrelated

Adverse Drug Reaction secondary to second drug added to combat the new symptoms

ACE inhibtors

Dry cough

Anti histamines

Sedation Increase fall

Anti-Cholinesterase

Urinary Incontinence

Oxybutynin

Urinary retention, constipation

NSAIDs

Raised blood pressure

Anti hypertensive

Dizziness

Thiazide

Hyperuricaemia

Xanthine oxidase inhibitor (e.g. febuxostat)

GI upset Acute kidney injury

Anti hypertensives

Dizziness

Prochlorperazine

Parkinsonism

Statin

Muscle pain

Baclofen

Sedation

Haloperidol

Parkinsonism

Procyclidine

Dry mouth, Glucoma Retention of urine

Amitryptiline

Prolonged QT

Antiarrhythmics

Further arrhythmia

Tamsulosin

Postural dizziness

Vestibular sedatives

Sedation Increased frequency of falls

NSAIDs: Non-steroidal anti-inflammatory drugs

445

Pinpoint & prioritize the drugs to be discontinued specially which are of high risk in the elderly and with ambiguous indication

Determine beneficence of the drug from retrospective history

Patient better or same

Patient worse

Continue with drug disconitnued

Consider alternative with lesses side effects

Restart discontinued drug at lowest possible dose if no alternative or patient is still worse on the alternative drug

Fig. 2: Algorithm for a trial of discontinuation5 medical condition for the old.1 For example, a movement disorder induced by flupentixol may mimic Parkinsonâ&#x20AC;&#x2122;s disease, but this misinterpretation would be unlikely in a young person as this disease is uncommon in young.

EXAMPLES OF PRESCRIBING CASCADES

Among elderly people, common drug classes like anticholinergics (oxybutynin for overactive bladder in benign prostate enlargement), psychoactives (flupentixolmelitracen combinations for post menopausal symptoms), benzodiazepines as anxiolytic or sedative â&#x20AC;&#x201C; increase the risk of ADRs. In a case control study of 3512 patients (age 65 to 99 years), patients who had received an antipsychotic medication in the preceding 90 days were 5.4 times more likely to be prescribed anti Parkinson therapy than patients who had not received an antipsychotic (95% CI 4.8-6.1).3 Drugs like cholinesterase inhibitors (e.g., donepezil, rivastigmine, and galantamine), used for the management of dementia in older adults may cause diarrhoea and urinary incontinence. A prescribing cascade may occur when these symptoms are followed by a prescription of an anticholinergic (e.g. oxybutynin) to treat incontinence.

Table 1 shows some common examples of prescription cascades.4

CONSEQUENCE

There are several implications of prescribing cascades in practice. The ADRs associated with this phenomenon might create a significant negative health outcome.

Addition of a new drug always adds to the financial burden for the old age. In the subcontinent, the communication between a physician and a patient is not always an ideal one due to various practical reasons. As a result patient may not tell their physician when they experience seemingly trivial ADRs which may lead to poor quality of life. Moreover, patients may stop a medication by guessing on their own without consulting their physician ignorant of what impact it might create on their disease course or management.4

PREVENTION

The main precipitating factor for prescribing cascades is ADRs. So avoidance and/or early detection are essential to prevent this. In the elderly, drugs should be initiated at low doses with gradual titration towards desired effect.

Physicians should enquire thoroughly about the drug history and particularly search for a temporal relationship between a newly occurring symptom and a recently prescribed drug. Patients should be empowered with

CHAPTER 81

Discontinue or taper towards discontinution with adequate counselling, follow-up & monitoring for response

446

appropriate knowledge and skill regarding the ADRs of a prescribed drug and to identify them when occurring.

MISCELLANEOUS

The following strategies may be used once the new symptoms can be attributed as ADRs:

CONCLUSION

Prescribing cascades bear the potential to cause serious malfeasance to patients. Prescriber discretion, particularly in the elderly, is essential in this regard.

REFERENCES

1.

Dose reduction of the likely drug if the reaction is dose related

1.

2.

Choosing an alternative drug with a similar effect but with a reduced risk of ADR

Rochon PA, Gurwitz JH. Optimising drug treatment for elderly people: the prescribing cascade. BMJ 1997; 315:10969.

3.

De-prescribing: reassessment for the absolute necessity for the medicine causing the ADR and discontinuation if possible (Figure 2)

2.

Hunt LM, Kreiner M, Brody H. The changing face of chronic illness management in primary care: a qualitative study of underlying influences and unintended outcomes. Annals of Family Medicine 2012; 10:1–4.

4.

Application of safer prescribing strategies like FORTA (Fit fOR The Aged)6: FORTA is an evidence based age appropriate drug listing approach introduced by Wehling (2009) that label drugs both positively or negatively by categorizing them into 04 groups, ranging from category A (indispensable), B (beneficial), C (questionable) to D (avoid), on the basis of identifying overtreatment, undertreatment or mistreatment of a disease. Initial studies have showed significant improvement of over and under treatment by applying it.6 However, this promising utility is complex and yet to be proven in practice and hence require clinical validation.

3. Avorn J, Bohn RL, Mogun H, et al. Neuroleptic drug exposure and treatment of parkinsonism in the elderly: a case control study. Am J Med 1995; 99:48.

4.

Kalisch LM, Caughey GE, Roughead EE, Gilbert AL. The prescribing cascade. Aust Prescr 2011; 34:162-6.

5.

Lemay G, Dalziel B. Better prescribing in the elderly. CGS Journal of CME [Internet]. 2012; 2(3): 20-26. Available from: http://www.canadiangeriatrics.ca/default/index.cfm/ journals/canadian-geriatrics-society-journal-of-cme/cmejournal-vol-2-issue-3-2012/cme-journal-vol-2-issue-3-2012complete/

6. Wehling M. How to Use the FORTA (“Fit fOR The Aged”) List to Improve Pharmacotherapy in the Elderly. Drug Res (Stuttg) 2016; 66:57-62.

DOI: 10.1055/s-0035-1549935.

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From Guidelines to Rational Care A Perspective

Landmark trials testify to the benefits of early aggressive intervention of T2DM (or at least the lack of benefit of later intervention)1,2,3 There is evidence to suggest that there may be harm with aggressive intervention to reduce diabetes after an initial therapeutic window. There is also pathophysiologic evidence to support that there is a point of no return of the insult of hyperglycaemia beyond which there is continued progression of damage4.

Conversely through the legacy effect / metabolic memory phenomenon its is plausible that gains obtained from early aggressive care may accrue over time even if there is a modest relaxation of therapeutic targets or intensity at a later time.

Targets in T2DM in patients are an HbA1C generally < 7.0 with more intensive targets for patients with few comorbidities and longer life expectancy5. It must be remembered that the relationship between A1C and microvascular complications is curvilinear. While at a population level the greatest number of complications will be reduced by moving patients from poor to fair or good control, additional benefit is apparent with reductions from 7 -6%. It must be remembered that the population normal is around 5.5% for Indians6. It must also be noted that the while the average western patient is their sixth decade at the time of diagnosis of T2DM, the average Indian patient is his or her fourth or fifth decade. Thus the average Indian patient will theoretically live longer with diabetes and therefore will benefit from early aggressive control. Given the benefit of early intervention and the apparent lack of it later, it is apparent that achieving A1Cs as near normal as possible in the first few years of care is desirable. With modern medications that work without significant hypoglycemia, â&#x20AC;&#x153;near euglycemiaâ&#x20AC;? may be achievable especially when mulitple drugs are used together.

As we continue to unravel the pathophysiology of diabetes and newer targets for therapy have emerged (the so called egregious eleven7). A mass of opinion has emerged with early evidence that targeting multiple pathophysiologic targets early in T2DM may be beneficial although long term studies are awaited. Such approaches may lead to meaningful remissions early in diabetes.

Other approaches including early use of insulin have been demonstrated to provide remissions.

Clinical practice recommendations (CPR) by various societies are at variance with this evolving knowledge.

It is prudent to demand evidence of benefit of early aggressive multi-pronged care; however it must be

Krishna G Seshadri

remembered that many guidances have a strong slant towards cost-effectiveness in a health care system with finite and rationed national resources for health care.

These do not allow for systems in which patients pay out of pocket and may want a choice that will allow them into a more aggressive treatment care pathway in the early years even if it may be expensive. It is also important to start creating models of cost benefit in systems such as India where duration of diabetes is longer in a lifetime is longer, patients are at their most productive time of their lives and cost paradigms are different.

Until recently, most major CPRs would recommend a period of lifestyle changes prior to starting pharmacotherapy. This stance has been reluctantly given up of late by some but not all societies. Except one none the societies recommend initial combinations. The ADA recommends initial combination with A1C > 9. Obviously there is a disconnect here between the targets and the ability of this graded tortoise paced intervention.

Let us assume that a 40 year old woman has presented to you with new onset T2DM and an initial A1C of 7.5.

She has no comorbidities. Given Indiaâ&#x20AC;&#x2122;s health trajectory she has around 35 or more years of life and diabetes. Her target A1C should be less than 6.5 and atleast an attempt should be made to achieve and maintain an A1C of 6.0 or less. Lifestyle changes with help and other bells and whistle added achieves a modest A1C benefit of 0.22.

In the Look Ahead trial there was an initial drop of 0.6 but this could not be sustained. Clearly medications are required.

In this situation most guideline would recommend metformin (MF) - let us say the wait to MF is around 3 months. MF would bring the A1C from 7.5 to 6.8 in most instances - may be 6.5 but not 6.0. (remember the influence of initial A1C on the potency of any OHA). It two drugs were to be started - for e.g. a DPPIV + MF in this situation the expected A1C lowering would be around 1.2, which you may decipher would lead us to an A1C o < 6.5 but not < 6.0 which would be desirable. When drugs are combined, the A1C reduction is seldom additive (in a predictable fashion) even if they are mechanistically synergistic8. It is thus obvious that in a patient with an A1C of 7.5 to reach an A1C of 6.0 we would need not two but three drugs.

One might argue that guidelines provide for sequential increase in drugs after three months. The counter to this is that guideline are blind to our track record of

MISCELLANEOUS

448

intensification. It has been demonstrated the median time to intensification in most practices is 2-3 years. By the time additional drugs are contemplated the patient has already lost a couple of years in the path of no return. It must be also remembered that guideline based practice also does not allow for patients who reach A1C goals to remain in it. The average time a patient remained above goal after achieving it was more than 50% of the follow up time9.

Clearly the time to act is the first visit and the number of drugs that must be used is more than one or two to reach the goal and stay there. As evidence evolves it may be worthwhile considering agents that work at different therapeutic targets.

In conclusion - current guideline driven care has done very little to provide aggressive optimal care for new and young diabetic despite evidence to show that this is the patient that will benefit with the book thrown at him or her. Our young population with a potential for long years with diabetes cannot afford the leisurely inertia ridden pace of the guideline based practice.

REFERENCES

1. The Action to Control Cardiovascular Risk in Diabetes Study Group* Effects of Intensive Glucose Lowering in Type 2 Diabetes. N Engl J Med 2008; 358:2545-2559.

2. Ray KK1, Seshasai SR, Wijesuriya S, Sivakumaran R, Nethercott S, Preiss D, Erqou S, Sattar N. Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials. Lancet 2009; 373:1765-72.

3.

UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sul- phonylureas or insulin compared with conven- tional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).

Lancet 1998; 352: 837–853.

4. Manigrasso MB, Juranek J, Ramasamy R, Schmidt AM. Unlocking the Biology of RAGE in Diabetic Microvascular Complications. Trends in endocrinology and metabolism: TEM 2014; 25:10.1016/j.tem.2013.08.002. doi:10.1016/j. tem.2013.08.002.

5.

Diabetes Care Volume 38, Supplement 1, January 2015

6.

Mohan V, Vijayachandrika V, Gokulakrishnan K, et al. A1C Cut Points to Define Various Glucose Intolerance Groups in Asian Indians. Diabetes Care 2010; 33:515-519. doi:10.2337/ dc09-1694.

7.

Schwartz SS, Epstein S, Corkey BE, Grant SFA, Gavin JR, Aguilar RB The Time Is Right for a New Classification System for Diabetes: Rationale and Implications of the β-Cell–Centric Classification Schema Diabetes Care 2016; 39:179-186.

8. Polidori D, Capuano G, Qiu R. Apparent subadditivity of the efficacy of initial combination treatments for type 2 diabetes is largely explained by the impact of baseline HbA1c on efficacy. Diabetes, Obesity & Metabolism. 2016; 18:348-354. doi:10.1111/dom.12615.

9. Khunti, K, Wolden, Thorsted BL, Andersen M, Davies MClinical Inertia in People With Type 2 Diabetes. Diabetes Care 2013; 36:3411-3417. http://dx.doi.org/10.2337/dc130331.

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INTRODUCTION

Publishing scientific papers are essential to disseminate research findings. They are also a measure of academic productivity and often assessed for promotion and grant application. However, there are more important reasons to publish. In the words of M. J. Mahoney, “I would urge you to write not because it is a good thing, not because it is nice to see your name in print, but rather because you will really get to know a field only if you contribute to it.1 For most people, writing does not come naturally and one needs to be aware of some basic rules in addition to continuous practice. Needless to say, publishing in a good scientific journal requires robust science and an efficient strategy that encompasses generation of ideas to submission of manuscript.2 In this article, I shall be covering on some generic aspects of medical writing before identifying the specific challenges facing the Indian medical writer.

SOME TECHNICAL ASPECTS OF WRITING A MANUSCRIPT

It is not necessarily the best thing to write in the conventional format of Introduction, methods, results and discussion. One effective and nonlinear way is to assemble all vital study materials, including protocols, final analyses, and references. The following reverse technique might actually be helpful (Table 1).

Table 1: Suggested steps to writing a manuscript Write Methodology section first (Easiest part, standardized, highest satisfaction for effort) Write the results section next Construct tables and figures based on the final analyses Develop an outline with major and minor points in each section Introduction and discussion next Abstract should be attempted after article is complete Title is reserved for the very end and should be catchy and informative

The Science and Art of Medical Writing Shankar Subramanian

SECTIONS OF THE PAPER

Most readers will just read the title and skip ahead. If the title appears interesting, some would read the abstract.

If a reader cannot extract the significance of an article from its title, they are unlikely to read further. The title should be specific to the study and should inform about the paper’s contents or main findings. Declarative titles are preferred over non specific ones like “A Study of . . . ” As mentioned in Table 1 above, the Abstract section is ideally written towards the end when it is easiest to summarize all aspects of the study. After the title, the abstract is often the only part of the manuscript read by most readers.

Only if the abstract incites curiosity in the reader will they venture to read the full article. Even here, most start with conclusions, then discussion, then results and lastly the most discerning ones will scrutinize the methods section.

It is therefore imperative that a lot of effort is devoted to a good title and a concise abstract.

The backgrounds aims to answer the question: Why was this study done? The research funnel in Figure 1 shows the three broad parts of the background. The initial part covers the magnitude and importance of the problem. The next part identifies the gap highlighting the novelty. The third part leads to the research question that the study attempts to answer and leads naturally to the methods section. The background should be brief and not read like an extensive review of literature.

The Methods section is the most important part from the viewpoint of the reviewer and the editor. This part contains details of the study design, study population, data collection, laboratory methods, and statistical analysis. In some ways, this is the easiest part to write as guidelines exist for each type of study (Table 2) that describe in detail about how to write this section.

The Results section is probably the most important part Broad concepts (defining research territory)

First draft Share it with the main co-authors Revise, read again; first for content, then for fluency, clarity, accuracy Authorship should be clearly stated in first draft (number and order of authors)3

Identify a Gap State the specific research in this gap

Fig. 1: The Research funnel

MISCELLANEOUS

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Table 2: Guidelines on Writing Specific Types of Studies

Table 3: Challenges facing the Indian Physician

Initiative

Source

External challenges

CONSORT Randomized, controlled trials

Type of study

http://www. consort-statement. org

1. Clinical work: heavy OPD load with no time in hands for anything else

STARD

Studies of diagnostic accuracy

http://www. consort-statement. org/stardstatement. htm

3. Administrative work: committee assignments

QUOROM

Systematic reviews and meta-analyses

http://www. consort-statement. org/Initiatives/ MOOSE/moose.pdf

STROBE

Observational studies in epidemiology

http://www.strobestatement.org

MOOSE

Meta-analyses of observational studies in epidemiology

http://www. consort-statement. org/Initiatives/ MOOSE/moose.pdf

of the paper. It usually has two parts. The first part is descriptive of the study populations involved while the second part deals with analysis and statistics. The analysis should be in congruence with the primary study question.

Each table or figure should be referred to in sequence and indicate the key findings. Data in tables and figures should not be replicated in text.

The Discussion section should cover a bit of background (why was the study done?), methods (what was done and how?) and results( what did you find). One starts with the key findings of the study. One should be careful not to replicate the results here but rater to interpret the same.

This is the place the results in context of other similar studies. If similar results exist the same can be displayed in a tabular form while if significantly different results have been found, one tries to explain the reason for the same. The findings are then extrapolated towards greater body of literature and the braoder implications and generalizability of the findings. One must highlight the strengths and limitations of the study. Finally one brings it all together succinctly to state how this study has added to medical literature and what more needs to be done.

The Reference list should be uptodate and relevant. One must read carefully the instructions to authors about references and should try to use specialized reference software, such as Zotero and Mendeley (both are available for free) or End Note (paid) to avoid making mistakes.

WHICH JOURNAL TO SEND THE ARTICLE?

The choice of the journal is decided by knowing the paper’s focus and strengths, correctly defining the target audience (general, specialist audience or highly targeted sub specialty audience) and knowing the journal’s impact factor and readership. With thousands of journals to choose from, the decision is best taken jointly between the authors as one must also keep in mind the time wasted

2. Teaching responsibilities 4. Personal time: Need to balance time between work and home Intrinsic challenges 1. Inability to begin, sustain and complete a manuscript: a. Only 15-20% abstracts become full texts b. Having multiple revisions, repeated analyses, and changes in the focus c. Procrastination 2. Not having basic knowledge about a. How to choose a topic and identify study question b. Poor access to specialists to design correct study c. Poor access to research methodology and Biostatistics 3. Barriers to medical writing skills a. English language and grammar b. Poor knowledge on literature search c. Journal access limited in resubmission if one submits the article to a very high impact factor journal, overestimating the value of one’s work. Once a journal is selected, follow the requirements for submission meticulously and proceed with electronic submission.

SUBMISSION AND REVIEW

The reviewers form the backbone of any jpournal and are suually expersts in the field in which your article in written. Some journals ask for reviewer suggestion from authors. It is a good idea to suggest reviwers who are likely to be fair and likely to give a favourable review. Do not choose reviewers from your known circle including family or institution. Handling reveiwer comments is as much science as it is art. One must make it a point to answer every query point wise. Be polite throughout. If you disagree with reviwer; ask if the change asked for affects the science in any way. If it does not, then accept and incorporate the change. If you tend to disagree with a reviwer on a point, politely point out your contrarian view with evidence and logic. Rejections are so common that authors need to get accustomed to them. remember, with each passing rejection, your manuscript becomes richer with corrections and almost always it will get accepted in the end.

CHALLENGES TO MEDICAL WRITING

In the typical academic setting, the challenges facing the Indian Physician are manifold (Table 3).

Table 4: Strategies to overcome barriers 1. Consistently devote 1 hour daily to write (without feeling ready or fully in control or awaiting inspiration) 2. Set target dates and complete parts of manuscripts 3. Ping pong ball approach: always write manuscript with a co-author. The manuscript should move frequently between both of you with every movement improving upon the previous.

STRATEGIES TO OVERCOME CHALLENGES

451

REFERENCES

1.

Mahoney MJ. Psychology of the Scientist. An evaluative review. Social Studies of Science 1979; 9:349-375

2. El Serag HB. Writing and Publishing medical papers.

Gastroenterology 2012; 142(2):197-200 3.

Lok AS. Authorship: who should be included and how should it be determined. Gastroenterology 2011;141:786â&#x20AC;&#x201C; 788.

CHAPTER 83

Many strategies have been proposed for overcoming barriers to writing (Table 4). One should not focus too much on structure, grammar, and spelling. Get the content on paper. Rest can follow. Table 1 suggests a non linear way that can be very helpful.

To conclude, writing and getting published can be an interesting and fulfilling process of continuing learning and improvement. Both the process and products of writing tend to correlate with the amount of effort invested.

Hiccups

C H A P T E R

84

S Avudaiappan

Blocks dopaminergic neurotransmission.

Recommended dose; 25-50 mg PO/IM q6-8 hours

INTRODUCTION

The term “hiccup” derives from the sound of the event “Hiccough” erroneously implies an association with respiratory reflexes. Also called “synchronous diaphragmatic flutter”. An involuntary, intermittent,spasmodic contraction of the diaphragm and intercostal muscles accompanied by sudden inspiration that ends with abrupt closure of the glottis, making the classic hiccup sound. Considered pathologic because serves no useful function. Normally brainstem action that closes the glottis never activated when brainstem stops respirations (one inhibited/one activated). Abnormal when both activated. Medulla controls both actions; damage to medulla can cause intractable hiccups. May involve dopamine, serotonin, opioid, calcium channel, GABA pathways. The causes and aetiology of hiccups are given in Table 1.

•

Calcium channel blockers -anti- spasmotic effect on smooth muscle

•

Nifedipine (Adalat)

•

Nimodipine (Nimotop)

•

Carvedilol –non –cardio selective beta blocker, Ca channel blocker and antioxidant

•

Amantadine -weak antagonist of NMDA receptor

•

MECHANISM OF HICCUPS

Zyprexa, serotonergic antagonist useful in brain injury

•

Metoclopramide, antiemetic with central antidopaminergic effect like, Recommended; 5-10 mg PO/IV q8 hours

•

Baclofen, which is a GABA(B) receptor agonist.

Acts primarily at the spinal cord level by inhibiting spinal afferent pathways.

•

Other useful drugs include-ketamine,valproic acid, lidocaine, benzodiazepines.

•

Combo – therapy ie COB (cisapride, omeprazole, baclofen) and COBG (add gabapentin)

The reflex arc for hiccups include the afferent pathway (periphery to central)-vagus, phrenic or thoracic sympathetic fibers; the central connection, phrenic nerve nuclei, inspiratory and glottis control centers in posterior lower medulla, reticular part of brainstem and hypothalamus. Efferent pathway is phrenic nerve to diaphragm. Involves the accessory respiratory muscles as well.

TREATMENT

Understanding the cause of hiccup is important in treatment aspect. For example hiccups due to cerebral ischemia or injury may improve with anti-coagulants, whereas due to meningitis may improve with antibiotics.

•

Haloperidol –Recommended; 1-4 mg PO/SL q8 hour.

• Droperidol.

REFERENCES

1.

Harrison’s principle and practices of internal medicine 19th edition.

•

NON-PHARMACOLOGIAL Hold breath

2. Davidson’s principles and practices of medicine 22nd edition.

•

Hyperventilate (re – breath into paper bag)

3.

CMDT 16.

4.

Ganong’s review of medical physiology 25th edition.

5.

Goodman & Gilman’s pharmacological basis of therepeutics 12th edition.

6.

Hiccups – etilogy and treatment. Drugdex® Consults.

Micromedex 2.0.Available from http://hslibrary.ucdenver. edu/.Accessed September 2011.

7.

Smith HS, Busracamwongs A. Management of hiccups in the palliative care population. Am J HospPalliat Care 2003; 20:149-54.

8.

Marinella M. Diagnosis and management of hiccups in the patient with advanced cancer. J Support Oncol 2009; 7:122127,130.

• Sneeze • Gargle •

Pressure on eyeballs or carotid sinus

•

Chest compression by pulling knees to chest or leaning forward

•

Rubbing 5 cervical vertebrae th

PHARMACOLOGICAL

•

Dopamine antagonists.

•

Chlorpromazine is approved for treating hiccups.

Table 1: Causes of Aetiology of Hiccups Etiology

10. Twycross R, Wilcock A. Symptom Management in Advanced Cancer. 3rd Edt. Radcliffe Medical Press. 2008.

Stroke, Infarct, SLE, Vascular disorder, Aneurysm, Basllar artery insufficiency

11. Antacid preparations containing simeticone.

National Formulary 62.bnf.org. September 2011.

Astrocytoma, Carvenoma, Brainstem tumors, Glloblastomas, Metastasis

Inflammation

Neuromyelltis, Multiple sclerosis, Pneumonia, Encephallitis, Meningitis

Trauma

Brain injury

Miscellaneous

Seizure, cranial herpes infection, hydrocephalus, parkinsons, tobacco use, multiple sclerosis

Peripheral Pathway Chest cavity

Mediastinal diseases, lymphadenopathy/diaphragmatic tumors, Mediastinal tumor, pleurisy, pulmonary edema

Heart

Myocardial ischemia

GIT

Esophageal tumors, GERD & gastritis, stomach volvulus, H-pylori, hepatomegaly, pancreatitis, gastric distention

Lower Abdomen

Gynecologic tumors, prostate cancer, intra-abdominal tumors, bowel obstruction

Miscellaneous

Cancers, nephrosis, UTI, psychological

Extrinsic Causes Surgery

Anesthetic agents, post-op disturbances

Chemotherapy Chemotheraputics,steroids Drugs

Anti-parkinson treatment,psychiatric meds, azithromycin, bisphosphonates (hypocalcemia), morphine (hypocapnea) sulfonamides, steroids, methydopa, diazapam, barbiturates, librium

Instrumental

Atrial pacing, catheter ablation, central venous cath, esophageal stent, bronchoscopy, tracheostomy, shaving beards

Miscellaneous

Electrolyte imbalance, ethanol users, TB, chronic renal failure, stress, anorexia

453

British

12. Summary of Product Characteristics RennieDeflatine Chewable Tablets. Accessed on the 28/09/2011.

13. Summary of Product Characteristics Chlorpromazine Elixir BP 25mg/5ml Oral Solution. Accessed on the 28/09/2011.

Last updated September 2010.

14. Summary of Product Characteristics Lioresal tablets 10mg (Baclofen). Accessed on the 28/09/2011.

15. Maréchal R, Berghmans T, Sculier P. Successful treatment of intractable hiccup with methylphenidate in a lung cancer patient. Support Care Cancer. 2003 Feb;11(2):126-8. Epub 2002 Dec 7.

16. Stueber D, Swartz CM. Carvedilol suppresses intractable hiccups. J Am Board Fam Med 2006; 19:418-21.

17. Porzio G, Aielli F, Verna L, Aloisi P, Galletti B, Ficorella C. Gabapentin in the treatment of hiccups in patients with advanced cancer: a 5-year experience. Clin Neuropharmacol 2010; 33:179-80.

18. Alderfer BS. et al. Treatment of intractable hiccups with olanzapine following recent severe traumatic brain injury.

J Neuropsychiatry Clin Neurosci 2006; 18:4, 551-552.

19. Petroianu G, Hein G, Petroianu A, Bergler W, Rüfer R. Idiopathic chronic hiccup: combination therapy with cisapride, omeprazole, and baclofen. Clin Ther 1997; 19:1031-8.

20. Petroianu G, Hein G, Stegmeier-Petroianu A, Bergler W, Rüfer R. Gabapentin “add-on therapy” for idiopathic chronic hiccup (ICH). J Clin Gastroenterol 2000; 30:321-4.

CHAPTER 84

Tumor

Causes

Watson M, Lucas C, Hoy A, Back I, Armstrong P. Hiccups Palliative Adults Network Guidelines. 3rd Edt 2011. Pg 99.

Examples

CNS Vascular

9.

C H A P T E R

85

Gynecological Malignancies: Prevalence, Early Diagnosis and Preventive Strategies from a Physician’s Perspective Jayanta Chatterjee

ABSTRACT

By 2025, 19.3 million new cancer cases are expected to be diagnosed each year. Gynaecological cancers include cancers of the female reproductive tract, namely of the cervix, ovary, fallopian tube, uterus, vulva and the vagina.

Among gynaecological cancers, cervical cancer is the most common cancer in women, accounting for 4% of all cancers diagnosed in 2012. A sub-set of genes, called oncogenes and tumor suppressor genes promote the growth of cancer. Mutation in these genes can be acquired (e.g., through smoking, aging, environmental influences) or inherited. Almost all cervical cancers and some cancers of the vagina and vulva are caused by a virus known as Human Papilloma virus (HPV).

Ovarian cancer is considered to be the most fatal of all gynaecological malignancies in the developed world.1 One of the paramount reasons for increased fatality from this disease is due to its late presentation.

The increasing incidence of obesity in the developed and developing world has significant implications for health.

The direct relationship between obesity and gynaecological cancers is well established. There appears to be a linear increase in endometrial cancer risk with increasing body mass index (BMI).2 Vulval cancer, although relatively uncommon, is one of the most psychologically disabling genital tract cancers.

Table 1: The efficiency of a screening test Screening result

True disease classification of apparently well population Diseased persons

Persons without disease

Positive

With disease and Without disease with positive test and with (true positive) positive test (false positive)

Negative

With disease and with negative test (false negative)

Without disease and with negative test (true negative)

Total

Total unknown cases of disease

Total persons without disease

Sensitivity = diseased persons with positive test / All persons in population with disease; Specificity = non-diseased persons with negative test / All persons in population with disease

There are many factors that cause gynecological cancers.

Screening and awareness of early signs and symptoms can result in the early detection of these cancers when treatment is more likely to be successful and a complete cure is a possibility. Diet, exercise and lifestyle choices play a significant role in the prevention of cancer. Additionally, knowledge of family history can increase the chance of prevention or early diagnosis by determining if someone may have a gene which makes them susceptible to cancer.

The United States Commission on Chronic Illness (CCI) conference on preventive aspects of chronic disease, held in 1951, defined screening as “the presumptive identification of un-recognized disease or defect by application of tests, examination, or other procedures which can be applied rapidly. Screening tests sort our apparently well persons who probably have a disease from those who probably do not. A screening test is not intended to be diagnostic.

Persons with positive or suspicious findings must be referred to their physicians for diagnosis and necessary treatment.” (Commission on Chronic Illness 1957) In a screening test there is no specific exposure or indication to suggest that the individual has any disease.

For example, routine testing of prostate specific antigen (PSA) in the male population.

Screening can be of different types such as mass screening where there is no selection of the screening population, or selective screening or multi-phased screening.3 Prior to developing a screening test, it is important to understand when we can screen a disease. The disease in question should be an important health problem. It may sometimes be difficult to define what an “important” health problem is. There should be an accepted and effective treatment available, if people with the disease are identified through screening. The disease should have a recognizable latent or early prodromal phase. There should be adequate facilities for diagnosis and treatment.

Screening should lead to prevention of disease progression following early detection and treatment and this should play a major impact on morbidity and mortality from the disease. There should be an accurate screening test with high sensitivity and specificity with an agreement of what is considered to be a positively screened case (Table 1).

Worldwide, cervical cancer remains the fourth most common malignancy in women accounting for 7% of all cancer related deaths in women.

455

Fig. 1: Normal Smear Over three-quarters of all new cases of cervical cancer are diagnosed between the ages of 25 and 64 years. It is the most common cancer in women below the age of 35 years.

The age specific incidence rates show two peaks, the first in women aged 30-34 and the second in women aged above 55 years. The primary recognised cause of cancer of cervix is human papillomavirus infection (HPV).

HPV 16 and 18 are considered to be high risk (HR) for developing cervical cancer.4,5 It is considered preventable as it has a recognizable precancerous condition and an accepted treatment modality for this precancerous stage.

Therefore, the principles of screening can be applied to this condition (NCIN, 2008).

The World Health Organization (WHO) International Association for Research on Cancer (IARC) identifies 13 types of HPV strains as oncogenic. These high risk types of HPV are: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68, have been shown to directly cause cervical cancer.

Adenocarcinomas are more commonly associated with HPV types 18 and 45 principally rather than type 16, which is the commonest HPV type for SCC (squamous cell carcinoma) of the cervix with lymphovascular space invasion (LVSI).5 In United Kingdom, the NHS Cervical Screening Program (NHSCSP) is widely recognized to be one of the most successful cancer prevention programs in the world.

Following the implementation in 1988 of a comprehensive, quality-assured, cytology-based program, there has been a progressive decline in the incidence of, and mortality from, cervical cancer. Since its introduction, the number of cervical cancer cases has decreased by 7% year on year. The program aims to reduce the number of women who develop invasive cervical cancer (incidence) and the number of women who die from it (mortality). It does this by regularly screening all women at risk so that conditions which might otherwise develop into invasive cancer can be identified and treated earlier (Figure 1). Thus the incidence of cervical cancer has dramatically decreased over the years in the screened population.6

CLINICAL TIP: SYMPTOMS OF CERVICAL CANCER

Though cervical cancer may be asymptomatic and a

dyskaryotic smear (Figure 2) may be the first abnormal finding, the commonest symptoms are listed below: •

Inter-menstrual bleeding

•

Post coital bleeding

•

Postmenopausal bleeding

•

Unpleasant Vaginal discharge

• Dyspareunia •

Rarely haematuria or backache (advanced disease)

CLINICAL TIP: URGENT REFERRAL

•

Referrals for colposcopy from primary care for women with high index of suspicion for malignancy on screening should be made via the two-week rule (TWR) to the gynaecological oncology team.

•

Screening is not appropriate for women who have symptoms, and conducting a cervical screening test may delay the proper diagnostic process in such cases. If the woman is symptomatic, such as experiencing bleeding between periods or after sex, she needs to consult her GP straight away.

The effectiveness of the program can also be judged by coverage. This is the percentage of women in the target age group (25 to 64) who have been screened in the last five years. If overall coverage of 80 per cent can be achieved, the evidence suggests that a reduction in death rates of around 95 per cent is possible in the long term.

Recently the direct cause and effect between HR-HPV infection and the development of cervical cancer has been clearly established, with almost 100% of cervical cancers containing HPV DNA.7 Women with no evidence of HRHPV infection are extremely unlikely to develop cervical cancer in the short to medium term. Hence use of HPV screening as a tool to triage women who are at high and low risk of developing cervical cancer has been recently introduced in the screening program.

Prevention strategies may be hugely relevant in recourse poor countries with the highest disease burden and absence of universal cervical screening program.

Risk factors for HPV infection include number of sexual partners, a relatively recent new sexual relationship and

CHAPTER 85

Fig. 2: Severe Dyskaryosis

MISCELLANEOUS

456

a history of previous miscarriage. Among HPV positive women, early age at first intercourse, long duration of the most recent sexual relationship and cigarette smoking are associated with development of CIN 3 ( high grade squamous intra-epithelial neoplasia).8 Smoking has been associated with an increased risk of SCC. A recent study by Parkin et al, suggested 7% of cases in 2010 were associated with smoking.9 A recent metaanalysis suggests a 50% increased risk of SCC in current smokers.10 Low socio-economic status has also shown to be a risk factor; with the risk multiplying by almost three times in most deprived areas.

A meta-analysis found risk of invasive cervical cancer in current users of combined oral contraceptive pills (COC) increases by 7% for each year of use.11 The risk increase for five years of use is approximately 40%. The risk increase is temporary, and risk returns to the level of a never-user after 10 years of stopping use. Like with smoking, the direct cause and effect from COC on cervical cancer is complicated by confounding sexual behavior.

Women with HIV/AIDS have a six times increased risk of developing cervical cancer and women who have undergone organ transplant have twice or more the risk, strongly suggesting that immunosuppressant plays an important role.

HR HPV testing has recently been introduced in the UK National Cervical Screening Program, both as a primary triaging investigation for low grade and borderline abnormality as well as a test of cure following treatment for high grade cervical dyskaryosis. Whilst the ARTISTIC (A Randomized Trial of HPV Testing in Primary Cervical Screening, n=25,000) trial has shown that routine HPV testing did not add significantly to the effectiveness of liquid based cytology (LBC) screening, primary HPV triaging has a higher negative predictive value.12 HPV vaccines are sub-unit vaccines made from the major protein of the viral-coat or capsid of HPV. Virus-like particles (VLPs) mimic the structure of the native virus but do not contain any viral DNA. There are currently two different HPV vaccines, Cervarix® contains VLPs for two HPV types (16 and 18 – bivalent vaccine) and Gardasil® contains VLPs for four HPV types (6, 11, 16 and 18 – quadrivalent vaccine). HPV vaccines are highly effective at preventing the infection of susceptible women with the HPV types covered by the vaccine. In clinical trials in young women with no evidence of previous infection, both vaccines were over 99% effective at preventing pre-cancerous lesions associated with HPV types 16 or 18.13 Current studies suggest that protection is maintained for at least ten years. Based on the immune responses, it is expected that protection will be extended further; long-term follow-up studies will provide further evidence regarding efficacy. Some other high-risk HPV types are closely related to those contained in the vaccines and vaccination has been shown to provide some crossprotection against infection by these types. Gardasil® is also 99% effective at preventing genital warts associated

with vaccine types in young women. A vaccination schedule of 0, 1, and 4-6 months is appropriate for both vaccines for girls being vaccinated at the age of 15 years and above. All three doses should ideally be given within a 12-month period. If the course is interrupted, it should be resumed using the same vaccine. It should not be repeated, ideally allowing the appropriate interval between the remaining doses. For girls aged less than 15 years of age Joint Committee on Vaccination and Immunization (JCVI) recommended a schedule of 0, 6-24 months for both vaccines. It is hoped that the vaccination program will avert 70% or more squamous cell cancer of the cervix by preventing HPV infection.14 Since the mid1970s the incidence of ovarian cancer in women over 65 has increased by more than 40%.

Worldwide, there are more than 239,000 new cases of ovarian cancer diagnosed each year.1 Epithelial ovarian cancer continues to be the most fatal of the female genital tract cancers in developed countries as majority of the patients are diagnosed at advanced stages with tumours of high grade, so the value of diagnostic and prognostic markers is limited. However, contrary to the commonly held perception, ovarian cancer is neither an asymptomatic disease nor a so-called ‘silent killer’.

The initial presenting symptoms are often associated with other conditions, especially abdominal and gastrointestinal disorders, till they become very obvious in advanced stage disease. Hence a better understanding of symptoms associated with ovarian cancer is required to adopt the correct screening strategies for early detection of disease.15 Most women will have had symptoms for months before seeking help. Unexplained fatigue, weight loss or change in bowel habit in women over 50 years old should also prompt further investigation and consideration of ovarian cancer.16 Nulliparity, personal and family history of cancer are some of the risk factors associated with developing ovarian cancer. Women who have had cancer of the breast, uterus, colon, or rectum have a higher risk of developing ovarian cancer as there is a greater likelihood that they carry the cancer predisposing genes.

Studies have suggested that postmenopausal women who take oestrogen hormone replacement by itself (oestrogen without progesterone) for 5 or more years have an increased risk of developing ovarian cancer. The overall increased risk was by 30% to 40% over the usual incidence. This risk is reversed on stopping hormone replacement therapy.17 The average woman has a 1.5-2% lifetime risk of developing ovarian cancer. For those carrying cancer predisposing gene mutations, this risk is increased. A strong family history of certain cancers may indicate the presence of hereditary gene mutations.

Women with a strong family history of ovarian or breast cancer have an increased risk of carrying a BRCA gene

457

Table 2: Symptoms of ovarian cancer according to disease stage (courtesy CRUK) Symptoms associated with spread of disease

Disease spread beyond the ovary

Late stage disease

• Lower abdominal pain

• Irregular periods or post menopausal bleeding

• Loss of appetite or a feeling of fullness in the abdomen

• Lower abdominal pain

• Nausea/vomiting

• Back pain

• Constipation

• Urinary frequency

• Tiredness

• Constipation

• Shortness of breath

• Dyspareunia

• Abdominal distension

• Abdominal bloating or feeling of fullness

• A swollen abdomen • Feeling of fullness or loss of appetite mutation which predisposes them to developing the disease. Women with a family history of cancer of the uterus, ovary, colon or rectum may have an increased risk of carrying a mismatch repair gene mutation (genes MLH1, MSH2, MSH6 or PMS2). This is termed Lynch Syndrome or Hereditary Non-polyposis Colorectal Cancer (HNPCC) and carriers have an increased risk of ovarian cancer as well as other cancers.

Heritable mutations in BRCA1 and BRCA2 genes account for approximately 8% to 13% of newly diagnosed ovarian cancer cases, which is probably under-reported, as routine genetic testing after diagnosis is still not widely prevalent.

The risk of developing ovarian cancer by the age of 70 in women carrying a BRCA 1 mutation is approximately 35%-60% and in women carrying a BRCA 2 mutation the risk is 10% to 27%. In comparison, women with Lynch Syndrome (Hereditary Non-polyposis Colorectal Cancer (HNPCC/Lynch syndrome), have a 12% risk of developing ovarian cancer and a 60% lifetime risk of both uterine and colon cancer.18 Similar to BRCA1 and BRCA2, changes in these genes can cause very early onset cancers, with some of the cancers occurring as early as age 25. These women and other female members of their family should be counselled about undergoing genetic testing. The use of COCPS in ovulation suppression in the early years and offering risk reduction surgery in the form of prophylactic bilateral salphingectomy after completion of family and oopherectomy from the age of 40, are some of the strategies being employed to prevent cancer developing in this high risk group of patients. Routine general population screening for ovarian cancer is not currently recommended. However, offering salphingectomies rather than tubal occlusion at the time of sterilisation seem to be one of the proposed preventative strategies being employed in reducing the risk of ovarian cancer in the future.

Recent hypothesis propose the development of ovarian high grade serous carcinoma by direct shedding and implantation of pre-cancerous serous tubal intraepithelial cells ( STIC cells) from the fimbria on the ovarian surface and accelerating to cancer development

due to chromosomal instability and by free reactive oxygen radicals.19 The National Institute for Health Care and Excellence (NICE) guidelines in the United Kingdom recommends initiating investigations for any women over 50yrs with suspected ovarian malignancy by performing a baseline Serum CA-125 and pelvic trans-vaginal ultrasound scan.

Currently the best known tumour marker used for screening, predicting and monitoring surveillance of ovarian cancer is cancer antigen -125 (CA-125).

The normal range for CA-125 is < 35 IU/L. CA-125 is raised above the normal range in serous epithelial and endometrioid ovarian cancer. CA-125 can be elevated in other cancers such as endometrial, breast, pancreatic, gastrointestinal, and lung cancers. CA-125 is also raised in benign gynaecological conditions such as pregnancy, inflammation, endometriosis, menstruation, and pelvic inflammatory disease.20 In women with pelvic mass, an elevated result has a sensitivity of 72% and specificity of 78% for ovarian cancer.21 Of early stage patients, only 50% have increased CA-125 compared with 90% of advanced stage patients. This means that CA-125 is not a good candidate for early screening of EOC.22 CA-125 is often not elevated in mucinous, clear-cell and borderline tumours. Hence developing an accurate biomarker will significantly improve clinical outcome and possibly survival from this cancer.

Majority of the genetic abnormalities associated with ovarian cancer are not inherited, but are acquired during a woman’s lifetime. The commonly noted ‘somatic’ or acquired mutations observed in epithelial ovarian cancer include mutations in tumour suppressor genes (such as p53 and PTEN), and genes for signaling molecules such as KRAS and the kinases.23 In the United Kingdom, a scoring system used in distinguishing ovarian masses is the risk of malignancy index (RMI). This is an algorithm based on the sum score of the product of trans-vaginal scan findings, CA-125 level in blood and the menopausal status and has been developed to distinguish between patients with benign

CHAPTER 85

Early Stage

458

and malignant pelvic masses. A RMI of 250 or more has 85% sensitivity and 97% specificity in distinguishing between benign and malignant ovarian masses, with an area under the receiver operating characteristic (ROC) curve of 0.83.24,25

MISCELLANEOUS

Endometrial carcinoma is the commonest gynaecological cancer in the developed world, with a rising incidence in the developing world. Worldwide in 2012, 527,600 women were diagnosed with uterine cancer. The mortality rate was 1.7 to 2.4 per 100,000 women.

Obesity delivers a two to five fold increase in the risk of endometrial cancer in both pre- and postmenopausal women. The increase in the risk of developing endometrial cancer in obese patients is likely to be due to increased oestrogen dependent endometrial stimulation.

Type 1 endometrial cancers account for the majority of the tumours and are oestrogen dependent endometrioid cancers with a good prognosis while type 2 cancers present later and carry a worse prognosis.

The increasing incidence of obesity in the developed world has significant implications for health and health economics. In 2008, a Department of Health census for England and Wales showed that 1 in 4 adult women were obese. One of the important reasons postulated for this changing prevalence, is the ever increasing number of overweight, obese and morbidly obese women in the post-menopausal age group. There appears to be a linear increase in endometrial cancer risk with increasing Body Mass Index (BMI) a threshold effect has also been noted, with an increase only among obese women with a BMI of 30 kg/m2 or higher. There is a 4-fold increase in the risk of developing endometrial cancer in obese patients due to increased oestrogen dependent endometrial stimulation.

Surgical management of obese and morbidly obese women with early stage endometrial cancer is extremely challenging due to the associated increased morbidity.26 Some of the endogenous risk factors associated with the development of endometrial cancer are increasing age, central obesity, physical inactivity, early menarche, late menopause, nulliparity, polycystic ovarian syndrome, family history, oestrogen-secreting tumours, diabetes mellitus, hypertension, history of breast cancer and Lynch syndrome. Women with Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), have an altered gene that increases the risk of bowel cancer and uterine cancer. Women with this gene have a 30â&#x20AC;&#x201C;60% risk of developing uterine cancer over their lifetime. They are screened for bowel cancer and may also have tests to check for early signs of endometrial cancer. Women with a rare genetic condition called Cowden syndrome have an increased risk of benign (non-cancerous) tumours and also some cancers. This includes uterine cancer, but the increase in risk is small. Oestrogen receptor modulators and hormonal therapy used in treatment of breast cancer can cause a theoretical increase in the development of uterine cancer.

The overall five year survival rate in uterine cancer across

all stages is currently around 80%.2 Majority of women will present early in the course of the disease when cure is more likely, so physicians need to be vigilant for symptoms suggesting this (Table 2).

The hallmark symptom of endometrial cancer is postmenopausal bleeding (5%-10% of all symptomatic patients will have underlying cancer) with bleeding occurring at least one year after the last menstrual period in the presence of other evidence of ovarian failure. In pre-and peri-menopausal women, endometrial cancer presents with inter-menstrual bleeding often on a background of irregular, dysfunctional menstruation suggesting anovulation. Pain, vaginal discharge and pyometra are rarer presentations of endometrial cancer and tend to be secondary to advanced malignancy.

The pathogenesis of development of endometrial cancer is the gradual progression from simple endometrial hyperplasia to complex endometrial hyperplasia without atypia and then to complex endometrial hyperplasia with architectural atypia, followed by progression to early invasive malignancy.

In women who wish to preserve fertility and conserve their uterus, such histological changes can be attempted to be reversed by treating with intra-uterine progesterone system like the mirena IUS and high dose progesterone.

Oestrogen levels are lower during pregnancy and when breast-feeding. The risk of endometrial cancer is lower in women who have had children. Breastfeeding for more than 18 months also decreases the risk of endometrial cancer. Taking contraceptives that combine estrogen and progestin (combination oral contraceptives) decreases the risk of endometrial cancer. The protective effect of combination oral contraceptives increases with the length of time they are used, and can last for many years after oral contraceptive use has been stopped. While taking oral contraceptives, women have a higher risk of blood clots, stroke, and heart attack, especially women who smoke and are older than 35 years. Physical activity at home (exercise) or on the job may lower the risk of endometrial cancer.27 At present clinical interventions like gastric bypass surgery and other dietary modifications in the morbidly obese patients are being undertaken to understand their potential long term benefits in reducing the risk of developing endometrial cancer in the future.

The baseline investigations in women with suspected endometrial cancer are a transvaginal ultrasound scan and an endometrial biopsy. Transvaginal ultrasound scan is an accurate and precise screening method for endometrial cancer. A meta-analysis of 35 studies using a 5 mm threshold to define abnormal endometrial thickening showed that 96% of women with cancer had endometrial thickness greater than 5 mm; the study reported a negative likelihood ratio of 0.08.28 Transvaginal ultrasound was also highly reliable in identifying postmenopausal women with vaginal bleeding who were unlikely to have underlying malignancy (endometrial

thickness of <5 mm), which would mean that unnecessary endometrial sampling could be avoided.

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Saso S, Chatterjee J, Georgiou E, Ditri AM, Smith JR, GhaemMaghami S. Endometrial cancer. BMJ 2011; 343:d3954.

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Bosch FX, Lorincz A, Munoz N, Meijer CJ, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol 2002; 55:244-65.

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Bosch FX, Munoz N. The viral etiology of cervical cancer.

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Sasieni P, Adams J, Cuzick J. Benefit of cervical screening at different ages: evidence from the UK audit of screening histories. Br J Cancer 2003; 89:88-93.

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Bosch FX, Castellsague X, de Sanjose S. HPV and cervical cancer: screening or vaccination? Br J Cancer 2008; 98:15-21.

8.

Deacon JM, Evans CD, Yule R, Desai M, Binns W, Taylor C, et al. Sexual behaviour and smoking as determinants of cervical HPV infection and of CIN3 among those infected: a case-control study nested within the Manchester cohort.

Br J Cancer 2000; 83:1565-72.

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Parkin DM. 2. Tobacco-attributable cancer burden in the UK in 2010. Br J Cancer 2011; 105 Suppl 2:S6-S13.

10. International Collaboration of Epidemiological Studies of Cervical C. Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int J Cancer 2007; 120:885-91.

11. International Collaboration of Epidemiological Studies of Cervical C, Appleby P, Beral V, Berrington de Gonzalez A, Colin D, Franceschi S, et al. Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies.

Lancet 2007; 370:1609-21.

12. Kitchener HC, Almonte M, Gilham C, Dowie R, Stoykova B, Sargent A, et al. ARTISTIC: a randomised trial of human papillomavirus (HPV) testing in primary cervical screening. Health Technol Assess 2009; 13:1-150, iii-iv.

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14. Bosch FX. HPV vaccines and cervical cancer. Ann Oncol 2008; 19 Suppl 5:v48-51.

15. Bankhead CR, Collins C, Stokes-Lampard H, Rose P, Wilson S, Clements A, et al. Identifying symptoms of ovarian cancer: a qualitative and quantitative study. BJOG 2008; 115:1008-14.

16. Mayor S. Consensus statement on ovarian cancer aims to settle dispute over symptoms. BMJ 2008; 337:a2007.

17. Greiser CM, Greiser EM, Doren M. Menopausal hormone therapy and risk of ovarian cancer: systematic review and meta-analysis. Hum Reprod Update 2007; 13:453-63.

18. Kehoe SM, Kauff ND. Screening and prevention of hereditary gynecologic cancers. Semin Oncol 2007; 34:40610.

19. Vang R, Shih Ie M, Kurman RJ. Fallopian tube precursors of ovarian low- and high-grade serous neoplasms.

Histopathology 2013; 62:44-58.

20. Hogdall EV, Christensen L, Kjaer SK, Blaakaer J, KjaerbyeThygesen A, Gayther S, et al. CA125 expression pattern, prognosis and correlation with serum CA125 in ovarian tumor patients. From The Danish â&#x20AC;&#x153;MALOVAâ&#x20AC;? Ovarian Cancer Study. Gynecologic Oncology 2007; 104:508-15.

21. Patsner B, Mann WJ, Chalas E. Predictive value of CA 125 for ovarian carcinoma in patients presenting with pelvic masses. Obstet Gynecol 1988; 71(6 Pt 1):949-50.

22. Nossov V, Amneus M, Su F, Lang J, Janco JM, Reddy ST, et al. The early detection of ovarian cancer: from traditional methods to proteomics. Can we really do better than serum CA-125? Am J Obstet Gynecol 2008; 199:215-23.

23. Hennessy BT, Coleman RL, Markman M. Ovarian cancer.

Lancet 2009; 374:1371-82.

24. Jacobs I, Davies AP, Bridges J, Stabile I, Fay T, Lower A, et al.

Prevalence screening for ovarian cancer in postmenopausal women by CA 125 measurement and ultrasonography.

BMJ 1993; 306:1030-4.

25. Davies AP, Jacobs I, Woolas R, Fish A, Oram D. The adnexal mass: benign or malignant? Evaluation of a risk of malignancy index. Br J Obstet Gynaecol 1993; 100:927-31.

26. Bergstrom A, Pisani P, Tenet V, Wolk A, Adami HO. Overweight as an avoidable cause of cancer in Europe. Int J Cancer 2001; 91:421-30.

27. Trentham-Dietz A, Nichols HB, Hampton JM, Newcomb PA. Weight change and risk of endometrial cancer. Int J Epidemiol 2006; 35:151-8.

28. Gull B, Karlsson B, Milsom I, Granberg S. Can ultrasound replace dilation and curettage? A longitudinal evaluation of postmenopausal bleeding and transvaginal sonographic measurement of the endometrium as predictors of endometrial cancer. Am J Obstet Gynecol 2003; 188:401-8.

29. Clark TJ, Mann CH, Shah N, Khan KS, Song F, Gupta JK. Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial cancer: a systematic quantitative review.

BJOG 2002; 109:313-21.

CHAPTER 85

A definitive diagnosis of endometrial cancer is histological with endometrial tissue sample being obtained either in the gynaecology outpatient setting using a Pipelle curette or by hysteroscopy and dilatation and curettage under general anaesthesia. A systematic review of different diagnostic evaluations showed that Pipelle biopsy leads to a high overall diagnostic accuracy when an adequate specimen is obtained (post-test probability of endometrial cancer of 81.7% for a positive test and 0.9% for a negative test).29 However, diagnostic hysteroscopy and directed endometrial sampling is the gold standard for ruling out endometrial malignancy where a distorted, irregularly thickened endometrial cavity is noted on ultrasound scan.

13. Cuzick J, Castanon A, Sasieni P. Predicted impact of vaccination against human papillomavirus 16/18 on cancer incidence and cervical abnormalities in women aged 20-29 in the UK. Br J Cancer 2010; 102:933-9.

Contribution of India in Medical Sciences

C H A P T E R

86

Saikat Datta, Sharmistha Bhattacherjee, Dibyayanam Sahoo

The art of tending to the sick is as old as the humanity itself. The ancient civilizations probably knew about the functions, physiology and anatomy of the human body in surprising details, and their art of tending the sick remains a proof of their knowledge. The Hippocratic Oath-which is still taken (though significantly modified) by doctors up to today- was compiled in Greece in the 5th century BC. Along with the Greeks, the Chinese, the Babylonians and Egyptians were practicing medical traditions since time immoral.

India, with its rich cultural heritage, has been in the forefront in contributing the medical science, and there is plenty of proof of the same. Indian medical tradition goes back to Vedic times. During that period, the Ashwinikumars- who were practitioners of medicinewere given a divine status. We also have a God of Medicine called Dhanvantari. Although very few ancient texts are available today, this method of healing was systematized in early times. The fact that the term Veda was attached to this body of thought testifies to this. The art of healing was considered a sacred one, and was spread among sages, hermits and medicos who roamed from place to place. Vaidyas, who generally belonged to Brahmin caste, were those who practiced solely this art.

Although there is no record as to when the plants and herbs started being used for medical purposes (herbalism), the use of plants, clays and soils are pretty ancient. Over time through emulation of the behavior of fauna a medicinal knowledge base developed and passed between generations.

One of the first Indian text dealing with medicine is Atharvaveda.1 The Atharvaveda also contain prescriptions of herbs for various ailments. Subsequently, the use of herbs to treat ailments, in a much broader way, later formed a large part of Ayurveda2.

Ayurveda-”complete knowledge for long life”- is one of the earliest medical system known to human civilization.

Charaksamhita and Sushrutasamhita, the two main texts of Ayurveda, are surprisingly alike the textbooks of modern medicine.

Charaka, in his compendium Charaksamhita, highlighted that life may be prolonged by human effort. The statement “A physician who fails to enter the body of a patient with the lamp of knowledge and understanding can never treat diseases. He should first study all the factors, including environment, which influence a patient’s disease, and then prescribe treatment. It is more important to prevent

the occurrence of disease than to seek a cure” highlights the fact that Charaka was more in favour of preventive medicine than the curative ones.3 Sushrutasamhita (commonly dated 6th Century BC) on the other hand, involves more on the therapy. Sushruta, one of the first to study human anatomy, described in details about various anatomical structures in his compendium.

Also Shashtrakarma, the art of surgery, was recognized as an important part of therapy in this compendium. In Sushrutasamhita, surgery was described under eight heads Chedya (excision), Lekhya (scarification), Vedhya (puncturing), Esya (exploration), Ahrya (extraction), Vsraya (evacuation) and Sivya (suturing).4 Shusruta’s forte was rhinoplasty (plastic surgery) and ophthalmialogy (ejection of cataracts).

Few researchers proposes that that the first mention of leprosy is described in Sushruta Samhita.5 However, The Oxford Illustrated Companion to Medicine holds that the mention of leprosy, as well as ritualistic cures for it, were described in the Atharvaveda, written before the Sushruta Samhita.6

SIDDHA MEDICINE

Siddha Medicine (Tamil Citta- or Tamil-maruttuvam) is a system of traditional medicine originating in ancient Tamilakam in South India.7 It was traditionally thought that siddhars- who were considered to be in possession of eight supernatural powers-laid the foundation to this system of medications. Agastya is considered to be the 1st siddhar.

Siddhars were of the concept that a healthy soul can only be developed through a healthy body, and so, they tried to develop a healthy body first. The drugs used by the Siddhars were either thavaram (herbal product), or thadhu (inorganic substances), or jangamam (animal products).8

UNANI MEDICINE

It is a form of medicine which was practiced in Mughal India and in Muslim culture in South Asia. It is actually a form of traditional PersoArabic medicine. This medicine enjoyed royal patronage during the Mughal period, which helped in its spread to different parts of India.9 In this system of medicine, any cause and or factor is countered by QuwwateMudabbiraeBadan (the power of body responsible to maintain health), the failing of which may lead to quantitatively or qualitatively derangement of the normal equilibrium of akhlat (humors) of body which constitute the tissues and organs. Subsequently, regional

therapy (IlajBilTadbeerwaIlajBilGhiza), pharmacotherapy (IlajBilAdvia) or surgery (IlajBilYad) were used to treat the subjects as needed.

YOGA

Modern medicine

The evolution of modern medicine in India is blurred.

There has been many scientists, researchers and physicians who have constantly tried to upgrade the knowledge of medicine and science of healing the sick. A few of them are mentioned below:

UPENDRANATH BRAHMACHARI (1873-1946)

UN Brahmachari was born in 1873 in Jamalpur, Bihar, where his father Nilmony Brahmachari was a doctor with the East Indian Railway. He started out to become a mathematician, and passed his BA in mathematics in 1893. Then he completed masters in Chemistry, before he joined Calcutta Medical College to obtain Licentiate in Medicine and Surgery degree in 1899. Subsequently, he worked with single minded determination in a small ill equipped room in the Campbell Hospital (presently NRS Medical College) to discover a new drug to cure Kalaazar.

After 5 years of toiling, Urea Stibamine was discovered, which quickly became essential for the treatment of Kalaazar.10

RAMNATH CHOPRA (1882-1973)

Ram Nath Chopra was born on August 17, 1882 at Gujranwala, Punjab. He had his early education at Jammu and Srinagar and collegiate studies at Government College, Lahore. After studying in England, he returned India to be the first professor of pharmacology in the newly established Calcutta School of Tropical Medicine in 1921. In his tenure, he conducted various studies on general pharmacology and pharmacotherapy, alongwith surveys on drug addiction. Professor Chopra was the 1st to establish a centre of study and research in pharmacology in India, at the Calcutta School of Tropical Medicine. His work encouraged research on Indian medicinal plants at different institutions. Certain indigenous substances like ispaghula, kurchi, rauwol, psoralea, cobra venom, etc. were included in Indian Pharmocopia by him. The books by Chopra and associates entitled “Indigenous

461

YELLAPRAGADA SUBBAROW (1895-1948)

SubbaRow can best be described as an unfortunate scientist who did not get his due recognition. Born in 1895, he worked at Harvard Medical School until 1940, when he went to Lederle Laboratories for research. His research led to the discovery of Polymyxin, an agent used even today. Aureomycin, the first of tetracycline, was also discovered by him. Fiske-SubbaRow method of colorimetric estimation of organic, inorganic and lopoid phosphorous in blood and urine has been one of the 100 most cited papers. Also, the discovery of folic acid, aminopterin and anti-pernicious factor (Vitamin B12) is credited to him. Methotrexate, the derivative of aminopterin, is still being used in various conditions.12

SUBHASH MUKHOPADHYAY (1931-1981)

A physician from Calcutta, Dr. Mukhopadhyay was the first one to create India’s first test tube baby in 1978, but never got due recognition of the same. Unfortunately, all the bureaucratic interventions and false accusations were too much for this eminent researcher. Finally, tired of being targeted for no reason whatsoever, he decided to take his own life in 198. 13

RONALD ROSS (1857-1932)

Sir Ronald Ross was born in Almora, India in 1857 to Sir C.C.G. Ross who was a general in the Indian army. In 1892 he became interested in malaria and on 20 August 1897, in Secunderabad, Ross made his landmark discovery. While dissecting the stomach tissue of an anopheline mosquito fed four days previously on a malarious patient, he found the malaria parasite and went on to prove the role of Anopheles mosquitoes in the transmission of malaria parasites in humans. By July 1898, he had demonstrated that mosquitoes could serve as intermediate hosts for bird malaria. After feeding mosquitoes on infected birds, he found that the malaria parasites could develop in the mosquitoes and migrate to the insects› salivary glands, allowing the mosquitoes to infect other birds during subsequent blood meals. Located on the Northern wall of the Presidency General (PG) Hospital, lies a arch shaped memorial dedicated to Ronald Ross, Nobel Prize winner of Medicine in 1902. Sadly, very few people from Kolkata are aware of this memorial.14,15

HARGOVIND KHORANA (1922-2011)

Born in Raipur, Punjab, he completed his MSc and went to the University of Liverpool for his PhD degree. At the age of 46, Hargovind Khorana shared the Nobel Prize for Physiology and Medicine in 1968 with Robert W Holley and Marshall W. Nierenberg for contributions towards elucidating the genetic code. In 1972, at the Massachusetts Institute of Technology, Hargovind’s team described a monumental achievement in chemical biology- the total chemical synthesis of a functional tRNA gene of yeast.

Khorana’s methods of extension of DNA polymers into synthetic gene, using polymerase and ligase enzymes

CHAPTER 86

Yoga is a system of exercises for physical and mental nourishment. The tradition of Yoga is a hoary one and has been kept alive by ascetics and hermits. The therapeutic qualities of yoga had special relevance for hermits who roamed from place to place, meditating. But Yoga is not only physical postures. The main aim of yoga is to achieve calm state of mind. It is essentially based on mind and body relationship aiming complete ‘homeostasis’ between the two, which can be attained through eight steps- namely Yama (moral behavior), Niyama (healthy habits), Asana (physical postures), Prayanama (breathing exercises), Pratyahara (sense withdrawal), Dharna (concentration), Dhyana (contemplation) and Samadhi (higher consciousness). The principles of yoga are Proper Relaxation, Proper Exercise, Proper breathing, Proper diet and Positive thinking and meditation.

Drugs of India”, “Glossary of Medicinal Plants of India” and “Poisonous Plants of India” had been popular encyclopedia of Indian medicinal plants.11

462

that link pieces of DNA together as well as methods that anticipated the invention of PCR, are widely used in biology laboratories for sequencing, cloning and engineering new organisms.16

MISCELLANEOUS

DWARKANATH KOTNIS

An Indian doctor from Solapur, Dr Kotnis gave up a bright career to join five other doctors to serve the sick and war driven in China during the Sino-Japanese war of 1938. He was affected by the mysterious disease which was affecting the Chinese soldiers and for which he was trying to find a cure, and he died in 1942.17 After these eminent scientists, there was a long period of void when the contribution of India to the medical science became negligible. New researches and newer molecules were out of sight then. But recently, newer drugs and Indian research molecules like Saroglitazaar for Diabetes18 and Arterolane Maleate and Piperaquine Phosphate (Synriam) for treatment of Malaria are showing rays of hope. Also, the biosimilar drugs being manufactured are probably the cheapest in India. The cheap price of the drugs, alongwith modern medical facilities being developed, is rapidly converting India into a favorite spot for medical tourism.

Unfortunately, India had also contributed something which is not so good. The rampant sale of over the counter medications without any control is definitely not something to be proud of. Also, the indiscriminate use of antibiotics has resulted in India being the forefront in producing resistant bugs. The New Delhi metallo-betalactamase 1 (NDM-1) enzyme, which makes a bacteria resistant to carbapenems, was first found in a Swedish patient treated in India. Although later the editor of Lancet apologized the naming, still it is well known that there is every possibility that some resistant strains are contribution of India.18 India has a rich cultural heritage, a strong social base and an impressive history. Her contributions to medical science over ages cannot be underestimated. But today, we seem to have lost our zeal to contribute. Very few medical students are going for a full-fledged research, and very few contributions are made to the medical science.

Let us try to rectify it, and try to contribute something for the sick. Only then can claim to be true descendants of Charaka and Sushruta.

KEY WORDS

Ayurveda, Charaka, Sushruta, Ronald Ross, Polymyxin

REFERENCES

1.

Bloomfield, Maurice, tr., Hymns of the Atharva-Veda together with Extracts from the Ritual Books and the Commentaries, In Sacred books of the East (Delhi: Motilal Banarsidass, 1964).Available at: http://www.sacred-texts. com/hin/av.htm

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13. “Test tube triumph & tragedy - Nobel for UK scientist stirs memory of a Bengal doctor”. The Telegraph (Calcutta). 5 October 2010.

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19. Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R, Chaudhary U, Doumith M, Giske CG, Irfan S, Krishnan P. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. The Lancet Infectious Diseases 2010; 10:597-602.