Indian Journal of Clinical Practice Dec 2016

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Volume 27, Number 7

December 2016, Pages 601–700

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Dr KK Aggarwal Group Editor-in-Chief IJCP Group, eMedinewS and eMediNexus Dr Veena Aggarwal MD, Group Executive Editor

IJCP Editorial Board Obstetrics and Gynaecology Dr Alka Kriplani, Dr Thankam Verma, Dr Kamala Selvaraj Cardiology Dr Praveen Chandra, Dr SK Parashar Paediatrics Dr Swati Y Bhave Diabetology Dr CR Anand Moses, Dr Sidhartha Das, Dr A Ramachandran, Dr Samith A Shetty, Dr Vijay Viswanathan, Dr V Mohan, Dr V Seshiah, Dr Vijayakumar ENT Dr Jasveer Singh, Dr Chanchal Pal Dentistry Dr KMK Masthan, Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar, Dr Rajiv Khosla, Dr JS Rajkumar Dermatology Dr Hasmukh J Shroff, Dr Pasricha, Dr Koushik Lahiri, Dr Jayakar Thomas Nephrology Dr Georgi Abraham Neurology Dr V Nagarajan, Dr Vineet Suri, Dr AV Srinivasan Oncology Dr V Shanta Orthopedics Dr J Maheshwari

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Volume 27, Number 7, December 2016 FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

605 50 Facts on HIV/AIDS

AMERICAN FAMILY PHYSICIAN

609 Treating Painful Diabetic Peripheral Neuropathy: An Update

Matthew J. Snyder, Lawrence M. Gibbs, Tammy J. Lindsay

619 Practice Guidelines 620 Photo Quiz COMMUNITY MEDICINE

622 Incidence of Cervical Lesions in a Tertiary Care Hospital in South India: A 5-year Analysis

Sana Aboosalih, Leena Dennis Joseph, Sai Shalini CN, Monica Kumbhat, Rajendiran S

629 Strategies to Reduce Medication Errors: Working to Improve Medication Safety

P Kasthuri

DIABETOLOGY

637 Predicting Clinical Outcome in Diabetics versus Nondiabetics with Acute Myocardial Infarction After Thrombolysis

Amgoth Banu Priya, Arun Prasath, C Ramakrishnan, SM Rajendran

641 Vitamin B12 Levels in Patients with Type 2 Diabetes Mellitus on Metformin

V Padma, NN Anand

645 Prevalence of Diabetic Neuropathy: A Prospective Study in a Tertiary Care Teaching Hospital in Kerala

Jeena Beegum N, Sujith Varma, Lejo Jacob, Abaedha Susan Kuriakose, Midhun K Roy

HEMATOLOGY

652 Pancytopenia: An Evaluation in a Tertiary Care Center

Uma Ramanathan, J Thanka, Lawrence Deruze, S Sri Gayathri

INTERNAL MEDICINE

658 N-hexane-induced Polyneuropathy

Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

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Dr KK Aggarwal

PK Maheshwari, Prabhat Agrawal, Akhilesh Singh, Divya, Bindu, Shalini Upadhyay

OBSTETRICS AND GYNECOLOGY

661 Maternal and Perinatal Outcome in Antepartum Hemorrhage in a Tertiary Care Center: An Observational Study

Ruby Bhatia, Parmjit Kaur, Gurdip Kaur, Satinder Kaur, Aman Dev, Santosh Kumari

OBSTETRICS AND GYNECOLOGY

Published, Printed and Edited by Dr KK Aggarwal, on behalf of IJCP Publications Ltd. and Published at E - 219, Greater Kailash Part - 1 New Delhi - 110 048 E-mail: editorial@ijcp.com

666 A Retrospective Study of Prevalence of Hepatitis B, Hepatitis C and HIV in Pregnant Women and Their Perinatal Outcome

Navneet Kaur, Parneet Kaur

PEDIATRICS

Printed at New Edge Communications Pvt. Ltd., New Delhi E-mail: edgecommunication@gmail.com

673 A Study of Sociodemographic Profile of Children with Severe Acute Malnutrition Under 5 Years of Age and Caregivers Characteristics

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Mudit Kumar Aggarwal, V Krishna Agarwal, S Agarwal

EXPERT’S VIEW

678 What Health Problems are Associated with Hypertension?

Editorial Policies

Rajiv Garg

CONFERENCE PROCEEDINGS

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680 46th Annual Conference of Endocrine Society of India (ESICON 2016) 687 10th World Stroke Congress 2016 MEDILAW

690 A Known Phenomenon is not Medical Negligence AROUND THE GLOBE

692 News and Views LIGHTER READING

696 Lighter Side of Medicine

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Group Editor-in-Chief IJCP Group, eMedinewS and eMediNexus

50 Facts on HIV/AIDS 1. Acquired immune deficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV), which damages the immune system, lowering the resistance of the body to fight off infections.

14. HIV spreads through transfusion of unscreened (HIV-positive) blood.

2. AIDS is the advanced stage (stage 4) of HIV infection.

16. HIV infection can be passed from a mother to her child through breastfeeding.

3. Progression from HIV infection to AIDS, if untreated, may take 8-10 years. In young children, it usually develops much faster.

17. HIV spreads by unsterilized infected needles or syringes, especially those used for injecting drugs.

4. HIV-positive people may remain asymptomatic but can still pass on the virus to others.

5. Seventy-eight million (69.5-87.6 million) people have become infected with HIV since the start of the epidemic (end 2015).

15. HIV can spread from an infected woman to her child during pregnancy and childbirth.

18. Used infected razor blades, knives or tools that cut or pierce the skin also carry some risk of spreading HIV. 19. Touching, hugging, shaking hands, coughing and sneezing will not spread the virus.

6. Thirty-five million (29.6-40.8 million) people have died from AIDS-related illnesses since the start of the epidemic (end 2015).

20. HIV/AIDS cannot be transmitted through toilet seats, telephones, plates, glasses, eating utensils, towels, bed linen, swimming pools or public baths.

7. Globally 36.7 million (34.0-39.8 million) people were living with HIV (end 2015).

21. Up to 70% of partners of people with HIV are also HIV-positive.

8. About 1.1 million (9,40,000-1.3 million) people died from AIDS-related illnesses (end 2015).

9. About 2.1 million (1.8-2.4 million) people became newly infected with HIV (end 2015).

22. Practicing safe sexual behaviors such as using condoms prevents HIV transmission.

23. All pregnant mothers should get HIV test done.

10. About 18.2 million (16.1-19.0 million) people were receiving antiretroviral therapy (June 2016).

24. A blood test is the most accurate way to tell if someone is infected with HIV.

11. People with HIV are at risk of developing active tuberculosis disease.

25. Most tests for HIV/AIDS check for the presence of antibodies to the virus.

12. Transmission of HIV/AIDS can be prevented.

26. If the result of an HIV/AIDS test is negative, this means the person tested is not infected or it is too early to detect the virus.

13. HIV spreads through unprotected sex with an HIV-positive person.

Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

605

FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF 27. Infection may not be detected up to the first few weeks to few months.

mixing of these secretions with secretions of an HIV-positive person does not transmit HIV.

28. Even if the first test is negative, the test should be repeated 6 months after any possible exposure to HIV infection.

40. HIV does not spread by mosquitoes or other insects.

29. The time period when an infected person does not test as HIV-positive is called ‘window period’.

30. All people, including children, are at risk for HIV/ AIDS, including occupational risk.

31. People who have a sexually transmitted infection (STI) are at greater risk of getting HIV and of spreading HIV to others.

32. Persons suffering from STIs have a 5-10 times higher risk of becoming infected with HIV if they have unprotected sexual intercourse with an HIVinfected person.

33. If both partners are not treated for a STI, they will continue infecting each other with the STI. 34. The more sex partners people have, the greater the risk that one of them will have HIV/AIDS and pass it on.

35. Antiretroviral therapy (ART) should be started at the earliest to prevent HIV transmission to sexual or drug using partner/s or from the mother to the infant during pregnancy or breastfeeding.

36. People with STIs should seek prompt treatment and avoid sexual intercourse or practice safe sex.

37. Men with HIV are less likely to be diagnosed and put on ART and are more likely to die of HIVrelated causes than women.

38. Internal secretions, which can harbor HIV virus, are blood (including menstrual blood, semen, vaginal secretions, breast milk, peritoneal fluid, brain fluid, pleural lung fluid, pericardial heart fluid, etc. These secretions, when mixed with secretions of another person infected with HIV transmit HIV. 39. External secretions, which do not harbor the HIV virus are saliva, tear, sweat, urine and feces. The

41. HIV counseling and testing can help in the early detection of HIV infection, to get the support services for those who are infected.

42. Counseling helps to manage other infectious diseases they might have, and learn about living with HIV/AIDS and how to avoid infecting others.

43. Counseling and testing can also help those not infected to remain uninfected through education about safer sex.

44. Pre-exposure prophylaxis with tenofoviremtricitabine in high risk patients and who are committed to medication adherence and close follow-up can reduce the risk of HIV infection by 48-75%.

45. Drinking alcohol or taking drugs interferes with judgment. Even those who understand the risks of AIDS and the importance of safer sex may become careless after drinking or using drugs.

46. Young people need to be educated that there is no vaccination and no cure for HIV/AIDS. 47. WHO recommends innovative HIV-self-testing and partner notification approaches to increase HIV testing services among undiagnosed people.

48. Prevention is the only protection against HIV/ AIDS. 49. ABC for safe sex: Abstain, Be faithful to your partner and if you cannot, use Condoms.

50. 90-90-90 is a treatment target to help end the AIDS epidemic. By 2020, 90% of all people living with HIV will know their HIV status; 90% of all people with diagnosed HIV infection will receive sustained ART and 90% of all people receiving ART will have viral suppression.

■■■■

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Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

2016

AMERICAN FAMILY PHYSICIAN

Treating Painful Diabetic Peripheral Neuropathy: An Update MATTHEW J. SNYDER, LAWRENCE M. GIBBS, TAMMY J. LINDSAY

ABSTRACT Painful diabetic peripheral neuropathy occurs in approximately 25% of patients with diabetes mellitus who are treated in the office setting and significantly affects quality of life. It typically causes burning pain, paresthesias, and numbness in a stockingglove pattern that progresses proximally from the feet and hands. Clinicians should carefully consider the patient’s goals and functional status and potential adverse effects of medication when choosing a treat­ment for painful diabetic peripheral neuropathy. Pregabalin and duloxetine are the only medications approved by the U.S. Food and Drug Administration for treating this disorder. Based on current practice guidelines, these medica­tions, with gabapentin and amitriptyline, should be considered for the initial treatment. Second-line therapy includes opioid-like medications (tramadol and tapentadol), venlafaxine, desvenlafaxine, and topical agents (lidocaine patches and capsaicin cream). Isosorbide dinitrate spray and transcutaneous electrical nerve stimulation may provide relief in some patients and can be considered at any point during therapy. Opioids and selective serotonin reuptake inhibitors are optional third-line medications. Acupuncture, traditional Chinese medicine, alpha lipoic acid, acetyl-l-carnitine, primrose oil, and electromagnetic field application lack high-quality evidence to support their use.

Keywords: Diabetic peripheral neuropathy, diabetes mellitus, stocking-glove pattern, functional status, potential adverse

effects

P

ainful diabetic peripheral neuropa­thy (DPN) occurs in approximately 30% of patients with diabetes melli­ tus who are hospitalized and in 25% of patients with diabetes who are treated in the office setting.1 It develops as a late manifestation of uncontrolled or long-standing diabetes.1 As many as 12% of patients with painful DPN do not report symptoms, and 39% of patients with the disorder do not receive any treatment.2

Distal symmetric polyneuropathy, which is characterized by burning pain, paresthesias, and numbness that follows a stocking-glove pattern and progresses proximally, occurs in approximately 26% of patients with DPN. Less than 20% of patients with diabetes expe­rience dynamic mechanical allodynia (pain

MATTHEW J. SNYDER, DO, FAAFP, is associate program director of the Saint Louis University Family Medicine Residency Program in Belleville, Ill., which is affiliated with Scott Air Force Base.

LAWRENCE M. GIBBS, MD, FAAFP, is an assistant clinical professor in the Saint Louis University Family Medicine Residency Program, Belleville.

TAMMY J. LINDSAY, MD, FAAFP, is an associate clinical professor with the Department of Family and Community Medicine at Saint Louis University School of Medicine, St. Louis, Mo. Source: Adapted from Am Fam Physician. 2016;94(3):227-234.

in response to stroking lightly), thermal hyperalgesia (increased sensitivity to pain by thermal stimuli), or pain attacks.

Poorly controlled blood glucose lev­els, especially greater variation in glucose levels, contribute to the occurrence and severity of painful DPN.3 A 2012 Cochrane review of two randomized controlled tri­als (RCTs; n = 1,228) found that enhanced glucose control in patients with type 1 diabetes significantly reduced the risk of developing DPN (risk difference = 1.84%; 95% confidence interval [CI], –1.11 to –2.56). A similar analysis of four RCTs in patients with type 2 diabetes, however, did not show a statistically significant reduction in the rate of DPN with enhanced glucose control.4 Cardiovascular risk factors, including age, tobacco use, hypertension, obesity, dyslipidemia, and peripheral artery disease, are also associated with an increased risk of painful DPN.1 Pharmacologic and nonpharmacologic interventions are available for the treat­ment of painful DPN. However, there are few high-quality, head-to-head clinical tri­als comparing these therapeutic approaches, and because the available studies use varying methodologies, it is difficult to know which treatment strategy may be most effective.

Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

609

AMERICAN FAMILY PHYSICIAN PHARMACOLOGIC TREATMENT OPTIONS Only two medications, pregabalin and duloxetine, have been approved by the U.S. Food and Drug Admin­istration (FDA) for the treatment of DPN. Guidelines from national organizations such as the American Academy of Neurology, however, recommend the use of a broader range of medications.

Clinicians should consider the patient’s age, healthrelated quality-of-life goals, physical function, and comorbidities, as well as the possible adverse effects of medication use, in the management of pharmacologic therapy. Additionally, medication dosages and the duration of therapy should be regu­lated and titrated based on regular patient feedback regarding pain relief, improved function, and adverse effects.1 Figure 1 presents a treatment algorithm for painful DPN based on available evi­dence.1-3,5-8 Selected medications and their dosages, costs, and numbers needed to treat (NNTs) are presented in Table 1.1,7,9-14 Table 2 lists common adverse effects of medications used to treat painful DPN.3,12,13,15 Common drug interactions are described in Table 3.16

Anticonvulsants Anticonvulsants, including topiramate, valproate, oxcar­bazepine, lamotrigine, and lacosamide, as well as the newer calcium channel alpha-2-delta ligand class anticonvulsants (gabapentin and pregabalin), have been studied for the treatment of painful DPN. Based on a recent meta-analysis, both the American Academy of Neurology and Toronto guidelines recommend pregabalin as the first-line medication for painful DPN, with gabapen­tin as the first-line alternative.3 Pregabalin provides consistent pain relief based on a dose-dependent response com­ pared with placebo. A meta-analysis of seven RCTs (n = 1,596) comparing pregabalin with placebo showed that dosages of 300 mg daily and 600 mg daily (or divided twice daily) resulted in greater than 50% pain reduction in 39% and 47% of patients, respectively, vs. 22% with placebo.

Onset of action occurred at five days with 300 mg and at four days with 600 mg. Dosing at 150 mg daily was ineffective.1-3 Common adverse reactions to pregabalin (Table 23,12,13,15) produced discontinuation rates of 9.8% (300 mg) and 14.6% (600 mg).1 Pregabalin had similar effectiveness to amitriptyline in relieving painful DPN with fewer adverse events (18% vs. 43%, P < .0001).1 Health-related quality-of-life measures including social

610

Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

Management of Painful Diabetic Peripheral Neuropathy Initial evaluation Rule out other causes of neuropathy* Establish treatment goals Optimize glycemic control First-line therapy Anticonvulsants

Antidepressants (TCAs and SNRIs)

Pregabalin†

Amitriptyline‡

Gabapentin

Duloxetine

Second-line therapy SNRIs§

Opioid-like drugs

Topical treatments

Venlafaxine

Tramadol||

Lidocaine 5% patch

or

or

or

Desvenlafaxine

Tapentadol ER

Capsaisin 0.075% cream

Third-line therapy SSRIs

Opioids¶

Citalopram

Oxycodone controlled release

or Paroxetine or Escitalopram May consider adding at any time:

Isosorbide dinitrate spray (30 mg applied to the bottom of feet before bedtime) Transcutaneous electrical nerve stimulation

Figure 1. Algorithm for the management of painful diabetic periph­eral neuropathy.

Information from references 1 through 3, and 5 through 8.

ER = Extended release; SNRI = Serotonin-norepinephrine reuptake inhibitor; SSRI = Selective serotonin reuptake inhibitor; TCA = Tricyclic antidepressant. *Other causes of neuropathy include malignancy, alcohol use, human immunodeficiency virus infection, isoniazid use, and chemotherapy. †Pregabalin

should be used cautiously in patients with heart failure and in persons concomitantly using thiazolidinediones, because cases of decompensated heart failure with pregabalin use have been reported.1 In addition, renal insufficiency (creatinine clearance ≤ 30 mL per minute per 1.73 m2 [0.50 mL per second per m2]) requires dose adjustment.3 ‡Amitriptyline is the only TCA with good evidence of benefit for treating diabetic

neuropathy. TCAs should also be used cautiously and should generally be avoided in older adults because of adverse anticholinergic effects.3,6 TCAs are contraindicated in patients with cardiovascular disease (including unstable angina, recent myocardial infarction, heart failure, and abnormal cardiac conduction) and glaucoma.3 Twelve-lead electrocardiography should be performed in all patients older than 40 years to assess for QT prolongation because TCAs may increase the risk of torsades de pointes. §May

consider combination therapy with pregabalin and gabapentin2,5; however, clinicians should be cautious to avoid serotonin syndrome.

||Tramadol lowers the seizure threshold and should be avoided in patients with epilepsy or in those at risk of seizures.7 ¶Opioids should be used with caution because long-term use is associated with numerous adverse effects and increased morbidity and mortality.

If opioids are used, oxycodone is commonly prescribed, but alternatives include methadone, levorphanol, and morphine.

AMERICAN FAMILY PHYSICIAN Table 1. Medications for the Treatment of Painful Diabetic Peripheral Neuropathy Initial dosage

Maximum dosage

Cost†

Comments

Pregabalin

300 mg divided twice daily

600 mg divided twice daily

NA ($370)

NNT = 5 to 8, NNH = 9 to 16‡

Gabapentin

1,200 mg divided three times daily

3,600 mg divided three times daily

$10 ($330)

NNT = 3, NNH = 4‡

10 mg daily at bedtime

150 mg daily at bedtime or divided twice daily

$14 (NA)

NNT = 1 to 3, NNH = 28 (major adverse events), 6 (minor adverse events)‡

Medication* Anticonvulsants

Tricyclic antidepressants Amitriptyline

Serotonin-norepinephrine reuptake inhibitors Duloxetine

60 mg daily or divided twice daily

120 mg daily or divided twice daily

$32 ($240)

NNT = 5, NNH = 17‡

Venlafaxine

150 mg daily

225 mg daily

$14 ($322)

NNT = 3, NNH = 16

Desvenlafaxine

200 mg daily

400 mg daily

NA ($560)

NNT = 9, NNH = 6 to 14‡

Tramadol

50 mg every 4 to 6 hours

100 mg every 6 hours $8 (NA) (maximum 400 mg per day)

NNT = 4, NNH = 8

Tapentadol ER

100 mg twice daily

250 mg twice daily

NA ($520)

NNT = 9 to 10, NNH = 5‡

Lidocaine 5% patch

1 patch daily

3 patches daily

$240 (NA)

NNT = 4

Capsaicin 0.075% cream

Four times daily

NA

NA ($22 per 55-g tube)

NNT = 7

Isosorbide dinitrate spray

30 mg at bedtime applied to bottom of feet

NA

NA

NA

Opioid-like medications

Topical medications

Selective serotonin reuptake inhibitors Citalopram

10 mg daily

40 mg daily

$6 ($215)

NNT = 7

Paroxetine

10 mg daily

40 mg daily

$9 ($170)

NNT = 7

Escitalopram

10 mg daily

20 mg daily

$9 ($250)

NNT = 7

10 mg twice daily

40 mg twice daily

$175 (NA)

NNT = 6, NNH = 13

Opioids Oxycodone controlled release§

ER = Extended release; NA = Not available; NNH = Number needed to harm; NNT = Number needed to treat. *Listed in order of category and recommended use. †Estimated

retail price of one month’s treatment based on lowest dosage provided. Cost for generic listed first; brand name in parentheses, when available. Information obtained from https://www.familywize.org/drug-price-look-up-tool/ and www.amazon.com (accessed November 21, 2015).

‡Varies

in dose-dependent fashion.

§If

opioids are used, oxycodone is commonly prescribed, but other agents, including methadone, levorphanol, and morphine, may be considered. Most studies of opioids for treating neuropathic pain are short-term studies; benefit from long-term use is less certain.

Information from references 1, 7, and 9 through 14.

functioning, mental health, bodily pain, and vitality all improved, and sleep interference decreased with pregabalin administration.2,3 Gabapentin at dosages of 1,200 mg daily or greater is more effective than placebo and has been shown to have an effect similar to pregabalin (8% to 13% reduction in symptoms) based

on nine RCTs (n = 1,604). Compared with amitriptyline, similar effectiveness was noted in at least five RCTs. Pregabalin is preferred to gabapentin as a first-line medication because of the availability of higherquality studies on its effects, more predictable pharmacokinetics, shorter titration periods, the option

Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

611

AMERICAN FAMILY PHYSICIAN Table 2. Adverse Effects of Medications Commonly Used to Treat Painful Diabetic Peripheral Neuropathy Medication

Adverse effect

Patients experiencing adverse effect (%)

Pregabalin

Somnolence

5 to 40

Gabapentin

Amitriptyline

Dizziness

5 to 38

Peripheral edema

4 to 17

Headache

2 to 13

Weight gain > 7%

5

Somnolence

22 to 48

Dizziness

22 to 28

Weight gain > 7%

5

Dry mouth

2 to 89

Insomnia

35

Fatigue

11 to 34

Headache

11 to 21

Dizziness

5 to 16

Serotoninnorepinephrine reuptake inhibitors

Nausea

10 to 32

Somnolence

8 to 28

Tramadol

Tapentadol ER

Lidocaine 5% patch Capsaicin 0.075% cream Opioids

Dizziness

6 to 25

Constipation

7 to 19

Dyspepsia

9 to 18

Constipation

30

Nausea

30

Drowsiness

30

Nausea

27

Anxiety

18

Diarrhea

16

Dizziness

15

Vomiting

13

Constipation

12

Restlessness

11

Headache

10

Few high-quality studies have investigated the effectiveness of valproate, topiramate, carbamazepine, oxcarbazepine, lamotrigine, and lacosamide. Thus, these agents are not recommended for the treat­ment of painful DPN.2,17

Tricyclic Antidepressants Amitriptyline is an effective first-line medi­cation for younger adults.1,3 A 2011 systematic review of three RCTs studied the effects of amitriptyline vs. placebo in patients with painful DPN. Amitriptyline had 43% more responders (at least 20% pain reduction) than placebo, reducing pain by 58% to 63% on a five-point pain scale.2 Lower-quality evidence from a 2015 Cochrane review of four RCTs including 382 patients with all causes of neuropathic pain showed that amitriptyline use led to a statistically significant benefit (relative risk = 2.0; 95% CI, 1.5 to 2.8; NNT = 5).18 Health-related quality-of-life outcomes were not studied.

Despite its potential for benefit, amitrip­tyline is associated with significant adverse anticholinergic effects in up to one-third of patients (Table 23,12,13,15), and its use should be avoided in older adults and monitored with caution in other patients. For other tricyclic antidepressants (i.e., imipramine, desipramine, and nortriptyline), 11 RCTs provide insufficient highquality evidence to determine whether they are effective treat­ments for painful DPN.2,19,20

Serotonin-Norepinephrine Reuptake Inhibitors

No adverse effect significantly different from placebo

—

Burning at application site

54 to 63

Constipation

34

Drowsiness

29

Nausea

27

Dizziness

22

Hyperalgesia

< 20

Vomiting

12

ER = Extended release.

Information from references 3, 12, 13, and 15.

612

for twice-daily dosing, and no dosing adjustment requirement in patients with renal impairment.

Nonetheless, gabapentin has few drug interactions and is the less expensive generic option.1,3 Compared with pregabalin, which improves numerous quality-of-life measures, the only quality-of-life measures improved with gabapentin are mental health and vitality.2

Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

Duloxetine is a first-line medication that received FDA approval in 2004 for treating painful DPN.1-3,21 A 2014 Cochrane review of eight studies (n = 2,728) showed that duloxetine at 60 mg daily led to at least 50% pain reduction at 12 weeks (NNT = 5; 95% CI, 4 to 7) vs. placebo.9 Furthermore, a 2011 mul­ticenter RCT (n = 272) showed duloxetine at 60 mg daily to be noninferior to pregabalin at 300 mg daily in patients with an inadequate pain response to treatment with gabapentin over a 12-week period.22 Duloxetine has also been shown to be effective and toler­able in the management of painful DPN in older adults.23

AMERICAN FAMILY PHYSICIAN Table 3. Common Drug Interactions in the Treatment of Painful Diabetic Peripheral Neuropathy Medication

Interaction

Pregabalin gabapentin

May increase toxic effects of CNS depressants,* SSRIs, thiazolidinediones Toxic effects may be increased by CNS depressants,* AcCHS inhibitors, hydroxyzine, and magnesium sulfate May increase toxic effects of CNS depressants,* QTc-prolonging agents,† SSRIs, St. John’s wort, sulfonylureas, tramadol, and warfarin

Amitriptyline

Effectiveness can be decreased by St. John’s wort, AcCHS inhibitors, and carbamazepine Toxic effects can be increased by CNS depressants,* QTc-prolonging agents,† SSRIs, St. John’s wort, antiemetics (e.g., 5-HT3 antagonists, ondansetron), antipsychotic agents, and bupropion Absolutely contraindicated with MAO inhibitors Duloxetine

May increase toxic effects of CNS depressants,* antiplatelet agents, alpha and beta agonists, anticoagulants (e.g., warfarin), antipsychotic agents Absolutely contraindicated with MAO inhibitors May decrease effects of TCAs and linezolid Toxic effects may be increased by CNS depressants,* alcohol, antiemetics (e.g., 5-HT3 antagonists, ondansetron), antipsychotic agents, metoclopramide Effectiveness may be decreased by CYP1A2 inducers‡

Venlafaxine

May increase toxic effects of CNS depressants* and SSRIs May decrease effectiveness of alpha-2 agonists Absolutely contraindicated with MAO inhibitors and linezolid Toxic effects may be increased by CNS depressants,* CYP2D6 inhibitors,§ CYP3A4 inhibitors,|| and SSRIs

Tramadol

May increase toxic effects of CNS depressants* and SSRIs Toxic effects may be increased by CNS depressants,* SSRIs, and TCAs

Tapentadol ER

Absolutely contraindicated with MAO inhibitors and mixed agonist and antagonist opioids May increase toxic effects of CNS depressants,* diuretics, and desmopressin Toxic effects may be increased by alcohol, amphetamines, anticholinergic agents, and magnesium sulfate

Opioids (oxycodone controlled release)

May increase toxic effects of CNS depressants,* MAO inhibitors, and SSRIs Effectiveness of medication can be increased by CYP3A4 inducers¶ Toxic effects may be increased by CNS depressants*

AcCHS = Acetylcholinesterase; CNS = Central nervous system; CYP = Cytochrome P450; ER = Extended release; MAO = Monoamine oxidase; SSRI = Selective serotonin reuptake inhibitor; TCA = Tricyclic antidepressant. *Opioids, zolpidem, pregabalin, gabapentin, TCAs, and tramadol. †Amiodarone,

azithromycin, clarithromycin, fluoxetine, haloperidol, risperidone, and sotalol.

‡Carbamazepine, §Amiodarone,

phenobarbital, and rifampin.

celecoxib, cimetidine, clomipramine, desipramine, duloxetine, haloperidol, imipramine, isoniazid,

ketoconazole, lidocaine, methadone, pioglitazone, and sertraline. ||Amiodarone, cimetidine, clotrimazole, cyclosporine, desipramine, diltiazem, efavirenz, erythromycin, fluconazole, grapefruit juice, haloperidol, metronidazole,

sertraline, tetracycline, and verapamil. ¶Carbamazepine,

dexamethasone, efavirenz, fosphenytoin, phenytoin, and St. John’s wort.

Information from reference 16.

Other serotonin-norepinephrine reuptake inhibi­tors (SNRIs) that are used for the treatment of painful DPN include venlafaxine and desvenlafaxine. Although they are considered second-line medications, these SNRIs are often better tolerated and have fewer drug interactions than amitriptyline, one of the first-line medications.

A 2004 trial showed that higher doses of venlafaxine (150 to 225 mg) led to greater improvements in pain scores than placebo.24 A 2007 Cochrane review of three studies of venlafaxine for general neuropathic pain showed an NNT of 3 (95% CI, 2.2 to 5.1).10 A 2014 RCT (n = 412) showed desvenlafaxine at dosages of

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AMERICAN FAMILY PHYSICIAN 200 and 400 mg daily to be more effective than placebo in relieving pain associated with DPN, based on a decrease of approximately one point on a 10-point pain rating scale, as well as in improving activity impairment at all doses.11

Opioid-like Medications Tramadol, a synthetic, centrally-acting opioid-like medi­cation, has also been studied for the treatment of painful DPN. A 2006 Cochrane review of four trials compar­ing tramadol with placebo showed a significant reduc­tion in neuropathic pain with tramadol at daily dosages of 100 to 400 mg.7 A subsequent meta-analysis of three of these trials (n = 303) found an NNT of 4 (95% CI, 2.8 to 6.3) for at least 50% pain relief with tramadol vs. placebo.7 Extended-release tapentadol, another opioid-like medication, received FDA approval in 2012 for use in the treatment of general neuropathic pain (i.e., not specifically for painful DPN).25 In 2011, a 12-week study (n = 395) demonstrated statistically significant pain relief in patients who were treated with tapentadol (30% pain reduction = 65%; 50% pain reduction = 34.9%; least-squares mean difference of –1.3; 95% CI, –1.70 to –0.92; P < .001) vs. placebo.13 These positive findings were largely echoed by a later 12-week study comparing tapen­tadol at dosages of 100 to 250 mg twice daily vs. placebo.26 TOPICAL MEDICATIONS Isosorbide dinitrate spray, lidocaine 5% patch or plaster, and capsaicin 0.075% cream should also be considered for the treatment of painful DPN.2

Isosorbide Dinitrate Spray Isosorbide dinitrate is a vasodilator and smooth-muscle relaxant that produced an 18% pain score reduction when sprayed on the skin of areas affected by painful DPN in one small RCT of 22 patients.2,27 It can be introduced at any time as an adjunctive treatment.

Lidocaine Lidocaine 5% patch or medicated plaster treatment resulted in comparable pain relief (30% to 50% response) to that of pregabalin (66.7% vs. 69.1%; one RCT, n = 204). Greater improvement in quality-of-life scores and fewer adverse effects occurred in the lidocaine group than in the pregabalin group.28

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Capsaicin Treatment with capsaicin 0.075% cream applied to the painful area four times daily resulted in significant pain relief (50% pain reduction; odds ratio [OR] = 2.37; 95% CI, 1.32 to 4.26) but also adverse events that led to withdrawal from the study (OR = 4.02; 95% CI, 1.45 to 11.06).27 A 2014 systematic review of three RCTs revealed the superiority of capsaicin 0.075% to placebo (stan­dardized mean deviation [SMD] = –0.91; 95% credible interval [CrI], –1.18 to –0.08, large), but not to tricyclic antidepressants (SMD = –0.13; 95% CrI, –1.03 to 0.74, small) or SNRIs (SMD = 0.45; 95% CrI, –0.49 to 1.36, small).15 The primary adverse effect is burning at the application site, which improves with longer duration of treatment.

Other concentration levels and combination treatments have also been studied. Notably, combining capsaicin 0.025% with doxepin 3.3% led to decreased skin irritation compared with capsaicin alone (one RCT, n = 200, 61% vs. 81% reduction in skin irritation).29 ALTERNATIVE MEDICATIONS

Selective Serotonin Reuptake Inhibitors Selective serotonin reuptake inhibitors are considered third-line medications for treatment of painful DPN because of a lack of high-quality studies supporting their benefit.5 Citalopram, paroxetine, and escitalopram appear to be mildly effective for treating painful DPN, whereas fluoxetine does not. Combined data from four small studies reveal an NNT of 7 for pain reduction with this class of medications.30

Opioids Despite concerns about dependency and lower-quality evidence for the benefit of chronic opioid therapy for nonmalignant pain,12 guidelines suggest a possible benefit for patients with painful DPN.2,5,31 However, monotherapy with opioids is not a first-line treatment and should be reserved for patients who do not achieve pain relief goals and functional improvement with other therapies.2,5 Notably, most studies on the use of opioids for neuropathic pain are short-term studies.14 Chronic opioid use leads to tolerance and hyperalgesia.32 A 2013 Cochrane review of 14 RCTs (n = 845, 12-week duration or less) analyzed the use of opioids for general neuropathic pain. The review evaluated the effectiveness of methadone, levorphanol, morphine, and controlled-release oxycodone and found that opioids demonstrated superior pain relief compared with placebo (greater than 33% pain relief = 57% vs.

AMERICAN FAMILY PHYSICIAN 34%; NNT = 4; 95% CI, 2.7 to 7.7; greater than 50% pain relief = 47% vs. 30%; NNT = 6; 95% CI, 3.0 to 50.0).12 Treatment with opi­oids did not, however, result in improvement in many aspects of emotional or physical functioning, as mea­sured by various validated questionnaires. In contrast, a 2014 Cochrane review assessing the use of controlled-release oxycodone (three studies, n = 204) in the treatment of painful DPN found insufficient evidence to support its role in therapy.33 OTHER TREATMENTS

Acupuncture Acupuncture, which has been the focus of 75 lowquality RCTs; traditional Chinese medicine, which typically includes acupuncture and herbal medicine; and elec­tromagnetic field application are not currently recom­mended for the treatment of painful DPN because large, high-quality RCTs are lacking.2,34-36

Alpha Lipoic Acid Alpha lipoic acid is an antioxidant substance that has been studied for treatment of neuropathic pain. Based on a 2012 meta-analysis (n = 448), alpha lipoic acid (600 mg) administered intravenously daily for three weeks led to a decrease in reported neuropathic pain for up to one year (standardized mean symptom score reduction = –2.81; 95% CI, –4.16 to –1.46, P = .0001). However, studies investigating long-term clinical improvement are lacking. Oral administration did not produce a clinically significant symptom score reduction.1,37

Acetyl-l-Carnitine Acetyl-l-carnitine, based on a 2008 meta-analysis of two RCTs (n = 1,679), and primrose oil, based on three small RCTs, demonstrated an improvement in nerve conduction but a lack of clinically significant long-term improvement in symptom scores.38,39

Transcutaneous Electrical Nerve Stimulation The results of several small studies suggest that transcutaneous electrical nerve stimulation (TENS) should be considered as a treatment for painful DPN.40 An RCT involving 31 participants showed that 15 of 18 (83%) patients receiving TENS had improved pain scores (reduction from 3.17 to 1.44 on a 5-point scale) vs. five of 13 (38%) patients receiving sham treatments (reduction from 2.98 to 2.38).41 In another small RCT (n = 19), pain scores were reduced by 27% with six weeks of TENS therapy.42 TENS can be started at any time during therapy as an adjunct to other treatments.

REFERENCES 1. Spallone V, Lacerenza M, Rossi A, Sicuteri R, Marchettini P. Painful dia­betic polyneuropathy: approach to diagnosis and management. Clin J Pain. 2012;28(8):726-743.

2. Bril V, England J, Franklin GM, et al.; American Academy of Neurol­ogy; American Association of Neuromuscular and Electrodiagnostic Medicine; American Academy of Physical Medicine and Rehabilitation. Evidencebased guideline: Treatment of painful diabetic neuropathy [published correction appears in Neurology.

2011;77(6):603]. Neurol­ogy. 2011;76(20):1758-1765.

3. Ziegler D, Fonseca V. From guideline to patient: a review of recent rec­ ommendations for pharmacotherapy of painful diabetic neuropathy. J Diabetes Complications.

2015;29(1):146-156.

4. Callaghan BC, Little AA, Feldman EL, Hughes RA. Enhanced glucose control for preventing and treating diabetic neuropathy. Cochrane Database Syst Rev. 2012; (6): D007543.

5. Moulin D, Boulanger A, Clark AJ, et al.; Canadian Pain Society. Phar­macological management of chronic neuropathic pain: revised consen­sus statement from the Canadian Pain Society. Pain Res Manag. 2014;19(6):28-335.

6. Vieweg WV, Wood MA, Fernandez A, Beatty-Brooks M, Hasnain M, Pan­durangi AK. Proarrhythmic risk with antipsychotic and antidepressant drugs: implications in the elderly. Drugs Aging. 2009;26(12):997-1012.

7. Hollingshead J, Dühmke RM, Cornblath DR. Tramadol for neuropathic pain. Cochrane Database Syst Rev. 2006;(3):CD003726.

8. Finnerup NB, Attal N, Haroutounian S, et al.

Pharmacotherapy for neu­ ropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol.

2015;14(2):62-173.

9. Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neurop­athy, chronic pain or fibromyalgia.

Cochrane Database Syst Rev. 2014;(1):CD007115.

10. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain.

Cochrane Database Syst Rev. 2007;(4):CD005454.

11. Allen R, Sharma U, Barlas S. Clinical experience with desvenlafaxine in treatment of pain associated with diabetic peripheral neuropathy. J Pain Res. 2014;(7): 39-351.

12. McNicol ED, Midbari A, Eisenberg E. Opioids for neuropathic pain. Cochrane Database Syst Rev. 2013;(8): CD006146.

13. Schwartz S, Etropolski M, Shapiro DY, et al. Safety and efficacy of tapentadol ER in patients with painful diabetic peripheral neuropathy: results of a randomizedwithdrawal, placebo-controlled trial. Curr Med Res Opin.

2011;27(1):151-162.

14. Dowell D, Haegerich TM, Chou R. CDC Guideline for prescribing opi­oids for chronic pain—United States, 2016.

MMWR Recomm Rep. 2016;65(1):1-49.

15. Griebeler ML, Morey-Vargas OL, Brito JP, et al.

Pharmacologic inter­ventions for painful diabetic

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AMERICAN FAMILY PHYSICIAN neuropathy: an umbrella systematic review and comparative effectiveness network meta-analysis [published cor­rections appear in Ann Intern Med. 2015;162(8):600, and Ann Intern Med. 2015;162(10)739].

Ann Intern Med. 2014;161(9):639-649.

16. Lexicomp. online.lexi.com Accessed March 5, 2015.

[subscription

required].

17. Wiffen PJ, Derry S, Moore RA, Kalso EA. Carbamazepine for chronic neuropathic pain and fibromyalgia in adults.

Cochrane Database Syst Rev. 2014;(4):CD005451.

18. Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;(7):CD008242.

19. Hearn L, Derry S, Phillips T, Moore RA, Wiffen PJ. Imipramine for neuro­ pathic pain in adults. Cochrane Database Syst Rev. 2014;(5):CD010769.

20. Hearn L, Moore RA, Derry S, Wiffen PJ, Phillips T. Desipramine for neuro­pathic pain in adults. Cochrane Database Syst Rev. 2014;(9):CD011003.

21. Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, et al.

Comparative affinity of duloxetine and venlafaxine for serotonin and norepineph­rine transporters in vitro and in vivo, human serotonin receptor sub­types, and other neuronal receptors. Neuropsychopharmacology. 2001; 25(6):871-880.

22. Tanenberg RJ, Irving GA, Risser RC, et al. Duloxetine, pregabalin, and duloxetine plus gabapentin for diabetic peripheral neuropathic pain management in patients with inadequate pain response to gabapentin: an open-label, randomized, noninferiority comparison. Mayo Clin Proc.

2011;86(7):615-626.

23. Skljarevski V, Frakes EP, Sagman D, Lipsius S, Heinloth AN, Dueñas Ten­tori HJ. Review of efficacy and safety of duloxetine 40 to 60 mg once daily in patients with diabetic peripheral neuropathic pain. Pain Res Treat.

2012;2012:898347.

polyneuropathy: an open-label, non-inferiority two-stage RCT study. Curr Med Res Opin. 2009;25(7):1663-1676.

29. Argoff CE. Topical analgesics in the management of acute and chronic pain. Mayo Clin Proc. 2013; 88(2): 195-205.

30. Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological treatment of neuropathic pain. Pain.

2010;150(3):573-581.

31. Chou R, Fanciullo GJ, Fine PG, et al.; American Pain Society-American Academy of Pain Medicine Opioids Guidelines Panel. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain.

2009; 10(2):113-130.

32. Chang G, Chen L, Mao J. Opioid tolerance and hyperalgesia. Med Clin North Am. 2007;91(2):199-211.

33. Gaskell H, Moore RA, Derry S, Stannard C. Oxycodone for neuro­pathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2014;(6):CD010692.

34. Weintraub MI, Herrmann DN, Smith AG, Backonja MM, Cole SP. Pulsed electromagnetic fields to reduce diabetic neuropathic pain and stimu­late neuronal repair: a randomized controlled trial. Arch Phys Med Reha­bil.

2009;90(7):1102-1109.

35. Galuppo M, Giacoppo S, Bramanti P, Mazzon E. Use of natural com­pounds in the management of diabetic peripheral neuropathy. Mol­ecules. 2014;19(3):877-2895.

36. Chen W, Yang GY, Liu B, Manheimer E, Liu JP. Manual acupuncture for treatment of diabetic peripheral neuropathy: a systematic review of randomized controlled trials [published correction appears in PLoS One. 2014;9(3):e91110]. PLoS One. 2013;8(9):e73764.

37. Mijnhout GS, Kollen BJ, Alkhalaf A, Kleefstra N, Bilo HJ. Alpha lipoic acid for symptomatic peripheral neuropathy in patients with diabetes: a meta-analysis of randomized controlled trials. Int J Endocrinol. 2012;2012:456279.

38. Evans JD, Jacobs TF, Evans EW. Role of acetyl-L-carnitine in the treat­ment of diabetic peripheral neuropathy. Ann Pharmacother. 2008;42(11):686-1691.

24. Rowbotham MC, Goli V, Kunz NR, Lei D. Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study [published correction appears in Pain. 2005;113(1-2): 248].

Pain. 2004;110(3):697-706.

39. Halat KM, Dennehy CE. Botanicals and dietary supplements in diabetic peripheral neuropathy. J Am Board Fam Pract. 2003;16(1):47-57.

25. Tzschentke TM, Christoph T, Kögel B, et al. (-)-(1R,2R)3-(3-dimeth­y lamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride (tapentadol HCl): a novel mu-opioid receptor agonist/norepinephrine reuptake inhibitor with broad-spectrum analgesic properties. J Pharmacol Exp Ther. 2007;323(1):265-276.

40. Dubinsky RM, Miyasaki J. Assessment: efficacy of transcutaneous elec­trical nerve stimulation in the treatment of pain in neurologic disorders (an evidencebased review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2010;74(2):173-176.

26. Vinik AI, Shapiro DY, Rauschkolb C, et al. A randomized withdrawal, placebo-controlled study evaluating the efficacy and tolerability of tapentadol extended release in patients with chronic painful diabetic peripheral neuropathy. Diabetes Care. 2014;37(8):2302-2309.

41. Kumar D, Marshall HJ. Diabetic peripheral neuropathy: ameliora­ tion of pain with transcutaneous electrostimulation. Diabetes Care. 1997;20(11):1702-1705.

27. Wong MC, Chung JW, Wong TK. Effects of treatments for symp­toms of painful diabetic neuropathy: systematic review. BMJ. 2007; 335(7610):87.

42. Forst T, Nguyen M, Forst S, Disselhoff B, Pohlmann T, Pfützner A. Impact of low frequency transcutaneous electrical nerve stimulation on symptomatic diabetic neuropathy using the new Salutaris device. Dia­betes Nutr Metab. 2004;17(3):163-168.

28. Baron R, Mayoral V, Leijon G, Binder A, Steigerwald I, Serpell M. 5% lidocaine medicated plaster versus pregabalin in post-herpetic neuralgia and diabetic

43. Lindsay TJ, Rodgers BC, Savath V, Hettinger K. Treating diabetic periph­eral neuropathic pain. Am Fam Physician.

2010;82(2):151-158.

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Practice Guidelines CARDIOMYOPATHY AND MYOCARDITIS IN COMPETITIVE ATHLETES: RECOMMENDATIONS FROM THE AHA/ACC The American Heart Association (AHA) and American College of Cardiology (ACC) have provided recommendations regarding eli­gibility and disqualification of competitive athletes with cardiovascular abnormalities. The full guidelines can be found at http://circ.ahajournals.org/content/132/22/ e256.full. This summary focuses on cardiomyopa­thy and myocarditis.

Recommendations Hypertrophic Cardiomyopathy

per­ sons with suspected acute myocarditis no earlier than three to six months after initial presentation.

These persons can then partici­ pate in training and competition, assuming their ventricular systolic function and serum markers of myocardial injury, inflamma­tion, and heart failure are normal, as well as that no relevant arrhythmias are seen on the Holter monitor or exercise electro­cardiography. It has not been determined if resuming participation is contingent on whether myocarditis-related late gadolinium enhancement on cardiovascular magnetic resonance imaging has resolved. If a person has or is suspected to have myocarditis, he or she should not compete if there is inflammation.

Hypertrophic cardiomyopathy (HCM), which occurs in one in 500 persons, is a common nontraumatic cause of sudden death in young persons. For persons who are positive for the HCM genotype, competing in competitive athletics is reasonable if no symptoms or evidence of left ventricular hypertrophy on echocardiography or cardiac magnetic resonance imaging are present, and especially if there is also no family his­tory of related sudden death. Persons who likely have HCM with clinical manifesta­tions such as ventricular hypertrophy should not participate in most competitive sports, except low-intensity class 1A versions as described in the classification of sports in the full guidelines. Providing medication such as beta blockers to persons with cardiac-related symptoms or ventricular tachyarrhythmia and placing a prophylactic implantable cardioverter-defibrillator (ICD) in persons with HCM are not recommended if the only reason for doing so is to allow participation in high-intensity sports. These medications may actually inhibit a person’s best physical performance, and the ICDs can have associ­ated complications.

Arrhythmogenic Right Ventricular Cardiomyopathy

Myocarditis

Until more study results are available, ath­letes with symptomatic dilated cardiomyopa­thy, primary nonhypertrophied restrictive cardiomyopathy, and systemic infiltrative cardiac myopathies with secondary cardiac involvement (e.g., sarcoidosis) should not participate in most competitive sports, with the possible exception of low-intensity class 1A versions in select cases.

Before a return to competitive sports is allowed, resting echocardiography, Holter monitoring for 24 hours, and exercise elec­trocardiography should be performed in

Source: Adapted from Am Fam Physician. 2016;94(3):249-250.

Persons with arrhythmogenic right ventricu­lar cardiomyopathy, or those with a bor­derline or possible diagnosis, should not compete in most competitive sports, except possibly the low-intensity class 1A versions as described in the full guidelines. Placing a prophylactic ICD is not recommended if the only reason for doing so is to allow participa­tion in highintensity sports.

Pericarditis Persons in the acute phase of pericardi­tis should not play competitive sports and should return to play only if there is no evidence of active disease (e.g., effusion on echocardiography) and inflammation serum markers are normal. If there is possible myo­cardial involvement, participation decisions should be based on disease course, and those with chronic pericarditis and constriction should be disqualified entirely.

Other Myocardial Diseases

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Photo Quiz ACUTE ONSET OF ELBOW SWELLING A 50-year-old man presented with swelling in his right elbow that began 10 days earlier. He had no history of injury to the arm, but he often rested his elbows on his desk at work. The elbow was not painful, and there was no arthralgia. He did not have a fever. His medical history was significant for chronic glomerulonephritis.

He had been on hemo­dialysis for one year.

Physical examination revealed a spherical, fluctuant swelling over the posterior por­tion of the right elbow (Figure 1). There was no redness or tenderness to palpation, and range of motion was normal.

Question Based on the patient’s history and physical examination findings, which one of the fol­lowing is the most likely diagnosis?

A. Lipoma arborescens.

B. Olecranon bursitis.

C. Olecranon fracture.

D. Triceps tendon avulsion.

Figure 1.

SEE THE FOLLOWING PAGE FOR DISCUSSION.

Source: Adapted from Am Fam Physician. 2016;94(3):243-244.

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AMERICAN FAMILY PHYSICIAN Discussion

Summary Table

The answer is B: olecranon bursitis. This is a relatively common condition that most often affects men between 30 and 60 years of age.1 The classic finding is posterior elbow swelling that is fluctuant and clearly demarcated.

It is often described as a “goose egg” over the olecranon process. The patient may report pain in the area of fluctuance, but the swelling is often painless, especially in noninflamma­tory, aseptic bursitis. The onset of olecranon bursitis may be sudden if it is secondary to infection or acute trauma. Range of motion in the elbow is usually normal, but there may be a slight limitation of the end range of flexion because of pain or bursal thickening.

Condition

Characteristics

Lipoma arborescens

Painless, boggy swelling; Normal unilateral or bilateral

Olecranon bursitis

Normal Fluctuant and demarcated posterior elbow swelling; traumatic or caused by infection, crystal deposition, or systemic disease

Traumatic nonseptic bursal inf lamma­ tion of the olecranon is common because of the superficial location of the bursa. There are several other possible causes of inflam­mation of the bursa, including infection, crystal deposition (gout or pseudogout), and systemic disease (rheumatoid arthritis, sys­temic lupus erythematosus, and uremia).2 The main risk factor for traumatic olecranon bursitis is repetitive pressure on the elbow.2 Persons who often rest their elbows on hard surfaces may develop bursitis; hence it is sometimes called “student’s elbow.” A protective elbow padding, avoidance of pressure to the elbow, and limitation of activities are effective treatments.

Lipoma arborescens is a rare nonneo­ plastic intraarticular lesion that most commonly affects the knee and the supra­patellar bursa, and rarely affects the elbow joint. It presents as painless, boggy joint swelling with recurrent effusion. It is usually monoarticular but may occur bilaterally.

Range of motion

Olecranon fracture

Deformity, swelling, pain

Limited

Triceps tendon avulsion

Painful swelling; palpable gap proximal to the olecranon

Limited

present with deformity, swelling, and pain. They have decreased range of motion and are often unable to fully extend the elbow.

Triceps tendon avulsion should be sus­pected in patients with a history of trauma who present with pain and swelling in the elbow. It usually follows indirect trauma but can occur after a direct blow to or fall on the elbow.

The examination reveals swelling and a palpable gap proximal to the olecra­non. With a complete rupture of the tendon, there is significant loss of extension range of motion and strength.

REFERENCES 1. Del Buono A, Franceschi F, Palumbo A, Denaro V, Maffulli N. Diagnosis and management of olecranon bursitis. Surgeon. 2012;10(5):297-300.

2. Baumbach SF, Lobo CM, Badyine I, Mutschler W, Kanz KG. Prepatellar and olecranon bursitis: literature review and development of a treatment algorithm. Arch Orthop Trauma Surg. 2014;134(3):359-370.

■■■■

Olecranon fractures are a diverse group of injuries that often involve the elbow joint. Patients typically have a history of an injury. Patients with an olecranon fracture

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COMMUNITY MEDICINE

Incidence of Cervical Lesions in a Tertiary Care Hospital in South India: A 5-year Analysis SANA ABOOSALIH*, LEENA DENNIS JOSEPH†, SAI SHALINI CN‡, MONICA KUMBHAT#, RAJENDIRAN S†

ABSTRACT In gynecological practice, there are several lesions localized to the uterine cervix, which include several inflammatory, benign, premalignant and malignant lesions. While lesions of the cervix are a major cause of morbidity in all age groups, cervical premalignant and malignant lesions are picked up on Pap smear. With proper screening and treatment, mortality from carcinoma of the cervix can be greatly reduced, which has been seen in the developed countries. The exact incidence of cervical lesions is not available in this part of India, where an active Pap screening is lacking. Poverty, literacy levels and urbanization are all significantly related to cervical cancer incidence and mortality. With the wide range of pathologies in the uterine cervix, some lesions may appear exuberant and can be misdiagnosed as malignant. Hence this study was taken up, with the objective to analyze the spectrum of cervical lesions, with an emphasis on the histological and morphological aspects. A retrospective analysis over a period of 5 years was done, studying all the cervical biopsies that were received in the Dept. of Pathology, Sri Ramachandra Medical College, Chennai. A total of 882 cases of cervical lesions over this period of 5 years were studied.

There were 107 cases (12.13%) of malignancies, 62 cases (7.03%) were premalignant, 233 cases of benign endocervical polyps (26.42%) and inflammatory pathology was observed in 480 cases (54.42%). Malignant lesions were seen in an age group of 28-80 years, majority of non-neoplastic lesions were seen in women of the reproductive age group.

Keywords: Cervical lesions, polyps, cervical intraepithelial neoplasia, carcinoma cervix

T

he uterine cervix is the lower portion of the uterus, which is connected to the vaginal canal.

The cervix carries out many functions, which aid to the overall reproductive health and well-being of women.1 In gynecological practice, it is known that the uterine cervix can host a spectrum of lesions.

These lesions may be neoplastic or non-neoplastic in nature. Lesions of the cervix are a major cause of morbidity in all age groups. Services from biopsy and hysterectomy specimens constitute majority of the gynecological specimens received in the Dept. of Pathology. While inflammatory conditions like chronic cervicitis, microglandular adenosis, etc. form

majority of lesions in the reproductive age group, they resolve with proper treatment. Poverty, illiteracy, low socioeconomic status and inadequate sanitation and hygiene practices are implied in the cause of increased inflammatory pathology. However, primary malignant disease of the cervix is also common and unless picked up at an earlier stage, is a major cause of mortality among women, especially those pertaining to the lower socioeconomic group who present at later stages of this disease. Carcinoma of the cervix is on the declining trend in India, according to the populationbased registries; yet it continues to be a major concern for women health in India.2

*MBBS Graduate †Professor ‡Associate Professor #Postgraduate Dept. of Pathology Sri Ramachandra University, Chennai, Tamil Nadu Address for correspondence Dr Leena Dennis Joseph Professor Dept. of Pathology Sri Ramachandra University, Chennai, Tamil Nadu E-mail: leenadj@gmail.com

The exact incidence of various cervical lesions is not available in this part of India, where an active Pap screening is not in place. The cervix with its various pathologies can sometimes appear exuberant and be misdiagnosed as malignant. Hence, a detailed histological and morphological study of the spectrum of lesions of the cervix was taken up over a period of 5 years, with the aim to analyze the various types of premalignant and malignant lesions of the cervix in our patients, which will help us to understand the prevalence of different cervical lesions and help to plan and implement screening as well as awareness programs to prevent and treat the same.

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COMMUNITY MEDICINE MATERIAL AND METHODS This is a retrospective analysis over a period of 5 years. All the cervical biopsies received in the Dept. of Pathology, Sri Ramachandra Medical College and Research Institute, Chennai, were specimens for the study. The data was obtained from the archival material of the histopathology division in our hospital. The data was analyzed and the incidence and age distribution of the various lesions were studied.

a

b

c

d

RESULTS A total of 882 cases of cervical lesions that were biopsy and hysterectomy specimens over this period of 5 years were studied. There were 107 cases (12.13%) of malignancies which included 96 cases of squamous cell carcinoma and 11 cases of adenocarcinoma. The squamous cell carcinoma cases were divided into keratinizing and nonkeratinizing types (Fig. 1). They were also graded on the basis of differentiation.

Sixty-two cases (7.03%) were premalignant (cervical intraepithelial neoplasia, CIN). Of these 15 cases presented as CIN 1, 14 cases presented as CIN 2 and 33 cases were that of CIN 3.

Inflammatory pathology was observed in 480 cases (54.42%). This included chronic cervicitis, Nabothian cysts, regenerative hyperplasia, ulceration and microglandular adenosis. Benign endocervical polyps were recorded in 233 cases (26.42%) (Fig. 3).

As for the age distribution, malignant lesions were seen in an age group of 28-80 years, benign polyps were

Figure 2. Benign and inflammatory pathology of the cervix: Chronic cervicitis (H&E x100) (a); squamous metaplasia (H&E x40) (b); Nabothian cysts (H&E x40) (c) and benign endocervical polyp (H&E x40) (d).

Cervical lesions Malignant cases 7% 12%

55% 81% 26%

Premalignant conditions Inflammatory pathology Bening endocervical polyps

Figure 3. The pie diagram shows the distribution of the various cervical lesions.

seen in an age group of 20-68 years, and inflammatory conditions were seen in those between 22 and 78 years.

DISCUSSION

a

c

b

d

Figure 1. Malignant lesions of the cervix: Well-differentiated squamous cell carcinoma of cervix (H&E x40) (a); moderately differentiated squamous cell carcinoma (H&E x40) (b); adenocarcinoma of the cervix (H&E x100) (c) and adenocarcinoma of the cervix (H&E x40) (d).

The cervix is a host to a spectrum of conditions which may be inflammatory, benign, premalignant or malignant. The exact incidence of various cervical lesions is not available in this part of India, where an active Pap screening is not in place.

According to a latest study by Freddie Bray et al, the worldwide cancer burden is on a projected surge from 14 million new cases in 2012 to 24 million by 2035, with the greatest increases happening in developing countries. India is one of the most populous countries in the world and has a rapidly rising cancer incidence and mortality rate.3 Amongst women, cervical cancer is one of the major cancers in India. Cervical cancer is also one of the most preventable cancers through early detection and treatment. In India, studies are showing

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COMMUNITY MEDICINE that cervical cancer rates are uniformly decreasing in all urban and rural registries.4 Despite the decreasing trend, cervical cancer is still a major cancer and analysis of the various conditions affecting the cervix would help in planning and organization of programs for its control. If treatment is administered during the earliest stages of cervical cancer, 5-year survival rates can be increased to more than 90%. Unfortunately, despite the availability of methods for prevention, more than 95% of women in India have never been screened for cervical cancer. Moreover, women in India are most often diagnosed during later stages of cervical cancer, significantly reducing survival prognosis.5 Every year in India; 1,22,844 women are diagnosed with cervical cancer and 67,477 die from the disease.

India has a population of 432.2 million women aged 15 years and older who are at risk of developing cancer.

It is the second most common cancer in women aged 15-44 years. India also has the highest age standardized incidence of cervical cancer in South Asia at 22, compared to 19.2 in Bangladesh, 13 in Sri Lanka and 2.8 in Iran. Therefore, it is vital to understand the epidemiology of cervical cancer in India.2 Our study is also consistent with this finding, in this region of India where the malignant lesions were seen in an age group of 28-80 years. Most common type of carcinoma was squamous cell carcinoma, 95 cases and only 11 cases of adenocarcinoma was reported in the study.

In this study of the spectrum of cervical lesions, the most commonly encountered pathology is of the inflammatory type at 81%, which is consistent with various studies from India and around the world, which say that inflammatory are more commonly seen than neoplastic conditions of the cervix. The age range of inflammatory lesions in our region was 22-78 years.

Studies from other parts of the country show both chronic nonspecific cervicitis and polypoidal endocervicitis commonly found in the sexually active period of women i.e., 30-60 years, with a peak incidence in the age group 41-50 years. Chronic nonspecific cervicitis was associated with other histological changes like squamous metaplasia, koilocytosis, epidermidization and Nabothian cyst. Worldwide cervical inflammatory lesions are extremely common in sexually active females, at least at the microscopic level.6 In our study, majority of cervical lesions were in the 4th to 5th decade of life. Chronic nonspecific cervicitis was the most common histological diagnosis made (50%). No case was seen before menarche. This is similar in other reports from India.7 It is a common phenomenon in postmenopausal women. Certain

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lesions of chronic nonspecific cervicitis had co-existing squamous metaplasia, Nabothian cysts, dysplasia and ulceration. Chlamydia trachomatis and other pathogens are associated with upper genital tract infections, pregnancy complications or sexually transmitted infections (STIs). Neglected asymptomatic patients can serve as a reservoir of STI, which underscores the importance of combined culture and Pap smear examination. Staphylococcus aureus (42%) is found to be the most common organism causing cervicitis besides Escherichia coli (2%), Chlamydia (6%) and Klebsiella (2%). The findings of this study should make women aware of the importance of periodic screening for sexually transmitted diseases (STDs) and also help health professionals design control measures for chronic cervicitis.8 Cervical intraepithelial neoplasia (CIN) include all cases of CIN 1, CIN 2 and CIN 3. Out of 882 cases, only 7.03% cases of CIN (including CIN1, 2 and 3) were diagnosed based on the typical histological findings. Highest incidence of CIN was in the 5th to 6th decade. This study also highlights that the highest incidence of squamous cell carcinoma in the 5th decade and this finding is consistent with the study done by Dhakal et al.9 The majority of all grades of CIN can be attributed to human papilloma virus (HPV) infection especially with the cancer associated types of HPV.10 Cervical carcinogenesis must involve the presence of additional promoting factors, since only a minority of patients harboring HPV develop cervical dysplasia.

Bacterial vaginosis has been suggested as an intriguing possible co-factor in cervical carcinogenesis. A metaanalysis study with over 10,000 women and in addition a database of more than 1 million cervical smears, confirmed a positive association between bacterial vaginosis and cervical pre-cancerous lesions.11 Low education and socioeconomic status, young age at marriage or first sexual intercourse, high parity and male partners sexual behavior are established risk factors for carcinoma of the cervix. With the advent of HPV vaccination, there is a global declining trend of cervical carcinoma and CIN.12 Full use of this vaccination is not present in India and more awareness needs to be generated to achieve better levels of prevention of this disease.

Premalignant and malignant glandular lesions of the cervix are known to often cause diagnostic problems as various benign and malignant lesions appear exuberant and may be a challenge for the practicing pathologist, considering the different morphologies these tumors may have and the overlapping features with other

COMMUNITY MEDICINE benign and malignant glandular lesions from and outside the cervix. In this review, the spectrum of histopathologic appearances of cervical lesions, emphasizing morphologic key features and knowing the general trend of cervical lesions is useful.13 Cervical cytology is frequently being used to screen for cervical diseases, histopathological examination of the biopsies of cervical lesions is the single best gold standard for the diagnosis of the non-neoplastic lesions of the cervix. Studies show that there is good correlation between cervical cytology and histopathology. The regular screening of women by Pap smear is a costeffective method for early detection of premalignant and malignant cervical lesions and secondary prevention of carcinoma cervix.14 In our 5-year retrospective study, 882 cases of cervical lesions were reported, of these 12.13% cases were malignant, 7.03% cases were premalignant, 80.84% cases were nonmalignant. Nonmalignant lesions included 54.45% inflammatory pathology and 26.42% cases to be benign endocervical polyps. This data clearly shows that nonmalignant cervical pathologies are much common than malignant and premalignant lesions of the cervix in our region. This finding is in keeping with previous reports from developing countries, where benign lesions are more common than malignant lesions. Various reports from other parts of the world; however, show malignant lesions to be more than benign cervical lesions and the reason for this can be attributed to the fact that an active “Pap screening” program is not in place in our country.

Many benign hyperplastic or reactive processes that occur in the female genital tract may be mistaken for neoplasms both clinically and pathologically.

Awareness of the features of such lesions will aid in their correct diagnosis and prevent overtreatment of benign processes.15 The relationship between education and cancer incidence in this rural population has shown that the risk of cervical cancer is inversely associated with increasing educational levels. Also HPV positivity in the rural population of Dindigul district was found to be inversely associated with education level.16 Therefore, the role of education in the determinants of cervical cancer is evident. Education is the fundamental factor among the sociodemographic and reproductive determinants of cervical cancer in low socioeconomic categories. Public awareness through education and improvements in living standards can play an important role in reducing the high incidence of cervical cancer in India. These findings further stress the importance of

formulating public health policies aimed at increasing awareness and implementation of cervical cancer screening programs. Targeted interventions can lead to a decrease in the projected increases in cancer burden through effective primary prevention strategies, alongside the implementation of vaccination, early detection and effective treatment programs.

CONCLUSION This analysis highlighted the spectrum of cervical premalignant, malignant and inflammatory lesions in women of varying age groups in our hospital. The incidence of CIN is 7.03% and that of cancer is 12.13% and 54.42% is representative of an inflammatory pathology. The incidence of premalignant and malignant cervical lesions are very less in developed countries, where Pap smear is actively used for screening. Its effectiveness has to be used in this part of India by increasing its awareness among physicians and patients.

REFERENCES 1. Domblae V, Gundalli S, Sonali. Histopathological analysis of uterine lesions in hysterectomy specimens. Int J Sci Res. 2015;4(5):2171-4.

2. Sreedevi A, Javed R, Dinesh A. Epidemiology of cervical cancer with special focus on India. Int J Womens Health.

2015;7:405-14.

3. Stewart BW, Bray F, Forman D, Ohgaki H, Straif K, Ullrich A, et al. Cancer prevention as part of precision medicine: ‘plenty to be done’. Carcinogenesis. 2016;37(1):2-9.

4. Badwe RA, Dikshit R, Laversanne M, Bray F. Cancer incidence trends in India. Jpn J Clin Oncol. 2014;44(5): 401-7.

5. Beining RM. Screening for cervical cancer: an exploratory study of urban women in Tamil Nadu, India. PhD (Doctor of Philosophy) Thesis, University of Iowa, 2012.

Available at: http://ir.uiowa.edu/etd/2820.

6. Poste P, Patil A, Andola SK. Incidence of non-neoplastic cervical pathologies recorded at a medical college. Int J Appl Sci Res Rev. 2015;2(2):39-50.

7. Saravanan S, Arnold J, Arul P. Histomorphological spectrum of lesions of the cervix, a retrospective study in a tertiary care hospital. J Evolut Med Dent Sci. 2015;4(59):10326-9.

8. Raghavi PS. Magnitude of chronic cervicitis and its related factors among women attending gynaecology OPD in a tertiary health centre - Tamil Nadu. Australas Med J. 2013;6(4):258.

9. Dhakal HP, Pradhan M. Histological pattern of gynecological cancers. JNMA J Nepal Med Assoc.

2009;48(176):301-5.

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COMMUNITY MEDICINE 10. Schiffman MH, Bauer HM, Hoover RN, Glass AG, Cadell DM, Rush BB, et al. Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J Natl Cancer Inst.

1993;85(12):958-64.

11. Gillet E, Meys JF, Verstraelen H, Verhelst R, De Sutter P, Temmerman M, et al. Association between bacterial vaginosis and cervical intraepithelial neoplasia: systematic review and meta-analysis. PLoS One. 2012;7(10):e45201.

13. Loureiro J, Oliva E. The spectrum of cervical glandular neoplasia and issues in differential diagnosis. Arch Pathol Lab Med. 2014;138(4):453-83.

14. Tamboli GD, Khatod LV. Accuracy of cytological findings in abnormal cervical smear by cyto-histological comparison. J Med Educ Res. 2013;3(2):19-24.

15. Medeiros F, Bell DA. Pseudoneoplastic lesions of the female genital tract. Arch Pathol Lab Med. 2010;134:393-403.

16.

12. Baldur-Felskov B, Munk C, Nielsen TS, Dehlendorff C, Kirschner B, Junge J, et al. Trends in the incidence of cervical cancer and severe precancerous lesions in Denmark, 19972012. Cancer Causes Control. 2015;26(8):1105-16.

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Franceschi S, Rajkumar T, Vaccarella S, Gajalakshmi V, Sharmila A, Snijders PJ, et al. Human papillomavirus and risk factors for cervical cancer in Chennai, India: a casecontrol study. Int J Cancer. 2003;107(1):127-33.

WHO Issues New Guidance on HIV Self-testing In advance of World AIDS Day, WHO has released new guidelines on HIV self-testing to improve access to and uptake of HIV diagnosis.

According to a new WHO progress report lack of an HIV diagnosis is a major obstacle to implementing the Organization’s recommendation that everyone with HIV should be offered antiretroviral therapy (ART). The report reveals that more than 18 million people with HIV are currently taking ART, and a similar number is still unable to access treatment, the majority of which are unaware of their HIV positive status. Today, 40% of all people with HIV (over 14 million) remain unaware of their status. Many of these are people at higher risk of HIV infection who often find it difficult to access existing testing services. HIV self-testing is a way to reach more people with undiagnosed HIV and represents a step forward to empower individuals, diagnose people earlier before they become sick, bring services closer to where people live, and create demand for HIV testing … (WHO, 29th November, 2016)

NIH Statement on World AIDS Day 2016 The National Institutes of Health (NIH) is supporting the development of new, innovative methods to prevent the spread of HIV, building on proven HIV prevention tools such as antiretroviral treatment; condoms; voluntary medical male circumcision and pre-exposure prophylaxis (PrEP), a daily pill that uninfected people can take to prevent infection. Earlier this week, NIH announced the start of HVTN 702, a large HIV vaccine efficacy trial in South Africa that builds on the modest success of the RV144 vaccine trial conducted in Thailand. In April, NIH launched the Antibody-Mediated Prevention Trial (AMP) to test whether a broadly neutralizing antibody delivered intravenously to uninfected individuals is safe, tolerable and effective at preventing HIV infection.

NIH is testing HIV prevention options that address the unique needs of women, such as a vaginal ring infused with the antiretroviral drug dapivirine, which reduced the risk of HIV infection by only a modest 27% in a large clinical trial reported this year… (NIH)

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Strategies to Reduce Medication Errors: Working to Improve Medication Safety P KASTHURI

ABSTRACT Strategies to improve medication safety focused on acute care settings. Twenty-six studies and descriptions of quality improvement projects were identified. Strategies used included recommendations from a nationwide voluntary organization to improve safety, education of nurses and other providers in safe practices and system change and technology.

Keywords: Medication errors, healthcare delivery, lack of communication, monitoring side effects of drugs, adverse drug reactions, sentinel events, high risk and alert medications, legal implications “I care not what others think of what I do, but I care very much about what I think what I do: That is character!”

—Theodore Roosevelt

BACKGROUND “Medication errors directly impact the lives of the patients and also leave a lasting negative impression on the minds of the people about the hospital.” It is one of the critical aspects involved in patient safety and hence was identified as one of the quality indicators for health professionals. The Institute of Medicine report, “To Err is Human: Building a Safer Health System”, has helped raise public awareness surrounding the issue of patient safety within hospitals. A number of legislative and regulatory steps have resulted in hospital authorities putting in place various systems to allow for error reporting and prevention. Medication errors are being closely scrutinized as part of these hospital based efforts.

The instances of medication errors are potentially lifethreatening and have common occurrences in hospitals.

Some of the strategies include medication-error analysis, computerized provider-order entry systems, automated dispensing cabinets, bar-coding systems, medication reconciliation, standardizing medicationuse processes, education and emergency-medicine, clinical pharmacists. Special consideration also needs to be given to the development of strategies for the pediatric population, as they can be at an elevated risk of harm. Regardless of the strategies implemented,

the prevention of medication errors begins and ends with the development of a culture that promotes the reporting of medication errors, and a systematic, nonpunitive approach to their elimination.

In United States, reducing medication errors and improving patient safety have become common topics of discussion for the federal and state legislators, the insurance industry, pharmaceutical companies, healthcare professionals and patients. However, improving the judicious use of medications and minimizing adverse drug reactions have always been key areas of research and study for those working in clinical pharmacology.

SOBERING STATISTICS “Medication errors are one of the nation’s leading causes of death and injury. A report of US medical institutes estimates that as many as 44,000 to 98,000 people die in US hospitals each year as a result of medication errors.

Government agencies, purchasers of group healthcare and healthcare providers are working together to make the US healthcare system safer for patients and the public.

MEDICATION ERRORS - STAGES Medication errors may occur at any stage of the medication process including:

Nursing Student Apollo College of Nursing, Chennai, Tamil Nadu E-mail: kasthurisenthil77@gmail.com

ÂÂ

Prescribing stage

ÂÂ

Transcription stage

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Dispensing stage

ÂÂ

Administration stage

ÂÂ

Reporting/Monitoring stage.

Table 1. Error-Prone Abbreviations

Prescription Stage The prescribing stage is one of the stages where medication errors occur most frequently, representing 71% of serious medication errors. Utilization of a verbal process at this stage can turn even a correct order into a medication error if it is misunderstood or misinterpreted.

Of the five stages, ordering/prescribing most often initiates a series of errors resulting in a patient receiving the wrong dose or wrong medication. In this stage, the wrong drug, dose or route can be ordered; also drugs to which the patient has known allergies.

Workload, knowledge about the prescribed drug and attitude of the prescriber, especially if there is a low perceived importance of prescribing compared with other responsibilities, are significantly associated with adverse drug reactions (ADEs).

Prescription The five 'rights': Reporting Errors

Prescription

Junior Doctor

Senior Doctor

Review of prescription

yyPatient yyDrug yyDose yyRoute yyTiming (frequency and duration) Use on-line aids to prescription and automated medication systems or uniform medication charts

Abbreviation

Why it’s a problem? Alternative

U (unit)

Mistaken for zero, number four or cc

Write “unit”

IU (international unit)

Mistaken for IV or number ten

Write “international unit”

QD (daily)

Mistaken for QID

Write “daily”

QOD (every other day)

Mistaken for QID and QD

Write “every other day”

Trailing zero (X.0 mg)

Decimal point is missed

Write X mg

Lack of leading zero (.X mg)

Decimal point is missed

Write 0.X mg

ÂÂ

Heparin, low molecular weight, injection

ÂÂ

Heparin, unfractionated, IV

ÂÂ

Insulin, subcutaneous and IV

ÂÂ

Lidocaine, IV

ÂÂ

Magnesium sulfate injection

ÂÂ

Methotrexate, oral, nononcologic use

ÂÂ

Nitroprusside sodium for injection

ÂÂ

Potassium chloride for injection concentrate

ÂÂ

Potassium phosphate injection

ÂÂ

Sodium chloride injection, hypertonic (more than 0.9% concentration)

ÂÂ

Warfarin.

Review of prescription

Guess that Prescription

Monitor clinical benefits and harms from treatment:

Handwritten prescriptions can be difficult to identify.

For example, in the following prescription the drug name Avandia was incorrectly interpreted as Coumadin.

yyBeneficial effects yyAdverse drug reactions yyDrug-drug interactions Monitor plasma concentrations or biomarkers to evaluate adherence, benefits and harms

Causes There are certain abbreviations used in prescriptions, which are error-prone as shown in Table 1.

High-Alert Medications The Institute for Safe Medication Practices has compiled a list of “high-alert” drugs. These medications require extra precaution because they can cause serious patient harm when used in error. ÂÂ

Amiodarone, IV

ÂÂ

Colchicine injection

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Including the Indication Including a drug’s indication on the prescription is a simple safety measure. The indication, whether handwritten or communicated helps pharmacists and others avoid confusion between look-alike drug names.

For example, if it is unclear whether a prescription says Celebrex or Cerebyx, a check mark in the “musculoskeletal” box would suggest that Celebrex is the desired drug.

COMMUNITY MEDICINE Ways to Minimize the Prescription Error Require that orders be read back. Orders given verbally, rather than in written form, are inherently problematic because of misinterpretations of names and strengths, etc. The key to a safe process is using “read back”. The staff member should record the order directly onto the prescription pad/order sheet/computer as the prescriber is relaying it and then should read back the information to the prescriber. The prescriber should request the read back if it is not offered. During this process, spell the drug name and strength of the medication. For example, errors have been reported when the number 15 has been misinterpreted as 50. Always say “one five” for 15 or “five zero” for 50.

Best Practice Recommendations for Prescriber ÂÂ

Training sessions caregivers.

ÂÂ

Awareness on educational initiatives.

ÂÂ

Audit and error reporting systems.

ÂÂ

Adopt a systems-oriented approach to medication error reduction.

ÂÂ

Medicine reconciliation or reviews systems.

ÂÂ

Use of computerized prescription system.

ÂÂ

Promote a nonpunitive atmosphere for reporting of errors which values the sharing of information about the causes of errors and strategies for prevention.

ÂÂ

of

prescriber/practitioner

Implement computerized prescriber order entry systems when technically and financially feasible in light of a hospital’s existing resources and technological development.

Transcription Stage Transcription errors occur when a communication issue occurs between the prescriber and the individual dispensing or administering the medication. The use of computerized provider-order entry (CPOE) systems can essentially eliminate the occurrence of these errors by having providers enter medication orders directly into the system. Some contributing factors to these errors include the multitude of names, dosage forms and strengths of various agents. Sound-alike medications and abbreviations also provide a significant obstacle to eliminating these errors as well.

The Joint Commission requires that at least 2 patient identifiers be used for administering medications in a hospital setting. This strategy helps prevent medication errors due to sound-alike, look-alike names (LASA), such as the age of the patient, allergies, concomitant

medications, contraindications, therapeutic duplications on drugs.

Best Practice Recommendations for Medication Process ÂÂ

Contact prescriber if order is not legible.

ÂÂ

Do not use a trailing zero after the decimal.

ÂÂ

Include indications whenever possible.

ÂÂ

Utilize a system like prescription audit.

Dispensing Stage This is the process of providing the medication to the practitioner who will be administering the medication.

In Emergency Departments (EDs), automated dispensing cabinets fill the key role of dispensing for urgent and emergent medications. In some circumstances, particularly in EDs that dispense medications directly from the ED after hours, the final safety check by the pharmacist is circumvented.

Dispensing errors committed by individuals are often the result of error-prone systems and processes. Therefore, the main 10 strategies to reduce dispensing errors is to implement a system oriented approach rather than a punitive approach targeted at an individual.

10 Strategies for Minimizing Dispensing Errors 1. Ensure correct entry of the prescription.

2. Confirm that the prescription is correct and complete.

3. Beware of look-alike, sound-alike drugs.

4. Be careful with zeros and abbreviations.

5. Organize the workplace.

6. Reduce distraction when possible.

7. Focus on reducing stress and balancing heavy workloads.

8. Take the time to store drugs properly.

9. Thoroughly check all prescriptions.

10. Always provide thorough patient counseling.

Labeling and Storage ÂÂ

Separate problematic drugs (e.g., sedating agents or anesthetics).

ÂÂ

Separate and use auxiliary labels for different vaccines, tuberculin purified protein derivatives and other injectable products that may be confused.

ÂÂ

Separate external solutions, non-drug items, testing solutions, reagents and chemicals from internal products. External products such as benzoin and podophyllin should be labeled “for external

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COMMUNITY MEDICINE use only”. Hemoccult developers and glucose monitoring chemicals have been mistakenly used as eye drops. ÂÂ

Ways to Prevent Medication Errors in Nursing ÂÂ

Utilize at least two identifiers that are specific to the patient before administering medication. For example, along with the patient’s name, ask for his date of birth to make sure the prescription matches the patient.

ÂÂ

Ask the patient about allergies and reactions to medications before any new medication is administered.

ÂÂ

Avoid abbreviations, which can be easily misinterpreted when documenting medication allergies.

ÂÂ

Pay close attention to the patient’s critical diagnoses, which can affect not only the selection of medication but also dose and frequency.

ÂÂ

Note the patient’s current medication regimen and update the list at each doctor’s visit.

ÂÂ

Recognize which medications could cause serious harm if administered incorrectly.

ÂÂ

Learn and decipher drug names that are similar.

ÂÂ

Repeat the order when calling prescriptions into a pharmacy for a patient.

ÂÂ

Store “high alert” or similar-sounding drugs in separate areas, so they won’t be easily confused.

ÂÂ

Keep current or new information relating to prescription medications and their reactions.

Keep the storage area well-organized.

Drug Devices ÂÂ

The use of proper drug devices, along with adequate training, can have a significant impact on patient safety.

ÂÂ

Use the right syringes.

ÂÂ

Train staff to use the devices properly.

Best Practice Recommendations for Pharmacist ÂÂ

Institute pharmacy-based IV admixture systems.

ÂÂ

Automated dispensing systems.

ÂÂ

Remove concentrated potassium chloride (KCl) vials from nursing units and patient care areas.

Stock only diluted premixed IV solutions on units.

ÂÂ

Encourage pharmacy system software vendors to incorporate an adequate standardized set of checks into computerized hospital pharmacy systems (e.g., screening for duplicate drug therapies, for patient allergies, potential drug interactions, drug/ lab interactions, dose ranges).

ÂÂ

Maintain unit-dose distribution systems (either manufacturer prepared or repackaged by pharmacy) for all nonemergency medications.

ÂÂ

Have a pharmacist available on-call after hours of pharmacy operation.

Administration Stage The act of physically administering the drug to the patient represents the very last moment providers can catch errors before they can do harm. Nurses are absolutely critical personnel at this stage. These errors typically arise when the wrong drug is administered, or the right drug is administered in the wrong dose, via the wrong route or with an incompatible coadministered drug. This can also occur when the right drug is given to the wrong patient. A series of briefings are available to provide overviews of the evidence regarding the effectiveness and safety of interventions designed to improve medication administration safety.

Principles of Medication Administration Process ÂÂ

Provide Organizational and Executive Leadership.

ÂÂ

Promote effective team functioning.

ÂÂ

Respect human limits in process design.

ÂÂ

Anticipate the unexpected create a learning environment.

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Best Practice Recommendations for Nurses ÂÂ

Medication safety and quality education and training.

ÂÂ

Safer naming, labeling and packaging of medicines.

ÂÂ

Consider the use of machine-readable coding (i.e., bar-coding) in the medication administration process.

ÂÂ

Develop special procedures for high-risk drugs using a multidisciplinary approach. These include written guidelines, check lists, pre-printed orders, double-checks, special packaging, special labeling and education.

ÂÂ

Information on new drugs, infrequently used drugs, and nonformulary drugs should be made easily accessible to clinicians prior to ordering, dispensing and administering medications (e.g., have pharmacist round with doctors and nurses; distribute newsletters and drug summary sheets; use computer aids, and access to the physician desk reference, formularies and other resources).

COMMUNITY MEDICINE ÂÂ

ÂÂ

ÂÂ

Provide physicians, nurses, pharmacists and all other clinicians involved in the medication administration process with orientation and periodic education on ordering, dispensing, administering and monitoring medications.

Hospital Strategies

Educate patients in the hospital, at discharge and in ambulatory settings about the safe and accurate use of their medications.

Encourage the use of computer-generated or electronic medication administration records (EMAR).

ÂÂ

Hospitals and other healthcare organizations work to reduce medication errors by using technology

ÂÂ

Improving processes.

ÂÂ

Zeroing in on errors that cause harm.

ÂÂ

Building a culture of safety.

Pharmacy Intervention ÂÂ

Computerized physician order entry (CPOE).

Patient Safety Proposals

Monitoring Stage

ÂÂ

Bar-codes

This stage involves the activities following administration of a medication and observing the impact of pharmacotherapy. It can be particularly challenging to monitor patients for efficacy, side effects and toxicities, where multiple medications are administered to patients in a rapid and emergent fashion. This is not only within the traditional sense of monitoring on the inpatient side, but also includes patients discharged to home and ensuring that appropriate follow-up occurs. It is important that patients are given adequate discharge instructions and are counseled on potential self-monitoring techniques, as well as any possible harmful side effects that may occur.

ÂÂ

Safety reporting.

Monitoring Involves Observing the patient to determine if the medication is working, being used appropriately and not harming the patient documentation.

How can Monitoring Go Wrong? ÂÂ Lack of monitoring for side effects. ÂÂ Drug not ceased if not working or course complete. ÂÂ Drug ceased before course completed. ÂÂ Drug levels not measured, or not followed up on. ÂÂ Communication failures.

Patient Information ÂÂ Use patient-specific identifiers. ÂÂ Verify allergies and reactions. ÂÂ Highlight critical diagnoses and conditions. ÂÂ Update current medications. ÂÂ Standardize height and weight measurements.

System Change with Technology ÂÂ Culture change ÂÂ Drug name confusion ÂÂ Drug labeling ÂÂ Error tracking and public education.

CONCLUSION Safe medication use in physician practices can be achieved with many simple, low-cost system changes.

The key concepts in all of these strategies are to simplify and to standardize your systems related to medications.

While it does take effort, it doesn’t necessarily involve a large financial investment and it will improve the way your practice functions and the level of safety you can offer your patients.

SUGGESTED READING 1. Institute of Medicine. To err is human: building a safer health system. Washington, DC: National Academy Press; 1999.

2. Institute of Medicine. Preventing medication errors.

Washington, DC: National Academy Press; 2007.

3. Food and Drug Administration, Center for Drug Evaluation and Research. Drugs@FDA glossary of terms.

2007. Available at: www.fda.gov/Cder/drugsatfda/ glossary​.htm#M. 4. www.expresshealthcare.in health care. Vol. 8, 2008.

Insight into the business

5. Weant KA, Bailey AM, Baker SN. Strategies for reducing medication errors in the emergency department. Open Access Emerg Med. 2014;6:45-55.

6. Benjamin DM. Reducing medication errors and increasing patient safety: case studies in clinical pharmacology. J Clin Pharmacol. 2003;43(7):768-83.

7. The FDA and ISMP. Agency for Healthcare Research and Quality Brochures: "20 Tips to Help Prevent Medical Errors" and "20 Tips to Help Prevent Medical Errors in Children" (800) 358-9295. July 2006. Available at: http:// www.ismp.org/tools/errorproneabbreviations.pdf.

8. Food and Drug Administration. Think it Through: A Guide to Managing the Benefits and Risks of Medicines (888) 878-3256.

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COMMUNITY MEDICINE 9. Jenkins RH, Vaida AJ. Simple strategies to avoid medication errors. Fam Pract Manag. 2007;14(2):41-7.

10. Nair RP, Kappil D, Woods TM. 10 Strategies for minimizing dispensing errors Published Online. January 20, 2010.

11. Cohen MR. Medication Errors. 2nd Edition, Washington, DC: American Pharmacist's Association; 2007.

pharmacy characteristics associated with the dispensing of potentially clinically important drug-drug interactions.

Med Care. 2007;45(5):456-62.

14. Leape LL, Kabcenell A, Berwick D, Roessner J. Institute for Healthcare Improvement’s Breakthrough Series Guide Reducing Adverse Drug Events. Boston: Library of Congress, 1998.

12. Institute of Safe Medication Practices. Available at: www. ismp.org

15. Cohen MR, Anderson RW, Attilio RM, Green L, Muller RJ, Pruemer JM. Preventing medication errors in cancer chemotherapy. Am J Health Syst Pharm. 1996;53(7): 13. Malone DC, Abarca J, Skrepnek GH, Murphy JE, Armstrong EP, Grizzle AJ, et al. Pharmacist workload and 737-46.

■■■■

HVTN 702, the 1st New HIV Vaccine Efficacy Trial in 7 Years Begins in South Africa The first HIV vaccine efficacy study to launch anywhere in 7 years is now testing whether an experimental vaccine regimen safely prevents HIV infection among South African adults. The study, called HVTN 702, involves a new version of the only HIV vaccine candidate ever shown to provide some protection against the virus. HVTN 702 aims to enroll 5,400 men and women, making it the largest and most advanced HIV vaccine clinical trial to take place in South Africa, where more than 1,000 people become infected with HIV every day.

The experimental vaccine regimen being tested in HVTN 702 is based on the one investigated in the RV144 clinical trial in Thailand led by the US Military HIV Research Program and the Thai Ministry of Health. The Thai trial delivered landmark results in 2009 when it found for the first time that a vaccine could prevent HIV infection, albeit modestly. The new regimen aims to provide greater and more sustained protection than the RV144 regimen and has been adapted to the HIV subtype that predominates in southern Africa, a region that includes the country of South Africa… (NIH Press Release, November 28, 2016)

Common Drugs Soon to be Labeled ‘OTC’ Medicines for cough, cold, flu and pain relief, such as paracetamol, ibuprofen and other analgesics, may soon be available OTC without prescription. But while the Center is set to categorize more drugs as OTC, it is also drawing a legal regulatory framework to avoid misuse of high-risk drugs, especially antibiotics. Once these are in place, the government plans to make it mandatory for companies to label such drugs ‘OTC’ on the package, making it easier for consumers to distinguish, an official said. The Drugs Consultative Committee has recommended constitution of a sub-committee to recommend provisions/guidelines for classification and regulation of OTC products as well as modalities/amendments needed in the conditions of sale license…

(ET Health, Sushmi Dey, November 29, 2016)

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Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

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DIABETOLOGY

Predicting Clinical Outcome in Diabetics versus Nondiabetics with Acute Myocardial Infarction After Thrombolysis AMGOTH BANU PRIYA*, ARUN PRASATH*, C RAMAKRISHNAN†, SM RAJENDRAN‡

ABSTRACT Acute myocardial infarction can be considered as a potential epidemic for mankind (WHO 1982). Diabetes mellitus is one of the 6 primary risk factors identified for myocardial infarction. The aim of our study was to correlate the incidence of complications with diabetes by using ST segment resolution as a tool, thereby re-enforcing the role of incomplete ST resolution as a marker of worse clinical outcome in cases of diabetes with ST-elevated myocardial infarction in our population.

Keywords: Acute myocardial infarction, thrombolysis, ST segment elevation, reperfusion

T

he acute coronary syndrome includes unstable angina, non-ST segment elevation myocardial infarction (NSTEMI) and ST segment elevation myocardial infarction (STEMI). Diabetes mellitus is one of the 6 primary factors identified for myocardial infarction (MI), others being dyslipidemia, smoking, male gender, hypertension and family history of atherosclerotic arterial disease. Diabetes mellitus is a metabolic disorder which increases the rate of atherosclerosis progression of vascular occlusion.1 Even after prompt thrombolysis, the aftermath of diabetic patients is still worse than the nondiabetics, indicating impaired post-thrombolysis left ventricular function and prognosis.

cases of STEMI, offers an attractive and cost-effective solution to assess coronary reperfusion. Whereas coronary angiogram is a marker for epicardial reperfusion, ST segment resolution offers a better reflection of microvascular reperfusion. Although successful thrombolysis of the epicardial vessel is necessary for good prognosis, but the microvascular flow more strongly correlates with the outcome.

ST segment is, therefore, a better indicator of prognosis, and provides information, which cannot be assessed on basis of coronary angiogram alone.3,4 In fact, Schröder et al,5 reported that absence of ST segment resolution was the most powerful independent predictor of early mortality (p = 0.0001).

The aim of thrombolysis in acute MI is early and complete myocardial reperfusion.2 Incomplete or failed reperfusion is associated with increased risk of complications. Analysis of ST segment resolution on electrocardiogram (ECG), after fibrinolytic therapy, in

ST resolution can also be used as a tool to identify candidates for early invasive procedures such as percutaneous transluminal coronary angioplasty (PTCA), who are at risk of developing complications because of nonresolution of ST segment after initial thrombolytic therapy.6 Since, ECG is widely available even in developing nations, it is important to establish its effectiveness as a tool for assessing reperfusion as it will offer the cheapest alternative for assessing recovery and myocardial salvage.

*Postgraduate Dept. of General Medicine †Professor Dept. of General Medicine ‡Professor and Former HOD Dept. of General Medicine and Diabetology Sree Balaji Medical College and Hospital, Bharat University, Chennai, Tamil Nadu Address for correspondence Dr Amgoth Banu Priya Plot No.:1 & 2, CLC Works Road, Nagappa Nagar, Chromepet, Chennai, Tamil Nadu E-mail: priyaafrd@gmail.com

MATERIAL AND METHODS The prospective study was conducted at Sree Balaji Medical College and Hospital, Chennai from June 2015 to October 2015. All cases of acute MI with the diagnosis based on the World Health Organization

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637

DIABETOLOGY (WHO) criteria i.e., presence of any 2 of the following were included. ÂÂ

Chest pain consistent with acute MI of less than 24 hours duration.

ÂÂ

Electrocardiography changes i.e., ST segment elevation >0.2 mV in at least 2 contiguous chest leads or >0.1 mV in at least 2 contiguous limb leads.

ÂÂ

New or presumably new left bundle branch block on ECG.

ÂÂ

Raised levels of cardiac enzymes creatine phosphokinase-MB more than double of the reference value or positive troponin I test done with commercially available kits of trop I.

These patients came within 12 hours of chest pain and received streptokinase on presentation. Patients coming after 12 hours of chest pain and patients suffering from type 1 diabetes mellitus were excluded.

The study population was divided into two groups: Group A, nondiabetics (n = 50) and Group B, diabetics (n = 50).

Only those patients who were known cases of diabetes or in whom it was established during hospital stay by repeated blood glucose estimation, were included in Group B. A detailed history was taken, particularly of age, sex, occupation, address, history of smoking, diabetes mellitus, hypertension and family history of ischemic heart disease. Complete physical examination of patients was done upon presentation in emergency and important parameters such as pulse and blood pressure were noted. Patients were followed up daily.

Pulse, ECG changes and complications, if any, were monitored till death or discharge of the patient. The endpoint was a composite of recurrent ischemic chest pain, heart failure, arrhythmia or death.

consent of the patient/attendant was taken. Follow-up was conducted for each patient throughout his/her hospital stay. Fasting plasma glucose (FPG) was recorded from all patients, in the morning of day following hospital admission for differentiating new cases of diabetes, stress hyperglycemia and nondiabetic.

FPG measurements were repeated in stable condition prior to discharge from hospital.

The patients were also assessed for the complications during the follow-up. The major complications assessed were: Recurrent ischemic chest pain, heart failure, arrhythmia and death. Recurrent ischemic chest pain was assessed on the basis of history and ECG; heart failure was assessed on the basis of clinical examination, chest X-ray and echocardiography.

Arrhythmia was evaluated on the basis of continuous bedside monitoring of ECG. Tachycardia was defined as pulse rate >100 and bradycardia as ≤50/min.

Statistical Analysis All data was analyzed by SPSS (statistical package for social sciences) version 12.0 for windows, chi-square test was used to compare the demographic characteristics and completion in both groups with 0.05% level of significance.

RESULTS A total of 100 patients were investigated in this study, of which 70 (70%) were males and 30 (30%) were females. Table 1 shows the demographic characteristics of the study population at presentation. There was no significant difference in the comorbidities of the two groups with hypertension showing the most significant trend.

Table 1. Demographic Data at Time of Presentation

Time from onset of chest pain to presentation of patient in emergency was noted through the history. ECG recordings of patients were taken upon presentation in emergency. ST elevation was recorded in millimeters from the lead in which maximum elevation was observed. Injection streptokinase was given intravenously to each patient at a dose of 1.5 million units, diluted in 100 mL of normal saline, in 1 hour.

Demographic characteristics

Nondiabetic (Group A) (n = 50)

Diabetic (Group B) (n = 50)

Mean age

55.34 ± 14.38

58.30 ± 12.26

38 (76%)

32 (64%)

12 (24%)

18 (36%)

Time of thrombolysis in hours

5.88 ± 1.0

5.07 ± 1.3

Repeat ECG was performed after 60 minutes of administration of streptokinase (SK). ST resolution was observed in the lead with the maximum ST elevation.

ST resolution was defined as a reduction of >50% ST segment elevation after thrombolysis. Informed written

Hypertension

15 (30%)

26 (52%)

Hypercholesterolemia

10 (20%)

10 (20.2%)

Family history

9 (18.2%)

7 (14.8%)

Smoking

25 (50%)

24 (48%)

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Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

Gender Male Female

DIABETOLOGY DISCUSSIONS The time to reperfusion and complete reperfusion remain the key determinants for fibrinolysis.

Historically, ST resolution has been one of the markers used to access reperfusion in STEMI. Its importance cannot be denied as a prognostic indicator and the results of our study also reinforce this fact. However, its use as a cost-effective marker has been under utilized.

Several studies have reported similar angiographic7,8 or ECG 9,10 success in both type 2 diabetic and nondiabetic subjects, while others have shown that the diabetics have less complete resolution of ST elevation than the nondiabetics.11 To evaluate this issue, it has been hypothesized that type 2 diabetes might interfere with intravenous thrombolysis effectiveness, as estimated by angiographic or ECG criteria.

In our study, we observed that in nondiabetic MI 84% patients showed complete resolution and 16% showed failed resolution. But in case of diabetic MI, 13.8% patients showed complete resolution and 86% showed failed resolution. In our study, more complete ST resolution was seen in nondiabetic patient (84% vs. 16%, p < 0.001), whereas type 2 diabetic subjects presented with significantly higher incidence of failed ST resolution than nondiabetic subjects (88% vs. 14.8%, p < 0.001). This significant change in ST resolution between nondiabetic and diabetic group was similar with the study, which showed significant difference between nondiabetic and diabetic patients in relation to complete (35.1% vs. 69.2%, p < 0.001) and incomplete (66.8% vs. 32.6%, p < 0.001) resolution.11 Our results are also consistent with a published meta-analysis in which it was shown that type 2 diabetic subjects had less ST resolution after intravenous thrombolysis administration compared with nondiabetic subjects.7 Our results showed the frequency of complications in nondiabetics to be 32.9% compared to 79.8% in diabetics (p < 0.001), which was substantially higher in the latter.

This finding, therefore establishes a direct correlation between diabetics and the frequency of complications, reflected by less complete ST segment resolution in diabetics in our study (86%).

In our study, we noted that there was a significant interaction between diabetic status and failed ST resolution with respect to the occurrence of in-hospital recurrent ischemia (p < 0.0001). Recurrent chest pain is the most common complication observed in the study.

A study supporting our results showed that there was a significant interaction between diabetics status and treatment strategy with respect to the occurrence of

in-hospital recurrent inchemia.12 In that study, 32.5% diabetics and 22.1% nondiabetics developed recurrent ischemia after fibrinolysis (p < 0.001). As shown by another study, diabetic patients may have a greater residual lesion in the infarct-related artery after treatment with fibrinolytics, resulting in a higher rate of recurrent ischemia.

In our results, we observed that the interaction between diabetics status and failed ST resolution with respect to the development of heart failure was significant (p = 0.025). Heart failure is the major determinant for prognosis after MI. Since, some patients never had an echocardiography before this hospital admission to rule out prior heart failure, so any indication of heart failure post-thrombolysis was considered a new development.

Our results are supported by the findings of a study, which showed that in-hospital heart failure was more common among diabetics after fibrinolysis.12 In that study, 10% diabetics and 4.2% nondiabetics developed heart failure (p = 0.001).

We observed arrhythmias in 56% of diabetic patients as compared to 10% in nondiabetic patients (p < 0.0001).

The results clearly shows that arrhythmias are less frequent in nondiabetic patients. Failed ST segment resolution was associated with high frequency of occurrence of arrhythmias compared with complete resolution of both diabetics (p < 0.0001) and nondiabetics (p < 0.0001). Our results are supported by a study in which incidence of AV block and LBBB, detected in half of the dying patients, was 3 times more common in diabetics than in nondiabetics subjects.

In our study, mortality in diabetic group (only patients with failed ST resolution) was 6.4% compared to 0% in nondiabetic group (p = 0.014). A study supporting these findings was carried out by Timmer et al. According to their results, diabetes was associated with increased 30-day mortality. Diabetic mortality was 12.4% and nondiabetic mortality 6.9% after thrombolysis at 30-day endpoint. Small sample size of this study limits our conclusions. There was no post-hospital followup, so that is another weak factor of this study. Since, the hospital is equipped to deal with life-threatening emergencies, in-hospital death as a complication was not that high in any group.

The negative influence of diabetes on outcome after STEMI has been described previously. Because mortality remains particularly high in patients with diabetes after STEMI, it is important to define optimal treatment strategies including method of reperfusion therapy, in this population. In our study, it was proved

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DIABETOLOGY that reperfusion failed in a significant proportion of diabetic patients with STEMI in comparison with nondiabetic persons (86% vs. 16%). Similar results were obtained by Zairis et al.11 They proved that fibrinolysis may be less effective in diabetic patients. Angeja et al7 showed that microvascular flow is decreased in diabetic patients after fibrinolysis. Possibly, this is associated with increased platelet aggregation and reduced ability to induce endothelium-mediated vasodilation.

The higher risk of adverse events may be caused by enhanced thrombogenicity and impaired fibrinolysis.

Percutaneous coronary intervention (PCI) can be a better alternative in diabetics presenting with acute MI. However, the long-term outcome of these patients depends on the extent of coronary disease and residual left ventricular function, as well as the presence of other risk factors. Hence, aggressive secondary preventive measures such as tight glycemic control and lipidlowering may be just as important as the mode of reperfusion treatment for these patients.

So, due attention is required for the better management of diabetic MI patients. This should, however, be supplemented with further therapies and strategies directed towards the many abnormalities that are associated with diabetes, such as endothelial dysfunction, dysglycemia and coagulation and fibrinolytic disturbances.

Our study was limited by the fact that the prognosis after STEMI is affected by various factors such as age, gender, number of coronary risk factors presented by the patient, use of aspirin within 7 days and number of angina attacks the patient suffered. We could not assess these factors, which correlate strongly with mortality in our study. A multivariate analysis is required to exclude the importance of these confounding factors.

Stress hyperglycemia has a detrimental effect on thrombolytic outcome after acute MI. Diabetes can be differentiated from stress hyperglycemia with certainty only after the acute phase of the infarction. Thus, any attempt to identify undiagnosed diabetes in our study would have been biased because patients must survive the acute phase to be diagnosed. Another limiting factor was the nonrandomized nature of the research and small size of patients included in the study. In addition to this, it was also limited by the fact that it was a single center study.

CONCLUSION Frequency of in-hospital complications is more in failed ST resolution compared to complete ST resolution, in

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both diabetics and nondiabetics, post-thrombolysis.

Diabetic population, after thrombolytic therapy, has a higher incidence of adverse clinical outcomes than nondiabetics. Among diabetic patients with acute MI, fibrinolysis was associated with less complete ST segment resolution, suggesting impaired microvascular flow. Abnormal microvascular flow may contribute at least in part to the poorer outcomes observed in patients with diabetes and acute MI. REFERENCES 1. Bajzer CT. Acute myocardial infarction. In: Medicine Index. Cleveland Clinic Foundation; 2002. pp. 222-6.

2. van‘t Hof AW, Liem A, de Boer MJ, Zijlstra F. Clinical value of 12-lead electrocardiogram after successful reperfusion therapy for acute myocardial infarction.

Zwolle Myocardial infarction Study Group. Lancet.

1997;350(9078):615-9.

3. Schröder R. Prognostic impact of early ST-segment resolution in acute ST-elevation myocardial infarction.

Circulation. 2004;110(21):e506-10.

4. de Lemos JA, Braunwald E. ST segment resolution as a tool for assessing the efficacy of reperfusion therapy. J Am Coll Cardiol. 2001;38(5):1283-94.

5. Schröder R, Dissmann R, Brüggemann T, Wegscheider K, Linderer T, Tebbe U, et al. Extent of early ST segment elevation resolution: a simple but strong predictor of outcome in patients with acute myocardial infarction.

J Am Coll Cardiol. 1994;24(2):384-91.

6. Carlsson J, Kamp U, Härtel D, Brockmeier J, Meierhenrich R, Miketic S, et al. Resolution of ST-segment elevation in acute myocardial infarction - early prognostic significance after thrombolytic therapy. Results from the COBALT trial. Herz. 1999;24(6):440-7.

7. Angeja BG, de Lemos J, Murphy SA, Marble SJ, Antman EM, Cannon CP, et al; TIMI Study Group. Impact of diabetes mellitus on epicardial and microvascular flow after fibrinolytic therapy. Am Heart J. 2002;144(4):649-56.

8. Woodfield SL, Lundergan CF, Reiner JS, Greenhouse SW, Thompson MA, Rohrbeck SC, et al. Angiographic findings and outcome in diabetic patients treated with thrombolytic therapy for acute myocardial infarction: the GUSTO-I experience. J Am Coll Cardiol. 1996;28(7):1661-9.

9. Mak KH, Moliterno DJ, Granger CB, Miller DP, White HD, Wilcox RG, et al. Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction. GUSTO-I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries. J Am Coll Cardiol.

1997;30(1):171-9.

10. Ishihara M, Sato H, Kawagoe T, Shimatani Y, Kurisu S, Nishioka K, et al. Impact of diabetes mellitus on long term survival after acute myocardial infarction in patients with single vessel disease. Heart. 2001;86(2):133-8.

Cont'd on page 648...

DIABETOLOGY

Vitamin B12 Levels in Patients with Type 2 Diabetes Mellitus on Metformin V PADMA*, NN ANAND*

ABSTRACT Vitamin B12 is required for proper hematopoeisis, cardiovascular and neurocognitive function. Vitamin B12 deficiency is highly prevalent among patients with type 2 diabetes mellitus (T2DM) on metformin therapy. Aim: This study was carried out to evaluate the serum levels of vitamin B12 in patients with T2DM on metformin therapy. Material and methods: Hundred patients with T2DM within the age group of 45-80 years were recruited into this cross-sectional study. All the patients were on metformin therapy for a minimum of 5 years. Results: Vitamin B12 deficiency and borderline deficiency observed were 10.6% and 29% and 60.4% did not have vitamin B12 deficiency. B12 levels were lower in patients with more than 10 years of duration of diabetes and was statistically significant with a p value of 0.004. The average B12 levels in patients on metformin dose of >1,000 mg was 349 pg/dL and in patients with metformin dose above 1,000 mg was 215 pg/dL. The difference between the two groups was statistically significant with a p value of <0.002. Conclusion: There is a high prevalence of B12 deficiency among diabetic patients. It is important to screen for vitamin B12 deficiency before initiating metformin and later annually.

Keywords: Vitamin B12 deficiency, diabetes mellitus, peripheral neuropathy, metformin

V

itamin B12 is an essential micronutrient required for proper hematopoeisis, cardiovascular and neurocognitive function. Biochemical and clinical vitamin B12 deficiency is highly prevalent among patients with type 2 diabetes mellitus (T2DM) on metformin therapy. B12 deficiency presents with a variety of clinical manifestations like megaloblastic anemia, pancytopenia, impaired memory, dementia, peripheral neuropathy and subacute combined degeneration of the spinal cord.

Metformin is the most commonly prescribed antidiabetic drug in patients with T2DM and is a cornerstone in the treatment of T2DM. It is well-tolerated in most of the patients.

Due to the numerous benefits of metformin, some side effects are usually ignored and rarely investigated.

One such side effect is vitamin B12 deficiency.

Vitamin B12 or cobalamin plays an important role in DNA

*Professor Dept. of Medicine Sree Balaji Medical College, Chrompet, Bharath University, Chennai, Tamil Nadu Address for correspondence Dr V Padma 49, Mahalakshmi Street, East Tambaram, Chennai - 600 059, Tamil Nadu E-mail: padmaramesh86@yahoo.com, drpadmaramesh86@gmail.com

synthesis, hematopoeisis and neurological function.

Vitamin B12 deficiency is associated with hematological and neurocognitive dysfunction.1 This study was hence carried out to evaluate the serum levels of vitamin B12 in patients with T2DM on metformin therapy.

MATERIAL AND METHODS A total of 100 patients with T2DM within the age group of 45-80 years were recruited into this cross-sectional study. All the patients recruited were on metformin therapy for a minimum of 5 years.

Exclusion Criteria Patients with gastrectomy, small bowel resection, recent intake of vitamin B12, liver disease, chronic kidney disease and thyroid disease, patients on histamine 2 receptor blockers and vegetarians were excluded from this study. Participants were enrolled into this study after obtaining a written informed consent from each one of them.

Determination of serum vitamin B12 level was by using high performance liquid chromatography (HPLC). Vitamin B12 deficiency was defined as serum concentration of <200 pg/dL and borderline deficiency as 200-300 pg/dL. Concentrations >300 pg/dL were considered as normal. Statistical analysis was done using SPSS (Version 20.0) and the results were analyzed.

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641

DIABETOLOGY RESULTS

The difference between B12 levels in patients below 10 years of duration of diabetes and more than 10 years of duration of diabetes was statistically significant with a p value of 0.004.

B12 Levels and Metformin Dose Forty-six percent of patients were on a dose of <1,000 mg of metformin per day and 54% were on a dose of >1,000 mg of metformin per day. The average B12 levels in patients on metformin dose of <1,000 mg was 349 pg/dL and the levels in patients with metformin dose above 1,000 mg was 215 pg/dL

39

Percentage of patients

35 30 25

24

25 20 15 10

12

5 0 30-39

40-49

50-59

>60

Figure 1. Diabetics on metformin.

Table 1. Characteristics of the Patients Including Levels of B12 According to Duration of Diabetes Characteristics Age BMI

<10 years

>10 years

54 ± 34

57 ± 51

25.62 ± 4

26.64 ± 32

Systolic BP

134 ± 14.24

136 ± 16.52

Diastolic BP

82 ± 11.22

84 ± 11.24

422.34

224.21

B12 levels (pg/dL)

642

No. of patients

400 350 300 250 200 150 100 50 0 500 mg/day

500-1000 1000-1500 1500-2000 mg/day mg/day mg/day

>2000 mg/day

Figure 2. Average B12 levels in patients according to dosage of metformin.

(Fig. 2). The difference between the two groups was statistically significant with a p value of <0.002.

DISCUSSION Reports have shown that long-term metformin use has a significant impact on the concentration of vitamin B12 in patients with T2DM. Vitamin B12 or cobalamin plays an important role in DNA synthesis, hematopoeisis and neurological function. Vitamin B12 deficiency is associated with hematological and neurocognitive dysfunction.1

45 40

Average B12

Vitamin B12 levels (pg/dL)

Vitamin B12 deficiency and borderline deficiency observed were 10.6%, 29% and 60.4% did not have vitamin B12 deficiency. Most of the patients were between the ages of 50-59 years - 39%, followed by >60 years - 25%, 40-49 years - 24% and 30-39 years - 12% (Fig. 1). Of them, 62% were females and 48% were males.

The patients were divided according to the duration of diabetes into two groups: less than 10 years and more than 10 years of diabetes mellitus. The characteristics of patients with duration of therapy with metformin and B12 levels are shown in Table 1.

Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

The source of vitamin B12 is animal proteins. Vitamin B12 deficiency is due to insufficient dietary intake among alcoholics and vegetarians, malabsorption due to chronic atrophic gastritis, pernicious anemia, chronic pancreatitis, celiac disease and drugs like metformin and proton pump inhibitors.

Vitamin B12 deficiency results in disruption of the methylation process and increased accumulation of intracellular and serum homocysteine. Hyperhomocysteinemia has toxic effects on neurons and the vascular endothelium. This methylation reaction is essential in the conversion of dietary folate to its active metabolic form, tetrahydrofolate. Vitamin B12 is the co-factor that mediates the conversion of methylmalonyl coenzyme A (CoA) to succinyl-CoA. Vitamin B12 deficiency leads to increase in serum methylmalonic acid (MMA), causing defective fatty acid synthesis of the neuronal membranes.2 Vitamin B12 is also essential in the synthesis of neurotransmitters like serotonin and dopamine.3 Deficiency of dopamine and serotonin occurs with vitamin B12 deficiency, which is the cause

DIABETOLOGY of the neurocognitive or psychiatric manifestations.

Axonal demyelination, degeneration and later death due to vitamin B12 deficiency manifests as severe peripheral or autonomic neuropathy, subacute combined degeneration of the spinal cord, dementia and delirium.4 Hyperhomocysteinemia due to its cellular and vasculotoxic effects, is also associated with an increased risk of cardiovascular events.5 Several cross-sectional studies6 and case reports7 have demonstrated an increased frequency of vitamin B12 deficiency among T2DM patients. Metformin use has been demonstrated as the main factor associated with vitamin B12 deficiency among patients with T2DM.8 Studies on type 2 diabetic patients on metformin intake have demonstrated that the prevalence of vitamin B12 deficiency is from 5.8% to 33%.9 In a study by Qureshi et al,9 a high prevalence of vitamin B12 deficiency of 33% was seen in adult patients with T2DM.

Metformin-induced Vitamin B12 Deficiency Among Patients with T2DM In a randomized controlled trial by DeFronzo et al, metformin reduced the serum vitamin B12 levels by 22% and 29% when compared to glyburide and placebo, respectively.10 The risk of developing metformin associated vitamin B12 deficiency is increased by age, metformin dose and duration of treatment.11 In a case-control study done in China among 155 adult Chinese diabetic patients on metformin and 310 controls, for every 1 g/day increase in metformin there was an odds ratio (OR) of 2.9 (95% confidence interval [CI], 2.15-3.87) for developing vitamin B12 deficiency. Among patients treated with metformin for ≥3 years, the adjusted OR was 2.4 (95% CI, 1.46-3.91) when compared with diabetic patients who received metformin for ≤3 years.11

(This inhibitory effect is reversed with calcium supplementation).14 Vitamin B12 deficiency in patients with type 1 diabetes mellitus (T1DM) are due to: ÂÂ

Pernicious anemia due to chronic autoimmune gastritis is high among patients with T1DM, more than 3 to 5 folds when compared to general population.15

ÂÂ

Exhibit autoantibodies to intrinsic factor (AIF) type 1 and 215 and parietal cell antibodies (PCA)16 especially those diabetic patients with glutamate decarboxylase-65 (GAD-65) antibodies and HLADQA1*0501-B1*0301 haplotype.17

ÂÂ

Autoimmune hypothyroidism, celiac diseases are frequent comorbidities in patients with T1DM and they directly affect vitamin B12 metabolism.18 Dyserythropoiesis due to thyroid hormone deficiency, defective absorption due to reduced bowel motility, bacterial overgrowth and bowel wall edema also contribute to B12 deficiency.18

Celiac disease is associated with enteropathy, chronic diarrhea and anemia due to malabsorption of folate and vitamin B12.19 CONCLUSION

ÂÂ

Alterations in intrinsic factor (IF) levels

ÂÂ

Interaction with the cubulinendocytic receptor13

Clinical and biochemical vitamin B12 deficiency is highly prevalent among patients with both T1DM and T2DM. As there is a high prevalence of B12 deficiency among diabetic patients, it is clinically important to screen for vitamin B12 deficiency before initiating metformin and later annually. Vitamin B12 levels should be checked regularly among elderly patients with a history of long-term use of metformin (≥3-4 years), use of high doses of metformin (≥2 g/day), worsening diabetic distal polyneuropathy in the absence of other hematological abnormalities.20 Vitamin B12 levels <200 pg/mL is diagnostic of vitamin B12 deficiency. Measurement of serum MMA or homocysteine concentrations is more sensitive and specific for screening type 2 diabetic patients with borderline serum vitamin B12 concentrations of 200-400 pg/mL and mild-hematological manifestations.

Normal levels of serum homocysteine and MMA concentrations are 5-15 μmol/L and <0.28 μmol/L.20 It is important to screen vitamin B12 levels at diagnosis, then yearly for 3 years, then once in 5 years for life or if there are clinical signs of B12 deficiency.15

ÂÂ

Inhibition of the calcium-dependent absorption of the vitamin B12-IF complex at the terminal ileum

Treatment of B12 deficiency in adult patients with T2DM, intramuscular vitamin B12 in doses of 1,000 μg

Decrease in vitamin B12 absorption following metformin use starts as early as the 4th month of treatment.12 Clinical features of vitamin B12 deficiency develop only by 5-10 years, as there are a large amount of B12 stores in the body (liver), which do not get depleted that fast.13 The mechanisms to explain metformin-induced vitamin B12 deficiency in patients with T2DM are: ÂÂ

ÂÂ

Alterations in small bowel motility which stimulates bacterial overgrowth and vitamin B12 deficiency Competitive inhibition of vitamin B12 absorption

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DIABETOLOGY daily for a week, then weekly once for 4 weeks to correct vitamin B12 deficiency. Associated folate deficiency should be treated with oral folate in doses of 5 mg daily for 1-4 months.

Large, well-designed studies have to be done in future on vitamin B12 deficiency screening in diabetic patients and optimal supplementation dose among type 1 and type 2 diabetic patients to formulate guidelines for care of diabetic patients.

REFERENCES 1. Oh R, Brown DL. Vitamin B12 deficiency. Am Fam Physician. 2003;67(5):979-86.

2. Malouf R, Areosa Sastre A. Vitamin B12 for cognition.

Cochrane Database Syst Rev. 2003;(3):CD004326.

3. Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EH. Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry. 2000;69(2):228-32.

4. Selhub J, Morris MS, Jacques PF, Rosenberg IH. Folate-vitamin B-12 interaction in relation to cognitive impairment, anemia, and biochemical indicators of vitamin B-12 deficiency. Am J Clin Nutr. 2009;89(2): 702S-6S. 5. Selhub J. Public health significance of elevated homocysteine. Food Nutr Bull. 2008;29(2 Suppl):S116-25.

6. Aslinia F, Mazza JJ, Yale SH. Megaloblastic anemia and other causes of macrocytosis. Clin Med Res. 2006;4(3): 236-41.

7. Kumthekar AA, Gidwani HV, Kumthekar AB. Metformin associated B12 deficiency. J Assoc Physicians India.

2012;60:58-60.

8. Reinstatler L, Qi YP, Williamson RS, Garn JV, Oakley GP Jr. Association of biochemical B₁₂ deficiency with metformin therapy and vitamin B₁₂ supplements: the National Health and Nutrition Examination Survey, 1999-2006. Diabetes Care. 2012;35(2):327-33.

10. DeFronzo RA, Goodman AM. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus.

The Multicenter Metformin Study Group. N Engl J Med. 1995;333(9):541-9.

11. Ting RZ, Szeto CC, Chan MH, Ma KK, Chow KM. Risk factors of vitamin B12 deficiency in patients receiving metformin. Arch Intern Med. 2006;166(18):1975-9.

12. Wulffelé MG, Kooy A, Lehert P, Bets D, Ogterop JC, Borger van der Burg B, et al. Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med. 2003;254(5):455-63.

13. Andrès E, Noel E, Goichot B. Metforminassociated vitamin B12 deficiency. Arch Intern Med. 2002;162(19):22512.

14. Bauman WA, Shaw S, Jayatilleke E, Spungen AM, Herbert V. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin.

Diabetes Care. 2000;23(9):1227-31.

15. Van den Driessche A, Eenkhoorn V, Van Gaal L, De Block C. Type 1 diabetes and autoimmune polyglandular syndrome: a clinical review. Neth J Med. 2009;67(11):376-87.

16. De Block CE, De Leeuw IH, Van Gaal LF. High prevalence of manifestations of gastric autoimmunity in parietal cell antibody-positive type 1 (insulin-dependent) diabetic patients. The Belgian Diabetes Registry. J Clin Endocrinol Metab. 1999;84(11):4062-7.

17. De Block CE, De Leeuw IH, Rooman RP, Winnock F, Du Caju MV, Van Gaal LF. Gastric parietal cell antibodies are associated with glutamic acid decarboxylase-65 antibodies and the HLA DQA1*0501-DQB1*0301 haplotype in Type 1 diabetes mellitus. Belgian Diabetes Registry. Diabet Med. 2000;17(8):618-22.

18. Fein HG, Rivlin RS. Anemia in thyroid diseases. Med Clin North Am. 1975;59(5):1133-45.

19. Selimoğlu MA, Karabiber H. Celiac disease: prevention and treatment. J Clin Gastroenterol. 2010;44(1):4-8.

20.

9. Qureshi S, Ainsworth A, Winocour P. Metformin therapy and assessment for vitamin B12 deficiency: is it necessary?

Practical Diabetes. 2011;28(7):302-4.

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Mazokopakis EE, Starakis IK. Recommendations for diagnosis and management of metformin-induced vitamin B12 (Cbl) deficiency. Diabetes Res Clin Pract.

2012;97(3):359-67.

A1c should be Monitored in Diabetics who Quit Smoking Nonsmokers have a statistically significant lower A1c and more favorable lipid profile compared to smokers.

Smoking cessation does not lead to an increase in A1c in long-term and may reduce vascular complications in diabetes by its favorable impact on lipid profile (increased HDL cholesterol). People with diabetes, when they stop smoking, should be followed up very closely and their weight and A1c monitored. These findings from a systematic review and meta-analysis are reported November 24, 2016 in Cardiovascular Diabetology.

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DIABETOLOGY

Prevalence of Diabetic Neuropathy: A Prospective Study in a Tertiary Care Teaching Hospital in Kerala JEENA BEEGUM N*, SUJITH VARMA†, LEJO JACOB*, ABAEDHA SUSAN KURIAKOSE*, MIDHUN K ROY*

ABSTRACT Aim: The aim of the study was to determine the prevalence of diabetic neuropathy in patients with type 2 diabetes mellitus in a 500 bedded tertiary care teaching hospital in South India. Material and methods: A prospective observational study conducted in 411 type 2 diabetic subjects inclusive of those known diabetic neuropathy (84). Diabetic neuropathy was diagnosed based upon medical records and esthesiometer readings. Results: The prevalence of neuropathy in diabetic population was found to be 20.43%. The prevalence of neuropathy was found to increase with increase in age (p < 0.001), body mass index (BMI) and fasting blood sugar. Conclusion: The study suggest that overall prevalence of diabetic neuropathy was found to be 20.43% and the age and BMI were common risk factors for diabetic neuropathy prevalence.

Keywords: Diabetic neuropathy, type 2 diabetes, fasting blood sugar, body mass index

D

iabetes has emerged as one of the major healthcare problem in India. Due to the tremendous increase in diabetic population, India is considered as the “diabetes capital of the world”.1 According to the estimate of International Diabetes Federation (IDF), total number of diabetic patients was found to be around 40.9 million in India and would further increase to 69.6 million by the year 2025.2 One of the major complications of diabetes mellitus is diabetic neuropathy. Diabetic neuropathy involves presence of signs and symptoms of peripheral nerve dysfunction in people with diabetes.3 Diabetic neuropathy can be classified into autonomic, proximal, focal and peripheral neuropathy. The major signs of diabetic peripheral neuropathy (DPN) are loss of vibratory sensations and altered proprioception, which are mainly due to large loss of fiber and impairment of pain, light touch and temperature. The symptoms usually start from toes and extend upwards to legs and hands. It is usually present as glove-stocking distribution

*Pharm D †Associate Professor and HOD Dept. of Pharmaceutics National College of Pharmacy Manassery, Mukkam, Calicut, Kerala Address for correspondence Jeena Beegum N Pharm D National College of Pharmacy, Manassery, Mukkam, Calicut, Kerala E-mail: beegumjeena@gmail.com

of numbness, sensory loss, parasthesia and pain.4 The major risk factors for diabetic neuropathy are increase in age, longer duration of diabetes and poor glycemic control. Cigarette smoking, hypertension, obesity, retinopathy, hyperlipidemia and microalbuminuria are some of the potential risk markers.5 As per the data given by the Center for Disease Control and Prevention (CDC), it was estimated that 9.3% of US population had diabetes.6 Most of the studies have proved that 30-50% of patients with diabetes gradually develop neuropathy.

Majority of the reported case of diabetic neuropathy are from Western developed countries, while there are less data from developing countries, mainly from South Asian countries.7 The aim of the present study was to find the prevalence of peripheral neuropathy among patients with a view to identify differential risk factors, which can lead to improved preventive measures for diabetic patients in South India.

MATERIAL AND METHODS The study was carried out by recruiting 411 consecutive type 2 diabetes mellitus patients attending the diabetic clinic in a multispecialty hospital in Kerala. Diagnosis and classification of type 2 diabetes mellitus was based on past medical history and fasting blood sugar (FBS) reading. In the study, the patients demographics and complete clinical data were collected, which included height, weight and body mass index (BMI).

DPN was assessed using esthesiometer, which is an electronic instrument used for measuring the severity of

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DIABETOLOGY

RESULTS Four hundred eleven patients were assessed for diabetic neuropathy and it was found that 20.43% of the study population had evidence of diabetic neuropathy. The gender-based categorization of diabetic neuropathy revealed that 58% of DPN patients were female (Fig. 1). The prevalence of diabetic neuropathy and its relationship with age of the patients was studied and it was seen that there was an increase in prevalence of DPN with increase in age (Table 1 and Fig. 2).

The intensity of DPN was studied according to the esthesiometer reading and patients were classified into â&#x20AC;&#x153;mild, moderate and severeâ&#x20AC;? neuropathy (Fig. 3).

The FBS of patients was analyzed and the results have shown that FBS were above the range of 100 for all the patients (Table 2). The BMI status of patients with DPN

Table 1. Age-based Classification of Study Population Age range

Percentage (%)

<40

2.77

41-50

10.26

51-60

22.77

61-70

27.55

>70

36.65

40 Percentage prevalenve of DPN

diabetic neuropathy. Esthesiometer works by measuring vibratory perception threshold (VPT) on the great toes.

The patients were initially requested to remove their shoes and socks and lie on a bed. The esthesiometer factor, that vibrates at 100 Hz with an amplitude proportional to the squares of the applied voltage was applied perpendicular to the test site with a constant and firm pressure. Subjects were initially familiarized with the sensation by holding the factor against the distal planar surface. VPT was measured at the distal plantar surface of the right great toe. The voltage was slowly increased at the rate of 1 v/s (volt/second) and the VPT was defined as the moment when the patient indicated he/she first felt vibration. The voltage occurred was recorded; 3 further cycles of reading at each site were done and recorded. Neuropathy was diagnosed if the VPT of the great toe >25 v. According to the data collected from esthesiometer, patients were classified into 3 groups mild, moderate and severe neuropathy.

36.65

35 30

27.55

25

22.77

20 15

10.26

10 5

2.77

0 <40

41-50

51-60

61-70

>70

Age group

Figure 2. Categorization of patients based on age.

Table 2. FBS-based Classification Study Population FBS range

Percentage (%)

50-100

0

100-150

63.88

150-200

13.88

200-250

5.55

250-300

11.11

>300

5.55

Mild

9% 8%

Female

Moderate Severe

Male

42% 58%

83%

Figure 1. Comparison of gender among study population.

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Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

Figure 3. Esthesiometer reading of DPN patients.

DIABETOLOGY Table 3. BMI-based Classification of Study Population BMI range

Percentage (%)

Class

15-19

11.11

Under weight

20-24

41.66

Normal

25-29

41.66

Over weight

>30

5.55

Obese

16 14

Frequency

12 10 8 6 4 2 0 Under weight

Normal

Over weight

Obese

BMI

Figure 4. Classification of patients based on BMI.

were recorded and found that the maximum number of patients came under normal and overweight category (Table 3 and Fig. 4).

DISCUSSION The study deals with identifying the prevalence of DPN in a study population of type 2 diabetic patients attending the diabetic clinic. Prevalence of DPN is the proportion of people in a population who have DPN at a specified point in time or over a specified period of time. All patients were screened for neuropathy using esthesiometer irrespective of symptoms of neuropathy or duration of disease.

About 411 diabetic patients attended the diabetic clinic and among them 84 patients were diagnosed to have neuropathy. The overall prevalence of DPN in the present study was found to be 20.43%. The study results shown that every 5th individual in the population had a chance of developing DPN.8 The result was found to be higher than the results obtained by a similar study conducted in a diabetic center, in South India by Ashok et al in 2002 (19.1%).9 Tesfaye and his co-workers have reported that 16-20% of all patients with diabetes are known to develop DPN.10 Thirty percent of hospitalized and 20% of community dwelling diabetic patients have peripheral neuropathy and annual incidence rate was

found to be approximately 2%.11 This reveals that the prevalence of neuropathy in our study appears to be lower than those in European countries.

A global prevalence study had suggested that there was an increased incidence of DPN in males than females, but in our study majority of DPN patients were females (58%). Advancing age, duration of diabetes, obesity and poor control of blood sugar level are the major risk factors for DPN. This study identified increasing age as a risk factor for all types of neuropathy- mild, moderate and severe. The majority of DPN subjects (36.65%) belonged to an age group >70, which confirms advancing age plays a major role in developing DPN in diabetes patients. Similar to this, Ashok et al reported increase in age is a major risk factor for DPN. Several other studies have also identified age as risk factor for DPN.12-16 In this study, 5.5% of subjects were noted as obese which shows that obesity is not a risk factor for DPN in our population. On this matter, various opinions were found in literatures.17,18 FBS reading were taken for all patients in the diabetic clinic and on statistical analysis it shown that there is no direct relationship with incidence of DPN and FBS reading.

CONCLUSION In summary, we report that using esthesiometer 20.43% of diabetic clinic population in Kerala have DPN. This suggests that tight control of blood sugar level is needed in known type 2 diabetic patients to prevent DPN problem in future.

REFERENCES 1. Mohan V, Sandeep S, Deepa R, Shah B, Varghese C. Epidemiology of type 2 diabetes: Indian scenario. Indian J Med Res. 2007;125(3):217-30.

2. Attal N, Cruccu G, Baron R, Haanpää M, Hansson P, Jensen TS, et al; European Federation of Neurological Societies. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol.

2010;17(9):1113-e88.

3. Bennett M. The LANSS Pain Scale: the Leeds assessment of neuropathic symptoms and signs. Pain. 2001; 92(1-2):147-57.

4. Boulton AJ, Armstrong WD, Scarpello JH, Ward JD. The natural history of painful diabetic neuropathy - a 4-year study. Postgrad Med J. 1983;59(695):556-9.

5. Katulanda P, Ranasinghe P, Jayawardena R, Constantine GR, Rezvi Sheriff MH, Matthews DR. The prevalence, patterns and predictors of diabetic peripheral neuropathy in a developing country. Diabetol Metab Syndr. 2012;4:21.

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DIABETOLOGY 6. Bril V, England J, Franklin GM, Backonja M, Cohen J, Del Toro D, et al; American Academy of Neurology; American Association of Neuromuscular and Electrodiagnostic Medicine; American Academy of Physical Medicine and Rehabilitation. Evidence-based guideline: Treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology.

2011;76(20):1758-65.

7. Dworkin RH, O’Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations.

Pain. 2007;132(3):237-51.

8. Rani PK, Raman R, Rachapalli SR, Pal SS, Kulothungan V, Sharma T. Prevalence and risk factors for severity of diabetic neuropathy in type 2 diabetes mellitus. Indian J Med Sci. 2010;64(2):51-7.

9. Ashok S, Ramu M, Deepa R, Mohan V. Prevalence of neuropathy in type 2 diabetic patients attending a diabetes centre in South India. J Assoc Physicians India.

2002;50:546-50.

10. Tesfaye S, Vileikyte L, Rayman G, Sindrup SH, Perkins BA, Baconja M, et al; Toronto Expert Panel on Diabetic Neuropathy. Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management. Diabetes Metab Res Rev. 2011;27(7):629-38.

and norepinephrine uptake. Neuropsychopharmacology.

1993;8(1):23-33.

12. Pirart J. Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973. Diabetes Care. 1978;1(4): 252-63.

13. Garrow AP, Boulton AJ. Vibration perception threshold - a valuable assessment of neural dysfunction in people with diabetes. Diabetes Metab Res Rev. 2006;22(5):411-9.

14. Tapp RJ, Shaw JE, de Courten MP, Dunstan DW, Welborn TA, Zimmet PZ; AusDiab Study Group. Foot complications in Type 2 diabetes: an Australian population-based study.

Diabet Med. 2003;20(2):105-13.

15. Garrow AP, Boulton AJ. Vibration perception threshold - a valuable assessment of neural dysfunction in people with diabetes. Diabetes Metab Res Rev. 2006;22(5):411-9.

16. Fernando DJ, Hutchison A, Veves A, Gokal R, Boulton AJ. Risk factors for non-ischaemic foot ulceration in diabetic nephropathy. Diabet Med. 1991;8(3):223-5.

17. Unnikrishnan RI, Rema M, Pradeepa R, Deepa M, Shanthirani CS, Deepa R, et al. Prevalence and risk factors of diabetic nephropathy in an urban South Indian population: the Chennai Urban Rural Epidemiology Study (CURES 45). Diabetes Care. 2007;30(8):2019-24.

18. Bansal D, Gudala K, Muthyala H, Esam HP, Nayakallu R, Bhansali A. Prevalence and risk factors of development of peripheral diabetic neuropathy in type 2 diabetes mellitus in a tertiary care setting. J Diabetes Investig. 2014;5(6): 11. Wong DT, Bymaster FP, Mayle DA, Reid LR, Krushinski JH, Robertson DW. LY248686, a new inhibitor of serotonin 714-21.

■■■■

Gestational Diabetes Increases CV Risk Despite Absence of Type 2 Diabetes Women with gestational diabetes are at a higher risk of cardiovascular outcomes, even in the absence of type 2 diabetes; but the risk for microvascular complications emerges only in those who subsequently develop type 2 diabetes, suggests a study published online November 7, 2016 in the journal Diabetes Care.

A1c Better Predictor of Prediabetes vs. Blood Glucose A prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study published online November 15 in Lancet Diabetes & Endocrinology has suggested that prediabetes definitions using A1c were more specific and compared to fasting glucose, A1c-based definitions of prediabetes had higher hazard ratios and better risk discrimination for chronic kidney disease, cardiovascular disease, peripheral arterial disease and all-cause mortality.

...Cont'd from page 640 11. Zairis MN, Lyras AG, Makrygiannis SS, Psarogianni PK, Adamopoulou EN, Handanis SM, et al. Type 2 diabetes and intravenous thrombolysis outcome in the setting of ST elevation myocardial infarction. Diabetes Care.

2004;27(4):967-71.

12. Hasdai D, Granger CB, Srivatsa SS, Criger DA, Ellis SG,

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Califf RM, et al. Diabetes mellitus and outcome after primary coronary angioplasty for acute myocardial infarction: lessons from the GUSTO-IIb Angioplasty Substudy. Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes. J Am Coll Cardiol.

2000;35(6):1502-12.

Every citizen of India should have the right to accessible, affordable, quality and safe heart care irrespective of his/her economical background

Sameer Malik Heart Care Foundation Fund An Initiative of Heart Care Foundation of India

E-219, Greater Kailash, Part I, New Delhi - 110048 E-mail: heartcarefoundationfund@gmail.com Helpline Number: +91 - 9958771177

“No one should die of heart disease just because he/she cannot afford it” About Sameer Malik Heart Care Foundation Fund

Who is Eligible?

“Sameer Malik Heart Care Foundation Fund” it is an initiative of the Heart Care Foundation of India created with an objective to cater to the heart care needs of people.

Objectives Assist heart patients belonging to economically weaker sections of the society in getting affordable and quality treatment.

Raise awareness about the fundamental right of individuals to medical treatment irrespective of their religion or economical background.

Sensitize the central and state government about the need for a National Cardiovascular Disease Control Program.

Encourage and involve key stakeholders such as other NGOs, private institutions and individual to help reduce the number of deaths due to heart disease in the country.

To promote heart care research in India.

All heart patients who need pacemakers, valve replacement, bypass surgery, surgery for congenital heart diseases, etc. are eligible to apply for assistance from the Fund. The Application form can be downloaded from the website of the Fund. http://heartcarefoundationfund.heartcarefoundation. org and submitted in the HCFI Fund office.

Important Notes The patient must be a citizen of India with valid Voter ID Card/ Aadhaar Card/Driving License.

The patient must be needy and underprivileged, to be assessed

by Fund Committee.

The HCFI Fund reserves the right to accept/reject any application for financial assistance without assigning any reasons thereof.

The review of applications may take 4-6 weeks.

All applications are judged on merit by a Medical Advisory Board who meet every Tuesday and decide on the acceptance/rejection of applications.

The HCFI Fund is not responsible for failure of treatment/death of patient during or after the treatment has been rendered to the patient at designated hospitals.

To promote and train hands-only CPR.

Activities of the Fund Financial Assistance

The HCFI Fund reserves the right to advise/direct the beneficiary to the designated hospital for the treatment.

Financial assistance is given to eligible non emergent heart patients.

Apart from its own resources, the fund raises money through donations, aid from individuals, organizations, professional bodies, associations and other philanthropic organizations, etc.

The financial assistance granted will be given directly to the treating hospital/medical center.

After the sanction of grant, the fund members facilitate the patient in getting his/her heart intervention done at state of art heart hospitals in Delhi NCR like Medanta – The Medicity, National Heart Institute, All India Institute of Medical Sciences (AIIMS), RML Hospital, GB Pant Hospital, Jaipur Golden Hospital, etc. The money is transferred directly to the concerned hospital where surgery is to be done.

Drug Subsidy

The HCFI Fund has the right to print/publish/webcast/web post details of the patient including photos, and other details. (Under taking needs to be given to the HCFI Fund to publish the medical details so that more people can be benefitted).

The HCFI Fund does not provide assistance for any emergent heart interventions.

Check List of Documents to be Submitted with Application Form Passport size photo of the patient and the family A copy of medical records Identity proof with proof of residence Income proof (preferably given by SDM)

The HCFI Fund has tied up with Helpline Pharmacy in Delhi to facilitate

BPL Card (If Card holder)

patients with medicines at highly discounted rates (up to 50%) post surgery.

Details of financial assistance taken/applied from other sources (Prime Minister’s Relief Fund, National Illness Assistance Fund Ministry of Health Govt of India, Rotary Relief Fund, Delhi Arogya Kosh, Delhi Arogya Nidhi), etc., if anyone.

The HCFI Fund has also tied up for providing up to 50% discount on imaging (CT, MR, CT angiography, etc.)

Free Diagnostic Facility

Free Education and Employment Facility

The Fund has installed the latest State-of-the-Art 3 D Color Doppler EPIQ 7C Philips at E – 219, Greater Kailash, Part 1, New Delhi.

HCFI has tied up with a leading educational institution and an export house in Delhi NCR to adopt and to provide free education and employment opportunities to needy heart patients post surgery. Girls and women will be preferred.

This machine is used to screen children and adult patients for any heart disease.

Laboratory Subsidy HCFI has also tied up with leading laboratories in Delhi to give up to 50% discounts on all pathological lab tests.

About Heart Care Foundation of India

Help Us to Save Lives The Foundation seeks support, donations and contributions from individuals, organizations and establishments both private and governmental in its endeavor to reduce the number of deaths due to heart disease in the country. All donations made towards the Heart Care Foundation Fund are exempted from tax under Section 80 G of the IT Act (1961) within India. The Fund is also eligible for overseas donations under FCRA Registration (Reg. No 231650979). The objectives and activities of the trust are charitable within the meaning of 2 (15) of the IT Act 1961.

Heart Care Foundation of India was founded in 1986 as a National Charitable Trust with the basic objective of creating awareness about all aspects of health for people from all walks of life incorporating all pathies using low-cost infotainment modules under one roof.

HCFI is the only NGO in the country on whose community-based health awareness events, the Government of India has released two commemorative national stamps (Rs 1 in 1991 on Run For The Heart and Rs 6.50 in 1993 on Heart Care Festival- First Perfect Health Mela). In February 2012, Government of Rajasthan also released one Cancellation stamp for organizing the first mega health camp at Ajmer.

Objectives Preventive Health Care Education Perfect Health Mela Providing Financial Support for Heart Care Interventions Reversal of Sudden Cardiac Death Through CPR-10 Training Workshops Research in Heart Care

Donate Now...

Heart Care Foundation Blood Donation Camps The Heart Care Foundation organizes regular blood donation camps. The blood collected is used for patients undergoing heart surgeries in various institutions across Delhi.

Committee Members

Chief Patron

President

Raghu Kataria

Dr KK Aggarwal

Entrepreneur

Padma Shri, Dr BC Roy National & DST National Science Communication Awardee

Governing Council Members Sumi Malik Vivek Kumar Karna Chopra Dr Veena Aggarwal Veena Jaju Naina Aggarwal Nilesh Aggarwal H M Bangur

Advisors Mukul Rohtagi Ashok Chakradhar

Executive Council Members Deep Malik Geeta Anand Dr Uday Kakroo Harish Malik Aarti Upadhyay Raj Kumar Daga Shalin Kataria Anisha Kataria Vishnu Sureka

This Fund is dedicated to the memory of Sameer Malik who was an unfortunate victim of sudden cardiac death at a young age.

Rishab Soni

HCFI has associated with Shree Cement Ltd. for newspaper and outdoor publicity campaign HCFI also provides Free ambulance services for adopted heart patients HCFI has also tied up with Manav Ashray to provide free/highly subsidized accommodation to heart patients & their families visiting Delhi for treatment.

http://heartcarefoundationfund.heartcarefoundation.org

HEMATOLOGY

Pancytopenia: An Evaluation in a Tertiary Care Center UMA RAMANATHAN*, J THANKA†, LAWRENCE DERUZE‡, S SRI GAYATHRI‡

ABSTRACT Objective: The aim of this study was to assess the clinical picture, bone marrow morphology and etiology of pancytopenia, as causes of pancytopenia are extensive. Material and methods: This was an observational study performed retrospectively analyzing cases of pancytopenia seen during the period of 2013-2015, at the Dept. of Pathology, Sri Ramachandra University, Chennai. Inclusion criteria: Patients were included in the study if they fulfilled the following 3 criteria: low hemoglobin or red blood cell count, low white blood cell count and reduced platelet count according to age-specific reference range. Exclusion criteria: Immunocompromised status, disease or therapy related; adequate platelet count on peripheral smear and inconclusive aspirates and biopsies. Results: Pancytopenia was found in a wide age range and was more common in males. Neoplastic diseases arising from or infiltrating the bone marrow (39.5%) accounted for the most common cause of pancytopenia. Others included hypoplastic/aplastic anemia and megaloblastic anemia. Conclusion: Pancytopenia is not a disease entity by itself, but rather a clinical manifestation of a number of diseases. Work-up of patients presenting with pancytopenia with bone marrow studies and ancillary tests is essential to rule out life-threatening illnesses.

Keywords: Pancytopenia, anemia, aplastic, megaloblastic, leukemia

P

ancytopenia is a reduction in the formed elements of blood leading to anemia, leukopenia and thrombocytopenia. The clinical suspicion of pancytopenia is raised when patients present with fever, recurrent infections, pallor and bleeding diathesis. The causes of pancytopenia are extensive and vary based on age, gender, ethnicity and geographic distribution.

OBJECTIVE The aim of this study is to assess the clinical picture, bone marrow morphology and etiology of pancytopenia.

MATERIAL AND METHODS The present study was an observational study for a period of 3 years from January 2013 to December 2015 at the Hematology Unit, Dept. of Pathology, Sri Ramachandra University, Chennai.

*Postgraduate †Professor and Head ‡Assistant Professor Dept. of Pathology Sri Ramachandra University, Chennai, Tamil Nadu Address for correspondence Dr Uma Ramanathan 43, Kothari Road, Nungambakkam Chennai - 600 034, Tamil Nadu E-mail: uma_89@hotmail.com

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Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

Inclusion Criteria Patients of all ages, clinical features, age-specific laboratory parameters including hemoglobin (Hb) estimation or red blood cell (RBC) count, white blood cell (WBC) count, platelet count and peripheral smears.

Patients were included in the study if they fulfilled the following 3 criteria: (i) low Hb or RBC count, (ii) low WBC count and (iv) reduced platelet count according to age-specific reference values. The normal values for various age groups is shown in Table 1. Ancillary tests for serum vitamin B12, folic acid, iron studies, lactate dehydrogenase (LDH), liver function tests, lipid profile and erythrocyte sedimentation rate (ESR) were also noted.

Exclusion Criteria Immunocompromised states, disease or therapy related. ÂÂ

Platelet counts, which were adequate on smear due to giant platelets, aggregates and microclots.

ÂÂ

Inconclusive aspirates and biopsies.

Three milliliter anticoagulated (dipotassium ethylenediaminetetraacetic acid, 5.4 mg) was collected in lavender top vacutainers. The samples were processed and analyzed in the Beckman Coulter (version LH 780) automated hematology analyzer.

Peripheral smears were stained by Leishman stain for all the cases examined. This was subsequently followed up by bone marrow aspiration and biopsy performed

HEMATOLOGY Table 1. Age-specific Laboratory Parameters Age

Hb (g/L) Mean (±2SD)

1 day 2 weeks 1 month

RBC [x10^12/L] Mean (±2SD)

WBC [x10^9/L] Mean (±2SD)

Platelets [x10^9/L]

180 (40)

6 (1)

18 (8)

100-450

165 (4)

4.9 (1.3)

14 (8)

170-500

140 (25)

4.2 (1.2)

12 (7)

200-500

2 months

112 (18)

3.7 (0.6)

10 (5)

210-650

3-6 months

126 (15)

4.7 (0.6)

12 (6)

200-550

1 year

126 (15)

4.5 (0.6)

11 (5)

200-550

2-6 years

125 (15)

4.6 (0.6)

10 (5)

200-490

6-12 years

135 (20)

4.6 (0.6)

9 (4)

170-450

12-18 years (male)

14.5 (2)

4.5 (4.9)

4.5-13.5 (7.8)

150-350

12-18 years (female)

14.0 (2)

4.1 (4.6)

4.5-13.5 (7.8)

150-350

Adult male

150 (20)

5 (0.5)

4-10

150-350

Adult female

135 (15)

4.3 (0.5)

4-10

150-350

Hb = Hemoglobin; RBC = Red blood cell; WBC = White blood cell; L = Liter.

RESULTS In the current study, 119 cases being evaluated for pancytopenia in a tertiary care set up were examined; age ranged from 1 to 80 years with a mean age of 50 years. Incidence of pancytopenia in various age groups in this study is shown in Figure 1. The proportion of pancytopenia was more in males with a male (M) to female (F) ratio of 1.33:1.

The incidence of the common manifestations among the patients is shown in Figure 2. Pallor and hepatosplenomegaly were among the more common signs elicited in the patients in this study.

Cellularity of the bone marrow among the cases, which presented as pancytopenia in our study were compared and correlated with reference to age. Only 42.9% of the cases showed a hypocellular marrow, while the rest were normocellular (47.9%) to hypercellular (9.2%).

The most common cause was neoplastic (39.5%). The distribution pattern of the various types of neoplastic lesions reported is given in Table 2. Incidence was more among men with a M:F of 2.4:1. Dysplastic

35 30 Incidence (%)

under aseptic precautions with the consent of the patients. Bone marrow aspirate smears, fixed in 95% alcohol, were stained with Leishman stain, while airdried smears were fixed with May-Grunwald-Giemsa stain. Bone marrow biopsies were decalcified, processed using Leica autoprocessor ASP 6025 and auto stained with hematoxylin and eosin (H&E) stains using Leica autostainer XL.

25

29.41

29.41 25.21

20

15.97

15 10 5 0 1-20

21-40

41-60

>61

Figure 1. Incidence of pancytopenia among various age groups in the study.

Cough (2) GI disturbances (2)

Giddiness (2) Seizures (2)

Bleeding diathesis (7)

Weight loss (3)

Fever (28) Breathlessness (11) Generalized weakness (18)

Symptoms (No. of cases)

Figure 2. Common symptoms of patients which were associated with pancytopenia in our study.

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HEMATOLOGY Table 2. Distribution Pattern of Neoplastic Diseases Causing Pancytopenia in Our Study Age (years)

1-20

21-40

41-60

>61

Total

Myelodysplastic syndrome

2

4

3

4

13/47

Myeloproliferative neoplasm

-

-

2

-

2/47

Myelofibrosis

-

-

-

1

1/47

Acute myeloid leukemia

2

2

2

5

11/47

Acute lymphoblastic leukemia

7

1

-

1

9/47

Acute leukemia

5

-

2

1

8/47

Others

-

(1- Diffuse large B-cell lymphoma)

(1-Plasma cell myeloma)

-

2/47

marrows were found to be more in the age group of 21-40 years and 61 years and above. Reticulin stains and cytogenetics helped to differentiate aplastic from hypoplastic myelodysplastic syndrome in our series.

Myeloproliferative neoplasms and myelofibrosis (MF) accounted for only 3 cases evaluated for pancytopenia.

Twenty-nine of the 47 cases were acute leukemias. Blasts were seen in 29.6% of the peripheral smears; 41.9% cases required biopsy confirmation due to diluted aspirates.

Ancillary tests such as immunohistochemistry (IHC) and flow cytometry to type specify the leukemias could not be done on 8 of the 29 cases due to logistic reasons.

Plasma cell myeloma and diffuse large B-cell lymphoma infiltrating the marrow were reported in 2 cases.

Hypoplastic marrows were reported in 25 cases, while 72% were confirmed to be aplastic. Comparison of the various features of aplastic anemia reported in our study is given in Table 3.

Of the 9 cases of megaloblastic anemias, 3 were identified with peripheral smears showing macrovalocytes and hypersegmented neutrophils in correlation with mean corpuscular volume (MCV) and vitamin B12 levels and subsequently confirmed on aspirate. Biopsy confirmation was required in 3 due to dilute aspirates.

LDH was found to be >250 IU/L in all but 3 cases and serum total bilirubin, direct bilirubin and indirect bilirubin were elevated in all cases. This finding can be attributed to ineffective erythropoiesis and intramedullary hemolysis. The marrow studies were normocellular in all the cases though the peripheral smears were suggestive of pancytopenia.

Five of the 6 cases associated with an inflammatory etiology showed hemophagocytosis on bone marrow examination. The specific etiologies could be confirmed with the help of clinical, microbiological and biochemical correlation in 3 of them. Two cases were diagnosed as granulomatous inflammation possibly of tuberculosis origin, but only one showed hemophagocytosis.

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Table 3. Features of Aplastic Anemia Variables

Findings

M:F

1.25:1 (Ratio)

Reticulocyte %

0.2-4% (Range)

Peripheral smear-Neutropenic leukopenia

16.6% (Incidence)

Cellularity <25%

27.8% (Incidence)

Prussian blue stain

Grade 3-4 (Incidence)

Ziehl-Neelsen stain for acid-fast bacilli were negative in both the cases. Another case was found to have malarial antigen positivity. Hemophagocytic lymphohistiocytosis (HLH) was confirmed in the last case in correlation with elevated levels of serum ferritin (>16,500 ng/mL), serum triglycerides (242 mg/dL) and serum LDH (576 IU/L) along with clinical parameters such as fever for more than 7 days and splenomegaly, with no underlying etiology. A cause could not be identified for the 2 cases showing hemophagocytosis on bone marrow examination with no significant biochemical factors.

Of the cases evaluated for pancytopenia, 26.9% were unclassified as marrow studies showed nonspecific changes. Sixteen of the 32 cases had a hypocellular marrow, 3 were hypercellular and the remaining were normocellular. Erythroid hyperplasia was seen in 8 cases.

DISCUSSION Pancytopenia is a finding that encompasses a broad range of etiological factors. It can primarily or secondarily involve the bone marrow. The causes can be classified based on decreased production due to congenital failure of the marrow, spaceoccupying lesions or ineffective hematopoiesis. Other causes include increased peripheral destruction or sequestration.

HEMATOLOGY The age and sex distribution of other studies in comparison to ours is given in Table 4.1-3 In a study done in Stanford University, USA, 250 aspirates were evaluated for pancytopenia among which 193 were taken from adults, while the remaining 57 were from children.4 The pattern distribution of the various causes of pancytopenia varied among different studies and is shown in Table 5.5-13 In comparison to studies that evaluated causes of pancytopenia in India, the current study showed neoplastic disease either arising from or infiltrating the marrow to be the most common cause. This is comparable to the study done by Weinzierl et al, which showed B-lymphoblastic leukemia in children and acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) in adults to be more common.4 MDS and MF accounted for a minor component in our study, which was comparable to a study done by Pathak et al.2 A study done in India by Jayachandran et al found that 9% of the cases evaluated for pancytopenia in their study were due to malignancies.3 A study done

by Jha et al showed that 97% of the acute leukemias studied presented with pancytopenia/bicytopenia, which was similar to our study. Subleukemic leukemia Table 4. Comparison of Age and Sex Distribution with Other Studies of Pancytopenia Study

Year

Mean age range (years)

M:F

Gayathri et al1

2011

42 (2-80)

1.2:1

2012

38.8 (15-30)

1:1.04

Pathak et al2 Jayachandran et

al3

Current study

2015

>14

-

2016

50 (1-80)

1.36:1

was reported in 31% of the cases in our study in comparison to Gayathri et al and Khunger et al who reported an incidence of 3.58% and 5% of subleukemic cases, respectively.1,10,14 Matsuda et al reported a case of hypoplastic chronic myeloid leukemia (CML).15 Similarly, one case of pancytopenia was found to be CML with myelofibrosis in our study.

Hypoplastic anemia and megaloblastic anemia were among the more common causes in India as opposed to similar studies done in western countries.3,6,7,9,10,12 Prashanth et al attributed these findings to the nutritional status in these areas. To confound this, a study done in Zimbabwe by Savage et al with a similar socioeconomic background like our country also published similar results with megaloblastic anemia being the more prevalent disease.8 Six cases in the current study were grouped under inflammation, either due to infectious or noninfectious etiology. Hemophagocytosis was seen in all but one case. One was associated with granulomatous inflammation possibly of tuberculosis origin, while the other was associated with malarial infection. HLH was diagnosed in one case following clinical and biochemical correlation, with no underlying etiology.

This observation in our study deviated from results of other studies in India, which showed more cases of inflammatory etiology to be associated with parasitic diseases like malaria, leishmaniasis and others like enteric fever.1,13 Lastly, the unclassified group comprised of cases where no specific etiology could be identified on both aspiration and biopsy. Review of literature suggests that it could be a stage of evolution into a particular disease process like aplastic anemia, MDS, refractory anemia, hypersplenism or systemic illness.4,13

Table 5. Comparison of Various Causes of Pancytopenia in Other Studies Study

Year

Country

No. of cases

Most common

International Agranulocytosis and Aplastic Anemia Study Group5

1987

Israel & Europe

319

Hypoplastic anemia

Varma and Dash6

1992

India

202

Hypoplastic anemia

Tilak and Jain7

1999

India

77

Megaloblastic

al8

1999

Zimbabwe

134

Megaloblastic anemia

Khodke et al9

2001

India

50

Megaloblastic anemia

2002

India

200

Megaloblastic anemia

2004

Pakistan

200

Megaloblastic anemia

2008

Nepal

148

Hypoplastic anemia

2011

India

134

Megaloblastic anemia

2016

India

119

Neoplastic

Savage et

Khunger et Ishtiaq et

al10

al11

Jha et al12 Prashanth B

Gandhi13

Present study

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HEMATOLOGY CONCLUSION Pancytopenia is not a disease entity by itself, but rather a clinical manifestation of a number of diseases. Workup of patients presenting with pancytopenia with bone marrow studies and ancillary tests is essential to rule out early life-threatening illnesses.

REFERENCES 1. Gayathri BN, Rao KS. Pancytopenia: a clinicohematological study. J Lab Physicians. 2011;3(1):15-20.

2. Pathak R, Jha A, Sayami G. Evaluation of bone marrow in patients with pancytopenia. J Pathol Nepal. 2012;2:265-71.

3. Jayachandran K, Gauri Shankar J. Aetiology of pancytopenia in a tertiary care hospital – Coimbatore, South India. J Assoc Physicians India. 2015;63: 4. Weinzierl EP, Arber DA. Bone marrow evaluation in newonset pancytopenia. Hum Pathol. 2013;44(6):1154-64.

5. International Agranulocytosis and Aplastic Anemia Study. Incidence of aplastic anemia: the relevance of diagnostic criteria. Blood. 1987;70(6):1718-21.

6. Varma N, Dash S. A reappraisal of underlying pathology in adult patients presenting with pancytopenia. Trop Geogr Med. 1992;44(4):322-7.

8. Savage DG, Allen RH, Gangaidzo IT, Levy LM, Gwanzura C, Moyo A, et al. Pancytopenia in Zimbabwe.

Am J Med Sci. 1999;317(1):22-32.

9. Khodke K, Marwah S, Buxi G, Yadav RB, Chaturvedi NK. Bone marrow examination in cases of pancytopenia.

J Indian Acad Clin Med. 2001;2(1&2):55-9.

10. Khunger JM, Arulselvi S, Sharma U, Ranga S, Talib VH. Pancytopenia - a clinico haematological study of 200 cases. Indian J Pathol Microbiol. 2002;45(3):375-9.

11. Ishtiaq O, Baqai HZ, Anwer F, Hussain N. Patterns of pancytopenia patients in a general medical ward and a proposed diagnostic approach. J Ayub Med Coll Abbottabad. 2004;16(1):8-13.

12. Jha A, Sayami G, Adhikari RC, Panta AD, Jha R. Bone marrow examination in cases of pancytopenia. JNMA J Nepal Med Assoc. 2008;47(169):12-7.

13. Kumar DB, Raghupathi AR. Clinicohematologic analysis of pancytopenia: study in a tertiary care centre. Basic Appl Pathol. 2012;5(1):19-21.

14. Jha A. Spectrum of hematological malignancies and peripheral cytopenias. J Nepal Health Res Counc.

2013;11(25):273-8.

15. Matsuda M, Miyazato H, Ueda S, Morita Y, Sakaguchi M, Tatsumi Y, et al. A case of hypoplastic chronic myelogenous leukemia initiating with pancytopenia. Int J Hematol.

2002;75(3):335-6.

7. Tilak V, Jain R. Pancytopenia - a clinico-hematologic analysis of 77 cases. Indian J Pathol Microbiol.

1999;42(4):399-404.

■■■■

Drug-resistant Superbug Spreads Globally in Cystic Fibrosis Patients A multidrug-resistant superbug infection that can cause life-threatening illness in people with cystic fibrosis (CF) has spread globally and is becoming increasingly virulent, according to a UK study reported November 11, 2016 in the journal Science. The superbug, a species of multidrug-resistant Mycobacterium abscessus can cause severe pneumonia and may be potentially life-threatening for these patients.

In the study "Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium", researchers from Cambridge and the Wellcome Trust Sanger Institute sequenced the genomes of more than 1,000 samples of mycobacteria from 517 cystic fibrosis patients at specialist clinics in Europe, the United States and Australia. And, it was found that most patients had acquired the transmissible forms of M. abscessus that had spread globally.

The researchers further suggested that the infection may be transmitted within hospitals via contaminated surfaces and through the air presenting a serious challenge to infection control practices in hospitals.

Patients infected with it require treatment with a combination of powerful antibiotics for 18 months or more, and fewer than one in three cases is cured.

(Source: Medscape)

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INTERNAL MEDICINE

N-hexane-induced Polyneuropathy PK MAHESHWARI*, PRABHAT AGRAWAL†, AKHILESH SINGH‡, DIVYA#, BINDU, SHALINI UPADHYAY¥

ABSTRACT Introduction: Solvents containing n-hexane, an aliphatic hydrocarbon, are used as cleaning agents in the printing, textile, furniture and shoemaking industries, is a well-known cause of peripheral neuropathy which usually presents as sensory deficit followed by progressive weakness predominantly involving lower extremity, which progress for some time even after discontinuation (coasting phenomenon) and have variable recovery. Since shoe factories are very common in Agra, this polyneuropathy is frequently found here. Case report: A 16-year-old boy, who worked in a shoe factory, was admitted with complaints of progressive weakness, tingling and numbness of both upper and lower limbs since last 15 days. On further inquiry, patient admitted glue sniffing for last 4 months. Examination revealed autonomic involvement, atrophy of the muscle mass especially between metatarsals, diminished power in distal muscles predominantly, lost pain and temperature in both limbs, while proprioception was lost in lower limbs only. Nerve conduction studies revealed demyelinating neuropathy with conduction blocks in median and ulnar nerves in forearm, peroneal across the knee and tibial nerve in the leg. Sural nerve biopsy revealed decreased density of large myelinated fibers with several focally swollen axons. Discussion: Peripheral neuropathy is very well-described after exposure to n-hexane, particularly in shoemakers. However, this polyneuropathy has different features; from the substance abuse related polyneuropathy and is usually sensorimotor type with demyelinating features; progression is insidious, which is explained by the slow and low level exposure after termination of exposure. Patients may continue to worsen for many weeks known as ‘‘coasting’’ phenomenon, n-hexane both clinically and electrophysiologically.

Keywords: N-hexane, peripheral neuropathy, glue sniffing, sensorimotor type, demyelinating features

N

-hexane, an aliphatic hexacarbon with many industrial uses, is a well-known cause of peripheral neuropathy, both in industrial settings and in recreation glue sniffers.1-5 The solvents containing n-hexane are used as cleaning agents in the printing, textile, furniture and shoemaking industries.

Certain kinds of special glues used in the roofing, leather and shoe industries also contain n-hexane. The usual presentation is one of early sensory symptoms, followed by progressive weakness predominantly involving lower extremity. After discontinuation of exposure, progression may continue for some time (‘‘coasting’’) and is followed by variable recovery. We report a patient from Agra with n-hexane neuropathy

*Professor and Head †Associate Professor ‡Assistant Professor #Ex-Junior Resident ¥Junior Residents Dept. of Medicine SN Medical College, Agra, Uttar Pradesh Address for correspondence Dr Prabhat Agrawal D-1, Sulahkul Nagar, Bodla Road, Agra - 282 010, Uttar Pradesh E-mail: prabhatagrawal321@gmail.com

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secondary to glue sniffing. Agra has lots of shoe factories and because of glue sniffing, every year we have 2-3 cases of peripheral neuropathy secondary to glue sniffing.

CASE REPORT A 16-year-old boy presented with complaints of progressive weakness, tingling and numbness. He had developed tingling and numbness in both feet 15 days earlier and over the next 7 days, these symptoms also involved both hands. Simultaneously, he also noticed bilateral leg weakness which progressed proximally to involve bilateral upper limbs causing difficulty in holding objects and writing. Thus, over a period of 2 weeks patient was unable to walk without support and was bedridden.

There was also a history of weight loss of about 4-5 kg. On enquiring further, he admitted to previous substance abuse including glue sniffing for the last 4 months. Hexane was the primary ingredient of the glue, which he used for sniffing. As he worked in a shoe factory, the glue was easily accessible to him.

According to the patient, he had stopped glue sniffing 20 days before the onset of symptoms.

INTERNAL MEDICINE Physical Examination General physical examination was normal, except mild pallor was present. Resting tachycardia was present.

Decreased heart rate variability with respiration on ECG was present suggesting autonomic involvement. All cranial nerves were intact. Examination of both hands and feet revealed atrophy of muscle mass especially between metatarsals. Fasciculations were absent.

Power of muscles showed predominantly weakness of distal muscles. Pain and temperature sensation were diminished up to the mid-shin in lower limbs and up to wrists in upper limbs. Proprioception was lost up to the ankle joint and was intact in the upper limb. Deep tendon reflexes were 1+ in the arms, knee reflex was 1+ and ankle reflex was absent. Plantar reflex was not elicitable.

Laboratory Evaluation Laboratory work-up revealed normal blood sugar, serum electrolytes, blood urea nitrogen, creatinine, calcium, liver function tests and hemogram was normal except low hemoglobin (9.0 g/dL). Erythrocyte sedimentation rate (ESR), serum protein electrophoresis, antinuclear antibody were normal. Hepatitis B surface antigen (HbsAg), human immunodeficiency virus (HIV) and anti-HCV (hepatitis C virus) serologies were normal. Cerebrospinal fluid (CSF) study was within normal limits. A sural nerve biopsy was performed, revealing decreased density of large myelinated fibers with several focally swollen axons.

Electrophysiological Evaluation Nerve conduction studies revealed diminished compound muscle action potential (CMAP) amplitudes, prolonged motor distal latencies and decreased motor conduction velocities, findings consistent with the demyelinating polyneuropathy. There was conduction block in several locations: median nerve in the forearm, ulnar nerve in the forearm, peroneal nerve across the knee and tibial nerve in the leg.

DISCUSSION Peripheral neuropathy is very well-described after exposure to n-hexane, particularly in shoemakers. The first report of n-hexane related toxic neuropathy was from Japan in 1963.6 In Agra, n-hexane is commonly used in shoemaking industry and neurotoxicity related to n-hexane is seen here commonly. There are also reports of glue sniffers or ‘‘huffers’’ developing peripheral neuropathy.

However, the polyneuropathy related to industrial/ occupational n-hexane toxicity has different features from the substance abuse related polyneuropathy. The sensory and motor dysfunction caused by industrial/ occupational n-hexane toxicity usually develops insidiously, which is explained by the slow and low level exposure. In glue sniffers and severely affected industrial workers the onset may be subacute and mimicking Guillain-Barré syndrome.7 Autonomic disturbances have been reported among glue sniffers but not in the industrial/occupational cases.8 Consistent with this finding, our patient had subacute onset and had autonomic disturbances.

Different central and peripheral nervous system problems can be caused by n-hexane intoxication but a sensorimotor polyneuropathy with demyelinating features is the most common presentation.9,10 Studies performed in experimental animals and people exposed to n-hexane in their workplaces have shown that the main metabolite of n-hexane in the organism is 2,5-hexanedione (2,5-HD). This metabolite is the primary cause of n-hexane-induced peripheral neuropathy and has neurotoxic effect. This toxic neuropathy is known to affect large diameter fibers especially in the lower extremities.11 Numbness is typically noted in the feet and hands and rarely spreads beyond the knees or wrists.

Weakness develops in the legs, then the arms and tends to affect distal muscles mostly. Marked distal atrophy and proximal weakness occurs in severe cases.

Muscle cramping and weight loss are common.7,8,11,12 In one large series of 93 patients, 57% had a sensory neuropathy and only 8.6% also had amyotrophy. Distal lower extremity numbness was the first symptom in 88% of patients.13 After exposure is terminated, patients may continue to worsen for many weeks, as our patient. The ‘‘coasting’’ phenomenon is well-described, both clinically and electrophysiologically,5,14 and is observed in other toxic neuropathies including acrylamide, thalidomide, triorthocresyl phosphate and the multiple cranial neuropathies of trichloroethylene.

The pathologic finding of n-hexane neuropathy is loss of large myelinated fibers with focally enlarged ‘‘giant’’ axons filled with neurofilaments and associated thinning of the overlying myelin.5,15 Such finding also has been described in methyl-nbutyl ketone, triorthocresyl phosphate, acrylamide and inherited giant axonal neuropathy. Based on pathological evidence, primary involvement is of axons

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INTERNAL MEDICINE beginning distally with proximal spread, followed by secondary involvement of myelin.

N-hexane polyneuropathy is one of the few toxic neuropathies, which exhibit electrophysiological features of both demyelination and axonal loss. Even though n-hexane neuropathy is primarily an axonal neuropathy, most electrophysiological studies report demyelinating features such as slowing of the nerve conduction velocity.

Electrophysiologic findings depend on the neuropathy’s severity. One study of 20 industrial workers exposed to n-hexane without neurologic manifestations revealed normal nerve conduction velocities and F responses, but decreased sensory nerve action potential (SNAP) amplitudes compared to controls.16 Same changes have been reported in persons without neurological disease who were exposed to n-methyl butyl ketone.17 Of 56 workers exposed to n-hexane in an offset printing shop, 46% had subclinical peripheral neuropathy evident on electrophysiological studies, with markedly diminished SNAP amplitudes, diminished motor conduction velocity, mildly prolonged motor distal latencies and reduced compound muscle action potential (CMAP) amplitudes. Among those with symptomatic neuropathy, motor nerve conduction velocities were markedly slowed. There has been no relationship between duration of employment and development of neuropathy, suggesting that some host factors like individual variability in the hepatic P-450 system play a role.6,16 Many others have emphasized the reduction in motor conduction velocities in severely affected patients.

Motor conduction velocities are slowest distally, with mildly slowed proximal conduction velocity (e.g., between the neck and axilla). F waves are usually absent. Conduction block was observed in our patient and has been described by several others.18 The subacute presentation of n-hexane neuropathy may mimic Guillain-Barré syndrome.7 The CSF findings, lack of improvement after immunomodulatory treatment and the neuropathological findings may help to distinguish between the two disorders.

Prognostic factor for recovery from n-hexane neuropathy includes the severity of illness with excellent clinical outcome in most patients with sensory neuropathy.

Among 93 industrial workers, 57% of whom had a sensory neuropathy, 34% a sensorimotor neuropathy and 9% amyotrophy, 92% achieved a full recovery after 4 years, while the remaining patients were left with only sensory abnormalities.13 There are relatively few

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data on recovery in severely affected huffers. However, among 3 huffers unable to walk at the peak of their neuropathy, 2 recovered with independent ambulation with persistent foot drops and 1 achieved full recovery.

Electrophysiological recovery paralleled clinical improvement.5,15,19 REFERENCES 1. Albers JA, Wald JJ. Industrial and environmental toxic neuropathies. In: Brown WF, Bolton CF, Aminof M J (Eds.).

Neuromuscular Function and Disease. Basic, Clinical and Electrodiagnostic Aspects. Philadelphia: WB Saunders Company; 2002;Vol. 2, 63:1143-68.

2. Oh SJ, Kim JM. Giant axonal swelling in “huffer’s” neuropathy. Arch Neurol. 1976;33(8):583-6.

3. Shirabe T, Tsuda T, Terao A, Araki S. Toxic polyneuropathy due to glue-sniffing. Report of two cases with a light and electron-microscopic study of the peripheral nerves and muscles. J Neurol Sci. 1974;21(1):101-13.

4. Towfighi J, Gonatas NK, Pleasure D, Cooper HS, McCree L. Glue sniffer’s neuropathy. Neurology. 1976;26(3):238-43.

5. Korobkin R, Asbury AK, Sumner AJ, Nielsen SL. Gluesniffing neuropathy. Arch Neurol. 1975;32(3):158-62.

6. Chang YC. Neurotoxic effects of n-hexane on the human central nervous system: evoked potential abnormalities in n-hexane polyneuropathy. J Neurol Neurosurg Psychiatry.

1987;50(3):269-74.

7. Smith AG, Albers JW. n-Hexane neuropathy due to rubber cement sniffing. Muscle Nerve. 1997;20(11):1445-50.

8. Bogucki A, Głuszcz-Zielińska A. Focal conduction block in n-hexane polyneuropathy. Muscle Nerve. 1999;22(3): 425-6.

9. Chang AP, England JD, Garcia CA, Sumner AJ. Focal conduction block in n-hexane polyneuropathy. Muscle Nerve. 1998;21(7):964-9.

10. Kuwabara S, Kai MR, Nagase H, Hattori T. n-Hexane neuropathy caused by addictive inhalation: clinical and electrophysiological features. Eur Neurol. 1999;41(3):163-7.

11. Kimura J. Polyneuropthies. In: Kimura J (Ed.).

Electrodiagnosis in Disease of Nevre and MusclePrinciples and Practice. New York: Oxford University Press; 2001;25:651-710.

12. Schaumburg HH, Berger AR. Human toxic neuropathy due to industrial agents. In: Dyck PJ, Thomas PK, Griffin JW, Low PA, Poduslo JF (Eds.). Peripheral Neuropathy.

3rd Edition, Philadelphia: Saunders; 1993. pp. 1533-48.

13. Iida M. Neurophysiological studies of n-hexane polyneuropathy in the sandal factory. Electroencephalogr Clin Neurophysiol Suppl. 1982;36:671-81.

14. Huang CC, Chu NS, Cheng SY, Shin TS. Biphasic recovery in n-hexane polyneuropathy. A clinical and electrophysiological study. Acta Neurol Scand.

1989;80(6):610-5.

Cont'd on page 677...

OBSTETRICS AND GYNECOLOGY

Maternal and Perinatal Outcome in Antepartum Hemorrhage in a Tertiary Care Center: An Observational Study RUBY BHATIA*, PARMJIT KAUR†, GURDIP KAUR*, SATINDER KAUR‡, AMAN DEV#, SANTOSH KUMARI¥

ABSTRACT Antepartum hemorrhage (APH) complicates 2-5% of all pregnancies. Placenta previa and placental abruptio remain the most common causes of APH. Any pregnancy with APH remains at increased risk for an adverse outcome even though bleeding has stopped and placenta previa has been excluded sonographically. An observational study was carried out in high dependency unit of obstetrics at Govt. Medical College and Rajindra Hospital, Patiala to study maternal and perinatal outcome in APH complicating pregnancy.

Keywords: Antepartum hemorrhage, placenta previa, abruptio placenta

H

emorrhage is the single most important cause of maternal death worldwide and is responsible for half of all postpartum deaths in developing countries.1 Antepartum hemorrhage (APH) is defined as any bleeding from female genital tract between fetal viability and delivery of the fetus.2 APH complicates 2-5% of all pregnancies.1 Obstetric hemorrhage remains the most important cause of maternal and perinatal morbidity and mortality in developing countries. APH and postpartum hemorrhage (PPH) are the leading causes for maternal mortality followed by sepsis and eclampsia in India. Placenta previa and placental abruptio remain the most common causes of APH. Any pregnancy with APH remains at increased risk for an adverse outcome even though bleeding has stopped and placenta previa has been excluded sonographically.

Hence, to study maternal and fetal outcomes and various risk factors associated with APH is the need

*Associate Professor †Professor ‡Assistant Professor Dept. of Obstetrics and Gynecology #Civil Surgeon Dept. of PSM ¥Postgraduate Student Dept. of Obstetrics and Gynecology Govt. Medical College and Rajindra Hospital, Patiala, Punjab Address for correspondence Dr Ruby Bhatia D-8, Medical College Campus, Patiala - 147 001, Punjab E-mail:drrubybhatia@yahoo.com

of the hour, so as to improve maternal and perinatal morbidity and mortality by providing efficient emergency services.

AIMS AND OBJECTIVES ÂÂ

To determine incidence and the type of APH.

ÂÂ

Associated risk factors for APH.

ÂÂ

To study maternal and perinatal outcome in APH complicating pregnancy.

MATERIAL AND METHODS It was an observational study carried out in high dependency unit of obstetrics at Govt. Medical College and Rajindra Hospital, Patiala for a period of 6 months with effect from November 2015 to May 2016. Antenatal women with chief complaint of bleeding per vaginum after the period of viability (≥24 weeks of gestation) admitted to high dependency unit were included in the study. A detailed history, thorough clinical examination with special reference to abdominal examination, laboratory test and ultrasound examination of pelvis for fetal well-being, placental localization, any evidence of placenta accreta and retroplacental hemorrhage, carried out in all the cases. Immediate resuscitative measures in the form of two wide bore 16 gauge cannulas for transfusion of crystalloids and colloid were taken in all the cases of APH. Adequate quantity of blood was arranged and transfused in all the cases of APH.

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OBSTETRICS AND GYNECOLOGY Sociodemographic characteristics were noted. Patients were grouped as placenta previa, abruptio placenta, combined (placenta previa and abruptio placenta both), local cause and indeterminate cause. Risk factors such as age, parity, pre-eclampsia, malpresentation, polyhydramnios, multiple pregnancy and smoking in present pregnancy were recorded. Past history of scarred uterus (previous cesarean one, two or more, myomectomy, check curettage, medical termination of pregnancy), placenta previa, abruptio placenta or any other risk factors were evaluated. Maternal complications in the form of anemia, hypovolemic shock, intrapartum hemorrhage, need for blood transfusion, need of cesarean section, PPH, peripartum hysterectomy, acute renal injury, disseminated intravascular coagulation (DIC) and maternal death were recorded. Perinatal outcome was evaluated in relation to prematurity, fetal growth restriction, low birth weight, low Apgar score

at 1 and 5 minutes, admission to neonatal intensive care unit (NICU) and stillbirth.

OBSERVATIONS A total of 2,040 births occurred during the study period with effect from 1st November 2015 to 31st May 2015.

Prevalence of APH was found to be 4.55% with a total of 93 cases. Abruptio placenta was encountered in 52 patients (2.54%), while placenta previa (1.81%) in 37 cases (Table 1). Only three cases were due to indeterminate causes (0.14%), while only one case had combined placenta previa as well as abruptio placenta.

Majority of the patients with APH were unbooked (82.76%) and reported as emergency admission in our high dependency unit. Only 16 patients with APH were booked with complete antenatal care (Table 2). It was observed that 77.41% of the women with APH were in

Table 1. Incidence of Antepartum Hemorrhage (Total 93 = 100%) Total births

Total APH

Abruptio placenta

Placenta previa

Combined

Indeterminate causes

Local cause

2,040

93

52

37

1

3

0

100

4.55

2.54

1.81

0.04

0.14

0

No. Percentage (%)

Table 2. Sociodemographic Characteristics in Antepartum Hemorrhage (Total 93 = 100%) Sociodemographic factors

No. of APH cases

% among APH cases

Abruptio placenta

NN

%

Booked

17

18.27

8

8.60

Unbooked

76

81.72

44

47.311

N

%

Placenta previa N

Indeterminate cause

Combined

%

N

%

N

%

8

8.60

1

1.07

0

0

29

31.18

2

2.15

1

1.07

Age <20

3

3.22

3

3.22

0

0

0

0

0

0

20-30

72

77.41

40

43.01

29

31.18

2

2.15

1

1.07

>30

18

19.35

9

9.67

8

8.60

1

1.07

0

0

Primi gravida

27

29.03

14

15.05

11

11.82

1

1.07

1

1.07

Gravida 2-3

46

49.46

26

27.95

18

19.35

2

2.15

0

0

Grand multipara (gravida >4)

20

21.50

12

12.90

8

8.60

0

0

0

0

Lower

75

80.64

44

47.31

28

30.10

2

2.15

1

1.07

Middle

14

15.05

6

6.45

7

7.52

1

1.07

0

0

Upper

4

4.30

2

2.15

2

2.15

0

0

0

0

Rural

57

61.29

32

34.40

22

23.65

2

2.15

1

1.07

Urban

36

38.70

20

21.50

15

16.12

1

1.07

0

0

Parity

Socioeconomic status

Residence

662

Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

OBSTETRICS AND GYNECOLOGY the age group of 20-30 years. The elderly gravida (>35 years) were encountered in 19.35% of the women with APH with equal distribution among placenta previa and abruptio placenta (Table 2). Majority of the women in the study group (49.46%) were gravida 2-3, but 21.50% of the patients with APH were grand multipara, which was significantly high in abruptio placenta (12.90%) as compared to placenta previa (8.60%) (Table 2). Majority of the patients were from low socioeconomic status (80.64%) and 61.29% were from rural areas (Table 2). Out of 37 patients of placenta previa, major degree placenta Table 3. Distribution According to the Type of Placenta Previa (Total 37 =1 00%) Types of placenta previa

No.

Percentage (%)

Type I

3

8.10

Type II

3

8.10

Type III

2

5.40

Type IV

29

78.37

Placenta accreta in type IV

2

5.40

previa was encountered in 29 cases (78.37%), while two cases of major degree placenta previa had placenta accreta (5.4%) (Table 3). Grand multipara was found to be the major risk factor and was encountered in 21.50% of the patients with APH, the incidence was higher in abruptio placenta (12.90%) than placenta previa (8.60%) (Table 4). The second most important risk factor was association with severe pre-eclampsia and eclampsia seen in 20.43% of the patients with APH. A significantly higher incidence of severe pre-eclampsia and eclampsia was observed in association with abruptio placenta (16.12%) as compared to placenta previa (4.30%) (Table 4). In 6.45% of the patients with APH, malpresentation was seen. The incidence of malpresentation was double in placenta previa (4.30%) than abruptio placenta (2.15%). Abruptio placenta was associated in 2.15% of the women each with polyhydramnios and premature rupture of membranes (PPROM). The prevalence of placenta previa was 13.97% in the women with previous one or more cesarean delivery, which was significantly higher than in abruptio placenta with previous cesarean delivery

Table 4. Risk Factors for Antepartum Hemorrhage (Total 93 = 100%) Risk factors

No. of APH cases

% among APH cases

Abruptio placenta

Placenta previa

Unknown cause

Combined

N

%

N

%

N

%

N

%

N

%

Grand multipara

20

21.50

12

12.90

8

8.60

0

0

0

0

Severe pre-eclampsia/ eclampsia

19

20.43

15

16.12

4

4.30

0

0

0

0

Maternal age (>35)

8

8.60

4

4.30

3

3.22

1

1.07

0

0

Malpresentation

6

6.45

2

2.15

4

4.30

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Present pregnancy

Polyhydramnios

2

2.15

2

2.15

PROM

2

2.15

2

2.15

Trauma

0

0

0

0

0

0

0

0

0

0

Smoking/drug misuse

0

0

0

0

0

0

0

0

0

0

First trimester bleeding

1

1.07

0

0

1

1.70

0

0

0

0

H/o previous LSCS

18

19.34

4

4.30

13

13.97

1

1.07

0

0

Previous 1 LSCS

13

13.97

4

4.30

8

8.60

1

1.07

0

0

Past history

0

Previous 2 LSCS

4

4.30

0

0

4

4.30

0

0

0

0

Previous 3 LSCS

1

1.07

0

0

1

1.07

0

0

0

0

H/o previous MTP/check curettage

10

10.75

3

3.22

6

6.45

1

1.07

0

0

H/o abruptio placenta

2

2.15

2

2.15

0

0

0

0

0

0

H/o placenta previa

4

4.30

0

0

4

4.30

0

0

0

0

H/o previous MROP

0

0

0

0

0

0

0

0

0

0

Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

663

OBSTETRICS AND GYNECOLOGY 11.82% of the cases with APH had atonic PPH, which were managed by uterine massage, uterotonics and balloon tamponade along with resuscitative measures.

Peripartum hysterectomy had to be performed in three (3.22%) patients of atonic PPH as a lifesaving measures (Table 5). One of the patient with abruptio placenta required MROP. DIC and acute renal injury was encountered in 2.15% of the cases each (Table 5). One of the patient with APH, with major degree placenta previa and placenta accreta with previous two lower

(4.30%) (Table 4). History of manual removal of the placenta (MROP) in previous pregnancy could not be ascertained. Two patients with major degree placenta previa with previous two cesarean sections were diagnosed placenta accreta on color Doppler.

The most dreaded maternal outcome associated with APH was anemia encountered in 34.40% of the patients, which indirectly increased the maternal morbidity and higher need for blood transfusion to 34.40% of the patient with APH (Table 5). Also,

Table 5. Maternal Outcome in Antepartum Hemorrhage (Total 93 = 100%) Maternal outcome

APH

Abruptio placenta

Placenta previa

Indeterminate cause

Combined

N

%

N

%

N

%

N

%

N

%

32

34.40

18

19.35

14

15.05

0

0

0

0

Nil

61

65.59

34

36.55

23

24.73

3

3.22

1

1.07

1-4

27

29.03

15

16.12

12

12.90

0

0

0

0

5-10

5

5.37

3

3.22

2

2.15

0

0

0

0

PPH

Severe anemia (<7 g%) Units of blood transfused

11

11.82

6

6.45

5

5.37

0

0

0

0

Intrapartum hemorrhage

3

3.22

2

2.15

1

1.07

0

0

0

0

Peripartum hysterectomy

3

3.22

2

2.15

1

1.07

0

0

0

0

DIC

2

2.15

1

1.07

1

1.07

0

0

0

0

Acute renal injury

2

2.15

1

1.07

1

1.07

0

0

0

0

MROP

1

1.07

1

1.07

0

0

0

0

0

0

Maternal mortality

1

1.07

0

0

1

1.07

0

0

0

0

Table 6. Perinatal Outcome in Antepartum Hemorrhage (Total 93 = 100%) Perinatal outcome

APH

Abruptio placenta

Placenta previa

Indeterminate causes

Combined

N

%

N

%

N

%

N

%

N

%

<34 weeks

14

15.05

10

10.75

3

3.22

1

1.07

0

0

34-36+6 weeks

47

50.53

19

20.43

26

27.95

1

1.07

1

1.07

32

34.40

23

24.73

8

8.60

1

1.07

0

0

Maturity Preterm

Term >37 weeks Birth weight <1.5 kg

14

15.05

09

9.67

4

4.30

1

1.07

0

0

1.5-2.5 kg

46

49.46

22

23.65

23

24.73

1

1.07

0

0

>2.5 kg

33

35.48

21

22.58

10

10.75

1

1.07

1

1.07

Apgar in 1 and 5 minutes <7

10

10.75

8

8.60

2

2.15

0

7-9

10

10.75

3

3.22

6

6.45

1

1.07

>9

49

52.68

17

18.27

29

31.18

2

2.15

1

1.07

NICU admission

22

23.65

12

12.90

9

9.67

1

1.07

0

0

Stillbirth

23

24.73

16

17.20

7

7.52

0

0

0

0

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Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

OBSTETRICS AND GYNECOLOGY segment cesarean section (LSCS) was lost due to intractable atonic PPH during cesarean delivery in spite of best efforts. Premature termination of pregnancy before 37 weeks was required in 65.58% cases to manage APH; 23.65% babies required NICU admission.

Almost quarter of the patients with APH had stillbirth with a higher incidence (17.20%) in abruptio placenta (Table 6).

DISCUSSION Antepartum hemorrhage was an important cause for maternal and perinatal morbidity and mortality. APH complicates 2-5% of all pregnancies.2 Incidence in our study is 4.55%, comparable to an incidence of 3% in studies conducted by Maurya et al3 and Singhal et al.4 In our study, 81.72% of cases were unbooked and 80.64% belonged to poor socioeconomic status. Majority were in the age group 20-30 years (77.41%) with 49.46% being multiparous, which is similar to Maurya et al, Singhal et al and Das et al;5 grand multiparity is a significant risk factor for APH as 21.50% patients were grand multipara. Incidence was higher in abruptio placenta 12.90% compared to 8.6% in placenta previa.

In our study, 20.43% of cases had severe pre-eclampsia and eclampsia; Singhal et al also reported hypertension in 22% of the cases in their study. Incidence of placenta previa in our study was 1.81% with a total of 37 cases.

Previous one or more cesarean delivery was a risk factor in 19.34% cases with APH correlated with the study of Serella et al.6 Eight cases of placenta previa had one previous section and four had previous two sections with an incidence of 8.60% and 4.30%, respectively, which is similar as reported by Pandey et al.7 Six cases of placenta previa (6.45%) had previous history of curettage; 4.30% cases had placenta previa in previous pregnancy also (Table 4).

Malpresentation was seen in 6.45% cases, which is comparatively lesser than found in study conducted

by Serella et al (18.03%).6 Perinatal mortality was as high as 24.73% in our study with maternal mortality of 1.07%, which is comparable to Singhal et al study with 23% perinatal mortality and maternal mortality of 2%. Arora et al and Khosla et al reported very high perinatal mortality of 61.5% and 53.5%, respectively.8,9 This difference may be due to better NICU care in our institute. Mean birth weight in our study was 2.4 kg comparable to Singhal et al.4 High neonatal morbidity was due to low birth weight related to preterm birth in (65.58%) and NICU admission in (23.65%). DIC and acute renal injury developed in 2.15% each in our study compared to 7% in Singhal et al4 study requiring blood products transfusion; 11.82% of cases had PPH managed with uterotonics, B-Lynch, bilateral uterine

artery ligation while three cases required peripartum hysterectomy. This is comparable to Singhal et al study,4 which had three women requiring peripartum cesarean hysterectomy.

CONCLUSION Prevalence of APH in our institute, which is a tertiary care center was 4.55%. Incidence of abruptio placenta (2.54%) is higher than placenta previa (1.81%). Grand multiparity, severe pre-eclampsia, increased maternal age and polyhydramnios were significant risk factors for abruptio placenta, while previous one or two cesarean delivery and previous curettage were major risk factors for placenta previa. All women with APH heavier than spotting or ongoing bleeding per vaginum should be assessed by consultant led care at tertiary hospitals, advised admission till bleeding stops and to establish the need for urgent intervention to manage maternal and fetal compromise. Prompt resuscitation of hypovolemia and blood administration is an absolute requirement for acceptable obstetric care. Good perinatal outcome is anticipated with early referral to tertiary care center, early cesarean section, liberal availability of blood products and timely neonatal resuscitation.

REFERENCES 1. Lalonde A, Daviss BA, Acosta A, Herschderfer K. Postpartum hemorrhage today: ICM/FIGO initiative 20042006. Int J Gynaecol Obstet. 2006;94(3):243-53.

2. Caric V, Bhide A. Antepartum hemorrhage (Chap 10). In: Arias F, Bhide A, Kaizad AS, Daftary DS. Ariasâ&#x20AC;&#x2122; Practical Guide to High Risk Pregnancy and Delivery, 4th Edition, Elsevier, India; 2014.

3. Maurya A, Arya S. Study of antepartum hemorrhage and its maternal and perinatal outcome. Int J Sci Res Pub. 2014;4(2):1-8.

4. Singhal S, Nymphaea, Nanda S. Maternal and perinatal outcome in antepartum hemorrhage: a study at a tertiary care referral institute. Int J Gynecol Obstet. 2007;9(2):1-4.

5. Das B. Antepartum hemorrhage in three decades. J Obstet Gynaecol India. 1975,25:636-7.

6. Sarella L, Chinta A. A study on maternal and perinatal outcome in placenta previa. Sch J App Med Sci. 2014;2(5A):1555-8.

7. Pandey VP, Pandey M. Study of antepartum haemorrhage and its maternal and perinatal outcome. Ann Int Med Den Res. 2016;2(1):384-9.

8. Arora R, Devi U, Majumdar R. Perinatal morbidity and mortality in antepartum hemorrhage. J Obstet Gynaecol India. 2001;51(3):102-4.

9. Khosla A, Dahiya V, Sangwan K, Rathore S. Perinatal outcome in antepartum hemorrhage. J Obstet Gynaecol India. 1989;9:71-3.

Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

665

OBSTETRICS AND GYNECOLOGY

A Retrospective Study of Prevalence of Hepatitis B, Hepatitis C and HIV in Pregnant Women and Their Perinatal Outcome NAVNEET KAUR*, PARNEET KAUR†

ABSTRACT Background: The incidence of hepatitis B, hepatitis C and human immunodeficiency virus (HIV) is increasing day by day and majority of transmission of these viruses occurs vertically from an infected carrier mother to the neonate. Up to 90% babies born to carrier mothers may also become carriers and are at high risk of developing chronic liver diseases at a younger age.

Objectives: The present study was done to know the prevalence, maternal and neonatal outcome in the hepatitis B, hepatitis C and HIV positive pregnant women. Material and methods: This retrospective study was done based on review of records of 2,194 pregnant women who came to the labor room of Dept. of Obstetrics and Gynecology, Govt. Medical College and Rajindra Hospital, Patiala, Punjab from 1st August 2015 to 31st March 2016 for delivery. Results: Amongst 2,194 pregnant women, 106 (4.83%) were either hepatitis B, hepatitis C or HIV positive and 2,088 (95.17%) were negative for any viral marker. Out of 106 women, 30 (28.30%), 43 (40.56%) and 31 (29.25%) women were positive for HIV, hepatitis C and hepatitis B, and the prevalence was 1.36%, 1.95% and 1.41%, respectively. Seventy-one (66.98%) women had vaginal delivery and 35 (33.01%) had cesarean section. Babies born with ≤2,500 g; 2,600-3,000 g and >3,000 g in weight were 41 (37.61%), 46 (42.20%) and 22 (20.18%), respectively.

Conclusion: Screening of all the pregnant women for HIV, hepatitis B and hepatitis C is necessary in order to identify those neonates at risk of transmission. Women who are tested positive should be treated properly and health education should be given to such women during antenatal visits and complications should be dealt with carefully.

Keywords: Human immunodeficiency virus, hepatitis B, hepatitis C, pregnancy, prevalence

H

epatitis is the inflammation of liver characterized by presence of inflammatory cells in the tissue of the organ. Hepatitis is acute when it lasts less than 6 months and chronic when it persists longer. Hepatitis B virus (HBV) is a member of the Hepadnaviridae family; it is a DNA virus with partially double-stranded DNA and a core antigen surrounded by a shell containing hepatitis B surface antigen (HBsAg).1 According to the World Health Organization (WHO), HBV infection affects more than 2 billion people worldwide and about 350 million of these remain infected chronically. Over

*Senior Resident †Professor Dept. of Obstetrics and Gynecology Govt. Medical College and Rajindra Hospital, Patiala, Punjab Address for correspondence Dr Navneet Kaur 267, SST Nagar/Sunder Nagar Near Guru Harkrishan Public School, Patiala - 147 001, Punjab E-mail: nav_neetu8@yahoo.in

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Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

20 million people are infected annually with this virus.2 Hepatitis C virus (HCV) infection is a globally prevalent pathogen and a leading cause of death and morbidity.

WHO estimates that 3% of the world population are chronically infected with HCV and almost 50% of all cases become chronic carriers and are at risk of liver cirrhosis and liver cancer.3 Both HBV and HCV are transmitted by sexual, parenteral and vertical route and leads to serious sequelae like chronic active hepatitis, cirrhosis and hepatocellular carcinoma.4 Viral hepatitis during pregnancy can lead to coagulation defects, postpartum hemorrhage (PPH), organ failure and is associated with high risk of maternal and fetal complications.5 There is a high rate of vertical transmission causing fetal and neonatal hepatitis leading to impaired physical and mental health later in life. Maternal rupture of membranes more than 6 hours increase the risk of mother-to-child transmission of HCV and HBV.6 Ideally, all pregnant women should be screened both for hepatitis B and hepatitis C. The HIV is a retrovirus which is transmitted by sexual, parenteral route and it has quite a high vertical

OBSTETRICS AND GYNECOLOGY transmission rate of about 30%, which is highest during the labor (40-80%). It attacks the CD4 helper cells and leads to an immunosuppressive state with progressive decrease in capacity to fight against infections. In 2014, an estimated 36.9 million people were living with HIV (including 2.6 million children) - a global HIV prevalence of 0.8% and in the same year 1.2 million died of acquired immune deficiency syndrome (AIDS)related illnesses.7 The biological interaction between HIV and pregnancy is not well-understood. It is said that pregnancy may accelerate HIV progression as pregnancy is associated with suppressed immune system independent of HIV status. However, the epidemiological evidence supporting this hypothesis is weak. A review investigating the effects of pregnancy on HIV progression found no evidence that pregnancy increased progression to an HIV-related illness or fall in CD4 count to fewer than 200 cells per cubic milliliter.8 People at high risk of HIV are also likely to be at risk for hepatitis B or hepatitis C co-infection and are thus associated with reduced survival and increased risk of progression to severe liver disease.9 However, highly active antiretroviral therapy (HAART) should be started immediately after the detection of virus and various protective measures should be taken to avoid transmission of any of three viruses.

These days prevalence of viral infections is on the rise and we are getting more and more pregnant females with these infections when tested during pregnancy.

The concern remains the effect of infections on pregnant females health and risk of vertical transmission.

Because of a significant increase in the number of positive pregnant cases, we decided to conduct a study to see the incidence of hepatitis B, hepatitis C and HIV, and correlation of various maternal parameters to positive status and to view maternal and fetal outcome.

MATERIAL AND METHODS This retrospective study was conducted to see the prevalence of the HIV, hepatitis B and hepatitis C in all the pregnant women who came to the labor room of Dept. of Obstetrics and Gynecology, Govt. Medical College and Rajindra Hospital, Patiala, Punjab from 1st August 2015 to 31st March 2016 for delivery. The study was conducted in 2,194 pregnant women and out of them, 106 women were positive for any of three markers and all the data were collected retrospectively.

The maternal parameters taken were age, unbooked/ booked status, referred, education status, positive status (HIV/hepatitis B/hepatitis C). The maternal and fetal outcome was then noticed in form of vaginal delivery/

cesarean section, birth weight and Apgar of baby. If the patient had a cesarean section done, its indication was also taken into account. The study included all the positive pregnant women irrespective of twin gestation who had crossed the period of viability and had come for delivery. After the delivery of baby, any postpartum complications were also noted down.

The study was done basically to see the prevalence of all three viral infections in pregnant women and to correlate them to the maternal parameters and fetal outcome.

RESULTS During the study, total number of subjects who delivered in the labor room from 1st August 2015 to 31st March 2016 were 2,194 and out of them 106 (4.83%) were either hepatitis B, hepatitis C or HIV positive and 2,088 (95.17%) were negative for any viral marker (Fig. 1). All pregnant women delivered at â&#x2030;Ľ28 weeks of gestation. Out of the 106 positive cases, 30 (28.30%) women were HIV positive, 43 (40.56%) were detected positive for hepatitis C and 31 (29.25%) were hepatitis B positive. Two (1.88%) cases were double positive i.e., one was positive for HIV and hepatitis B and the other was HIV and hepatitis C positive (Table 1).

The prevalence of the hepatitis B was 1.41%, hepatitis C was 1.95% and HIV was 1.36% thus indicating high incidence and prevalence for hepatitis C followed by hepatitis B and HIV. Twenty-five HIV positive women were already on ART and treatment was started in five pregnant women after the investigations. Forty-four women were primigravida who came to the labor room for delivery.

Total

Positive

2,088 (95.17%)

Negative

2,194 (100%)

106 (4.83%)

Figure 1. Total number of pregnant women and percentage of hepatitis B, hepatitis C and HIV positive women.

Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

667

OBSTETRICS AND GYNECOLOGY Table 1. Prevalence of Hepatitis B, Hepatitis C and HIV Positive Pregnant Women Viral markers Prevalence

HIV

Hepatitis B

Hepatitis C

Double positive

Total = 2,194

30 (1.36%)

31 (1.41%)

43 (1.95%)

2 (0.09%)

106 (4.83%)

Table 2. No. of Hepatitis B, Hepatitis C and HIV Positive Pregnant Women at Different Ages and Gestation Period Age (years)

≤25

26-30

>30

Total 19-40 (years)

No. Period of gestation (weeks) No.

59 (55.67%)

38 (35.84%)

9 (8.49%)

106 (100%)

≤34

34-40

>40

32-41 (weeks)

5 (4.72%)

86 (81.13%)

15 (14.15%)

106 (100%)

Of the total 106 pregnant women who delivered, it was found that 54 (50.94%) were booked. They were booked either in our institution or somewhere else.

Fifty-two (49.05%) women came totally uninvestigated and were unbooked. Eighty-one (76.42%) pregnant women were referred to our tertiary care hospital from outside (either Govt. or Private center) for either obstetrical or fetal indication. The education status of the pregnant women who came to our institution was also calculated and it was found that 36 (33.96%) were illiterate, 36 (33.96%) were educated up to school level and 10 (9.43%) were graduate.

The criteria of age of women was also taken in the study and it was found that there were 59 (55.67%) women of age ≤25 years, 38 (35.85%) women were of 26-30 years of age and 9 (8.49%) women were >30 years of age. If we take the period of gestation of women, there were only 5 (4.72%) women with gestation ≤34 weeks. A large number of women 86 (81.13%) were 34-40 weeks of gestation and 15 (14.15%) women were >40 weeks of gestation (Table 2); 39.62% positive pregnant women had anemia.

Regarding the outcome of all the positive pregnant women, out of 106, 71 (66.98%) had vaginal delivery and 35 (33.01%) had cesarean section (Fig. 2). The cesarean section were done for obstetrical indications only and cesarean sections done for fetal distress were only four and babies born to them were healthy with good Apgar score. Twelve women had cesarean due to previous cesarean section, in 3 women it was done due to oligohydramnios and restricted fetal growth, in 7 women due to cephalopelvic disproportion and it was done due to primi with breech in 5 women. There were only 14.15% preterm vaginal deliveries, which were all unbooked and were referred from other centers and their babies had good Apgar scores.

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Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

Three women came with a twin pregnancy, out of which two had a vaginal delivery and one had a cesarean section due to previous cesarean section. All twins had a good Apgar score. We had a favorable neonatal outcome in our study. Babies born with ≤2,500 g weight were 41 (37.61%), 46 (42.21%) babies were 2,6003,000 g in weight and 22 (20.18%) were >3,000 g in weight (Fig. 2). The Apgar score of the newborn babies was very good except two babies who had Apgar of

70

66.98%

60 50 40

33.01%

30 20 10 0 Vaginal delivery

Cesarean section

Figure 2. Maternal outcome of hepatitis B, hepatitis C and HIV positive pregnant women.

50 40

42.21% 37.61%

30 20.18%

20 10 0 ≤2,500 g

≤2,600-3,000 g

≥3,000 g

Figure 3. Birth weight of the newborn babies delivered to hepatitis B, hepatitis C and HIV positive pregnant women.

OBSTETRICS AND GYNECOLOGY 2/5/6 and 3/6/9 and out of these two, one woman was HIV positive and other was HCV positive and both of these women had vaginal deliveries at term gestation and were referred from other centers with premature rupture of membranes (PROM). Baby with low Apgar score died after 1 hour and other baby remained in nursery ICU for some time and survived.

We had three women who came with intrauterine death (IUD) at â&#x2030;Ľ35 weeks of gestation and one had a cesarean section done due to nonprogress of labor with scar tenderness in previous cesarean section in labor.

The other two delivered vaginally and one of them came with pregnancy-induced hypertension (PIH). All the three cases were unbooked and were referred from other centers at term gestation.

We had 27 (25.47%) women who had PPH after delivery and it was managed conservatively. Rest of the women had no postpartum complications due to good and optimum care of the mother after admission.

DISCUSSION Both viral hepatitis and HIV are a global health problem. The prevalence of hepatitis B and hepatitis C in our study was 1.41% and 1.95% as compared to Khakhkhar et al10 and Goyal et al,11 which showed a higher prevalence of 3.07% and 2.8%. The higher prevalence may be because they both did a 3-year study and we did a study of only 8 months. A study

by Dwivedi et al12 showed the prevalence of 0.9% of hepatitis B who took 4,000 women and it was almost double than our study and the prevalence was 3.03% in the study by Khokhar et al,13 because they also screened syphilis along with hepatitis B, hepatitis C and HIV. In the study by Gupta et al,14 prevalence of HIV was 0.88% and in our study it was 1.36%. In our study, two pregnant women had co-infection of HIV with hepatitis B and hepatitis C with no woman with co-infection with hepatitis B and hepatitis C was found as compared to one study by Bansal et al15 in which one woman had co-infection of HIV with hepatitis B and 4 had combined infection with hepatitis B and hepatitis C. The primigravida in our study were 41.50% which was similar to the study conducted by Shukla et al5 (41%) and incidence of the hepatitis B and hepatitis C was 37% and 4% concluding that hepatitis B was more common than hepatitis C, whereas in our study hepatitis C was more common than hepatitis B (40.57% and 29.25%).

It was seen that 2.69% and 0.41% women in age groups 21-25 years and 31-35 years, respectively were positive

for hepatitis B as compared to Khakhkhar et al10 in which the corresponding incidence was 4.20% and 1.37% which is higher than our study which may be because we screened three viral markers and they only screened hepatitis B in all the women in their study of the HIV positive women, we had 53.33%, 16.66% and 10% women in the age groups 20-24 years, 30-34 years and â&#x2030;Ľ35 years, respectively as compared to a study

by Gupta et al14 who had 34.6%, 17.7% and 4.2% in the same age groups. This difference may be because they enrolled large number of women in their study (3,529) and did only HIV screening in their women. We had 71.69% women with less than secondary level of education and a similar study by Elsheikh et al3 had 40% women who had the same level of education.

In our study, 39.62% women had anemia as compared to (29.3%) in the study by Maiques et al,16 which was less as compared to our study as they involved very less number of women in their study (2,194 vs. 480).

In the study by Safir et al17 who just screened hepatitis B and C, 15.8% pregnant women had PROM as compared to our study in which only 9.43% had PROM. There were 14.15% preterm vaginal deliveries and 2.83% intrauterine deaths in our study as compared to study by Shukla et al5 who had 17% preterm vaginal deliveries and 6% IUDs. In the study by Ryoo et al,18 12.6% had PPH in women who were hepatitis B positive and it was 25.47% in our study, which was almost double. The sample size was large in their study as compared to ours. They had one woman with twin pregnancy with hepatitis B and we had three twins with hepatitis B positivity in one woman. In our study, 7 women came with PIH and there was no woman with PIH in their study.

We had a 33.01% cesarean section rate in our study and it was almost similar to the study by Safir et al17 (32.2%). The incidence of low birth weight (<2,500 g) was 24.53% in our study as compared to 18.2% in their study and it was because we screened all the three parameters in our study. We had 97.24% live births and fetal mortality was seen in just 0.94%, whereas in the study by Karegoudar et el19 among the 53.85% of live births, fetal mortality was seen in 4.76%.

CONCLUSION Viral hepatitis and HIV are becoming a global health problem. In conclusion, prevalence of women who were positive either for hepatitis B, hepatitis C or HIV who came to our tertiary care center for delivery was 4.83%.

A high number of HCV positive pregnant women 43

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669

OBSTETRICS AND GYNECOLOGY (40.56%) came for delivery compared to HBsAg positive 31 (29.24%) and HIV 30 (28.30%) positive women and their prevalence in decreasing order was (1.95%, 1.41%, 1.36%), respectively. Being a tertiary care center, lot of patients are referred to this center. Also, large number of women who came for delivery were referred from other nearby centers 81 (76.42%). Almost 50% women were unbooked with no antenatal check-ups and were on no treatment from anywhere else. Quite a large number of uneducated positive pregnant women 36 (33.96%) came to our center in this study. Only two babies had poor Apgar score and the postpartum complications were also less in number (25.47%). We had no maternal death and just one neonatal death in the study.

Hence to conclude, proper antenatal screening should be done in all the pregnant women who are coming to antenatal clinics. Women who are diagnosed to be either of hepatitis B, hepatitis C or HIV positive should be investigated for any other associated risk factors and treated properly. Husband should also be screened and should be put on medication. All the required precautions should be taken in the positive women to prevent further transmission of the disease especially during delivery. Cesarean sections should be done in the women with ruptured membranes more than 6 hours and for obstetrical indications only and all the maternal and fetal complications should be dealt with vigilantly.

Acknowledgment I am highly thankful to all my teachers and my family who encouraged me in every aspect of my life. I am thankful to Dr Parneet Kaur who helped me in collecting the material and writing this topic. This paper has been possible due to joint effort of my co-author as well. I really appreciate the work of juniors who helped me in this topic a lot. This study has been conducted retrospectively, so no harm has been inflicted upon the patients involved in the study.

REFERENCES 1. Cunningham FG, Lenovo KJ, Bloom SL, Spong CY, Dashe JS, Hoffman BL, et al. Williams Obstetrics.

24th Edition, McGraw Hill; 2014. pp. 1090-2.

2. Ugbebor O, Aigbirior M, Osazuwa F, Enabudoso E, Zabayo O. The prevalence of hepatitis B and C viral infections among pregnant women. N Am J Med Sci. 2011;3(5):238-41 3. Elsheikh RM, Daak AA, Elsheikh MA, Karsany MS, Adam I. Hepatitis B virus and hepatitis C virus in pregnant Sudanese women. Virol J. 2007;4:104.

4. Sharma JB. Textbook of Obstetrics. 2014;1:550-4.

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5. Shukla S, Mehta G, Jais M, Singh A. A prospective study on acute viral hepatitis in pregnancy; seroprevalence and fetomaternal outcome in 100 cases. J Biosci Tech.

2011;2(3):279-86.

6. Dunkelberg JC, Berkley EM, Thiel KW, Leslie KK. Hepatitis B and C in pregnancy: a review and recommendations for care. J Perinatol. 2014;34(12):882-91.

7. UNAIDS (2015). "How AIDS changed everything" UNAIDS (2015), Fact Sheet. 2014.

8. Calvert C, Ronsmans C. HIV and the risk of direct obstetric complications: a systematic review and metaanalysis. PLoS One. 2013;8(10):e74848.

9. Floreani A. Hepatitis C and pregnancy. World J Gastroenterol. 2013;19(40):6714-20.

10. Khakhkhar VM, Bhuva PJ, Bhuva SP, Patel CP, Cholera MS. Seroprevalence of hepatitis B amongst pregnant women attending the antenatal clinic of tertiary care hospital, Jamnagar (Gujarat). Natl J Med Res. 2012;2(3):362-5.

11. Goyal LD, Kaur S, Jindal N, Kaur H. HCV and pregnancy: prevalence, risk factors, and pregnancy outcome in north Indian population: a case-control study. J Obstet Gynaecol India. 2014;64(5):332-6.

12. Dwivedi M, Misra SP, Misra V, Pandey A, Pant S, Singh R, et al. Seroprevalence of hepatitis B infection during pregnancy and risk of perinatal transmission.

Indian J Gastroenterol. 2011;30(2):66-71.

13. Khokhar N, Jethwa D, Lunagaria R, Panchal N, Badrakiya S, Badrakiya G. Seroprevalence of hepatitis B, hepatitis C, syphilis and HIV in pregnant women in a tertiary care hospital, Gujarat, India. Int J Curr Microbiol App Sci. 2015;4(9):188-94.

14. Gupta S, Gupta R, Singh S. Seroprevalence of HIV in pregnant women in North India: a tertiary care hospital based study. BMC Infect Dis. 2007;7:133.

15. Bansal V, Bansal A, Bansal AK, Kumar A. Seroprevalence of HBV in pregnant women and its co-infection with HCV and HIV. Int J Rec Sci Res. 2015;6(4):3590-3.

16. Maiques V, Garcia-Tejedor A, Diago V, Molina JM, Borras D, Perales-Puchalt A, et al. Perioperative cesarean delivery morbidity among HIV-infected women under highly active antiretroviral treatment: a case-control study.

Eur J Obstet Gynecol Reprod Biol. 2010;153(1):27-31.

17. Safir A, Levy A, Sikuler E, Sheiner E. Maternal hepatitis B virus or hepatitis C virus carrier status as an independent risk factor for adverse perinatal outcome. Liver Int. 2010;30(5):765-70.

18. Ryoo YG, Chang YH, Choi GS, Jeong WJ, Kim JW, Joung NK, et al. Hepatitis B viral markers in pregnant women and newborn infants in Korea. Korean J Intern Med. 1987;2(2):258-68.

19. Karegoudar D, Dhirubhai PR, Dhital M, Amgain K. A study of liver disorder and its consequences in pregnant women with jaundice in tertiary care centre in Belgaum, Karnataka, India. IOSR J Dent Med Sci. 2014;13(4):84-6.

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PEDIATRICS

A Study of Sociodemographic Profile of Children with Severe Acute Malnutrition Under 5 Years of Age and Caregivers Characteristics MUDIT KUMAR AGGARWAL*, V KRISHNA AGARWAL*, S AGARWAL*

ABSTRACT Objectives: This study aimed to determine anthropometry, clinical profile of children less than 5 years of age suffering from severe acute malnutrition (SAM) and caregivers sociodemographic characteristics. Material and methods: A prospective observational study was carried out including total of 48 children aged less than 5 years diagnosed as SAM. Detailed history including dietary and socioeconomic history was taken and anthropometric measurements were computed using standard instruments. Results: Of the 48 cases included in this study, 29 were marasmic, 16 were suffering from kwashiorkar and 3 were suffering from marasmic-kwashiorkar. The age ranged from 5 to 59 months with maximum children in the 12-36 months group.

In this study, the most common preceding infection was acute gastroenteritis (52.1%) followed by respiratory tract infection (27.1%). Escherichia coli was the most common organism (33.3%) cultured. Mid upper arm circumference (MUAC) was found <11.5 cm in 83.3%, while weight/height ratio was <-3SD in 93.8% cases. Majority cases were delivered at home (75%) with birth order >3 in 64.6%. 70.8% were nonexclusively breast-fed and 72.9% were given animal diluted milk. Weaning was done at less than 6-month of age in 68.8% and 81.3% were bottle-fed. Also, 41.7% of children were partially immunized. Caregivers were mainly housewives (20-30 years of age) and not formally educated (52.1%); 58.3% families were nuclear and 79.2% were inhabitating rural area. Maximum cases (33.3%) belonged to upper middle class according to Kuppuswamy classification.

Conclusion: Improper hygiene and feeding practices, large family size, recent infections and food fads are contributors to SAM.

Keywords: Severe acute malnutrition, sociodemographic profile, caregiver, mid upper arm circumference, less than 5-year children

T

he World Health Organization (WHO) estimates that globally nearly 20 million children less than 5 years of age suffer from severe acute malnutrition (SAM).1 A large majority of children with SAM live in South Asia and sub-Saharan Africa.

The recent National Family Health Survey (NFHS)-3 of India indicated that 6.4% (roughly 8 million) of under 5 children are classified as SAM in India.2,3 Undernutrition dramatically increases case fatality rate in children suffering from common illnesses such as diarrhea and pneumonia. Estimates suggest that globally SAM contributes to about 1 million child deaths every year; one child death every 30 seconds.1 The WHO and UNICEF proposed diagnostic criteria

*Dept. of Pediatrics Guru Kripa Jagrati Hospital and Research Centre Pvt. Ltd., Allahabad, Uttar Pradesh Address for correspondence Dr Mudit Kumar Aggarwal 124/A/1, Thornhill Road, Near Public Service Commission, Allahabad, Uttar Pradesh E-mail: drmudit.aggarwal@yahoo.com

for SAM in children aged 6-60 months are weight/ height <-3SD and/or presence of bipedal edema or mid upper arm circumference (MUAC) <115 mm (using WHO growth standards).1 MATERIAL AND METHODS A prospective observational study was conducted in Guru Kripa Jagrati Hospital, Allahabad from August 2013 to February 2015. The cases were consecutive children of either gender less than 5 years of age with SAM who presented in hospital for various complaints.

A case was diagnosed to have SAM if weight/height ratio <-3 SD of WHO 2006 growth standards and/or MUAC <115 mm and/or nutritional edema of both feet. Children with congenital malformation and known chronic diseases were excluded from the study.

Ethical clearance was obtained from Institutional Ethics Committee. Written consent was obtained from the next of kin. A detailed history including dietary, immunization and socioeconomic history was obtained. Thorough clinical examination including

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673

PEDIATRICS anthropometry was done according to standardized methodology. Relevant investigation was conducted as per case. A self-developed questionnaire with 8 survey items was used to capture information on the extent of the caregiver’s awareness of the child’s nutritional status. Statistical testing was conducted with the Statistical Package for the Social Sciences (SPSS), version 17.0. Continuous variables were presented as mean + SD or median if the data was unevenly distributed.

Categorical variables were expressed as frequencies and percentages.

RESULTS A total of 48 cases were taken; 43.8% were female and 56.2% were male. The mean age of the cases was 22.6 Table 1. Anthropometry

months. Anthropometric measures are shown in Table 1.

Twenty-four parameters including dietary practices, sociodemographic characteristics, immunization status and knowledge status of caregiver were studied (Tables 2-4). Among the dietary practices, exclusive breastfeeding appeared to be a protective factor against SAM. Diluted animal milk, bottle-feeding and early Table 2. Dietary Practices Breastfeeding Exclusive

29.2%

Nonexclusive

70.8%

Type of top feed Diluted animal milk

72.9%

Undiluted animal milk

14.6%

Formula feed

12.5%

Mode of feeding

Anthropometric measures MUAC <115 mm >115 mm Weight/Height ratio <-3SD >-3SD

83.3% 16.7% 93.8% 6.2%

Bottle-feeding

81%

Spoon-feeding

19%

Age of weaning Before 6 months

68.8%

At 6-7 months

18.8%

After 7 months

12.4%

Table 3. Sociodemographic Profile and Immunization Status Maternal education Illiterate Primary education Secondary education Higher education Paternal education Illiterate Primary education Secondary education Higher education Mother’s occupation Housewife Working women Father’s occupation Unemployed Business Service Housing Kuccha Pakka Water supply Municipal water Ground water

674

52.1% 8.3% 6.3% 33.3% 20.8% 37% 25% 16.7% 87.5% 12.5% 10.4% 56.3% 33.3% 60.4% 39.6%

Toilet Private Open-field Food habits Vegetarian Nonvegetarian Family size <5 members >5 members Place of delivery Home Hospital Birth order 1 2-3 >3 Immunization Partially immunized Nonimmunized Completely immunized

81.3% 18.7%

Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

72.9% 27.1% 87.5% 12.5% 41.7% 58.3% 75% 25% 15% 50% 35% 41.7% 39.6% 18.8%

Family income <Rs. 6,000/month >Rs. 6,000/month Kuppuswamy classification Kuppuswamy Class I Kuppuswamy Class II Kuppuswamy Class III Kuppuswamy Class IV Kuppuswamy Class V Comorbid disease Diarrhea Acute respiratory tract infection Tuberculosis Organism cultured Escherichia coli Shigella Haemophilus influenzae Pseudomonas Mycobacterium tuberculae

60.5% 39.5% 2.08% 33.3% 14.5% 22.91% 27.08% 52.1% 27.1% 8.3% 33.3% 12.5% 22.4% 20.3% 11.5%

PEDIATRICS Table 4. Sociodemography and Knowledge Status of Caregiver Marital status of caregiver Married

97.9%

Widow

2.1%

Awareness of benefits of colostrums Yes

33.3%

No Age groups of caregivers

66.7% 15-20 y

20-30 y

30-40 y

40-50 y

>50 y

Percentage

16.6%

62.5%

16.6%

14.3%

0

Aware of reason for admission

14.5%

60.4%

15.1%

2%

0

2%

2%

2%

2%

0

Unaware of reason for admission Reason for admission Vomiting

2%

8.3%

2%

0

0

Diarrhea

6.3%

8.3%

2%

2%

0

Coughing

0

8.3%

2%

0

0

Swollen limbs

8.3%

14.5%

10.4%

2%

0

Not eating well

0

10.4%

0

0

0

0

12.5%

0

0

0

Action taken for childâ&#x20AC;&#x2122;s condition

Weight loss

10.4%

41.66%

12.5%

2%

0

No action taken for childâ&#x20AC;&#x2122;s condition

6.25%

20.5%

4.2%

2%

0

12.5%

52%

10.4%

4.1%

0

Took child to traditional Healer

2%

6.2%

2%

0

0

Tried different feeds

2%

0

2%

0

0

0

4.1%

2%

0

0

Action taken by caregiver Immediately took child to clinic

Bought medicine at the pharmacy

weaning (before 6 months) were found to be higher among children with SAM. Sociodemographic features like illiterate mother, partial or nonimmunization, low family income and large family size contributed to SAM. It was observed that 66.7% caregivers were unaware of benefits of colostrum. Maximum cases occurred in patients with caregiver of age group 20-30 years; swollen limbs and diarrhea appeared to be the most common reason for the caregiver to seek medical advice. Majority of caregivers immediately took child to clinics; still a significant proportion took child to traditional healers.

DISCUSSION The parental education status was found to be possibly causally associated to SAM. This is observed in studies done in North Wollo in Ethiopia,4 other African countries,5,6 South-East Asian7-9 and Latin American countries.10 In a case-control study in Bangladesh, the maternal illiteracy was associated with a four-fold increase in the risk of SAM. It was found that maternal, rather than paternal illiteracy has a possible causal

association with SAM, which is consistent with earlier reports.6,11-14 A larger family size has possible causal association with SAM. The effect of a large family size with overcrowding and inadequate spacing has causal association in different studies as well.4,11,15 Elizabeth in 2012 described cases of edematous SAM who did not have the typical risk factor like poverty, ignorance and illiteracy, educated caregiver-some even being graduates.16 In the present study, it was found that exclusive breastfeeding during first 6 months of life protected against SAM. Bottle-feeding was shown in the present study to have an independent possible causal association for SAM, contrary to the result of others.11,15,17 A study from Uganda observed that neither the age of weaning nor the number of meals per day affected the incidence of stunting or underweight.6 In our study, 68.8% cases were weaned off milk before 6 months, 18.8% cases were weaned in 6-7 months and 12.5% were weaned in more than 7 months.

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PEDIATRICS Amsalu et al, found that late initiation of complementary diet beyond 12 months was an independent risk factor for SAM.15 On the other hand, studies from China and Kenya have shown that early introduction of complementary feeding before 6 months of age increased the risk of being underweight.18 In the present study, a significantly larger fraction of cases received weaning food which had a thin or watery consistency, rather than a semisolid one and independently influenced the risk of SAM. It is expected that the energy and protein content of diluted (thin or watery consistency) food item would be less than that of semisolid item. Kikafunda et al had observed that consumption of food with low energy density was associated with increased risk of stunting.6 The capacity of a weaning diet to prevent SAM depends on its nutritional quality as well as its volume.19 Studies on feeding practices show that the type of complementary feeding given is greatly influenced by traditional sociocultural beliefs and taboos. In most countries, including India, thin gruels like diluted milk, dilute starch-based liquid without good quality protein are favored as weaning food and semisolid and solids are introduced relatively late.16 The majority of caregivers (92%) knew why their child had been admitted to hospital. As regards the reasons caregivers mentioned for admission, 10.4% mentioned that the child was “not eating well” and "has lost weight" in 12.5%. These caregivers seemed to know that the child suffered from some degree of malnutrition.

One reason for admission given by 35.2% caregivers, was that the child had “swollen limbs”. Caregivers were not aware that the swelling could be linked to malnutrition. Other reasons for admission included coughing, vomiting and diarrhea. Most of the caregivers focused on the child’s symptoms as the reason for admission. They were not aware that the primary reason for admission was malnutrition.

Most caregivers 66.5% took some action to assist the child in addressing the illness, but 33.5% did nothing.

These caregivers probably did not realise that the child was malnourished and why the child was referred to the hospital after a routine child welfare clinic visit.

Seventy-nine percent caregivers immediately took the child to the clinic when they suspected that the child was not well. Some caregivers 10.2% took the child to a traditional healer first, and a small number of caregivers bought some medicine at a pharmacy or tried different feeds at home before they took the

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Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

child to the clinic. These findings are close to those of a study in Sri Lanka involving 1,102 children and their caregivers. Twenty-eight percent of the caregivers tried some home remedies before they took the child to the clinic, and 51% immediately took the child to the clinic.20 Most of the caregivers in this study were aware that they had to take the child to the clinic before its condition worsened. A small percentage of caregivers were still attached to traditional medicine. This poses a challenge as a child’s condition can deteriorate quickly, while the caregiver still trusted the traditional healer.

CONCLUSION Improper hygiene and feeding practices, large family size, recent infections and food fads are contributors to SAM. A community based approach with more focussed attention in health policy formulation for taking appropriate preventable and therapeutic strategies is required.

REFERENCES 1. World Health Organisation/UNICEF. WHO child growth standards and the identification of severe acute malnutrition in infants and children (2009). A joint statement by the World Health Organisation and the United Nation’s Children’s Fund. Available at: http://www.who. int/nutrition/publications//severemalnutrition/en/ index. html. Accessed on 26th June 2016.

2. International Institute of Population Sciences (IIPS) and Macro International. Mumbai: IIPS; National Family Health Survey of India (NFHS-3) 2005-06;1:196-7.

Mumbai: IIPS/Macro International 2007.

3. Sachdev HP, Kapil U, Vir S. Consensus Statement National Consensus Workshop on Management of SAM Children through Medical Nutrition Therapy. Indian Pediatr.

2010;47(8):661-5.

4. Haidar J, Abate G, Kogi-Makau W, Sorensen P. Risk factors for child under-nutrition with a human rights edge in rural villages of North Wollo, Ethiopia. East Afr Med J. 2005;82(12):625-30.

5. Ighogboja SI. Some factors contributing to protein-energy malnutrition in the middle belt of Nigeria. East Afr Med J. 1992;69(10):566-71.

6. Kikafunda JK, Walker AF, Collett D, Tumwine JK. Risk factors for early childhood malnutrition in Uganda.

Pediatrics. 1998;102(4):E45.

7. Jeyaseelan L, Lakshman M. Risk factors for malnutrition in south Indian children. J Biosoc Sci. 1997;29(1):93-100.

8. Islam MA, Rahman MM, Mahalanabis D. Maternal and socioeconomic factors and the risk of severe malnutrition in a child: a case-control study. Eur J Clin Nutr.

1994;48(6):416-24.

PEDIATRICS 9. Henry FJ, Briend A, Fauveau V, Huttly SR, Yunus M, Chakraborty J. Risk factors for clinical marasmus: a casecontrol study of Bangladeshi children. Int J Epidemiol.

1993;22(2):278-83.

10. Sakisaka K, Wakai S, Kuroiwa C, Cuadra Flores L, Kai I, Mercedes Aragón M, et al. Nutritional status and associated factors in children aged 0-23 months in Granada, Nicaragua. Public Health. 2006;120(5):400-11.

11. Mishra K, Kumar P, Basu S, Rai K, Aneja S. Risk factors for severe acute malnutrition in children below 5 y of age in India: a case-control study. Indian J Pediatr. 2014;81(8): 762-5.

12. Wamani H, Tylleskär T, Astrøm AN, Tumwine JK, Peterson S. Mothers’ education but not fathers’ education, household assets or land ownership is the best predictor of child health inequalities in rural Uganda. Int J Equity Health. 2004;3(1):9.

14. Abuya BA, Onsomu EO, Kimani JK, Moore D. Influence of maternal education on child immunization and stunting in Kenya. Matern Child Health J. 2011;15(8):1389-99.

15. Amsalu S, Tigabu Z. Risk factors for severe acute malnutrition in children under the age of five: a casecontrol study. Ethiop J Health Dev. 2008;22(1):21-5.

16. Elizabeth KE. Changing profile of undernutrition and edematous severe acute malnutrition (ESAM). Indian Pediatr. 2012;49(10):843.

17. Ghosh S, Shah D. Nutritional problems in urban slum children. Indian Pediatr. 2004;41(7):682-96.

18. Wang X, Wang Y, Kang C. Feeding practices in 105 counties of rural China. Child Care Health Dev. 2005;31(4):417-23.

19. Sajilata G, Singhal RS, Kulkarni PR. Weaning foods: a review of the Indian experience. Food Nutr Bull.

2002;23(2):208-26.

20.

13. Huq MN, Tasnim T. Maternal education and child healthcare in Bangladesh. Matern Child Health J. 2008;12(1):43-51.

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Peiris TDR, Wijesinghe DGNG. Nutritional status of under 5 year old children and its relationship with maternal nutrition knowledge in Weeraketiya DS Division of Sri Lanka. Tropical Agricultural Research. 2010;21(4):330-9.

Hormone Therapy is Effective for Both the Prevention and Treatment of Osteoporosis in Women A study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism suggests that menopausal hormone therapy (MHT) may improve the bone-health of women with osteoporosis. The researchers suggest that MHT is effective for both the prevention and treatment of osteoporosis.

“IVF Calculator” for the Prediction of Success Rate of in vitro Fertilization Cycle An “in vitro fertilization (IVF) calculator” can precisely predict the success rate prior to first IVF cycle, suggests a study published online in the BMJ. According to the researcher, David McLernon, at University of Aberdeen an “IVF calculator could help people get a more individualized estimate of their chances of having a baby.” The calculator can be used as a planning tool by the couples and “can help doctors to give their patients a more realistic and personalized perspective on their IVF experience.”

...Cont'd from page 660 15. Buxton PH, Hayward M. Polyneuritis cranialis associated with industrial trichloroethylene poisoning. J Neurol Neurosurg Psychiatry. 1967;30(6):511-8.

16. Chang CM, Yu CW, Fong KY, Leung SY, Tsin TW, Yu YL, et al. N-hexane neuropathy in offset printers.

J Neurol Neurosurg Psychiatry. 1993;56(5):538-42.

17. Allen N, Mendell JR, Billmaier DJ, Fontaine RE, O’Neill J. Toxic polyneuropathy due to methyl n-butyl ketone.

An industrial outbreak. Arch Neurol. 1975;32(4):209-18.

18. Oge AM, Yazici J, Boyaciyan A, Eryildiz D, Ornek I, Konyalioğlu R, et al. Peripheral and central conduction in n-hexane polyneuropathy.

Muscle Nerve.

1994;17(12):1416-30.

19. Kuwabara S, Nakajima M, Tsuboi Y, Hirayama K. Multifocal conduction block in n-hexane neuropathy.

Muscle Nerve. 1993;16(12):1416-7.

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EXPERT’S VIEW

What Health Problems are Associated with Hypertension?

RAJIV GARG

H

ypertension is the most important modifiable risk factor for coronary heart disease, stroke, congestive heart failure (CHF), end-stage renal disease (ESRD) and peripheral vascular disease.

Risk Factor Intervention Trial (MRFIT) revealed that the relative risk for CAD mortality was 2.3-6.9 times higher for persons with mild-to-severe hypertension than it was for persons with normal BP.3

Hypertension, if left untreated, is associated with an increased risk of mortality and is often described as a silent killer. Mild-to-moderate hypertension may lead to atherosclerotic disease in 30% of people and organ damage in 50% of people within 8-10 years after onset.

The relative risk for stroke ranged from 3.6 to 19.2. The population-attributable risk percentage for CAD varied from 2.3 to 25.6%, whereas the population-attributable risk for stroke ranged from 6.8% to 40%.

It has been demonstrated that for every 20 mmHg systolic or 10 mmHg diastolic increase in blood pressure (BP) above 115/75 mmHg, the mortality rate for both ischemic heart disease and stroke doubles.1 Uncontrolled and prolonged hypertension can lead to detrimental changes in the myocardial structure, coronary vasculature and conduction system of the heart. These changes in turn can lead to the development of left ventricular hypertrophy (LVH), coronary artery disease (CAD), various conduction system diseases and systolic and diastolic dysfunction of the myocardium.

Clinically, these changes present as angina or myocardial infarction, cardiac arrhythmias (especially atrial fibrillation) and CHF. Thus, hypertensive heart disease is a term applied generally to heart diseases— such as LVH, CAD, cardiac arrhythmias and CHF— that are caused by direct or indirect effects of raised BP. Although these diseases generally develop in response to chronically elevated BP, marked and acute elevation of BP can also lead to accentuation of an underlying predisposition to any of the symptoms traditionally associated with chronic hypertension.

In the Framingham Heart Study, it was seen that the age-adjusted risk of CHF was 2.3 times higher in men and three times higher in women when the highest BP was compared to the lowest BP.2 Data from Multiple

Senior Medical Specialist and Head Dept. of Medicine, ESI Hospital, Noida, Uttar Pradesh

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Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

Nephrosclerosis is one of the possible complications of long-standing hypertension. The risk of hypertensioninduced ESRD is higher in black patients, even when BP is under good control. Furthermore, patients with diabetic nephropathy who are hypertensive are also at high-risk for developing ESRD. The Framingham Heart Study found a 72% increase in the risk of all-cause death and a 57% increase in the risk of any cardiovascular event in patients with hypertension who were also diagnosed with diabetes mellitus.4 BP is also a powerful determinant of risk for ischemic stroke and intracranial hemorrhage; in fact, longstanding hypertension may manifest as hemorrhagic and atheroembolic stroke or encephalopathy.

Both the high systolic and diastolic pressures are harmful; a diastolic pressure of >100 mmHg and a systolic pressure of >160 mmHg are associated with a significant incidence of strokes.

The American Heart Association notes that individuals whose BP level is <120/80 mmHg have about 50% the lifetime stroke risk of that of hypertensive individuals.

Marked and acute elevation of BP can also lead to accentuation of an underlying predisposition to any of the symptoms traditionally associated with chronic hypertension.

The most common clinical presentations of hypertensive emergencies are cerebral infarction (24.5%), pulmonary edema (22.5%), hypertensive encephalopathy (16.3%) and CHF (12%). Other clinical presentations associated with hypertensive emergencies include intracranial

EXPERT’S VIEW hemorrhage, aortic dissection and eclampsia,5 as well as acute myocardial infarction.

Hypertension is also one of several conditions that have been increasingly recognized as having an association with posterior reversible encephalopathy syndrome (PRES), a condition characterized by headache, altered mental status, visual disturbances and seizures.6 Clinical trials have demonstrated the following benefits with antihypertensive therapy.1 ÂÂ

Average 35-40% reduction in stroke incidence

ÂÂ

Average 20-25% reduction in myocardial infarction

ÂÂ

Average >50% in heart failure.

Moreover, it is estimated that one death is prevented per 11 patients treated for Stage 1 hypertension and other cardiovascular risk factors when a sustained reduction of 12 mmHg in systolic BP over 10 years is achieved.1 However, for the same reduction is systolic BP reduction, it is estimated that one death is prevented per nine patients treated when cardiovascular disease or end-organ damage is present.1

REFERENCES 1. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Hypertension. 2003;42(6):1206-52.

2. Culleton BF, Larson MG, Kannel WB, Levy D. Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study. Ann Intern Med. 1999;131(1):7-13.

3. Mortality after 10 1/2 years for hypertensive participants in the Multiple Risk Factor Intervention Trial. Circulation.

1990;82(5):1616-28.

4. Chen G, McAlister FA, Walker RL, Hemmelgarn BR, Campbell NR. Cardiovascular outcomes in Framingham participants with diabetes: the importance of blood pressure. Hypertension. 2011;57(5):891-7.

5. Zampaglione B, Pascale C, Marchisio M, Cavallo-Perin P. Hypertensive urgencies and emergencies. Prevalence and clinical presentation. Hypertension. 1996;27(1):144-7.

6. Staykov D, Schwab S. Posterior reversible encephalopathy syndrome. J Intensive Care Med. 2012;27(1):11-24.

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679

CONFERENCE PROCEEDINGS

46th Annual Conference of Endocrine Society of India (ESICON 2016) ISSUES IN MANAGEMENT OF HYPERPROLACTINEMIA Dr Romesh Khardori, Norfolk, VA ÂÂ

Hyperprolactinemia does not always mean it is hyperprolactinemia, especially in asymptomatic cases.

ÂÂ

Secretion of prolactin is pulsatile; increases with sleep, stress, pregnancy and chest wall stimulation or trauma.

ÂÂ

Differential diagnosis of a large pituitary tumor with moderately elevated prolactin concentration

The study highlights the following observations: ÂÂ

In IDA, low free iron lead to decrease in beta cell secretion and mitochondrial oxidative capacity, thus reflecting pathophysiologic relation between iron metabolism and beta cell secretion.

ÂÂ

In T2DM without IDA, significantly increased iron, TNF alpha and insulin resistance (HOMA-IR) were observed. Conversely, mitochondrial oxidative capacity and TAOC were significantly decreased indicating oxidative stress. This clearly suggests a link between free iron and pro-oxidant, oxidative stress, inflammatory markers, insulin resistance and beta cell secretion in the pathogenesis of T2DM.

ÂÂ

In T2DM with IDA, marked improvement in insulin sensitivity correlated well with a significant increase in IL-6.

ÂÂ

Significant decrease in mitochondrial oxidative capacity was consistently observed in all 3 groups compared with control group.

zz Length of therapy with dopamine agonist (DA) zz Cardiac concerns in patients treated with DA zz OCD in patients on DA zz Hemorrhage in prolactinomas zz Effect of pregnancy on prolactinoma zz Effect of DA on offspring zz Effects of lactation on course of prolactinoma zz Management

prolactinoma.

of

resistant

or

aggressive

Conclusions ÂÂ

IDA without diabetes is associated with decreased mitochondrial oxidative capacity and decreased insulin secretion with no change in insulin sensitivity. This observation is highly relevant especially in the population with high prevalence of both diabetes mellitus and IDA and prompts us to question whether chronic IDA predisposes to the early development of diabetes mellitus.

ÂÂ

The improved insulin resistance and glycemic status in type 2 diabetes with IDA may give a falsely gratifying impression about the status of diabetes mellitus. Conversely, both diabetes and IDA can together worsen the oxidative stress and pathophysiology of diabetes mellitus despite improvement in insulin resistance.

ÂÂ

Injudicious supplementation of iron in type 2 diabetes mellitus without IDA may aggravate oxidative stress and deterioration of glycemic status. Large correlation studies are needed to establish as to what extent iron indices affect the mitochondrial oxidative capacity and oxidative

PN Shah USV India Oration IMPACT OF IRON INDICES, MITOCHONDRIAL OXIDATION CAPACITY, OXIDATIVE STRESS AND INFLAMMATORY MARKERS ON INSULIN RESISTANCE AND SECRETION: A PATHOPHYSIOLOGIC PERSPECTIVE Dr Jayanthi Ramesh, Andhra Pradesh Aim: To elucidate how iron deficiency anemia (IDA) influences the natural history of diabetes mellitus and to study the effect of iron indices, mitochondrial oxidative capacity and oxidative stress on insulin resistance and secretion in established cases of type 2 diabetes.

T2DM and oxidative stress: Significant decrease in TAOC in IDA in comparison with controls; significant decrease in TAOC in T2DM without IDA; no significant change in TAOC in T2DM with IDA compared with T2DM without IDA, but significant decrease compared to controls.

680

Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

CONFERENCE PROCEEDINGS stress and influence the pathophysiology of diabetes mellitus.

T1DM: RECENT ADVANCES

ÂÂ

Serious adverse events - More episodes of DKA seen in pump group vs. MDI. The difference confined to first year. Most DKAs were due to infection.

ÂÂ

Health economic analysis - If pump + DAFNE is to be cost-effective, true treatment effect must be higher than HbA1c of 0.5%.

ÂÂ

Reserve pumps as alternative therapy for people with particular indications.

Dr Paresh Dandona, New York ÂÂ

ÂÂ

ÂÂ

Advances in T1DM post discovery of insulin: Preparations of insulin: prolonged bioavailability; pramlintide with meals; CSII with the use of pumps; CGM; closed loop system: ongoing work; first system licensed by FDA. Triple therapy: Addition of dapagliflozin to insulin and liraglutide - Has favorable effects in terms of blood glucose control.

However, triple ketoacidosis.

therapy

can

also

lead

to

MDI VS. INSULIN PUMP IN TYPE 1 DIABETES MELLITUS

Conclusion ÂÂ

Primary outcome improved in both groups.

ÂÂ

No significant difference in HbA1c change.

ÂÂ

Severe hypoglycemia rate fell overall with no difference between groups.

ÂÂ

HbA1c remained well above national and international targets.

ÂÂ

Small but significant improvement in HbA1c in favor of pumps.

ÂÂ

Structured training reduces the risk of severe hypoglycemia and leads to modest but long-lasting benefits in HbA1c.

Dr Simon Heller, UK

REPOSE Trial Background: Limitations of conventional insulin therapy (MDI) result in many people keeping their blood glucose at higher than the recommended levels.

Aims: To assess the effectiveness of pump versus optimized MDI for type 1 diabetes patients with both groups receiving same high quality structured training.

Skills training course: DAFNE (Dose Adjustment for Normal Eating).

Outcomes: HbA1c measured centrally; moderate and severe hypoglycemia, insulin dose, body weight; psychological outcomes - QoL; health economics.

Findings ÂÂ

Eleven patients switched from pump to MDI Change in HbA1c from baseline to 24 months: 10.4 to 9.7%; 7 switched from MDI to pump - Change in HbA1c from baseline to 24 months: 10.3 to 8.3%.

ÂÂ

Severe hypoglycemia - Incidence rate ratio was not significantly different in the two groups.

ÂÂ

Psychological outcomes - No difference between the groups for total DSQOL, SF12, EQ5D, WHOQOLBREF, HADS, HFS.

ÂÂ

DSQOL diet restriction - Evidence of better improvement in pump arm.

ÂÂ

Pump group had better improvement in DSQOL daily hassle or functions.

recommended

IN CONVERSATION WITH DR BALRAM SHARMA Dr Balram Sharma, Jaipur Why do blood glucose levels fall at night in patients with type 1 diabetes?

In type 1 diabetes, autoimmune destruction of pancreatic beta cells eventually leads to an absolute requirement for insulin replacement therapy. Insulin delivered exogenously is not subject to normal physiological feedback or counter regulatory mechanism, so it may induce hypoglycemia even in the presence of an intact counter-regulatory response. In addition, two other major defects in this homeostatic counter regulatory response contribute to the high frequency of hypoglycemia in type 1 diabetes.

First, within 5 years of disease diagnosis, almost all individuals with type 1 diabetes fail to generate an adequate glucagon response to hypoglycemia. Glucagon is the principal rapid-acting counter-regulatory hormone and the portal insulin-to-glucagon ratio is the major determinant of hepatic glucose production.

Reduced or absent glucagon release results in a marked impairment of glucose recovery from hypoglycemia.

Second, there is a failure in local regulation of beta- to alpha-cell signaling by insulin, zinc and possibly, the neurotransmitter gamma-aminobutyric acid during

Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

681

CONFERENCE PROCEEDINGS hypoglycemia, also plays an important role in the genesis of this defect.

How many people are expected to attend this year’s conference?

How does continuous glucose monitoring help?

Thirteen hundred registrations plus 200 on spot registration, making a total 15,000 registrations this year.

The evidences so far available regarding utility of CGMS in reducing hypoglycemia are quite conflicting.

These devices still have lots of limitations regarding issues of sensitivity, accuracy and precision. So, they do not provide final results which can help in treatment modifications, but the results obtained from CGMS reports have to be confirmed by SMBG or Lab before making any change in treatment. CGMS has to be calibrated by regular SMBG and it cannot replace SMBG by glucose meters.

How does a CGMS work?

CGMS basically monitors the glucose level in interstitial fluid by its sensor and that’s why there is a lag period in estimation of glucose levels and they may not correlate properly with blood or capillary glucose level. This may be even more troublesome during frequent change or rapid change in blood glucose level. So, if treating physician is planning some change in treatment, that must be confirmed first by Lab or glucose meters first.

What would you advise the practicing clinicians regarding the utility and efficacy of CGMS? These devices may tell you the pattern of glucose level in patients, but how accurate and precise this information is, still there is a debate going on. But, this newer modality needs improvement before it can be used confidently in routine clinical practice.

What are the key take home messages from your talk?

CGMS is a costly newer technology which can be helpful in selective type 1 diabetics who are highly motivated, using it regularly (more than a week), calibrating it routinely and at the same time also performing regular SMBG to be sure about the information gathered from CGMS before making any treatment decision.

The utility of these devices in type 2 diabetics is still not established for which more evidence in form of dedicated RCTs are required.

TETE-A-TETE WITH DR RAJESH KHADGAWAT Dr Rajesh Khadgawat, New Delhi What is on the scientific program agenda for ESICON 2016?

The program is based on dissemination of endocrinology knowledge to the periphery. To get advance knowledge so that doctors can use it in their practice.

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Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

What should the participants look for in this year’s talks?

Different clinical endocrine situations where treatment is difficult, different endocrine problems are addressed this year, knowledge about various endocrine diseases is also strengthened.

Are there any other interesting areas that participants should be aware of?

Type 2 diabetes mellitus, thyroid related problems, obesity, gestational diabetes, etc. are interesting areas that participants should be aware of.

How would you sum up ESICON 2016?

ESICON 2016 fills the gap in the complex knowledge of endocrinology for those working in the periphery. It aims to provide specific knowledge via different patterns of lectures, debate, symposia and workshops. It is a huge success till now as it received around 250 abstract papers for the presentation and registration of 1,500 delegates making it a huge success.

A DIALOGUE WITH DR PRAKASH KESWANI Dr Prakash Keswani, Jaipur Why does Grave’s disease occur?

Grave’s disease occurs because of faulty interplay of immune system. There is increase in thyroid stimulating antibodies (LATS). This leads to increased stimulation of thyroid gland resulting in excess formation of thyroid hormone.

How do you treat a patient with Grave’s disease?

First, we treat these patients with antithyroid (thionamides) drugs. We make patients euthyroid. Later on, if required. Patients are subjected to radioactive therapy or surgery depending on demand of disease.

Is antithyroid drug therapy for Graves’ disease relapse as effective as radioiodine treatment?

If relapse occurs, it is always beneficial to go for radioactive iodine therapy, if not contraindicated.

What are the key take home messages from your talk?

Hyperthyroidism is completely curable. Proper and timely intervention is required.

CONFERENCE PROCEEDINGS 1.4/100 patient years. Duration of diabetes at death was 5.7 ± 4.8 years. Chronic complications were proliferative DR in 3.7% and overt nephropathy in 3%.

GENETIC DISORDERS OF THE PITUITARY-THYROID AXIS Dr VKK Chatterjee, UK ÂÂ

RTHb - Raised fT4 and fT3; non-suppressed TSH.

ÂÂ

RTHb - Clinical features zz Childhood

- Failure retardation, ADHD

to

thrive,

ÂÂ

Costs of care of T1DM in India – Income is low, supplies are expensive, health insurance is rarely utilized.

ÂÂ

In the clinic-base study, 81% patients had no funding; 87% were spending for diabetes management “Out of Pocket”.

ÂÂ

Direct cost of care per patient-year is about Rs. 27,915.

ÂÂ

Patients of poor socioeconomic status (SES) have poorer glycemic control. This is related to cost of supplies, access to care and knowledge or attitudes to health.

ÂÂ

Summary

growth

zz Adults - Goiter, tachycardia, increased metabolic

rate, low bone mineral density, dyslipidemia.

ÂÂ

RTHa - Clinical features zz Growth retardation zz Macrocephaly zz Skeletal dysplasia zz Dyspraxia zz Constipation zz Skin tags

zz A1c <7.5% is seen in only 1/4th of children

zz Low fT4:fT3 ratio

zz Higher mortality and increased risk of severe

zz Raised muscle creatine kinase

chronic complications

zz Mild normocytic anemia.

zz Cost of care is high zz SES and education impact A1c

CHILDHOOD TYPE 1 DIABETES IN INDIA: THE CURRENT REALITIES

zz Provision of insulin/strips favorably impact

A1c.

Dr Eash Bhatia, Lucknow ÂÂ

Type 1 diabetes is the most common form of diabetes in children and adolescents in India.

ÂÂ

It account for about 85% of childhood diabetics in India.

ÂÂ

Prevalence/incidence of T1DM approximately 1-10/1,00,000/year.

ÂÂ

Constraints to management of T1DM in India:

in

India

is

DHEA REPLACEMENT IS REQUIRED IN CLINICAL PRACTICE Dr Pramila Kalra, Bengaluru ÂÂ

DHEA use can cause androgenic side effects: Various side effects, including acne, hair loss, hirsutism and deepening of voice, have been reported with the use of physiological doses of DHEA in women. Facial hair growth and voice changes may be irreversible.

ÂÂ

DHEA and psychiatric disorders: No conclusive benefit.

ÂÂ

DHEA and antiageing: no proven use.

ÂÂ

One of the serious DHEA side effects is heart palpitations or arrhythmias.

zz Caregivers zz Inadequate specialized centers zz Poorly trained pediatricians zz Lack of diabetes educators and nutritionists zz Patients/families zz Inadequate knowledge zz Negative attitudes zz Social/economic issues - High cost; lack of

universal insurance.

ÂÂ

In a clinic based-study, the presenter and his colleagues assessed 512 patients with T1DM with age of onset ≤18 years. Mean HbA1c was 8.6 ± 1.9%.

About 5.8% patients developed coma and seizures.

Total deaths were 28/279; a mortality rate of

IN CONVERSATION WITH DR NIKHIL TANDON Dr Nikhil Tandon, New Delhi What have been the latest developments in the field of diabetes management?

There have been gradual developments in pumps, which are more intelligent. We have smart and intelligent

Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

683

CONFERENCE PROCEEDINGS pumps which have close loops and have sensors which give you information of prevailing glucose and then cause insulin release accordingly. These obviously need to be refined. This is a big step forward as this helps keep sugar much better controlled. These are in their early days, primarily for T1D and are very expensive.

On a health system basis what is emerging is a lot of education. Things are technology-assisted but technology even now is not enough to take over the management. So, technology-assisted management with appropriate patient training, also using nonphysician healthcare providers to fill in the educational gap, has become very important.

Do you see diabetes management is changing in the coming years?

It has to change. We must differentiate management from medication. Medicines will come, they have their own pipeline, they will be more expensive with the passage of time. What’s important is how do we ensure that people take timely medication, appropriately over the period. This is what needs to be incorporated.

What lifestyle changes do you advocate for preventing diabetes?

The changes are usual, but they have to be culturally tailored; we need to clearly understand. It has to be the patient’s effort. He/she is the final implementer, but it can’t only be the patient who is responsible. We have to have enabling facilities and we need to have a favorable environment.

If someone says, I live in a place where I cant go for a walk and you tell him to go for a walk, how is it the patient’s fault?

There are huge issues of urban planning, and of development, issues of what you are subsidizing.

Do you yourself follow any diet rules?

I don’t follow any particular diet rule, but I ensure that my consumption is moderate.

BARIATRIC SURGERY IN DIABETICS Dr Shehla Shaikh, Mumbai What is the criteria for doing bariatric surgery in diabetics?

Morbidly obese patients with BMI >35-40 having 1 to 2 comorbidities.

What are the long-term success rates of bariatric surgery?

According to the studies, at 2 years the remission rate is 60-72%, which reduces the recurrence in 50% of patients by 5 years.

How do you summarize your talk?

It is pre-emptive to advocate for BMI less than 35, till we have more data available with us. It is a good option for morbidly obese patients. Parameters other than BMI include duration of disease, C-peptide levels, insulin status of the patient prior to surgery and glycemic control. All these assists in choosing a right candidate, which will increase the success rate of the surgery.

DIABETES AND INFLAMMATION Dr Krishna G Seshadri, Chennai ÂÂ

Diabetes is an inflammatory disorder.

ÂÂ

Our learning about it can help us prevent the progression of diabetes.

ÂÂ

While novel therapies are existing, simple interventions like low calorie diet and physical exercise give hope for millions.

■■■■

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Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

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CONFERENCE PROCEEDINGS

10th World Stroke Congress 2016 BUILDING AND TRAINING A STROKE UNIT TEAM Prof Gary Ford, Oxford, United Kingdom

ÂÂ

Adding ezetimibe increases the effect of statins and contributes to plaque regression and stabilization.

ÂÂ

Statins do not cause brain hemorrhage.

ÂÂ

Team work is necessary to deliver high quality stroke care.

ÂÂ

Consider the whole patient pathway, focus on patient outcomes.

ÂÂ

Develop a strategy and plan.

ÂÂ

Identify a team leader, assign roles to other team members.

ÂÂ

Registries are powerful tools to estimate and monitor the burden of disease.

ÂÂ

Agree who is needed in the multidisciplinary stroke team.

ÂÂ

ÂÂ

Consider the impact of the Stroke Unit environment on team working.

A registry is a file of documents containing uniform information about individual persons, collected in a systematic and comprehensive way.

ÂÂ

Use quality improvement approaches - Plan, Do, Study, Act.

We first need to define the disease, clarify the study population and develop the questionnaire.

ÂÂ

ÂÂ

Build team morale; praise members, tell patient stories.

Then, we need to capture the data on standardized forms by trained staff.

Develop team members; feedback, mentor trainees.

ÂÂ

ÂÂ

Data entry, data cleaning should be continually done.

ÂÂ

As a leader, lead by example; allow others to take credit, be positive, be accountable.

ÂÂ

Safe data storage, data security and confidentiality remain challenges.

ÂÂ

The issues of data ownership and access need to be addressed early.

ÂÂ

Legal issues and the need for consent may arise.

Prof J David Spence, London, Ontario, Canada

ÂÂ

Nutrition is much more important than most physicians think it is.

Data dissemination is needed to allow registry findings to guide policy and practice.

ÂÂ

Strong leadership and adequate funding are needed for a registry to succeed in the long-term.

ÂÂ

STROKE PREVENTION IN THE 21ST CENTURY: LIFESTYLE, LIPID-LOWERING DRUGS AND NUTRITION IN STROKE PREVENTION

ÂÂ

ÂÂ

Dietary cholesterol is harmful.

ÂÂ

Egg yolk and red meat have harms beyond the cholesterol content, related to the intestinal microbiome; egg yolk and red meat should be avoided by patients at risk of stroke, particularly those with renal impairment (including the elderly).

ÂÂ

ÂÂ

ÂÂ

ÂÂ

The best diet for stroke prevention is the Cretan Mediterranean diet.

Toxicity from cyanide in cyanocobalamin among subjects with renal impairment obscures the benefit of B vitamins to lower homocysteine.

Use of B vitamins to lower homocysteine does reduce the risk of stroke, but we should use methylcobalamin instead of cyanocobalamin.

Lipid-lowering drugs reduce the risk of stroke.

ESTIMATING THE BURDEN OF DISEASE: HOW TO ESTABLISH A STROKE REGISTRY? Dr N Venketasubramanian Ramani, Singapore

TETE-A-TETE WITH DR DEBASHISH CHOWDHURY Dr Debashish Chowdhury, New Delhi What are the new targets in prevention of post-stroke cognitive decline? ÂÂ

Augmenting cholinergic deficits.

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Augmenting and treating comorbidities.

ÂÂ

Neuroprotection.

What are the issues in treating vascular dementia? ÂÂ

Not enough is known about pathophysiology.

ÂÂ

No drug affecting molecular mechanism.

ÂÂ

No viable biological marker.

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CONFERENCE PROCEEDINGS What is your opinion on IV thrombolytic therapy? ÂÂ

Useful but only till united by window period.

well as offering interventional treatment in remote hospitals in the flying interventionalist concept.

ÂÂ

Cannot be applied in many cases.

A DIALOGUE WITH DR SUBHASH KAUL

ÂÂ

What we need is a drug which will not only thrombolyse but also have neuroprotection.

IN CONVERSATION WITH DR SHIRISH M HASTAK Dr Shirish M hastak, Mumbai How has the management of stroke changed in the last 1 year?

More doctors are now aware of thrombolytics.

What is the most important factor in successful thrombolytic therapy?

System in place, passion for treating patients in time.

Where does IV thrombolysis stand in stroke management, considering the global debate on IV thrombolysis vs. mechanical thrombectomy?

Many more patients may be helped by IV thrombolytics in comparison to mechanical thrombectomy.

REVASCULARIZATION: THROMBOLYSIS AND THROMBECTOMY Dr H Audebert, Germany Stroke management in specialized facilities, offering thrombolytic treatment to ischemic stroke patients and mechanical thrombectomy in patients with proximal cerebral artery occlusion have become the most powerful therapeutic strategies in acute stroke care.

Organization of stroke care in Stroke Units (or Stroke Centers) is the backbone of successful local stroke management.

The close relationship between onset-to-treatment time and effects on outcome is applicable for both thrombolysis and thrombectomy. Early recognition of suitable patients, triage to appropriate facilities and optimized procedures in pre-hospital and in-hospital care are all challenging local and regional set-ups.

Close collaboration with emergency medical services is essential for both transport to the primary hospital and for interhospital transport of patients who need interventional treatment in referral stroke centers.

Telemedicine can help in remote differential diagnosis, initiation of thrombolysis and selection of patients with indication for mechanical thrombectomy. New approaches of optimizing stroke management include the implementation of mobile stroke treatment units with CT scanner and point-of-care lab on board as

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Dr Subhash Kaul, Hyderabad What is the prevalence of stroke in India?

Around 525/1,00,000.

Is there a genetic basis to stroke?

Possibly, as indicated by positive family history in onethird of stroke cases and as shown by genetic studies done by us in Hyderabad.

Last year your study on the impact of bilingualism on cognitive outcome after stroke was published. Can you please illuminate us on that?

Patients with bilingualism recover faster and better from cognitive deficits following stroke.

How do you see stroke management changing in the coming times?

There is going to be more emphasis on stroke prevention drugs and more prevalent use of thrombectomy in acute ischemic stroke.

STROKE PREVENTION IN THE 21ST CENTURY ASYMPTOMATIC CAROTID STENOSIS: HOW SHOULD IT BE MANAGED? Prof J David Spence, London, Ontario, Canada ÂÂ

The risk of stroke or death is now lower (~0.5%/year) with intensive medical therapy than with stenting or endarterectomy.

ÂÂ

Most patients (90%) with asymptomatic carotid stenosis would be better off with intensive medical therapy than with either stenting or endarterectomy.

ÂÂ

Asymptomatic stenosis is not a “ticking time bomb”; the risk of stroke at the time of carotid occlusion is very low (0.3%); prevention of occlusion is not a valid indication for intervention.

ÂÂ

The few patients at high enough risk to benefit from stenting or endarterectomy can be identified by transcranial Doppler embolus detection; other methods are in development.

ÂÂ

Routine intervention for asymptomatic stenosis is unwarranted and could be regarded as unethical.

ÂÂ

Randomized trials are now testing best medical therapy against stenting or endarterectomy; a moratorium on routine intervention should be observed until those trials are completed.

CONFERENCE PROCEEDINGS ÂÂ

Intensive medical therapy includes lifestyle modification, intensive lipid-lowering therapy, antiplatelet agents and effective control of blood pressure - it is not just a bit of aspirin and statin.

ÂÂ

Explain to them about the medical aspects of their illness.

ÂÂ

Give facts about the response to treatment.

ÂÂ

Many of the problems with which patients present have psychosomatic basis and they have to be addressed to make them feel comfortable and help them in overcoming their suffering.

TETE-A-TETE WITH DR A SHIVARAMAKRISHNA Dr A Shivaramakrishna, Shimoga As a neurologist, what differences do you see between the healthcare delivery systems of our country and those in other countries?

IN CONVERSATION WITH DR DHEERAJ KHURANA Dr Dheeraj Khurana, Chandigarh

ÂÂ

Nonavailability of good medical facilities (equipment) and medical expertise at peripheries.

How do you intend to change or improve stroke management strategies in India?

ÂÂ

Lack of public awareness about treatment of neurological disorders.

ÂÂ

Delay in initiating treatment for acute neurological disorders like stroke and epilepsy because of lack of awareness and misconceptions in the public.

The most important direction in improving the stroke situation in India is firstly to improve awareness in public on recognition of stroke symptoms, so that they may seek early treatment. This should be closely followed by promoting the formation of Stroke Centers in hospitals across various regions. This would go a long way in promoting organized stroke cure in this country.

What are the most common issues you manage in clinical practice? ÂÂ

Headache, Stroke and Seizures are the common neurological conditions. But there are a lot of misconceptions about these disorders and educating patients and their relatives is a priority.

What recommendations do you give regarding patients who are feeling great level of stress and anxiety as a result of their disorder? ÂÂ

Give sufficient time in educating them about their illness.

ÂÂ

To listen to them carefully, and patiently.

How has stroke imaging changed over the recent years?

The basic requisite for stroke imaging is a CT scan.

Multimodal CT imaging like CT angiography and CT perfusion have become available over the years, which give valuable information about stroke mechanisms.

MRI is also an excellent imaging modality which gives more detailed parenchymal information, e.g.: Diffusion weighted imaging can show acute ischemic stroke lesion. However, in the acute setting, a CT scan remains the preferred modality.

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MEDILAW

A Known Phenomenon is not Medical Negligence A patient filed a case against his treating doctor alleging that he had negligently treated him and when his line of treatment was not successful, the doctor referred him to a higher centre for treatment.

The ureteral stone migrated during surgery.

Proceed

My GP referred me to a surgeon,who failed to do a successful surgery for my ureteral stone and later referred me to a higher centre.

A known phenomenon cannot be a cause for negligence.

Lesson: In an order DMC/DC/F.14/Comp.615/2010, the Council observed that migration of ureteral stone during surgery is a known phenomenon documented in medical literature, hence, prima facie no medical negligence can be attributed on the part of the doctor.

CASE OVERVIEW Patient X filed a complaint against Dr A and Dr B with the medical council alleging medical negligence in the treatment that had been given to him at Hospital Y. The following documents were examined by the Council: Complaint filed by patient X, joint written statements of Dr A and Dr B, written statement of Dr C, Medical Superintendent of Hospital Y, medical records and other documents placed on record.

Council Observations The Council noted that patient X was diagnosed to have ureteric stone. Therefore, a laparoscopic ureterolithotomy was planned for 29.7.2009. The stone could not be localized hence, it was decided to convert the laparoscopic procedure into an open procedure.

However, owing to the difficult anatomy in the region of kidney, the surgeon was unsuccessful in removing the stone. The operation notes of the surgeon mention this fact.

The attendants of the patient were informed about this including the further plan of percutaneous nephrolithotomy (PCNL) and double J (DJ) stent removal in a higher centre, a fact that is evident from the postoperative orders documented in the medical records of the hospital.

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The patient was discharged from Hospital Y on 6.8.2009.

The Executive Committee also observed that the discharge summary did not mention the fact that the stone has not been removed during surgery, although it did mentioned a follow-up in OPD after 6 weeks and DJ stent to be removed. The patient has probably filed this complaint because of this lack of communication. The Council noted that migration of ureteric stone during this procedure is a known phenomenon and is welldocumented in medical literature. Hence, no medical negligence can be attributed on the part of Drs A and B in the treatment administered to Patient X.

Council Judgement Based on its observations, the Council disposed of the complaint as it found that the concerned doctors had followed the standard surgical protocol in managing the ureteral stone in this patient. The Council; however, directed the hospital to ensure better record keeping and doctor-patient communication.

Reference 1. DMC/DC/F.14/Comp.615/2010/, dated 7th June, 2010.

LEGAL IMPLICATIONS OF MEDICAL RECORDS Medical records are documents that include complete details about the patientâ&#x20AC;&#x2122;s history, clinical findings,

MEDILAW results of diagnostic tests, pre- and postoperative care, patient’s progress and medication/s administered. If written correctly, notes will support the doctor about the correctness of treatment.1 Hospital medical records are a documentary evidence as per the Indian Evidence Act, 1872, as amended up to August 1, 1952 & 1961. Hence, they are usually required in cases of medical negligence under the Consumer Protection Act or in criminal courts.2 The legal system relies mainly on documentary evidence in cases of medical negligence. Medical records are one of the most important aspect on which practically almost every medicolegal battle is won or lost.1 Therefore, it is essential to ensure the integrity of medical records as without them you are deprived of any means to defend the allegation of negligence or professional misconduct.

Good records mean good defence, poor records mean poor defence, no records mean no defence.3

References 1. Bali A, Bali D, Iyer N, et al. Management of medical records: facts and figures for surgeons. J Maxillofac Oral Surg. 2011;10(3):199-202.

2. Singh S, Sinha US, Sharma NK. Preservation of medical records - an essential part of health care delivery. Indian Internet Journal of Forensic Medicine & Toxicology.

2005;3(4).

(SC)128, the Supreme Court of India held that “… The medical practitioner has a discretion in choosing the treatment which he proposes to give to the patient and such discretion is wider in cases of emergency, but, he must bring to his task a reasonable degree of skill and knowledge and must exercise a reasonable degree of care according to the circumstances of each case.”

A doctor is not guilty of negligence if he has acted in accordance with the practice, which is accepted as proper by a reasonable body of medical professionals.

The onus to prove negligence lies on the complainant.

In Dr. Devendra Madan And Ors. vs Shakuntala Devi on 25 October, 2002, I (2003) CPJ 57 NC, the National Consumer Disputes Redressal observed that “…the complainant has to prove, (1) that there was a breach of duty on the part of the doctor; and (2) that the breach of duty was the real cause of the damage complained of and such damage was reasonably foreseeable.”

A mere allegation of negligence will be of no help to the Complainant as was alleged in Smt. Savitri Singh v.

Dr. Ranbir PD. Singh and others. 2004;(1) CPJ 25 (Bihar).3

References 1. Yadav M, Singh H, Sharma G, et al. Recent scenario of criminal negligence in India Doctor, community & apex court. JIAFM. 2005;27(4):252-7.

2. Murthy KK. Medical negligence and the law. Indian J Med Ethics. 2007;4(3):116-8.

3. Thomas J. Medical records and issues in negligence.

Indian J Urol. 2009;25(3):384-8.

3. Joga Rao SV. Medical negligence liability under the consumer protection act: A review of judicial perspective.

Indian J Urol. 2009;25(3):361-71.

WHEN IS A PHYSICIAN LIABLE FOR NEGLIGENCE?

CIVIL VS CRIMINAL NEGLIGENCE

A physician may be held liable for negligence only if he did not possess the requisite skill which he professed to have possessed or that he failed to exercise, with reasonable competence in the given case, the skill which he did possess.1 However, physicians cannot give a warranty of the perfection of their skill or a guarantee of cure. If a doctor has adopted a practice that is considered “proper” by a reasonable body of medical professionals who are skilled in that particular field, he or she will not be held negligent only because something went wrong.2 It is a known fact that with the best skill in the world, things sometimes went wrong in medical treatment or surgical operation. A doctor was not to be held negligent simply because something went wrong.3 In a landmark judgement in Laxman Balkrishna Joshi vs Trimbak Bapu Godbole And Anr on 2 May, 1968 AIR 1969

“…For negligence to amount to an offence, the element of mens rea must be shown to exist. For an act to amount to criminal negligence, the degree of negligence should be much higher i.e. gross or of a very high degree …

To prosecute a medical professional for negligence under criminal law it must be shown that the accused did something or failed to do something which in the given facts and circumstances no medical professional in his ordinary senses and prudence would have done or failed to do. The hazard taken by the accused doctor should be of such a nature that the injury which resulted was most likely imminent.” Jacob Mathew vs State of Punjab and Anr: 5th day of August 2005:334/2005/SCI/ 144-145 of 2004. “… For civil liability only damages can be imposed by the court but for criminal liability the doctor can also be sent to jail (apart from damages which may be imposed on him in a civil suit or by the consumer fora)…” Martin F. D’Souza vs Mohd. Ishfaq, 3541 of 2002, dated 17.02.2009.

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AROUND THE GLOBE

News and Views Study Suggests Stress Echo as a Rational Option to Evaluate Chest Pain in ER Results of a new study presented in November 28, 2016 at the Radiological Society of North America (RSNA) 2016 Annual Meeting in Chicago suggest that using stress echo to evaluate patients with chest pain in the emergency room leads to fewer hospitalizations versus using coronary CT angiography.

may not be necessary. In 451 patients with SDN, 36.6% underwent re-excision. Two melanomas were diagnosed in the re-excision specimens. The study is reported online November 9, 2016 in the Journal of the American Academy of Dermatology.

Robotic Approach to Renal Stones Allows Complete Stone Removal with Zero Fragmentation

Two-year efficacy and safety results from the randomized EXXELERATE study published online November 15, 2016 in The Lancet show that certolizumab pegol + methotrexate is not superior to adalimumab + methotrexate in patients with active rheumatoid arthritis suggesting that patients may be switched to a second TNF inhibitor without a washout period after primary failure to a first TNF inhibitor.

Robotic pyelolithotomy (RPL) and nephrolithotomy (RNL) are safe and reasonable options for removing renal stones in select patients, says a multicenter evaluation of RPL and RNL for treating renal stones published online in European Urology, October 27, 2016.

The robotic approach allows for complete removal of the renal stone without fragmentation, thereby maximizing chances for complete stone clearance in one procedure.

According to the researchers, RPL in particular, allows stone removal without encroaching the parenchyma, reducing chances of bleeding and loss of nephrons.

Individual Treatment Reduces Severity of PTSD More Effectively Than Group Therapy

Study Suggests CRP as a Biomarker for Bipolar Disorder

A randomized clinical trial analyzing the effect of group versus individual cognitive processing therapy (CPT) in active-duty military seeking treatment for post-traumatic stress disorder (PTSD) concluded that CPT delivered in an individual format was more efficacious in treating symptoms of PTSD compared with CPT delivered in a group format. Follow-up at 6 months showed that the significant reductions in PTSD persisted. The findings of the trial are published online November 23, 2016 in JAMA Psychiatry.

Compared with healthy individuals, C-reactive protein (CRP) concentrations were moderately increased in people with bipolar disorder during depression and euthymia and more substantially increased during mania, suggesting an increased inflammatory burden in mania. These findings from a systematic review and meta-analysis was published online November 9 in Lancet Psychiatry.

HRT has Favorable Impact on Bone Health in Menopausal Women The benefit of hormone replacement therapy (HRT) on bone density and microarchitecture, as assessed by trabecular bone score (TBS), persists after its withdrawal, says a new study published online November 17, 2016 in the Journal of Clinical Endocrinology & Metabolism.

The effect of HRT on TBS and bone mineral density was still evident for at least 2 years after withdrawal.

Exposure to maternal rheumatoid arthritis (RA) was associated with an increased risk of childhood epilepsy, while no such association was observed with exposure to paternal RA suggesting a role for changes in the intrauterine environment. Results from a nationwide cohort study including all singletons born in Denmark from 1977 to 2008 through individual linkage to nationwide Danish registries was published online before print November 16, 2016 in Neurology.

Re-excision of All Dysplastic Nevi with Severe Atypia may not be Necessary

Hypertension in Children is Underdiagnosed and Undertreated

A retrospective single institution study suggests that routine re-excision of all severely dysplastic nevi (SDN)

A retrospective cohort study aggregating electronic health record data on >1.2 million pediatric patients

Certolizumab Pegol as Good as Adalimumab in Rheumatoid Arthritis

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Rheumatoid Arthritis in the Mother Increases Risk of Childhood Epilepsy

AROUND THE GLOBE from 196 ambulatory clinics across 27 states in the US concluded that hypertension and prehypertension were infrequently diagnosed among pediatric patients.

Guidelines for diagnosis and initial medication management of abnormal BP in pediatric patients are not routinely followed. These findings are published online November 22, 2016 in the journal Pediatrics.

Global Leaders Agree to Promote Health to Achieve SDGs Leaders from governments and United Nations organizations, city chiefs and health experts from around the world made two landmark commitments to promote public health — stressing the links between health and wellbeing and the United Nations 2030 Agenda for Sustainable Development and its Sustainable Development Goals — and to advance health through improved management of urban environments. The 9th Global conference on health promotion, co-organized

by WHO and the National Health and Family Planning Commission of the People’s Republic of China in Shanghai, which concluded recently agreed: ÂÂ

ÂÂ

The Shanghai Declaration on Health Promotion, which commits to make bold political choices for health, stressing the links between health and wellbeing and the United Nations 2030 Agenda for Sustainable Development and its Sustainable Development Goals.

The Shanghai Healthy Cities Mayors’ Consensus, which contains a commitment by more than 100 mayors to advance health through improved management of urban environments.

(Source: WHO)

534 Pradhan Mantri Jan Aushadhi Kendras Functioning in 26 States/UTs With a view to achieving the objective of making available quality medicines at affordable prices, the Government has been taking several regulatory and fiscal measures from time to time. In order to provide further relief to the common man in the area of healthcare, a countrywide campaign for ensuring availability of quality generic medicines at affordable prices to all, in the name of “Pradhan Mantri Jan Aushadhi Yojana” (PMJAY) has been started. As on date, there are 534 Pradhan Mantri Jan Aushadhi Kendras (PMJAK) functioning over 26 States/UTs. The PMJAY is being implemented by the Bureau of Pharma PSUs of India (BPPI). This information was provided by the Minister of State (MoS) in the Ministry of Chemicals and Fertilizers, Shipping, Road Transport & Highways Sh.

Mansukh L. Mandaviya in the Lok Sabha… (Ministry of Chemicals and Fertilizers, 22nd November, 2016)

NCCN Launches Campaign on Vincristine Safety The National Comprehensive Cancer Network (NCCN) has launched a new safety campaign for vincristine “Just Bag It: The NCCN Campaign for Safe Vincristine Handling in a Mini IV-Drip Bag”. The campaign advises healthcare professionals to always dilute vincristine in a 50 mL mini-IV drip bag and never in a syringe. This precaution is to prevent accidental administration of the vincristine into the spine and also greatly decreases the chances of improper dosage. Vincristine is an important chemotherapeutic agent used primarily in the treatment of patients with leukemia and lymphoma.

Long-term Testosterone Beneficial in Hypogonadal Men Long-term treatment with an injectable form of testosterone improves sexual and urinary function in men with hypogonadism. The 8-year registry data also showed that in hypogonadal men with type 2 diabetes, testosterone also improved glycemic control. These findings were presented November 3, 2016 at the Sexual Medicine Society of North America Fall 2016 Scientific Meeting in Scottsdale, Arizona.

Study Reports Association Between Short Sleep and Greater Intake of Sugar-sweetened Beverages People who sleep 5 or fewer hours during the night also tend to drink more sugar-sweetened beverages compared to people who sleep more than 5 hours, according to a study published online November 9, 2016 in Sleep Health. “Directionality of this relationship cannot be determined from this study”, said the authors.

Although caffeinated drinks could account for impaired sleep, it is possible that short sleep could influence one’s appetitive drive for sugared caffeine drinks.

Even Modest Daily Activity may Reduce Mortality Risk in Women In a study reported online November 2, 2016 in the American Journal of Preventive Medicine, moderate to vigorous physical activity was associated with a substantially lower mortality risk. Light physical activity was associated with lower mortality risk, but only within women with low moderate to vigorous physical activity.

A New Drug for Hepatitis B The FDA has approved tenofovir alafenamide (TAF), to be sold as Vemlidy, for adults with chronic hepatitis B infection with compensated liver disease. It is a prodrug

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AROUND THE GLOBE for tenofovir, an antiviral agent previously approved under the name Viread for HIV and HBV infection. This new drug comes with a boxed warning about risk of lactic acidosis and severe hepatomegaly with steatosis, as well as post-treatment severe acute exacerbation of hepatitis B.

Constipation Linked to Chronic Kidney Disease Severe constipation was associated with a higher risk for both chronic kidney disease (CKD) and kidney failure. In a retrospective study of over 3.5 million veterans in the US reported in the Journal of the American Society of Nephrology, those with constipation had a 13% higher likelihood of developing CKD and a 9% higher likelihood of developing kidney failure compared with those without constipation.

Endovascular Therapy may Benefit Patients with Large Ischemic Score and Large Mismatch Profiles In properly selected patients, endovascular therapy appears to benefit patients with large ischemic score and large mismatch profiles. In a matched case-control study reported in JAMA Neurology, November 7, 2016 endovascular therapy was significantly associated with a favorable shift in the overall distribution of 90-day modified Rankin Scale scores, higher rates of independent outcomes, and smaller final infarct volumes. It was also associated with numerically lower rates of parenchymal hematoma type 2, hemicraniectomy and 90-day mortality.

Study Shows Diagnostic Value of Florbetapir F 18 Imaging in Patients with Cognitive Impairment

which is usually a formality within around 60 days, the EU will be the first major market for this product.

The fixed-ratio combination of insulin glargine, a basal insulin analog and lixisenatide will be available as a solution for injection (insulin 100 units/mL with lixisenatide 33 or 50 µg/mL) and will be known as Suliqua.

‘White Coat’ Hypertension is a Risk Factor for Cardiac Events in the Elderly Among adults 60 and older with other risk factors such as diabetes, obesity or a history of heart problems, people who also experienced white coat hypertension were more than twice as likely to experience cardiac events like a heart attack or stroke in subsequent years, says a study published November 8, 2016 in the Journal of the American College of Cardiology.

Patient Risk Factors may Personalize Melanoma Screening A person’s risk factors for melanoma could be used to tailoring skin self-examination and surveillance programs for melanoma, according to the populationbased Melanoma Patterns of Care study published online November 9, 2016 in JAMA Dermatology. Among highrisk patients, those with many nevi were more likely to have melanoma on the trunk, those with a family history of melanoma were more likely to have melanomas on the limbs and those with a personal history were more likely to have melanoma on the head and neck.

Smokers More Prone to Develop Abdominal Aortic Aneurysms

According to the Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study published online October 31, 2016 in JAMA Neurology, amyloid PET in addition to routine assessment in patients with cognitive impairment has a significant effect on diagnosis, diagnostic confidence and drug treatment. Diagnostic confidence in Alzheimer disease diagnosis increased by 15.2% in amyloid and decreased by 29.9% in amyloid-negative scans.

Smokers are nearly twice as likely to develop an abdominal aortic aneurysm compared to the general population, and quitting smoking can substantially reduce this risk, according to a new research published in Arteriosclerosis, Thrombosis and Vascular Biology, a journal of the American Heart Association. The study found the lifetime risk of an abdominal aortic aneurysm was: 1 in 17 among all study participants, 1 in 9 among current smokers, 1 in 9 among those in the top third of smoking pack-years (number of cigarettes smoked over a lifetime), whether a current or former smoker and 1 in 12 among current female smokers.

EMA Approves Combination of Insulin Glargine and Lixisenatide

Graft Fibrosis Risk High Post-pediatric Liver Transplantation

The European Medicines Agency (EMA) has given its go ahead to a combination of insulin glargine (Lantus, Sanofi) and the GLP-1 agonist lixisenatide (Adylxin, Sanofi), for the treatment of type 2 diabetes. If approved,

Most children who received liver transplants developed mild fibrosis or cirrhosis within 10 years of undergoing the procedure, says a new study of 20 years of follow-up of children who underwent liver transplant presented

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AROUND THE GLOBE at the American Association for the Study of Liver Diseases annual meeting in Boston. About 77% of patients transplanted in childhood developed mild fibrosis or cirrhosis in protocol liver biopsies 10 years post transplant. Potentially modifiable factors associated with fibrosis include episodes of acute cellular rejection, positive serum autoantibodies and the use of steroids.

Biodegradable Mesh may Prevent Fistula After Pancreatectomy

USB stick. Any HIV in the sample triggers an acidity change, which the chip transforms into an electrical signal. This is sent to the USB stick, which shows the result on a computer or electronic device. The results published November 10, 2016 in the journal Scientific Reports show 95% accuracy over 991 blood samples. The median time to detection was 20.8 minutes in samples with >1000 copies RNA.

Women Surpass Men in Memory Tests

In patients undergoing distal pancreatectomy, wrapping the cut surface of the pancreas with a biodegradable polyglycolic acid mesh reduced the rate of clinically relevant postoperative pancreatic fistula. The rate of clinically relevant POPF (Grade B or C) was significantly lower in the polyglycolic acid mesh group than in the control group; 11.4% vs. 28.3%, respectively. These findings of a small multicenter randomized trial are reported online October 26, 2016 in JAMA Surgery.

Bystander CPR in Children According to analysis of data from the Cardiac Arrest Registry to Enhance Survival presented November 12 at the American Heart Association 2016 Scientific Sessions in New Orleans, bystander CPR was provided in 1,814 of 3,900 instances (46.5%) of out-of-hospital cardiac arrests in children younger than 18 years and was significantly associated with improved overall survival and neurologically favorable survival.

Conventional CPR had improved outcomes compared with compression-only CPR. The study also published online simultaneously in JAMA Pediatrics.

Drinking Sugary Beverages Increase Prediabetes Risk A study in the Journal of Nutrition says that regular intake of sugar-sweetened beverages (SSBs), but not diet soda intake, is associated with a greater increase in insulin resistance and a higher risk of developing prediabetes in a group of middle-aged adults. The highest SSB consumers (>3 servings/week) had a 46% higher risk of developing prediabetes vs those who did not consume SSB.

A New HIV Test on a USB Stick British researchers have developed a new pH sensing semiconductor for point-of-care detection of HIV-1 viremia. The test, which uses a mobile phone chip, requires a drop of blood to be placed onto a spot on the

Women have better tendency to retain, encode, store and consequently recall information and past experiences than men, which signifies that women have better memories compared to men, suggests a study published online in the journal Menopause. According to the present study the mental performance is directly related to estradiol level in the body, suggesting that the pre- or perimenopausal women have better memories than the postmenopausal women, because in the latter there a significant drop in the level of estradiol hormone.

World Medical Association came in Support of IMA’s Protest Against the Dissolution of Medical Council of India A nation-wide protest against the Union Government’s proposal “to dissolve the Medical Council of India (MCI) and replace it with National Medical Commission” was held by the members affiliated to Indian Medical Association, on Wednesday. IMA members wrote a letter to Union Health Minister JP Nadda, stating that the IMA members are in support of the amendments in the existing IMC Act but are truly against the dissolution of MCI and its replacement with National Medical Commission.

Dr KK Aggarwal, National President (Elect) and Secretary General and Dr SS Agarwal, National President of the IMA, said in the letter: “IMA supports suitable amendments in the existing IMC Act. IMA is against scrapping it totally and making it a non-autonomous body.”

In the support of the protest, World Medical Association (WMA) has also extended its support to the IMA. Dr. Ardis Hoven, Chair of the WMA said in a statement that: “The autonomy of the medical profession is under threat throughout the world... The new commission proposed by the Indian government effectively means that non-doctors handpicked by the government will be regulating the medical profession without any autonomy. That is unacceptable.”

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LIGHTER READING

HUMOR

Lighter Side of Medicine MY WATCH IS 5 MINUTES SLOW Three men were standing on a hill. The decided to throw their watches down the hill.

The first man threw his watch and it broke when it hit the bottom of the hill.

Then the second man did the same thing, and it also broke.

The third man threw his watch down the hill, but ran down the hill to catch it, so it didn’t break.

The other two men were very confused, so they asked how that was possible.

The third man told them, “Oh it wasn’t that difficult. My watch is 5 minutes slow.”

SMELLING AND HEARING An elderly woman goes to the doctor. She says, “Doc, it’s terrible, I pass gas all the time.

Fortunately, it’s odorless and silent, otherwise I’d be mortified. For example, I’ve passed gas ten times just since we’ve been talking, but it’s odorless and silent so you can’t tell.” The doctor gives her some green pills and tells her to take one a day and come back in a week.

The woman comes back after taking the pills for a week. She says, “Doc, there’s been a change but not for the better. I still pass gas all the time, but while it’s still silent, now it smells terrible!”

first, in the morning, with the older boy to see the preacher in the afternoon.

The preacher, a huge man with a booming voice, sat the younger boy down and asked him sternly, “Do you know where God is, son?” The boy’s mouth dropped open, but he made no response, sitting there wide-eyed with his mouth hanging open. So, the preacher repeated the question in an even sterner tone, “Where is God?!” Again, the boy made no attempt to answer. The preacher raised his voice even more and shook his finger in the boy’s face and bellowed, “Where is God?!”

The boy screamed and bolted from the room, ran directly home and dove into his closet, slamming the door behind him. When his older brother found him in the closet, he asked, “What happened?”

The younger brother, gasping for breath, replied, “We are in BIG trouble this time.” (“I just LOVE reading next line again and again”) ..........“GOD is missing, and they think we did it !”

Dr. Good and Dr. Bad SITUATION: A patient with Crohn’s disease needed a painkiller.

Take any painkiller

Give Nimesulide

The doctor says, “Well, I’m glad we cleared up your sinus blockage. Now we’ll have to work on your hearing.”

Two little boys, aged 8 and 10, are excessively mischievous. They are always getting into trouble and their parents know all about it. If any mischief occurs in their town, the 2 boys are probably involved.

The boys’ mother heard that a preacher in town had been successful in disciplining children, so she asked if he would speak with her boys.

The preacher agreed, but he asked to see them individually. So, the mother sent the 8-year-old

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© IJCP Academy

TWO NAUGHTY BOYS

LESSON:

Nimesulide is safe in IBD. A study in Scand J Gastroenterol.

2015;50(3):255-63 reviewed evidence for NSAIDs in patients with quiescent inflammatory bowel disease. Most patients with IBD tolerated these medications, while in the sole clinical trial of NSAIDs, 20% experienced a clinical and laboratory documented relapse of disease, within 7-10 days of NSAID ingestion. Though data on COX-2-selective NSAIDs are somewhat unclear, but nimesulide, celecoxib and etoricoxib do not appear to be associated with relapse of disease. The study concluded that conventional NSAIDs may cause clinical relapse in about 20% of patients with quiescent IBD, which may be due to dual inhibition of the COX enzymes. Certain COX-2-selective NSAIDs appear to be safe.

Information for Authors Manuscripts should be prepared in accordance with the ‘Uniform requirements for manuscripts submitted to biomedical journals’ compiled by the International Committee of Medical Journal Editors (Ann. Intern. Med. 1992;96: 766-767).

Indian Journal of Clinical Practice strongly disapproves of the submission of the same articles simultaneously to different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts submitted by authors who have done so.

The boxed checklist will help authors in preparing their manuscript according to our requirements. Improperly prepared manuscripts may be returned to the author without review. The checklist should accompany each manuscript.

Authors may provide on the checklist, the names and addresses of experts from Asia and from other parts of the World who, in the authors’ opinion, are best qualified to review the paper.

Covering letter –

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The covering letter should explain if there is any deviation from the standard IMRAD format (Introduction, Methods, Results and Discussion) and should outline the importance of the paper.

Principal/Senior author must sign the covering letter indicating full responsibility for the paper submitted, preferably with signatures of all the authors.

Articles must be accompanied by a declaration by all authors stating that the article has not been published in any other Journal/Book. Authors should mentioned complete designation and departments, etc. on the manuscript.

Manuscript – Three complete sets of the manuscript should be submitted and preferably with a CD; typed double spaced throughout (including references, tables and legends to figures).

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The manuscript should be arranged as follow: Covering letter, Checklist, Title page, Abstract, Keywords (for indexing, if required), Introduction, Methods, Results, Discussion, References, Tables, Legends to Figures and Figures.

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All pages should be numbered consecutively beginning with the title page.

Note: Please keep a copy of your manuscript as we are not responsible for its loss in the mail. Manuscripts will not be returned to authors.

Title page Should contain the title, short title, names of all the authors (without degrees or diplomas), names and full location of the departments and institutions where the work was performed,

name of the corresponding authors, acknowledgment of financial support and abbreviations used.

– The title should be of no more than 80 characters and should represent the major theme of the manuscript.

A subtitle can be added if necessary.

– A short title of not more than 50 characters (including inter-word spaces) for use as a running head should be included.

– The name, telephone and fax numbers, e-mail and postal addresses of the author to whom communications are to be sent should be typed in the lower right corner of the title page.

– A list of abbreviations used in the paper should be included. In general, the use of abbreviations is discouraged unless they are essential for improving the readability of the text.

Summary – The summary of not more than 200 words. It must convey the essential features of the paper.

– It should not contain abbreviations, footnotes or references.

Introduction – The introduction should state why the study was carried out and what were its specific aims/objectives.

Methods – These should be described in sufficient detail to permit evaluation and duplication of the work by others.

– Ethical guidelines followed by the investigations should be described.

Statistics The following information should be given: – The statistical universe i.e., the population from which the sample for the study is selected.

– Method of selecting the sample (cases, subjects, etc. from the statistical universe).

– Method of allocating the subjects into different groups.

– Statistical methods used for presentation and analysis of data i.e., in terms of mean and standard deviation values or percentages and statistical tests such as Student’s ‘t’ test, Chi-square test and analysis of variance or non-parametric tests and multivariate techniques.

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Confidence intervals for the measurements should be provided wherever appropriate.

Results – These should be concise and include only the tables and figures necessary to enhance the understanding of the text.

Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

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Discussion –

This should consist of a review of the literature and relate the major findings of the article to other publications on the subject. The particular relevance of the results to healthcare in India should be stressed, e.g., practicality and cost.

References These should conform to the Vancouver style. References should be numbered in the order in which they appear in the texts and these numbers should be inserted above the lines on each occasion the author is cited (Sinha12 confirmed other reports13,14...). References cited only in tables or in legends to figures should be numbered in the text of the particular table or illustration. Include among the references papers accepted but not yet published; designate the journal and add ‘in press’ (in parentheses). Information from manuscripts submitted but not yet accepted should be cited in the text as ‘unpublished observations’ (in parentheses).

At the end of the article the full list of references should include the names of all authors if there are fewer than seven or if there are more, the first six followed by et al., the full title of the journal article or book chapters; the title of journals abbreviated according to the style of the Index Medicus and the first and final page numbers of the article or chapter. The authors should check that the references are accurate. If they are not this may result in the rejection of an otherwise adequate contribution.

Examples of common forms of references are: Articles Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes.

Q. J. Expt. Physiol. 1955;40:89-111.

Figures – Two complete sets of glossy prints of high quality should be submitted. The labelling must be clear and neat.

– All photomicrographs should indicate the magnification of the print.

– Special features should be indicated by arrows or letters which contrast with the background.

– The back of each illustration should bear the first author’s last name, figure number and an arrow indicating the top. This should be written lightly in pencil only. Please do not use a hard pencil, ball point or felt pen.

– Color illustrations will be accepted if they make a contribution to the understanding of the article.

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Do not use clips/staples on photographs and artwork.

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Illustrations must be drawn neatly by an artist and photographs must be sent on glossy paper. No captions should be written directly on the photographs or illustration. Legends to all photographs and illustrations should be typed on a separate sheet of paper. All illustrations and figures must be referred to in the text and abbreviated as “Fig.”.

Please complete the following checklist and attach to the manuscript: 1. Classification (e.g. original article, review, selected summary, etc.)_______________________________ 2. Total number of pages ________________________ 3. Number of tables ____________________________ 4. Number of figures ___________________________

Books

5. Special requests _____________________________

Stansfield AG. Lymph Node Biopsy Interpretation Churchill Livingstone, New York 1985.

6. Suggestions for reviewers (name and postal address)

Articles in Books

2.____________ 2.________________

Strong MS. Recurrent respiratory papillomatosis. In: Scott Brown’s Otolaryngology. Paediatric Otolaryngology Evans JNG (Ed.), Butterworths, London 1987;6:466-470.

3.____________ 3.________________

4.____________ 4.________________

Tables –

These should be typed double spaced on separate sheets with the table number (in Roman Arabic numerals) and title above the table and explanatory notes below the table.

Legends – These should be typed double spaces on a separate sheet and figure numbers (in Arabic numerals) corresponding with the order in which the figures are presented in the text.

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698

The legend must include enough information to permit interpretation of the figure without reference to the text.

Indian Journal of Clinical Practice, Vol. 27, No. 7, December 2016

Indian 1.____________Foreign 1.________________

7. All authors’ signatures________________________ 8.

Corresponding author’s name, current postal and e-mail address and telephone and fax numbers __________________________________________

Online Submission Also e-Issue @ www.ijcpgroup.com For Editorial Correspondence

Dr KK Aggarwal

Group Editor-in-Chief Indian Journal of Clinical Practice E-219, Greater Kailash Part-1 New Delhi - 110 048. Tel: 40587513 E-mail: editorial@ijcp.com Website: www.ijcpgroup.com

R.N.I. No. 50798/1990 Date of Publication 13th of Same Month Date of Posting 13-14 Same Month

POSTAL REGISTRATION NO. DL (S)-01/3200/2015-2017 Posted in N.D. PSO New Delhi