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Volume 27, Number 10
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Volume 27, Number 10, March 2017 FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF
905 India Sees Improved Sex Ratio and Decline in Infant Mortality Rate: National Family Health Survey
KK Aggarwal
AMERICAN FAMILY PHYSICIAN
907 Systemic Lupus Erythematosus: Primary Care Approach to Diagnosis and Management
Nguyet-Cam Vu Lam, Maria V. Ghetu, Marzena L. Bieniek
918 Practice Guidelines 919 Photo Quiz COMMUNITY MEDICINE
923 Knowledge and Attitude of Infertile Couples Attending IRM: A Prospective Observational Study
Akshaya Kumar Mahapatro, Indumathi Joy, Kundavi Shankar, Thankam Varma
929 Case of Mix-up or Switching of Gametes, Embryos – Glaring Omission Under ART Bill, India
Sonali Kusum
GASTROENTEROLOGY
935 A Case Report of Pancreatic Lipomatosis
N Jeeva, S Arun Kumar, Joga Veera Balaji, Deepa James
HEMATOLOGY
937 The Wide Clinical Spectrum of Raised Fetal Hemoglobin in Adults
Pratik Vora, Sakshi Singh, Jemima Bhaskar, Manish Mehta, Ami Trivedi
INTERNAL MEDICINE
940 A Case of Kerosene Poisoning Complicated with Right-sided Pleural Effusion: An Unusual Presentation
Monika Maheshwari
942 A Study to Probe the Biological Lag of Electrolyte Imbalance Due to Diuretics
Sudhakar M Parhate, Ashtaputre, Renuka Harwani, Khalid Inamdar
OBSTETRICS AND GYNECOLOGY
948 Bilateral Single System Ectopic Ureters with Secondary Calculi in an Adult: Case Report
Gopi Kishore M, Suhasini G, Prasad PVGS, Sainadh AV
955 Antepartum Hemorrhage: An Obstetrician’s Nightmare
Surya Malik, Khushpreet Kaur, Parneet Kaur
OPHTHALMOLOGY
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959 To Study the Efficacy and Safety of Tacrolimus (0.1%) in Vernal Keratoconjunctivitis
Jitender Phogat, Sumit Sachdeva, Manisha Rathi, Nikunj Bhatt, Shikha Nailwal, Marisha Bishnoi
ORTHOPEDICS
Printed at New Edge Communications Pvt. Ltd., New Delhi E-mail: edgecommunication@gmail.com
964 Study of Transverse Patellar Fractures Treated with Modified Tension Band Wiring
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Mithun Mohan, DK Govindaraju, BS Jayakrishna Reddy
RHEUMATOLOGY
970 Effect of Adjuvant Atorvastatin Therapy on Disease Activity in Active Rheumatoid Arthritis: A Tertiary Care Center Study in India
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EXPERT’S VIEW
975 How can One Reduce Cardiovascular Mortality in Patients with Hypertension?
Nandini Mukherjee
CONFERENCE PROCEEDINGS
979 69th Annual National Conference of Indian Psychiatric Society (ANCIPS 2017) 983 72nd Annual Conference of the Association of Physicians of India (APICON 2017) MEDILAW
987 Doctors are Required to Provide Emergency Medical Care without Waiting for the Police Report AROUND THE GLOBE
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990 News and Views LIGHTER READING
996 Lighter Side of Medicine
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FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF
Dr KK Aggarwal
Group Editor-in-Chief IJCP Group, eMedinewS and eMediNexus
India Sees Improved Sex Ratio and Decline in Infant Mortality Rate: National Family Health Survey ÂÂ
A latest survey by the government has shown positive trends in key health indicators, including an improvement in sex ratio at birth and a decline in infant mortality rate (IMR) during 2015-16.
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The National Family Health Survey-4 (NFHS-4) for 2015-16 unveiled by the Health Ministry was conducted after collecting information from 6 lakh households, 7 lakh women and 1.3 lakh men and for the first time provides district level estimates.
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IMR declined from 57 to 41 per 1,000 live births between NFHS-3 (2005-06) and NFHS-4. IMR has declined substantially in almost all the states during the last decade. It dropped by more than 20 percentage points in Tripura, West Bengal, Jharkhand, Arunachal Pradesh, Rajasthan and Odisha.
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IMR substantially declined over the period from 79 per 1,000 live births in NFHS-1 (1992-93) to 41 per 1,000 live births in NFHS-4. Sex ratio at birth (number of females per 1,000 males) improved from 914 to 919 at the national level over the last decade with the highest in Kerala (1,047), followed by Meghalaya (1,009) and Chhattisgarh (977). Haryana also witnessed a significant increase from 762 to 836. Institutional births "dramatically" increased by 40 percentage points from 38.7% in NFHS-3 to 78.9% in NFHS-4. There was an increase of 34.1% institutional births in public facility, while the Empowered Action
Group (EAG) in Assam experienced more than a 40 percentage point increase. ÂÂ
The proportion of women who received at least 4 antenatal care visits for their last birth has increased by 14 percentage points from 37% to 51.2% over the decade (2005-15), while there has been a substantial increase of 20 or more percentage points in seven states.
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Total fertility rate (TFR) too declined to 2.2 children per woman from 2.7 in NFHS-3 moving closer to target level of 2.1.
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There was considerable decline in the TFR in each of the 30 states in India with the maximum decline observed in Uttar Pradesh (1.1 child) followed by Nagaland (1.0 child), Arunachal Pradesh and Sikkim (0.9 child each). Bihar, however, failed to register substantial decline.
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Children within the age of 12-23 months have been fully immunized (BCG, measles and 3 doses each of polio) and DPT increased by 18 percentage points from 44% in NFHS-3 to 62% in NFHS-4.
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The survey found that the full immunization coverage increased in Punjab, Bihar and Meghalaya by 29 percentage point each, while in Rajasthan, Uttar Pradesh, Jharkhand and Chhattisgarh it increased by 28 percentage points each.
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There was a decline in percentage of underweight children by 7 percentage points, a consequence of improved child feeding practices and focus on nutritional aspects of children.
Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
905
FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF ÂÂ
There was "substantial" decline of anemia among children aged 6-59 months as it declined from 69% in NFHS-3 to 58% in NFHS-4.
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The maximum decrease was reported in Assam with 34 percentage points followed by Chhattisgarh (30 percentage points), Mizoram (26 percentage points) and Odisha (20 percentage points).
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In category of children under the age of 3 years, who were breast-fed within 1 hour of birth, there was substantial increase of 19 percentage points between NFHS-3 and NFHS-4.
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Unmet needs for family planning has shown a decline, pointing towards increased outreach of family planning methods. Contraceptive prevalence rate among currently married women increased by 7 percentage points from NFHS-1 (41%) to NFHS2 (48%), 8 percentage points from NFHS-2 to NFHS-3 (56%).
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Malnutrition has been coming down, thanks to supplementary nutrition and efforts at the health facilities. Mortality due to malnutrition is also coming down.
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Institutional delivery had gone up, it should have been more than 90%, which it has not reached yet.
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There was a need to increase the number of PG seats in the medical field. Currently, there are 65,000 MBBS doctors against 26,000 plus PGs. The demand and supply gap is so much that every young doctor recruited to the field spends his time preparing for PG. The effort now is to kick up the PG seats.
ÂÂ
About Accredited Social Health Activists (ASHAs), the Ministry officials said there was no proposal for providing fixed salaries to them and they will get incentives.
ÂÂ
There was a shortage of Auxiliary Nurse Midwifery (ANMs). Some states like Bihar have as high as 25% shortage. Nationally there is a 15% shortage in this regard.
The contraceptive prevalence rate decreased by 2 percentage points from NFHS-3 to NFHS-4 (54%), but pills and condom usage have shown increasing trend. ■■■■
906
Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
(Source: PTI)
AMERICAN FAMILY PHYSICIAN
Systemic Lupus Erythematosus: Primary Care Approach to Diagnosis and Management NGUYET-CAM VU LAM, MARIA V. GHETU, MARZENA L. BIENIEK
ABSTRACT Systemic lupus erythematosus is an autoimmune disease that affects many systems, including the skin, musculoskeletal, renal, neuropsychiatric, hematologic, cardiovascular, pulmonary, and reproductive systems. Family physicians should be familiar with the manifestations of lupus to aid in early diagnosis, monitoring patients with mild disease, recognizing warning signs that require referral to a rheumatologist, and helping to monitor disease activity and treatment in patients with moderate to severe disease. The American College of Rheumatology has 11 classification criteria for lupus. If a patient meets at least four criteria, lupus can be diagnosed with 95% specificity and 85% sensitivity. All patients with lupus should receive education, counseling, and support. Hydroxychloroquine is the cornerstone of treatment because it reduces disease flares and other constitutional symptoms. Low-dose glucocorticoids can be used to treat most manifestations of lupus. The use of immunosuppressive and cytotoxic agents depends on the body systems affected. Patients with mild disease that does not involve major organ systems can be monitored by their family physician. Patients with increased disease activity, complications, or adverse effects from treatment should be referred to a rheumatologist. To optimize treatment, it is important that a rheumatologist coordinate closely with the patient’s family physician to improve chronic care as well as preventive health services.
Keywords: Systemic lupus erythematosus, autoimmune disease, hydroxychloroquine, low-dose glucocorticoids, immunosuppressive and cytotoxic agents, rheumatologist
S
ystemic lupus erythematosus (SLE) is an autoimmune disease that affects the skin and musculoskeletal, renal, neuropsychiatric, hematologic, cardiovascular, pulmonary, and reproductive systems. Its course is typically recurrent, with periods of relative remission followed by flares. SLE can be fatal and significantly increases the risk of cardiovascular disease.
SLE affects about 300,000 persons in the United States.1 It is twice as prevalent in black persons as in white persons, and it is 10 times more common in females than in males.2 Over the past decade, the five-year survival rate of patients with SLE has improved to more than 95% because of more effective recognition and treatment of infectious and renal complications.3,4 Because patients with SLE are living longer, the focus
NGUYET-CAM VU LAM, MD, is associate program director at St. Luke’s Family Medicine Residency, St. Luke’s University Hospital, Bethlehem, Pa. MARIA V. GHETU, MD, is clinical faculty and staff geriatrician at St. Luke’s Family Medicine Residency, St. Luke’s University Hospital, Bethlehem, Pa. MARZENA L. BIENIEK, MD, is a rheumatologist in Whitehall, Pa., who is affiliated with St. Luke’s University Hospital. Source: Adapted from Am Fam Physician. 2016;94(4):284-294.
of care should be comprehensive, including preventive services in addition to treatment.5 ROLE OF THE PRIMARY CARE PHYSICIAN A qualitative study in the United Kingdom noted a lack of detailed knowledge about SLE by family physicians and the need for more cohesive health care.6 There is a need for well-coordinated, multidisciplinary health care teams including subspecialists and family physicians to improve chronic care and preventive health services for these patients.7 A committee of the American College of Rheumatology (ACR) recommended that the role of primary care physicians is understanding the manifestations of SLE to aid in early diagnosis, treating and monitoring patients with mild disease, recognizing warning signs to refer to a rheumatologist appropriately, and helping to monitor disease activity and treatment in patients with moderate to severe disease.8 DIAGNOSIS SLE is difficult to diagnose in primary care because many of the symptoms (e.g., fatigue, rash, joint pain) are nonspecific and overlap with those of more common
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AMERICAN FAMILY PHYSICIAN conditions. Furthermore, biomarkers are often negative or normal early in the course of the illness. The most common presenting symptoms are constitutional, such as fatigue, weight loss, and fever without a focal infection, occurring in up to 90% of patients.9 Other common presenting symptoms include arthralgia and myalgia, which occur in up to 95% of patients with SLE.10 Less common presenting symptoms include malar rash (31%), photosensitivity (23%), pleuritic chest pain (16%), new-onset Raynaud phenomenon (16%), and mouth sores (12.5%).11 Table 1 lists the differential diagnosis.12
Initial Evaluation SLE should be suspected in a patient with symptoms in at least two of the following organ systems: constitutional, musculoskeletal, skin, renal, neuropsychiatric, hematologic, cardiac, pulmonary, gastrointestinal, or reticuloendothelial.8 Specific symptoms are listed in Table 2.8,13 Discoid rash (positive likelihood ratio [LR+] = 18), malar rash (LR+ = 14), unexplained seizures or psychosis (LR+ = 13), and photosensitivity (LR+ = 11) provide the strongest evidence in favor of SLE.14
Table 1. Differential Diagnosis of Systemic Lupus Erythematosus Differential diagnosis
Distinguishing features
Diagnostic approach
Adult-onset Still disease Arthralgia, fever, lymphadenopathy, Tests for elevated ESR, leukocytosis, and anemia splenomegaly Behรงet syndrome
Aphthous ulcers, arthralgia, uveitis
Recurrent oral ulcers plus two of the following: eye lesions, genital ulcers, skin lesions
Chronic fatigue syndrome
Persistent and unexplained fatigue that Tests to rule out other diseases: complete blood count, ESR, significantly impairs daily activities CRP, complete metabolic panel, TSH, urinalysis
Endocarditis
Arterial emboli, arthralgia, fever, heart Positive echocardiography findings with vegetation on heart murmur, myalgia valve; positive blood culture
Fibromyalgia
Poorly localized pain above and below waist 11 of 18 sites (bilateral) perceived as painful. Posteriorly, the on both sides, involving neck, back, and chest sites are: occiput, trapezius, supraspinatus, gluteal, greater trochanter. Anteriorly, they are: low cervical, second rib, lateral epicondyle, knee
HIV infection
Arthralgia, fever, lymphadenopathy, malaise, Western blot assay for detection of HIV antibodies myalgia, peripheral neuropathy, rash
Inflammatory bowel disease
Diarrhea, peripheral arthritis, rectal bleeding, Colonoscopy to assess disease activity; measure CRP level, tenesmus platelets, and ESR; test for anemia
Lyme disease
Arthritis, carditis, erythema migrans, neuritis Serologic testing for Lyme disease
Mixed connective tissue Arthralgia, myalgia, puffy fingers, Raynaud Tests for elevated ESR and hypergammaglobulinemia, positive disease phenomenon, sclerodactyly anti-U1RNP antibodies Psoriatic arthritis
Psoriasis before joint disease, nail changes Inflammatory articular disease and more than three of the in fingers and toes following: psoriasis, nail changes, negative rheumatoid factor, dactylitis, radiographic evidence of new bone formation in hand or foot
Reactive arthritis
Acute nonpurulent arthritis from infection Clinical diagnosis to identify triggers; serologic findings of elsewhere in the body recent infections may be present
Rheumatoid arthritis
Morning joint stiffness lasting more than one Positive tests for rheumatoid factor and anticyclic citrullinated hour; affected joints are usually symmetric, antibodies; synovial fluid reflects inflammatory state tender, and swollen
Sarcoidosis
Cough, dyspnea, fatigue, fever, night sweats, Chest radiography, bilateral adenopathy with biopsy revealing rash, uveitis noncaseating granuloma, elevated angiotensin-converting enzyme level
Systemic sclerosis
Arthralgia, decreased joint mobility, myalgia, Tests for specific autoantibodies Raynaud phenomenon, skin induration
Thyroid disease
Dry skin, fatigue, feeling cold, weakness
Measure TSH
CRP = C-reactive protein; ESR = Erythrocyte sedimentation rate; HIV = Human immunodeficiency virus; TSH = Thyroid-stimulating hormone. Information from reference 12.
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Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
AMERICAN FAMILY PHYSICIAN Table 2. Diagnostic Criteria for Systemic Lupus Erythematosus System
ACR criteria*
SLICC criteria†
Cardiac/pulmonary
Pleuritis (pleuritic pain or rub, or pleural effusion), or pericarditis (documented by electrocardiography, rub, or pericardial effusion)
Serositis (pleurisy for more than one day, pleural effusion, or pleural rub; pericardial pain more than one day, pericardial effusion, pericardial rub, or pericarditis)
Hematologic
Hemolytic anemia, or leukopenia (< 4,000 cells per mm3), or lymphopenia (< 1,500 cells per mm3), or thrombocytopenia (< 100,000 cells per mm3)
Hemolytic anemia
Positive ANA result
Positive ANA result
Elevated anti-dsDNA, anti-Sm, or antiphospholipid antibodies
Elevated anti-dsDNA, anti-Sm, or antiphospholipid antibodies, low complement (C3, C4, CH 50), or direct Coombs test (in the absence of hemolytic anemia)
Discoid rash
Chronic cutaneous lupus
Photosensitivity
Nonscarring alopecia
Immunologic
Leukopenia (< 4,000 cells per mm3) more than once or lymphopenia (< 1,000 cells per mm3) more than once Thrombocytopenia (< 100,000 cells per mm3)
Oral ulcers or nasal ulcers
Oral ulcers or nasal ulcers
Musculoskeletal
Nonerosive arthritis involving two or more joints
Synovitis involving two or more joints, or tenderness at two or more joints and at least 30 minutes of stiffness in the morning
Neuropsychiatric
Seizure or psychosis
Seizures, psychosis, mononeuritis complex, myelitis, or peripheral or cranial neuropathy
Renal
Persistent proteinuria > 0.5 g per day or > 3+ on urine dipstick testing, or cellular casts
Urinary creatinine (or 24-hour urinary protein) > 500 mg, or red blood cell casts
Skin/mucosal
Malar rash
Acute cutaneous lupus or subacute cutaneous lupus
ACR = American College of Rheumatology; ANA = Antinuclear antibodies; Anti-dsDNA = Anti–double-stranded DNA antibodies; Anti-Sm = Anti-Smith antibodies; SLICC = Systemic Lupus International Collaborating Clinics. *At least four of 11 ACR criteria required for diagnosis. †At
least four of 13 SLICC criteria, including at least one clinical criterion and one immunologic criterion, required for diagnosis, or patient must
have had biopsy-confirmed lupus nephritis in the presence of a positive ANA or anti-dsDNA result. Information from references 8 and 13.
Once SLE is suspected, the initial evaluation should include an antinuclear antibody (ANA) test.15 This is a highly sensitive test, with positive results in about 94% of patients with SLE.15 SLE is unlikely in a patient with negative results. However, it also has low specificity, and may be positive in healthy patients. Although most patients with SLE have positive ANA test results, most patients with positive ANA results do not have SLE. If results show a 1:40 titer or higher, more specific tests should be performed, including measurement of anti–double-stranded DNA (anti-dsDNA), anti-Smith, anti-RNP, anticardiolipin, and beta-2 glycoprotein antibodies and lupus anticoagulant; elevated levels of one or more of these biomarkers increase the likelihood of SLE. Similarly, low levels of complements C3 and C4 increase the likelihood of SLE.8 Other tests that should be performed at initial evaluation include urinalysis, comprehensive metabolic panel, complete blood count, and direct
Coombs test. The erythrocyte sedimentation rate (LR+ = 5.3 if greater than 100 mm per hour) and C-reactive protein level are useful to quantify disease activity.14
Diagnostic Criteria Diagnosis of SLE begins with a high index of suspicion. The ACR has 11 diagnostic criteria for SLE8; if a patient meets at least four, SLE can be diagnosed with 95% specificity and 85% sensitivity.16,17 The criteria include malar or discoid rash; photosensitivity; oral ulcers; arthritis; serositis; abnormal ANA titers; and renal, neurologic, hematologic, or immunologic disorders.8 Figure 1 presents an algorithm for diagnosis of SLE in the primary care setting.8 In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) revised and validated the ACR criteria.13 In the SLICC system, a patient must meet at least
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AMERICAN FAMILY PHYSICIAN disease progression are older age at diagnosis, black race, and low income.23
Diagnosis of SLE Patient has symptoms from 2 or more of the following systems: constitutional, musculoskeletal, skin, renal, gastrointestinal, pulmonary, cardiac, reticuloendothelial, hematologic, neuropsychiatric (Table 2)
Suspect SLE
At least 4 ACR criteria present (Table 2)
Diagnose SLE
Check ANA
Musculoskeletal System Negative: very low probability of SLE
Positive: complete blood count with differential, urinalysis, anti-dsDNA, antiSm, anticardiolipin antibodies
No organ involvement or typical laboratory finding: SLE unlikely
High titer to antidsDNA or anti-Sm specific for SLE
At least 4 ACR criteria present (Table 2)
Diagnose SLE
Figure 1. Algorithm for diagnosis of SLE in the primary care setting. ACR = American College of Rheumatology; ANA = Antinuclear antibodies; Anti-dsDNA = Antiâ&#x20AC;&#x201C;double-stranded DNA antibodies; Anti-Sm = Anti-Smith antibodies; SLE = Systemic lupus erythematosus. Information from reference 8.
four criteria, including at least one abnormal clinical criterion and one abnormal immunologic criterion, or the patient must have biopsy-confirmed lupus nephritis and elevated ANA or anti-dsDNA levels.13 The SLICC criteria, which have not been endorsed by the ACR, have greater sensitivity (97%) but lower specificity (84%) compared with the ACR criteria.13 Because the SLICC criteria have not been tested for the purpose of diagnosis, the ACR criteria continue to be the diagnostic standard.13 Table 2 compares the ACR and SLICC criteria.8,13 MANIFESTATIONS AND MANAGEMENT There are many manifestations of SLE, and multiple organ systems may be affected (Table 3).8-11,18-21 Fatigue and arthralgia are present in almost all patients with SLE, whereas renal involvement manifests in about 50% of patients.22 The most important predictors of
910
The management of SLE depends on the system involved. All patients with SLE should receive education, counseling, and support. Hydroxychloroquine is the cornerstone of treatment because it reduces disease flares and other constitutional symptoms.24,25 Low-dose glucocorticoids can be used to treat most manifestations. Figure 2 is an algorithm for managing SLE.8,24-31
Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
Musculoskeletal involvement is present in 95% of patients with SLE and manifests as arthralgias, myalgias, or nonerosive inflammatory arthritis.10 The arthritis is usually symmetric and polyarticular, with a predilection for smaller joints. Fibromyalgia is also more common among patients with SLE. Antimalarials and low-dose glucocorticoids are firstline agents used to treat arthritis pain associated with SLE.26,32 Hydroxychloroquine is favored over chloroquine because it is less toxic. Nonsteroidal antiinflammatory drugs can be used as adjunctive therapy to treat joint pain.
Integumentary System About 70% to 80% of patients with SLE develop skin lesions during the course of disease.18 Malar rash occurs in about 30% of patients.18 Acute and subacute cutaneous lupus rash (Figure 3) can present anywhere on the body, but most commonly occurs on sun-exposed areas. Patients with SLE should use sunscreens with sun protective factors of 15 or higher.32 Mucous membrane involvement, hair loss, and Raynaud phenomenon are also common (Figure 4).
Urinary System The visceral organ most commonly involved in SLE is the kidney.18 Although almost all patients with SLE have immunoglobulin deposits in the glomeruli, only 50% develop clinical renal disease.22 Screening for nephritis with urinalysis and serum creatinine measurement should be done at three- to six-month intervals.8,33 When a patient with SLE has clinical or laboratory features that suggest nephritis, 24-hour urine testing for protein or a spot urine protein:creatinine ratio should be obtained.27 Referral for renal biopsy should be considered in patients with proteinuria of at least 1 g in 24 hours, or at least 0.5 g in 24 hours with hematuria or cellular casts. A combination of glucocorticoid plus immunosuppressant is more effective than glucocorticoids alone in preserving renal
AMERICAN FAMILY PHYSICIAN Table 3. Common Symptoms of Systemic Lupus Erythematosus Symptoms
Lifetime prevalence Treatment
Prevention and screening
Arthralgia
95%
Glucocorticoids, hydroxychloroquine, methotrexate, nonsteroidal anti-inflammatory drugs
â&#x20AC;&#x201D;
Fatigue
90%
Aerobic exercise (possibly)
Minimize exertion, get adequate sleep
Cutaneous lupus
70% to 80%
Topical glucocorticoids, chloroquine, hydroxychloroquine
Use sunscreen and wear protective clothing
Hematologic symptoms
Most patients
Azathioprine, mycophenolate, rituximab; transfusion for anemia (possibly)
Monitor and treat infection, especially in patients with leukopenia
Renal symptoms
50%
Azathioprine, cyclophosphamide, glucocorticoids, mycophenolate
Urinalysis and serum creatinine test every three months
Cardiovascular symptoms
28% to 40%
Antihypertensive agents, cholesterol-lowering agents
Treat risk factors aggressively
Neuropsychiatric symptoms
12% to 23%
Glucocorticoids; anticonvulsants, antidepressants, Control aggravating factors and and antipsychotics for depression and headaches; symptoms antithrombotic agents and cyclophosphamide for thrombotic symptoms and cerebritis
Pulmonary symptoms
16%
Depends on type of involvement and â&#x20AC;&#x201D; severity; azathioprine, cyclophosphamide, glucocorticoids, mycophenolate, plasmapheresis
Information from references 8 through 11, and 18 through 21.
Management of SLE Provide patient education, counseling, and support
Mild SLE (no major organ involvement) Constitutional symptoms: hydroxychloroquine, with or without low-dose systemic glucocorticoids or methotrexate; then azathioprine, methotrexate, or mycophenolate; then rituximab or belimumab Discoid lupus: sunscreen use; topical corticosteroid/ tacrolimus; topical acitretin, with or without hydroxychloroquine, with or without systemic glucocorticoids; then add azathioprine or switch to mycophenolate or methotrexate Polyarthritis: hydroxychloroquine, with or without lowdose systemic glucocorticoids; then add methotrexate or rituximab; NSAIDs as adjunctive therapy Uncomplicated digital or cutaneous vasculitis: systemic glucocorticoids, with or without hydroxychloroquine, with or without methotrexate; then add azathioprine or mycophenolate; then switch to IV cyclophosphamide
Moderate to severe SLE Alveolitis: systemic glucocorticoids plus mycophenolate or IV cyclophosphamide; then add rituximab or IV immune globulin; maintain with azathioprine or mycophenolate Antiphospholipid syndrome: anticoagulation, with or without hydroxychloroquine, then add direct thrombin inhibitor Lupus nephritis: systemic glucocorticoids plus mycophenolate; then IV cyclophosphamide; then add rituximab or switch to azathioprine; angiotensin-converting enzyme inhibitor and hydroxychloroquine as adjunctive therapy Mononeuritis/central nervous system lupus: systemic glucocorticoids, with or without IV cyclophosphamide, then add rituximab, IV immune globulin, or plasmapheresis Myocarditis: systemic glucocorticoids plus IV cyclophosphamide, with or without hydroxychloroquine; then rituximab, belimumab, or IV immune globulin Pericarditis: NSAIDs; then systemic glucocorticoids plus hydroxychloroquine; then add mycophenolate, azathioprine, or methotrexate; then add belimumab or rituximab Pulmonary artery hypertension: systemic glucocorticoids plus IV cyclophosphamide, or mycophenolate plus endothelin receptor antagonist; then add rituximab and phosphodiesterase-5 inhibitor; then add prostaglandin analogue; maintain with prostaglandin analogue Thrombocytopenia: systemic glucocorticoids, with or without hydroxychloroquine; then add azathioprine or mycophenolate; then add rituximab or IV cyclophosphamide or IV immune globulin
Figure 2. Algorithm for management of SLE. IV = Intravenous; NSAIDs = Nonsteroidal anti-inflammatory drugs; SLE = Systemic lupus erythematosus. Information from references 8, and 24 through 31.
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Figure 4. Raynaud phenomenon.
Nervous System A
The nervous system is affected in about 12% to 23% of patients with SLE.11 Neuropsychiatric manifestations of SLE include headaches, seizures, cerebrovascular disease, psychosis, cranial neuropathy, and movement disorder.35 Magnetic resonance imaging of the brain should be considered in patients with headache or seizure because white matter lesions are common in neuropsychiatric SLE.35 Treatment includes glucocorticoids and cyclophosphamide.26,30,31 Ocular manifestations are common in SLE. Keratoconjunctivitis sicca occurs in 25% of patients.18 Anterior uveitis, keratitis, and episcleritis are less common.18,36 Patients with SLE who have ocular pain and visual impairment require urgent evaluation by an ophthalmologist.36 Although up to 90% of patients with SLE have fatigue,9 there is currently no proven pharmacologic treatment for this symptom.37,38 Aerobic exercise may help, but studies thus far have shown mixed results.21,39-41
Hematologic System
B
Figure 3. Subacute cutaneous lupus rash on the (A) neck and (B) back.
function in patients with SLE.32 Standard treatment includes mycophenolate or cyclophosphamide plus a glucocorticoid.27-29,34
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Hematologic abnormalities associated with SLE can include leukopenia, lymphopenia, hemolytic anemia, and thrombocytopenia.18 Patients with severe leukopenia are at increased risk of infection, and patients with anemia may need supportive care and transfusion.
Cardiovascular System Premature-onset cardiovascular disease is much more common in women with SLE. Compared with an
AMERICAN FAMILY PHYSICIAN Table 4. Medications Used to Treat SLE Medications
Indications
Dosage
Monitoring and precautions
Cost*
Azathioprine
Lupus nephritis, severe SLE
1.5 to 2.5 mg per kg per day
CBC and complete metabolic panel at least every three months to monitor for myelosuppression, hepatotoxicity, and lymphoproliferative disorders
$21 ($410) for 60 50-mg tablets
Belimumab
SLE
10 mg per kg IV per day
Monitor for serious infection and malignancies
NA ($1,630) per 400-mg vial
Cyclophosphamide
Lupus nephritis, severe SLE
1 to 3 mg per kg per day
$365 (NA) CBC and complete metabolic panel at least every three months to monitor for 30 50-mg capsules for myelosuppression, malignancy, immunosuppression, and hemorrhagic cystitis
Glucocorticoids
Low dose for treating SLE without major organ damage; higher doses for cerebritis, lupus nephritis, refractory conditions, and thrombocytopenia
Low dose: â&#x2030;¤ 10 mg prednisone per day
Glucose levels every three to six months, and total cholesterol level and bone density testing annually; use with caution in patients with hypertension, hyperglycemia, hyperlipidemia, osteoporosis, or infection
$5 (NA) for 30 10-mg tablets; $9 (NA) for 60 20-mg tablets
Hydroxychloroquine
Long-term protective effect on SLE-related organ damage
200 to 400 mg per day
Ophthalmologic examination every six to 12 months to monitor for macular damage
$41 ($197) for 30 200-mg tablets
Methotrexate
Arthritis, cutaneous lupus, serositis, severe SLE
7.5 to 25 mg per week
$15 (NA) for 12 CBC and complete metabolic panel at least every three months to monitor 2.5-mg tablets for myelosuppression, hepatic fibrosis, and pulmonary infiltrates and fibrosis
Mycophenolate
Lupus nephritis, refractory SLE
2 to 3 g per day
CBC and complete metabolic panel at least every three months to monitor for myelosuppression and infection
$49 ($1,880) for 240 250-mg capsules
Nonsteroidal antiinflammatory drugs
Lupus joint pain
Depends on preparation
CBC and renal testing annually; use with caution in patients with gastrointestinal bleeding, liver or kidney disease, or hypertension
Depends on preparation
Rituximab
Refractory severe SLE
Two 1-g doses IV, two weeks apart
CBC every two to four months; use with caution in patients with history of infusion reaction
NA ($12,000 to $15,600) per 1-g infusion
Higher dose: 40 to 60 mg prednisone per day
CBC = Complete blood count; IV = Intravenously; NA = Not available; SLE = Systemic lupus erythematosus. *Estimated retail cost based on information obtained at http://www.goodrx.com (accessed March 9, 2016). Cost for generic listed first; brand name in parentheses, when available. Information from references 8, 24 through 27, 55, and 56.
age-matched group in the Framingham cohort, women 35 to 44 years of age who had SLE had a greatly increased risk of myocardial infarction (rate ratio = 52; 95% confidence interval, 22 to 98).42 The increased risk of accelerated atherosclerosis suggests that there are other SLE-related factors, such as renal disease, cytokines, inflammatory mediators, antiphospholipid antibodies, oxidized low-density lipoprotein, and adverse effects of treatment, that cause accelerated cardiovascular disease.19,43 SLE is an independent risk factor for the development of atherosclerosis,
and is identified as such by the American Heart Association.19,44 It is important to counsel patients to reduce traditional cardiovascular risk factors such as smoking and obesity, and to have routine screenings for diabetes mellitus, hypertension, and dyslipidemia. The recent Joint National Committee-8 guideline for hypertension and the Adult Treatment Panel IV guideline for hyperlipidemia do not make separate recommendations for patients with SLE.45,46 Family physicians should be aware of the increased risk of cardiovascular events in patients with SLE, and should
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AMERICAN FAMILY PHYSICIAN Table 5. Follow-Up and Monitoring for Selected Complications of SLE Complication
Frequency of follow-up
Prevention, monitoring, and management
Every three to six months
History for features of SLE, physical examination, CBC, creatinine level, urinalysis, anti-dsDNA, complements; keep all health maintenance screenings and vaccinations up to date
Cardiovascular abnormalities49,57
Every visit
Optimal lupus control with minimal glucocorticoid use; judicious use of antimalarial and other immunosuppressive agents; smoking cessation, adequate exercise, low-cholesterol diet, lipid-lowering therapy, blood pressure control, screening for diabetes mellitus
Infection8,57
Every visit
Assure that vaccinations are up to date; judicious use of immunosuppressive agents
Malignancy57,58
Yearly
Assure that routine cancer screenings are up to date; screen for high-risk cancers (e.g., hematologic, non-Hodgkin lymphoma, lung, cervical)
Moderate to severe SLE with complications8
Frequent
Monitor in conjunction with rheumatologist and lupus care subspecialists
New-onset nephritis8,27
Monthly or more frequently
Urinalysis, 24-hour urinary protein level, creatinine clearance, CBC, levels of cholesterol, calcium, phosphorus, alkaline phosphatase, sodium, and potassium; useful to assess complements and anti-dsDNA
Receiving high-dose glucocorticoids8,57
Every visit
Consider steroid-sparing agent; use lowest dose possible to achieve optimum disease control; glucose testing every three to six months; cholesterol testing annually; DEXA every one to two years; maintain high index of suspicion for avascular necrosis if patient has acute joint pain
Receiving hydroxychloroquine8,36
Every six to 12 months
Ophthalmologic examination to screen for retinal toxicity; keep dosage to no more than 6.5 mg per kg per day
Receiving immunosuppressive or cytotoxic agents8
Every one to two weeks initially, then every one to three months
CBC and liver function testing at baseline, then every one to two weeks at initiation of therapy, then one to three months; judicious use of immunosuppressive medications, vigilance for signs and symptoms of infection; routine cancer screening; avoidance of live vaccines; if live vaccines are needed, administer one month after therapy completion
Receiving low-dose glucocorticoids8
Every visit to every one to two years
Keep dosage as low as possible; healthy diet with adequate physical activity; smoking cessation; annual cholesterol and glucose testing; consider DEXA every one to two years for patients receiving long-term therapy
Renal abnormalities8,27,54
Every three months or Regular screening for proteinuria and hematuria; regular serum creatinine more frequently, depending level; for patients with chronic kidney disease, vaccination with 13-valent on disease state pneumococcal conjugate vaccine or 23-valent pneumococcal polysaccharide vaccine, as indicated
Severe hemolytic anemia8
Weekly
Hematocrit and reticulocyte count; may require transfusion
Severe thrombocytopenia (< 50,000 cells per mm3)8
Weekly
Platelet count weekly initially; may require transfusion
None; mild, stable
SLE8
Anti-dsDNA = Antiâ&#x20AC;&#x201C;double-stranded DNA antibodies; CBC = Complete blood count; DEXA = Dual energy x-ray absorptiometry; SLE = Systemic lupus erythematosus. Information from references 8, 27, 36, 49, 54, 57, and 58.
take steps to optimize risk in accordance with national guidelines. Although guidelines do not address this need, patients with SLE may benefit from treatment with a statin because of their increased 10-year risk of a cardiovascular event.47,48 Blood pressure should also be treated to a goal similar to that for patients with comorbid conditions such as diabetes (less than 140/90 mm Hg).44,45,47,49
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Respiratory System Lung involvement in SLE can vary from minor pleuritic pain in serositis to life-threatening complications such as alveolar hemorrhage.50 Pleuritis occurs in 17% to 60% of patients with SLE.50,51 Treatment is based on the type and severity of lung involvement, and may include glucocorticoids, immunosuppressive agents, and plasmaphersis.32,52
AMERICAN FAMILY PHYSICIAN Reproductive System
REFERENCES
Pregnant women with SLE have an increased risk of spontaneous abortions, stillbirths, and fetal growth restriction.26 Pregnancy may also increase disease activity and precipitate disease flares.20 Although women with SLE can use most contraceptive methods, those with antiphospholipid syndrome should not use estrogen-containing contraceptives because of an increased risk of thrombosis.53 Women with recurrent pregnancy loss should be screened for antiphospholipid syndrome.
1. Helmick CG, Felson DT, Lawrence RC, et al.; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008;58(1):15-25.
MONITORING AND COMPLICATIONS All patients with SLE should receive ongoing education, counseling, and support. Those with mild SLE that does not involve major organ systems can be monitored by primary care physicians.8 Patients with increased disease activity, complications, or adverse effects from treatment should be referred to a rheumatologist.8 Family physicians can monitor disease activity and therapy in patients with moderate to severe SLE.8 Measurement of anti-dsDNA antibodies, complements, and creatinine; a complete blood count; and urinalysis should be performed every three to six months to monitor disease activity.8 Annual eye examinations are required for patients receiving hydroxychloroquine.36 Screening for dyslipidemia, diabetes, and osteoporosis should be performed regularly in patients receiving glucocorticoids. For patients with chronic kidney disease who are receiving long-term immunosuppressive therapy, immunization with 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine should be considered.54 Live vaccines should not be given to patients with SLE when they are receiving immunosuppressive therapy, and they should be delayed for at least one month after completion of the therapy. Table 4 includes details for monitoring medications used in SLE treatment.8,24-27,55,56 Patients with SLE have a higher mortality rate due to circulatory disease, infections, renal disease, nonHodgkin lymphoma, and lung cancer.57 Damage related to SLE is most common in the musculoskeletal (15%), neuropsychiatric (11%), cardiovascular (9%), and hematologic (3%) systems.57 Osteoporosis is a potentially preventable complication of SLE.57 The incidence of non-Hodgkin lymphoma is increased three- to fourfold compared with the general population.57 Table 5 describes recommendations for monitoring manifestations and complications related to SLE.8,27,36,49,54,57,58
2. Somers EC, Marder W, Cagnoli P, et al. Populationbased incidence and prevalence of systemic lupus erythematosus: the Michigan Lupus Epidemiology and Surveillance program. Arthritis Rheumatol. 2014;66(2):369-378. 3. Bernatsky S, Boivin JF, Joseph L, et al. Mortality in systemic lupus erythematosus. Arthritis Rheum. 2006;54(8): 2550-2557. 4. Jakes RW, Bae SC, Louthrenoo W, Mok CC, Navarra SV, Kwon N. Systematic review of the epidemiology of systemic lupus erythematosus in the Asia-Pacific region: prevalence, incidence, clinical features, and mortality. Arthritis Care Res (Hoboken). 2012;64(2):159-168. 5. Burgos PI, Alarcón GS. Preventive health services for systemic lupus erythematosus patients: whose job is it? Arthritis Res Ther. 2010;12(3):124. 6. Hale ED, Treharne GJ, Lyons AC, et al. “Joining the dots” for patients with systemic lupus erythematosus: personal perspectives of health care from a qualitative study. Ann Rheum Dis. 2006;65(5):585-589. 7. Yazdany J, Tonner C, Trupin L, et al. Provision of preventive health care in systemic lupus erythematosus: data from a large observational cohort study. Arthritis Res Ther. 2010;12(3):R84. 8. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Guidelines for referral and management of systemic lupus erythematosus in adults. Arthritis Rheum. 1999;42(9): 1785-1796. 9. Zonana-Nacach A, Roseman JM, McGwin G Jr, et al. Systemic lupus erythematosus in three ethnic groups. VI: Factors associated with fatigue within 5 years of criteria diagnosis. LUMINA Study Group. LUpus in MInority populations: NAture vs Nurture. Lupus. 2000;9(2): 101-109. 10. Zoma A. Musculoskeletal involvement on systemic lupus erythematosus. Lupus. 2004;13(11):851-853. 11. Cervera R, Khamashta MA, Font J, et al.; European Working Party on Systemic Lupus Erythematosus. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore). 2003;82(5):299-308. 12. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill; 2012. 13. Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic
Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
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AMERICAN FAMILY PHYSICIAN lupus erythematosus. Arthritis Rheum. 2012;64(8): 2677-2686.
treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken). 2012;64(6):797-808.
14. Narain S, Richards HB, Satoh M, et al. Diagnostic accuracy for lupus and other systemic autoimmune diseases in the community setting. Arch Intern Med. 2004;164(22): 2435-2441.
28. Henderson L, Masson P, Craig JC, et al. Treatment for lupus nephritis. Cochrane Database Syst Rev. 2012;(12):CD002922.
15. Hietarinta M, Lassila O. Clinical significance of antinuclear antibodies in systemic rheumatic diseases. Ann Med. 1996;28(4):283-291. 16. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25(11):1271-1277. 17. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725. 18. Cojocaru M, Cojocaru IM, Silosi I, Vrabie CD. Manifestations of systemic lupus erythematosus. Maedica (Buchar). 2011;6(4):330-336. 19. Sinicato NA, da Silva Cardoso PA, Appenzeller S. Risk factors in cardiovascular disease in systemic lupus erythematosus. Curr Cardiol Rev. 2013;9(1):15-19. 20. Bertsias G, Fanouriakis A, Boumpas DT. Treatment of systemic lupus erythematosus. In: Firestein GS, Budd RC, Gabriel SE, McInnes IB, O’Dell JR, eds. Kelly’s Textbook of Rheumatology. 9th ed. Philadelphia, Pa.: Saunders Elsevier; 2013:1304-1330. 21. Del Pino-Sedeño T, Trujillo-Martín MM, Ruiz-Irastorza G, Cuellar-Pompa L, de Pascual-Medina AM, SerranoAguilar P; Spanish Systemic Lupus Erythematosus CPG Development Group. Effectiveness of nonpharmacologic interventions for decreasing fatigue in adults with systemic lupus erythematosus: a systemic review. Arthritis Care Res (Hoboken). 2016; 68(1):141-148. 22. Drakoulogkona O, Barbulescu AL, Rica I, Musetescu AE, Ciurea PL. The outcome of patients with lupus nephritis and the impact of cardiovascular risk factors. Curr Health Sci J. 2011;37(2):70-74. 23. Petri M, Purvey S, Fang H, Magder LS. Predictors of organ damage in systemic lupus erythematosus: the Hopkins Lupus Cohort. Arthritis Rheum. 2012;64(12):4021-4028. 24. Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis. 2010;69(1):20-28. 25. Wallace DJ, Gudsoorkar VS, Weisman MH, Venuturupalli SR. New insights into mechanisms of therapeutic effects of antimalarial agents in SLE. Nat Rev Rheumatol. 2012;8(9):522-533. 26. Muangchan C, van Vollenhoven RF, Bernatsky SR, et al. Treatment algorithms in systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2015; 67(9):1237-1245. 27. Hahn BH, McMahon MA, Wilkinson A, et al. American College of Rheumatology guidelines for screening,
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29. Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis. 2012;71(11):1771-1782. 30. Fernandes Moça Trevisani V, Castro AA, Ferreira Neves Neto J, Atallah AN. Cyclophosphamide versus methylprednisolone for treating neuropsychiatric involvement in systemic lupus erythematosus. Cochrane Database Syst Rev. 2013;(2):CD002265. 31. Bertsias GK, Ioannidis JP, Aringer M, et al. EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs. Ann Rheum Dis. 2010;69(12):2074-2082. 32. Madhok R, Wu O. Systemic lupus erythematosus. BMJ Clin Evid. 2009;2009:1123. 33. Dall’era M, Wofsy D. Clinical features of systemic lupus erythematosus. In: Firestein GS, Budd RC, Gabriel SE, McInnes IB, O’Dell JR, eds. Kelly’s Textbook of Rheumatology. 9th ed. Philadelphia, Pa.: Saunders Elsevier; 2013:1283-1303. 34. Appel GB, Contreras G, Dooley MA, et al.; Aspreva Lupus Management Study Group. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009;20(5):1103-1112. 35. Muscal E, Brey RL. Neurologic manifestations of systemic lupus erythematosus in children and adults. Neurol Clin. 2010;28(1):61-73. 36. Sivaraj RR, Durrani OM, Denniston AK, Murray PI, Gordon C. Ocular manifestations of systemic lupus erythematosus. Rheumatology (Oxford). 2007;46(12): 1757-1762. 37. Merrill JT, Burgos-Vargas R, Westhovens R, et al. The efficacy and safety of abatacept in patients with nonlife-threatening manifestations of systemic lupus erythematosus: results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebocontrolled trial. Arthritis Rheum. 2010;62(10):3077-3087. 38. Hartkamp A, Geenen R, Godaert GL, Bijl M, Bijlsma JW, Derksen RH. Effects of dehydroepiandrosterone on fatigue and well-being in women with quiescent systemic lupus erythematosus: a randomised controlled trial. Ann Rheum Dis. 2010;69(6):1144-1147. 39. Neill J, Belan I, Ried K. Effectiveness of nonpharmacological interventions for fatigue in adults with multiple sclerosis, rheumatoid arthritis, or systemic lupus erythematosus: a systematic review [published correction
AMERICAN FAMILY PHYSICIAN appears in J Adv Nurs. 2007;57(2):225]. J Adv Nurs. 2006; 56(6):617-635. 40. Tench CM, McCarthy J, McCurdie I, White PD, D’Cruz DP. Fatigue in systemic lupus erythematosus: a randomized controlled trial of exercise. Rheumatology (Oxford). 2003;42(9):1050-1054. 41. Balsamo S, Santos-Neto LD. Fatigue in systemic lupus erythematosus: an association with reduced physical fitness. Autoimmun Rev. 2011;10(9):514-518. 42. Manzi S, Meilahn EN, Rairie JE, et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol. 1997;145(5):408-415. 43. Zuily S, Regnault V, Selton-Suty C, et al. Increased risk for heart valve disease associated with antiphospholipid antibodies in patients with systemic lupus erythematosus: meta-analysis of echocardiographic studies. Circulation. 2011;124(2):215-224. 44. Mosca L, Benjamin EJ, Berra K, et al. Effectivenessbased guidelines for the prevention of cardiovascular disease in women—2011 update: a guideline from the American Heart Association [published corrections appear in Circulation. 2011;123(22):e624 and Circulation. 2011;124(16):e427]. Circulation. 2011;123(11):1243-1262. 45. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8) [published correction appears in JAMA. 2014;311(17):1809]. JAMA. 2014;311(5):507-520. 46. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/ AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [published correction appears in J Am Coll Cardiol. 2014;63(25 pt B):3024-3025]. J Am Coll Cardiol. 2014;63(25 pt B):2889-2934.
48. Bruce IN, Urowitz MB, Gladman DD, Hallet DC. The natural history of hypercholesterolaemia in systemic lupus erythematosus. J Rheumatol. 1999;26(10):2137-2143. 49. McMahon M, Hahn BH, Skaggs BJ. Systemic lupus erythematosus and cardiovascular disease: prediction and potential for therapeutic intervention. Expert Rev Clin Immunol. 2011;7(2):227-241. 50. Keane MP, Lynch JP III. Pleuropulmonary manifestations of systemic lupus erythematosus. Thorax. 2000;55(2): 159-166. 51. Todd NW, Wise RA. Respiratory complications in the collagen vascular diseases. Clin Pulm Med. 1996;3(2): 101-112. 52. Carmier D, Marchand-Adam S, Diot P, Diot E. Respiratory involvement in systemic lupus erythematosus. Rev Mal Respir. 2010;27(8):e66-e78. 53. Culwell KR, Curtis KM, del Carmen Cravioto M. Safety of contraceptive method use among women with systemic lupus erythematosus: a systematic review. Obstet Gynecol. 2009;114(2 pt 1):341-353. 54. Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2012;61(40): 816-819. 55. Goldberg A, Katzap E. Belimumab for the treatment of systemic lupus erythematosus. Int J Clin Rheum. 2010;5(4):407-413. 56. U.S. Food and Drug Administration. FDA news release. FDA approves Benlysta to treat lupus. http://www.fda. gov/NewsEvents/Newsroom/PressAnnouncements/ ucm246489.htm. Accessed April 1, 2015. 57. Gordon C. Long-term complications of systemic lupus erythematosus. Rheumatology (Oxford). 2002;41(10): 1095-1100. 58. Bernatsky S, Boivin JF, Joseph L, et al. An international cohort study of cancer in systemic lupus erythematosus. Arthritis Rheum. 2005; 52(5):1481-1490.
47. Esdaile JM, Abrahamowicz M, Grodzicky T, et al. Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic 59. Gill JM, Quisel AM, Rocca PV, Walters DT. Diagnosis lupus erythematosus. Arthritis Rheum. 2001;44(10): of systemic lupus erythematosis. Am Fam Physician. 2003;68(11):2179-2187. 2331-2337. ■■■■
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Practice Guidelines are advised to use the CRAFFT (car, relax, alone, forget, friends, trouble) screening questionnaire.
AAP UPDATES RECOMMENDATIONS FOR ROUTINE PREVENTIVE PEDIATRIC HEALTH CARE The American Academy of Pediatrics (AAP) has updated recommendations for preventive pediatric health care services, including evidence-based screenings and assessments that should be addressed at well-child visits. The recommendations are organized by age: infancy, early childhood, middle childhood, and adolescence. The most recent changes to the schedule were approved by the AAP Committee on Practice and Ambulatory Medicine, Bright Futures Periodicity Schedule Workgroup. A complete schedule is available at http://www.aap.org/periodicityschedule.
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Depression. Screening for depression is recommended annually for children and adolescents 11 through 21 years of age. Suicide is a leading cause of death in this age group.
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Dyslipidemia Screening. Because of concerns about the growing epidemic of obesity in this population, screening for elevated blood cholesterol levels is now recommended in children nine to 11 years of age.
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Hematocrit or Hemoglobin. In addition to the universal screening recommended at 12 months of age to detect iron deficiency anemia, physicians should conduct a risk assessment to determine if hematocrit or hemoglobin screening is needed in children at 15 and 30 months of age.
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Sexually Transmitted Infection/Human Immunodeficiency Virus (HIV) Screening. Screening for HIV infection is recommended in adolescents 16 to 18 years of age. Statistics show that one in four new HIV infections occurs in persons 13 to 24 years of age, and approximately 60% of younger persons with HIV infection are unaware that they are infected.
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Cervical Dysplasia. Screening for cervical dysplasia is no longer recommended annually from 11 through 21 years of age but instead should begin at 21 years of age.
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Critical Congenital Heart Disease. Screening for critical congenital heart disease with pulse oximetry is now recommended. This should be performed in the hospital before newborn discharge.
These updates address a variety of topics. Changes include the following: ÂÂ
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Vision Screening. In addition to routine visual acuity screening at four and five years of age and in cooperative three-year-olds, instrumentbased screening can be offered to assess risk at other ages (i.e., at 12 and 24 months of age, and at well visits from three to five years of age). The recommendation for vision screening is now a risk-based assessment instead of routine screening beginning at 18 years of age. Evidence shows that fewer new vision problems develop in young adults at low risk. Oral Health. Fluoride varnish application should begin at six months of age and continue through five years of age. This recommendation was added to address dental caries, which is the most common chronic disease in young children. Alcohol and Drug Use Assessment. To screen adolescents for drug and alcohol use, physicians
Source: Adapted from Am Fam Physician. 2016;94(4):324.
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AMERICAN FAMILY PHYSICIAN
Photo Quiz FOOT DEFORMITY AT TIME OF DELIVERY IN A PREMATURE INFANT A female infant was born at 35 weeks’ gestation by spontaneous vaginal delivery, following induction of labor for premature rupture of membranes. The pregnancy was otherwise uncomplicated. The newborn required three minutes of positive pressure ventilation, but transitioned well on room air over the next hour and did not require further treatment in the neonatal intensive care unit. At the time of birth, physical examination showed that the newborn’s right foot was grossly externally rotated (Figure 1). There was no crepitus on palpation of the foot, ankle, or leg, and a bilateral hip examination was unremarkable. The newborn spontaneously dorsiflexed and plantar-flexed the foot. The foot could be easily moved into normal alignment with gentle traction but returned when released. Her legs were equal in length. There were no dysmorphic features, no evidence of sacral dimple, and no signs of spina bifida. The remainder of the physical examination, including musculoskeletal and neurologic findings, was normal.
Figure 1.
B. Paralytic calcaneus foot deformity. C. Posteromedial bowing of the tibia. D. Talipes calcaneovalgus. E. Talipes equinovarus.
Question Based on the patient’s history and physical examination findings, which one of the following is the most likely diagnosis? A. Congenital vertical talus.
SEE THE FOLLOWING PAGE FOR DISCUSSION
Source: Adapted from Am Fam Physician. 2016;94(4):314-316.
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AMERICAN FAMILY PHYSICIAN Discussion
Summary Table
The answer is D: talipes calcaneovalgus. Talipes calcaneovalgus, also known as positional calcaneovalgus foot deformity, is relatively common and associated with intrauterine positioning. Although studies are limited, one study estimated an incidence of seven or eight per 1,000 births.1 On physical examination, the affected foot will be in a slightly abducted and valgus position. There may be tibial torsion. The infant is able to spontaneously move the affected limb, the foot is easily reduced into a normal or near-normal position, and the legs are of equal length.
Condition
Characteristics
Congenital vertical talus
Foot rigidly fixed in valgus rotation because of structural deformity (dorsal dislocation at the medial column of the foot at the talonavicular joint or dislocation of the entire midfoot at the hindfoot); cannot be passively reduced; associated with genetic syndromes, such as trisomies 13 and 18
Paralytic calcaneus foot deformity
Valgus rotation and dorsiflexion; the infant cannot spontaneously move the foot, but it can be reduced by the examiner; may occur with meningocele, trisomies, and polio
Posteromedial bowing of the tibia
Tibial deformity causing leg-length discrepancy; the foot can be abducted with valgus rotation
Talipes calcaneovalgus
Foot abducted, valgus rotation, occasional tibial torsion; can be easily reduced by the examiner, and the infant is able to spontaneously move it; equal leg length
Talipes equinovarus
Foot is excessively plantar-flexed, and the forefoot is medially rotated in the varus position; does not resolve spontaneously
Typically, the abnormality resolves spontaneously over a few months; however, stretching or splinting is sometimes needed for full resolution.2 Because talipes calcaneovalgus is associated with congenital hip dislocation, particularly from breech delivery, hip instability should be ruled out.3 Many other conditions in the differential diagnosis do not resolve spontaneously and should be ruled out. Congenital vertical talus, or rocker-bottom foot, has a similar presentation. However, unlike talipes calcaneovalgus, the foot is rigidly fixed in valgus rotation because of structural deformity. The deformity includes a dorsal dislocation of the medial column of the foot at the talonavicular joint or dislocation of the entire midfoot on the hindfoot.2 It cannot be passively reduced by the examiner and will not resolve spontaneously, requiring prompt orthopedic referral for surgery or serial casting. This condition is often associated with neuromuscular disease or genetic syndromes, such as trisomies 13 and 18.3 A paralytic calcaneus foot deformity presents as valgus rotation and dorsiflexion. There is partial to full paralysis of plantar flexion, and the patient is unable to move it back into alignment spontaneously; it can be reduced by the examiner. It may occur with a number of disorders, including meningocele,4 trisomies, and polio.2,3 Posteromedial bowing of the tibia is a more proximal deformity that can cause the foot to be abducted with valgus rotation. It is most commonly associated with leg-length discrepancy. The length discrepancy and the foot deformity often improve during skeletal growth, but nearly all patients need some treatment ranging from orthotics (e.g., shoe lift) to surgical management, including epiphysiodesis or osteotomy.2 Talipes equinovarus, commonly known as club foot, is a relatively common diagnosis occurring in
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approximately one per 1,000 births, and affects boys twice as often as girls.5,6 The foot is excessively plantarflexed, and the forefoot is medially rotated in the varus position so that the sole of the foot points medially and sometimes superiorly. This deformity does not resolve spontaneously. Treatment includes stretching and splinting, with minor surgical procedures to more extensive reconstructive surgery.6 REFERENCES 1. Widhe T, Aaro S, Elmstedt E. Foot deformities in the newbornâ&#x20AC;&#x201D;incidence and prognosis. Acta Orthop Scand. 1988;59(2):176-179. 2. Sarwark JF. Essentials of Musculoskeletal Care. 4th ed. Rosemount, Ill.: American Academy of Orthopaedic Surgeons; 2010:1042-1044. 3. Graham JM, Sanchez-Lara PA. Smithâ&#x20AC;&#x2122;s Recognizable Patterns of Human Deformation. 4th ed. Philadelphia, Pa.: Elsevier; 2016:30-33. 4. Westcott MA, Dynes MC, Remer EM, Donaldson JS, Dias LS. Congenital and acquired orthopedic abnormalities in patients with myelomeningocele. Radiographics. 1998;12(6):1155-1173. 5. Keret D, Ezra E, Lokiec F, Hayek S, Segev E, Wientroub S. Efficacy of prenatal ultrasonography in confirmed club foot. J Bone Joint Surg Br. 2002;84(7):1015-1019. 6. Bridgens J, Kiely N. Current management of clubfoot (congenital talipes equinovarus). BMJ. 2010;340:c355.
2017
COMMUNITY MEDICINE
Knowledge and Attitude of Infertile Couples Attending IRM: A Prospective Observational Study AKSHAYA KUMAR MAHAPATRO*, INDUMATHI JOY†, KUNDAVI SHANKAR‡, THANKAM VARMA#
ABSTRACT Objective: The purpose of this present study was to evaluate the knowledge of infertile couples about the risk factors associated with infertility and to assess their attitude towards various methods of infertility treatment. Study design: This prospective observational study of knowledge and attitude of infertile couple was carried out in our hospital. The present study was conducted on all the subfertile couples (n = 223) who presented for an initial assessment to our outpatient department (OPD) by giving a questionnaire paper containing 16 knowledge-based and 7 attitude-based questions in English. Their level of knowledge was assessed by giving score 1 to correct answer, zero for wrong and those do not know the answer. Their level of knowledge was scored as inadequate (scored <50%), moderately adequate (scored >50 to <75%) and adequate (>75%) regarding infertility. Result: Out of the 223 couples, prevalence of primary and secondary infertility was 73% and 27%, respectively. The mean duration of infertility was 4.46 ± 3.32 years. On scoring their level of knowledge, (n = 115) had inadequate, (n = 101) had moderately adequate and (n = 7) had adequate knowledge. There was no statistically significant difference found (p = 0.97) in the knowledge in relation to their educational qualification and type of infertility (p = 0.657) among the participants. Conclusion: We discovered that the knowledge about the risk factors associated with infertility is generally limited among the participants, in spite of their higher education level and there needs to be an educative counseling session in all the infertility clinics to create an awareness among the married couples.
Keywords: Infertility, knowledge, attitude, assisted reproductive technique, counseling, awareness
I
t is the dream of every married couple to have a child, which will bring happiness and joy into their life. Most people assume that they will have children when they want and spend time and energy trying to get pregnant, but get frustrated then they find that to have a baby when wanted is not so simple.1 Infertility is a disease of the reproductive system, which affects both men and women with almost equal frequency.2 The World Health Organization (WHO) defines primary infertility as inefficiency to conceive after a year of unprotected sex and secondary if not conceived following previous pregnancy. Infertility is a global phenomenon that affects between 60 million to 168 million people worldwide.3 Psychologically,
*Post Doctoral Fellowship †Associate Consultant ‡Senior Consultant #Medical Director Institute of Reproductive Medicine, Madras Medical Mission, Chennai, Tamil Nadu Address for correspondence Dr Akshaya Kumar Mahapatro Vijay Shanthi Infiniti, Tower 1-6A, Chettipedu, Chennai, Tamil Nadu E-mail: dr.aks73@gmail.com
the infertile woman exhibits significantly higher psychopathology in the form of tension, hostility, anxiety, depression, self-blame and suicidal ideation.4 Social stigma regarding infertility is especially common across South Asia. For e.g., in Andhra Pradesh, India 70% of women experiencing infertility reported being punished with physical violence for their failure.5 A global survey of almost 17,500 women (mostly of childbearing age) from 10 countries revealed that knowledge regarding fertility and biology of reproduction was poor.6 Many women have little awareness of the period of the month in which they are most fertile and when to seek treatment.7,8 The risk factors for infertility include obesity, advanced maternal age, menstrual irregularities sexually-transmitted infections, smoking, alcohol consumption and many others.9 Increasing the level of knowledge of these factors may help to decrease the incidence of infertility by allowing couples to avoid certain risk factors that might lead to it. This knowledge may also help wider society to understand and empathize with the infertile couple, which may lead to a decrease in the psychological burden to those affected.10 Moreover, patient education
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COMMUNITY MEDICINE has been found to be a key aspect of patient satisfaction with infertility care.11,12 Psychological distress is seen as both cause and effect of infertility and quite common in infertile couple.13 Researches exploring the knowledge, behaviors, perceptions and practices regarding infertility or certain treatment options have been carried out in developed countries but very limited data is available from the Indian population despite high prevalence of infertility. This present study was conducted in our hospital to evaluate the knowledge of infertile couples attending to outpatient department (OPD) about the risk factors associated with infertility and to assess their attitude towards various methods of infertility treatment. MATERIAL AND METHODS This prospective observational study of knowledge and attitude of infertile couples was carried out in our hospital. The present study was conducted during the period of November 2014 to August 2015, on all the infertile couples (n = 223) who presented for an initial assessment to our OPD. Recruitment was based on the couple’s willingness to answer the questionnaire in English. Couples, who were unable to read English were excluded from the study. The couples were informed about the study and offered knowledge- and attitude-based questionnaires during clinical history taking. The questionnaire contains 16 knowledgebased and 7 attitude-based questions. Their response was collected immediately during history taking. Their level of knowledge was assessed by giving score 1 to correct answer, zero for wrong and those do not know the answer. Those who scored <50% were considered to have inadequate, those with scores >50 to <75% as moderately adequate and those with scores >75% adequate knowledge regarding infertility. Statistical analysis was done by frequency, percentage calculation and Chi-square test using SPSS software.
RESULTS
Demographic Information Out of 223 couples, the prevalence of primary infertility was (n = 162) and that of secondary infertility was (n = 61). The mean duration of infertility was 4.46 ± 3.32 years. Out of 223 female partners, the mean female age (years) was 30.03 ± 4.25. Among 223 female partners, 108 (48.4%) were graduates and 99 (44.4%) were postgraduates. Mean male age was 33.94 ± 4.73 years. One hundred thirty-one (58.7%) of male partners were graduates and 78 (35%) were postgraduates (Table 1).
Knowledge and Misconceptions Regarding Related to Infertility Table 2 shows the response of infertile towards risk factors associated with infertility. In our study, most of the patients (>70%) of respondents were aware about the common risk factors such as advanced age, obesity, irregular menstrual cycle, stress, environmental pollutant, fertile period and advantages of regular exercise. But less than 50% of respondents were aware about the other common risk factors such as genital tracts infection which leads to tubal block, common symptoms of endometriosis, which also leads to infertility. In our study, 41% had misconception that use of oral contraceptive affect their fertility status and 48% were not aware about the OCP role, this misconception may have led to unwanted pregnancy loss. About 61% respondents were aware that increase in frequency of intercourse increases the chance of pregnancy rate, but 70% of the respondents had the false belief that lying down in bed for long time after sexual intercourse increases the chances of pregnancy. We found 33% of respondents had misconception that delay in pregnancy runs in families and 30% had no knowledge about the
Table 1. Demographic Data Parameters Mean age of female (years)
30.03 ± 4.25
Range 20-43 years
Mean age of male (years)
33.94 ± 4.73
Range 26-48 years
Education of female
Graduates - 108 (48.4%)
Postgraduates - 99 (44.4%)
Education of male
Graduates 131 (58.7%)
Postgraduates - 78 (35%)
Type of infertility
Primary - 162 (72.6%)
Secondary - 61 (27.4%)
4.46 ± 3.32
Range 1-17 years
Mean duration of infertility
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COMMUNITY MEDICINE Table 2. Response of Couple About Knowledge-based Questionnaire Questions
Yes
No
Donâ&#x20AC;&#x2122;t know
Do you think increasing age in women may delay to achieve pregnancy?
167 (74.9%)
38 (17%)
18 (8.1%)
Does obesity in a women delay the fertility?
173 (77.6%)
23 (10.3%)
27 (12.1%)
Do you think irregular cycle may be a cause for delay in achieving pregnancy?
180 (80.7%)
21 (9.4%)
22 (9.9%)
Does pain in the lower abdomen during periods and during sexual intercourse delays pregnancy?
44 (19.7%)
76 (34.1%)
103 (46.2%)
What do you mean by fertile period in a women having regular cycle?
166 (74.4%)
39 (17.5%)
18 (8.1%)
Do you think foul smelling discharge P/V in a women is a cause for pregnancy delay?
39 (17.5%)
58 (26%)
126 (56.5%)
Does OCP use in past delay conception in the women?
92 (41.3%)
29 (13%)
102 (55.7%)
Do you think frequency of intercourse increases the chance of pregnancy?
136 (61%)
56 (25.1%)
31 (13.9%)
Does lying down in bed for long time after sexual intercourse increase the pregnancy chance?
157 (70.4%)
30 (13.5%)
36 (16.1%)
Do you think stressful life in a woman affects her fertility?
202 (90.6%)
10 (4.5%)
11 (4.9%)
Do you think delay in pregnancy runs in families?
73 (32.7%)
83 (37.2%)
67 (30%)
Do you think exposure to environmental pollutant reduce fertility?
101 (45.3%)
46 (20.6%)
76 (34.1%)
Do you think regular exercise by a woman increases her fertility?
171 (76.7%)
20 (9%)
32 (14.3%)
Does smoking reduce sperm parameters in men?
200 (89.7%)
7 (3.1%)
16 (7.2%)
Do you think increasing age in men reduces fertility?
126 (56.5%)
58 (26%)
39 (17.5%)
Do you think a women conceived previously might have problems to conceive again?
69 (30.9%)
117 (52.5%)
37 (16.6%)
Table 3. Response of Couple About Attitude-based Questionnaire Questions Do you think infertility is a disease?
Yes
No
18 (8.1%)
205 (91.9%)
H - 7 (3.1%)
W - 14 (6.3%)
Both - 202 (90.6%)
Who is being blamed for infertility in the society?
H - 1 (0.4%)
W - 123 (55.2%)
Both - 99 (44.4%)
Do you think it is socially acceptable to have a test-tube baby?
161 (72.2%)
58 (26%)
NW - 4 (1.8%)
If a couple cannot have a child, do you think they should adopt?
169 (75.8%)
47 (21.1%)
NW - 7 (3.1%)
Do you think your husband should donate sperm to help an infertile couple to have a baby?
121 (54.3%)
94 (42.1%)
NW - 8 (3.6%)
107 (48%)
108 (48.4%)
NW - 8 (3.6%)
Who do you think it should be investigated first?
Are you interested to donate your egg to help an infertile couple to have a baby?
hereditary nature of infertility. In our study, 90% of female partners were aware that smoking reduces the sperm parameters in men and 57% were aware that increased age in men also reduces fertility.
Attitude Towards Infertility and Its Social Consequences Table 3 shows the response of infertile patients to some attitudinal statements towards infertility and its social consequences. In our study, 92% of patients did not want to label infertility as a disease and 91% correctly were that it was a problem of the couple and
needed investigation of the couple simultaneously. In our study, we found that 55% of females were blamed by the family members and society in spite of the fact that the cause may be related to any one of the partner. In our study, we found >70% patients were aware about the mode of treatment available such as in vitro fertilization (IVF) and adoption. Interestingly, we found that 54% of infertile couples husbandâ&#x20AC;&#x2122;s were willing to help infertile couple by sperm donation but response of infertile females towards egg donation was equivocal (48%). Tables 4-6 showing about their level of knowledge and its correlation.
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COMMUNITY MEDICINE Table 4. Correlation of Type of Infertility with Levels of Knowledge Type of infertility
Inadequate knowledge
Moderately adequate knowledge
Adequate knowledge
P value
Primary
85 (52.46%)
72 (44.44%)
5 (3.08%)
NS (0.657)
Secondary
30 (49.18%)
29 (47.54%)
2 (3.27%)
Table 5. Female Education with Levels of Knowledge Education
Inadequate knowledge
Moderately adequate knowledge
Adequate knowledge
P value
High school
6 (2.7%)
5 (2.2%)
0
NS (0.977)
3 (1.3%)
2 (0.9%)
0
Graduates
Higher secondary
56 (25.1%)
49 (22%)
3 (1.3%)
Postgraduates
50 (22.4%)
45 (20.2%)
4 (1.8%)
Table 6. Levels of Knowledge Knowledge
No.
Percentage (%)
Inadequate knowledge
115
51.6
Moderately adequate knowledge
101
45.3
7
3.1
Adequate knowledge
DISCUSSION Although there is widespread acknowledgment of the importance of patient education within the infertility field, there is limited research into the knowledge which infertile patients actually possess and also the way they gain infertility-related information in resource poor settings where health literacy is typically low. According to Bunting and Boivin et al 2007,14 knowledge about fertility issues is a core motivator for fertility problems. A Global survey revealed inadequate knowledge of women regarding fertility;6 our study also demonstrated that the participants had inadequate knowledge about the risk factors associated with infertility. But the knowledge regarding the potential risk factors associated with infertility was high. In our study, 75% of female partners were aware that increasing age results in decline in fertility which is similar to the study by Bunting and Boivin et al (2008),10 but there was lack of awareness of the significance of age for declining fertility among childless Canadian women15 and Australian women,16 and among the university students in Sweden.17 In our study, we found that 77% were aware that obesity has negative effects on fertility which is similar to Abolfotouh et al,18 Brannian et al,19 Bunting et al study (2013),20 and Daniluk et al study (2015).15 In our study, we found that 81% women were aware that irregular cycles may be a cause for delay in pregnancy, but in Abolfotouh et al18 study only 64%
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were aware about it. In our study, only 20% of female partner considered dysmenorrhea and dyspareunia as a risk factor for fertility but no other study considers it as a risk factor. It is crucial to know about the fertile period for a women, when she should try to conceive. In our study, fertile period was well-known to 74% participants similar to Linda Rae Bennet9 study, but in Ali et al21 and an Australian study only 46% and 32%, respectively were aware about it. The higher percentage in our study could be due to higher educational qualification of female partners and prevalence of more referral patients. In our study, 82.5% of female partners were not aware about genital tract infections as a risk factor for infertility. Since, diagnosis and treatment of genital tract infections can prevent the major sequel, the tubal block, awareness of genital tract infection as a risk factor is highly required in our society. In our study, 41.3% believed that use of OCP affects fertility and 107 (55.7%) didnâ&#x20AC;&#x2122;t know its effect, but in Ali et al21 study, 61% correctly highlighted use of OCP affecting fertility. Study conducted by Bunting10 also highlighted that participants had a false belief that use OCP as a risk factor for in fertility. In our study, 70% female partners had belief that lying in bed after intercourse increases the pregnancy chance, which is similar to Bunting and Boivin et al study in which participants believed in the myth that lying down for 10 minutes after sex increases the pregnancy rate.10 A randomized controlled trial by Custers et al22 at Netherland and Orief et al, Egypt23 reported that 15 minutes of immobilization after intrauterine insemination (IUI) significantly improves pregnancy rate as compared to immediate mobilization. From a psychological standpoint, women facing infertility exhibit significantly more tension, hostility, anxiety, depression, self-blame and suicidal ideation.4 In our study, 90% females were aware about the negative effect of stress on fertility, which is had
COMMUNITY MEDICINE similar to other studies. In our study, only 33% of couple belief that infertility runs in family but no other study commented on the hereditary nature of fertility. In our study, 45% couple believed that environmental pollutants reduce fertility chance. In our study, 77% women were aware that regular moderate exercise increases the fertility rate similar to Bunting and Boivin et al study but in Ali et al study only 13% participant knew about it. In our study, 90% of women thought that smoking reduces the sperm parameters, which is similar to other studies by Bunting and Boivin et al10 and Daniluk and Koert study.15 In our study, 56.5% women thought that increasing manâ&#x20AC;&#x2122;s age reduces the chance of fertility, which is similar to Daniluk and Koert et al study.15 In our study, we found that 52% women had the misconception that in case of previous spontaneous conception there will be no problem for further conception; due to this false belief there was delay in their consultation. Considering attitude of people in our study, 92% did not want to label infertility as a disease but in Ali et al study, only 56% opined that infertility is not a disease. In our study, we found 90% women answered that both partner should be investigated at same time, which is similar to Ali et al study21 and Bennett study.24 Unnecessary blame on a woman for infertility can potentially affect her self-esteem and might socially cripple her. In our study, we found that 55% of female partners thought that they were blamed by society for infertility and this is similar to Luna et al25 study in Latin America, but the percentage was higher than that of our study in studies by Ali et al21 and Sami et al26 in Pakistan. In our study, 72% agreed that to have a test tube baby is socially acceptable which is similar to Adashi et al study.8 Since, child adoption is an available option for infertile couples, many couples with incurable infertility in advanced countries are willing to adopt babies but are limited by the few babies available for adoption. In our study, we found that 76% infertile couples agreed for adoption as an option for infertile couples similar to other studies. In Kilic et al27 study, most of them stated adoption as the first choice if they had learned that they would never have a child in their future life. In Sohrabvand et al study,28 total 98.7% of responders opposed sperm donation. In a study by Hwang et al29 about the attitudes of infertile male patients toward use of artificial insemination by donor (AID) concluded about high acceptance of AID among infertile males. Although IVF techniques have been providing hope to infertile couples, male and female gametes and a healthy woman with a healthy uterus are required to apply these techniques. Donation programs have become a
resource for couples who cannot produce the requisite gametes.30 In our study, the attitude of infertile females towards egg donation was equivocal (50%), which was similar to Chliaoutakis et al study.31 In another study conducted in Turkey by Isikoglu et al,32 the proportion of positive respondents towards oocyte donation was nearly 85%. The proportions were 82.3% among fertile individuals and 86.7% among infertile ones. Westlander et al33 reported that in their study group, infertile women were more in favor of donating oocyte compared to fertile ones. In our study, we considered all the risk factors responsible for infertility but other studies included few risk factors. No study considered endometriosis, heredity and chance of infertility in a previously normally conceiving women and there was previous no such study including South Indian women. LIMITATIONS OF THE STUDY Only patients those were able to read English were included in spite of it not being the local language. Most of the patients attending our OPD were referred or previous treatment failure cases. Most of the couple included in our study were well-educated. CONCLUSION Infertility is a fairly common problem affecting 10-15% of the population. We discovered that the knowledge about infertility is generally limited among the participants. In spite of their higher education level, most of the couple coming to us had inadequate knowledge about the risk factors associated with infertility. In fact, there are a lot of misconceptions, such as OCPs can cause infertility. The cultural and religion perspective about ART is unclear, which has resulted in its reduced acceptability. Since, the prevalence of infertility is rising due to late marriages, career, stressful and altered lifestyles, we suggest there is a need for educative counseling sessions in all the infertility clinics to create an awareness among the married couples. REFERENCES 1. Holistic online com (online). 2000 [Cited 2007 Aug 10]; Available from URL: http://www.holisticonline.com/ remedies/infertility/inf_ introduction. htm. 2. Callahan LT, Caughey AB. Infertility and assisted reproductive technologies. In: Blueprints Obstetrics and Gynecology. 5th Edition, Lippincott Williams & Wilkins; 2008. pp. 275-89. 3. Neelofar S, Tazeen S. The cultural politics of gender for infertile women in Karachi, Pakistan. South Africa: InGender Studies Conference; 2006.
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COMMUNITY MEDICINE 4. Fido A. Emotional distress in infertile women in Kuwait. Int J Fertil Womens Med. 2004;49(1):24-8.
International Fertility Decision-making Study. Hum Reprod. 2013;28(2):385-97.
5. Daar A, Merali Z. Infertility and social suffering: the case of ART in developing countries. In: Vayena ERP, Griffin D (Eds.). Current Practices and Controversies in Assisted Reproduction. Geneva: World Health Organization; 2002.
21. Ali S, Sophie R, Imam AM, Khan FI, Ali SF, Shaikh A, et al. Knowledge, perceptions and myths regarding infertility among selected adult population in Pakistan: a crosssectional study. BMC Public Health. 2011;11:760.
6. What you never know about fertility. World Fertility Awareness Month; 2006.
22. Custers IM, Flierman PA, Maas P, Cox T, Van Dessel TJ, Gerards MH, et al. Immobilisation versus immediate mobilisation after intrauterine insemination: randomised controlled trial. BMJ. 2009;339:b4080.
7. Blake D, Smith D, Bargiacchi A, France M, Gudex G. Fertility awareness in women attending a fertility clinic. Aust N Z J Obstet Gynaecol. 1997;37(3):350-2. 8. Adashi EY, Cohen J, Hamberger L, Jones HW Jr, de Kretser DM, Lunenfeld B, et al. Public perception on infertility and its treatment: an international survey. The Bertarelli Foundation Scientific Board. Hum Reprod. 2000;15(2):330-4. 9. Namujju J. Knowledge, attitudes and practices towards infertility among adults 18-40 years in Kalisizo, Rakai District in Uganda. Uganda Scholarly Digital Library, Thesis, 2008. Available at: http://dspace.mak.ac.ug/ handle/123456789/972. Accessed on January 12, 2017. 10. Bunting L, Boivin J. Knowledge about infertility risk factors, fertility myths and illusory benefits of healthy habits in young people. Hum Reprod. 2008;23(8):1858-64. 11. Schmidt L. Infertile couples’ assessment of infertility treatment. Acta Obstet Gynecol Scand. 1998;77(6): 649-53. 12. Souter VL, Penney G, Hopton JL, Templeton AA. Patient satisfaction with the management of infertility. Hum Reprod. 1998;13(7):1831-6. 13. Negro-Vilar A. Stress and other environmental factors affecting fertility in men and women: overview. Environ Health Perspect. 1993;101 Suppl 2:59-64. 14. Bunting L, Boivin J. Decision-making about seeking medical advice in an internet sample of women trying to get pregnant. Hum Reprod. 2007;22(6):1662-8. 15. Daniluk JC, Koert E, Cheung A. Childless women’s knowledge of fertility and assisted human reproduction: identifying the gaps. Fertil Steril. 2012;97(2):420-6.
23. Orief YI, El-agwany AS, Darwish EAE, Salim NM. The effect of bed rest after intrauterine insemination on pregnancy outcome. Middle East Fertil Soc J. 2015;20:11-5. 24. Bennett LR, Wiweko B, Bell L, Shafira N, Pangestu M, Adayana IB, et al. Reproductive knowledge and patient education needs among Indonesian women infertility patients attending three fertility clinics. Patient Educ Couns. 2015;98(3):364-9. 25. Luna F. Assisted reproductive technologies in Latin America: some ethical and sociocultural issues. In: Vayena E, Rowe PJ, Griffin PD (Eds.). Medical, Ethical and Social Aspects of Assisted Reproduction. Geneva, Switzerland: World Health Organization; 2002. pp. 31-40. 26. Sami N, Ali TS. The cultural politics of gender for infertile women in Karachi, Pakistan: Proceedings of the FOTIM Gender Studies Conference; January 17-19, 2006; Pretoria, South Africa. 27. Kilic S, Ucar M, Yaren H, Gulec M, Atac A, Demirel F, et al. Determination of the attitudes of Turkish infertile women towards surrogacy & oocyte donation. Pak J Med Sci. 2009;25(1):36-40. 28. Sohrabvand F, Jafarabadi M. Knowledge and attitudes of infertile couples about assisted reproductive technology. Iranian J Reprod Med. 2005;3(2):90-4. 29. Hwang DS, Jeon TG, Park HJ, Park NC. The attitudes of infertile male patients toward the use of artificial insemination by donor: a korean regional survey. Korean J Urol. 2014;55(2):134-9.
16. Hammarberg K, Setter T, Norman RJ, Holden CA, Michelmore J, Johnson L. Knowledge about factors that influence fertility among Australians of reproductive age: a population-based survey. Fertil Steril. 2013;99(2):502-7.
30. Baykal B, Korkmaz C, Ceyhan ST, Goktolga U, Baser I. Opinions of infertile Turkish women on gamete donation and gestational surrogacy. Fertil Steril. 2008;89(4):817-22.
17. Skoog Svanberg A, Lampic C, Karlström PO, Tydén T. Attitudes toward parenthood and awareness of fertility among postgraduate students in Sweden. Gend Med. 2006;3(3):187-95.
31. Chliaoutakis JE, Koukouli S, Papadakaki M. Using attitudinal indicators to explain the public’s intention to have recourse to gamete donation and surrogacy. Hum Reprod. 2002;17(11):2995-3002.
18. Abolfotouh MA, Alabdrabalnabi AA, Albacker RB, AlJughaiman UA, Hassan SN. Knowledge, attitude, and practices of infertility among Saudi couples. Int J Gen Med. 2013;6:563-73.
32. Isikoglu M, Senol Y, Berkkanoglu M, Ozgur K, Donmez L, Stones-Abbasi A. Public opinion regarding oocyte donation in Turkey: first data from a secular population among the Islamic world. Hum Reprod. 2006;21(1):318-23.
19. Brannian JD. Obesity and fertility. S D Med. 201;64(7): 251-4.
33. Westlander G, Janson PO, Tägnfors U, Bergh C. Attitudes of different groups of women in Sweden to oocyte donation and oocyte research. Acta Obstet Gynecol Scand. 1998;77(3):317-21.
20. Bunting L, Tsibulsky I, Boivin J. Fertility knowledge and beliefs about fertility treatment: findings from the
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COMMUNITY MEDICINE
Case of Mix-up or Switching of Gametes, Embryos – Glaring Omission Under ART Bill, India SONALI KUSUM
ABSTRACT Infertility has been recognized as an alarming public health issue worldwide with estimated 48.5 million infertile globally and over 20 million infertile couples in India.1 In the background of rising infertility, couples around the world are resorting to assisted reproductive technologies (ART) including in vitro fertilization, surrogacy to attainment of parenthood ensuring child either genetically related with either or both couples or otherwise. However, in many cases, there has been gross errors in handling gametes, embryos by clinics or banks, leading to breach of medical ethics, violation of right to privacy, family formation of couples of patients, legal complexities. The objective of this paper was to identify such grave medical malpractices by the fertility clinics or banks, to emphasize on the unregulated, unmonitored functioning of such clinics in the absence of law and to demonstrate implicit biomedical legal issues through case studies. As a proposed conclusion to suggest for formulation of progressive, effective biomedical ethical standards to be complied by the clinics, banks for providing better reproductive healthcare and to suggest inclusion of the same in the proposed law. For the same, there was use of comparative legal perspectives, descriptive or analytical research methods following literature survey, relying on primary and secondary sources of data collection. There was use of comparative legal perspectives, descriptive research methods following literature survey, secondary data sources.
Keywords: Biomedical ethical safeguards, in vitro fertilization mix-up, surrogacy law, regulations India, switching gametes or embryos
U
nderstanding the cases of in vitro fertilization (IVF) mix-up or switching of gametes or embryos or misdirection of gametes are identified as “medical errors” which may occur or take place during the course of practice of assisted reproductive technology (ART), which essentially/inherently involves handling of human biological materials or gametes or embryos through the retrieval, processing, transfer and storage of human gametes and embryos. These medical errors may include use of wrong sperm for insemination, or mistakenly switched gametes or embryos resulting in fertilization, or any other manipulation during embryo transfer, implantation or use of the gametes or embryos in implantation not those originally intended for use in
Research Scholar National Law School of India University, Bangalore, Karnataka Ex-Assistant Professor Tata Institute of Social Sciences, Mumbai, Maharashtra Address for correspondence Dr Sonali Kusum Room No. 105, Narmada Girls Hostel National Law School of India University, Nagarbhavi, Bangalore - 560 072, Karnataka E-mail: sonali.lipi@gmail.com
the patient undergoing treatment, potentially leading to the birth of a child with a different genetic parentage than intended, or an unplanned genetic parentage causing negative consequences or harm for patients. These medical errors are subsequently discovered through DNA tests during the course of civil, legal formalities when the couple or the patient is seeking to apply for citizenship, passport or birth registration for the concerned surrogate child. While the Assisted Reproductive Technologies (ART) Bill 20142 is awaiting to be enacted, given effect, there are glaring commissions and unresolved issues under the proposed ART Bill 2014. A major lacuna under the Bill is the absence of provisions to address cases of mix-up or switching of gametes. Though under the relevant provisions of the Bill, there is statutory duties imposed on ART Banks “to follow highest possible standards for storage and handling of gametes and human embryos”,3 but there is no legal recourse or remedial measure under the Bill in case of failure to perform such duty by ART Banks. There have been series of such cases of mix-up or switching of gametes both nationally and internationally, while gametes are stored with the ART Bank for various reasons including deferred
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COMMUNITY MEDICINE use; these occurrences impair cardinal human rights established under constitution as well as human rights conventions including right to privacy, family formation, right to procreative or reproductive health thereby constituting breach of right to life, which leave the couples legally vulnerable without any legal remedy under such circumstances. Some of these cases are quoted as below: i. Canadian Intending couple mix-up of gametes at ART Bank in India, 2005 yr.4– yy A Toronto-based couple commissioned surrogacy in India in 2005 by availing the gestational services of an Indian surrogate mother who was carrying a fetus conceived of eggs from anonymous egg donor and intending father’s sperm resulting in birth of surrogate twins boy and surrogate girl in March 2006. The couple applied for citizenship to the Canadian High Commission in New Delhi by adducing proof of genetic connection between the couple and the surrogate child using DNA test that showed the boy was not genetically related, only girl child was genetically connected, this indicated an error or mix-up or switch or swapping of gametes in the Indian fertility lab. The Canadian Government permitted citizenship only for the genetically related twin girl but refused to issue citizenship to the other twin, leaving the couple stranded in India. The couple made an application on humanitarian and compassionate grounds for their nonbiological child to be granted citizenship, the Canadian Government issued a citizenship card and travel papers to the other twin only in the year 2012, almost 6 years after the couple commissioned surrogacy in India. ii. Dr KK Gopinathan vs. Anitha Jayadevan5 - Kerala couple mix-up of gametes at Clinic in Kerala, 2012 yr.– yy A Kerala-based couple named Mr and Mrs Anitha Jayadevan underwent intracytoplasmic sperm injection (ICSI) treatment using their own gametes, the sperm of her husband, her own ovum, respectively. Following a DNA test, it was found that there was no genetic connection with the intending mother and the fetus. The hospital authorities admitted a donor ovum was used for artificial insemination. The couple has filed a law suit in the High Court of Kerala against the Hospital authorities for ` 20,01,000 as damages. Ms Anitha has written a book titled as “Malicious medicine: my experience with fraud and falsehood in infertility clinics” (Malayalam language) on her testimony and recounting similar cases of mix-up
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and switching of gametes by infertility clinics among other misuse and malpractice of technology by clinics. iii. Baby X - New Zealand – mix-up, swapping of child post birth, 2015 yr.6– yy A New Zealand couple, Mr and Mrs Y, commissioned surrogacy in Chiang Mai Thailand using intending father’s sperm, egg donor from a family member and a local Thai woman to act as surrogate mother to carrying the same resulting in birth of baby X in Thailand. The couple applied for issue of travel documents for the surrogate child in compliance with the New Zealand Immigration Rules. A DNA test, was conducted that showed that the surrogate child had no genetic connection with the father, or the relative who donated the egg or to the surrogate. This indicated embryos were mixed-up during IVF or the baby was swapped after birth. New Zealand Family Court Judge held that “Baby X was not the child the concerned intended parents, this is another child altogether.” The couples were directed by the authorities to leave the Baby X surrogate child in a Thai orphanage. The Baby X was born with no genetic records, no identity even termed as “scrap of humanity”, investigation into the identification of the genetic parents of Baby X, showed nil records with the hospital authorities on the same. However, the couple sought to adopt the Baby X following the foreign adoption orders. This case manifest the legal, human crisis underlying such issues, gross violation of right to life of child. iv. A White couple had black twins following mix-up of gametes, UK, 2001 yr.7– yy UK-based White couple, named Mr and Mrs A, had black twins following an IVF mix-up at the ART Clinic owing to confusion over sperm, eggs or embryos belonging to a Black couple with those from a White couple. FINDINGS AND INFERENCES Progressive regulations on handling of gametes, embryos - A comparative foreign legal perspective: In the light of these cases, it is imperative to consider comparative foreign laws, regulations on the same. The UK Human Fertilization and Embryology Authority (HFEA)8 provides for code of practice for effective monitoring system of to ensure security, storing, handling of gametes and embryos. The UK HFEA Guidance Note was issued to all clinics centers with the main purpose to minimize, check use of wrong gametes
COMMUNITY MEDICINE or IVF mix-up cases, wrong infertility treatments. The UK HFEA recommends to the clinics and centers to ensure, maintain highest possible standards including effective monitoring for storage and handling of gametes and embryos. These guidelines are laid down as below:9 ÂÂ
All clinics handling, using of stored or donated gametes or biological materials are to be licensed by the HFEA.
ÂÂ
Periodic inspection of gametes, embryos or biological materials kept at the clinic by the Clinical and Scientific Inspectors. The UK HFEA also regularly inspects and monitors the same.
ÂÂ
ÂÂ
ÂÂ
Procedures for ‘cross-identification’ or doublechecking the identification of gametes embryos at three crucial stages namely the individuals undergoing treatment, the sperm and eggs at the time of insemination, the embryos and the patient at the time of embryo transfer. Double-check identification of the individuals undergoing treatment, the sperm and eggs at the time of insemination, and the embryos and the patient at the time of embryo transferred. Confirmation by the nurse, the embryologist and the gynecologist establishing patient’s identity. The source of gametes and embryos should be accurately recorded and labeled in a manner that is not susceptible to unauthorized or undetectable alteration.
ÂÂ
The location of gametes and embryos in such a manner to minimize unnecessary handlings, interventions in retrieving the same.
ÂÂ
Labeling with unique identification of an individual’s all biological material including gametes, embryos at all stages of treatment. Writing the names of the patients on both the lid and the bottom of the dish.
ÂÂ
Restricted Permissible access to such gametes, embryos only to such concerned or named Person in the center, for whom it is essential to their work. No Permission for any other person to access to gametes and embryos.
ÂÂ
Maintenance of records on the location of gametes and embryos along with each occasion of handling of gametes or embryos, source of gametes and embryos, the various procedures or recourse on embryo, egg or sperm sample collected kept from the date of collection.
The European Society of Human Reproduction and Embryology (ESHRE) - Handling and Identification of patients and their gametes and embryos:10
ÂÂ
Training of all the laboratory staff on handling of gametes, embryos is made mandatory.
ÂÂ
Development of written procedures describing the various phases or stages of handling of IVF techniques.
ÂÂ
All biological materials including gametes, embryos obtained from the patients should bear unique identification of the treated couple.
ÂÂ
Organization of incubators in such a manner so as to facilitate better identification of gametes and embryos.
ÂÂ
Double checks of patients and their gametes and embryos must be maintained, recorded at these stages: Insemination of oocytes, replacement of embryos, embryo freezing and thawing, respectively.
ÂÂ
Verification of patient’s identity should be performed at crucial stages such as at ovum retrieval, at semen recovery and embryo transfer procedures.
The American Society for Reproductive Medicine (ASRM)11 - Ethical Committee on Disclosure of medical errors involving gametes and embryos: ÂÂ
The ASRM imposes stringent ethical obligation on the Clinics to disclose errors at the earliest as soon as discovered without any further delay.
ÂÂ
To respect patient autonomy and practice fairness in treatment, delivery of services to patients.
ÂÂ
To uphold and recognize the patient’s right to know is compelling in case of such misdirection or medical error of mix-up or switching of gametes or embryos. Physicians are obligated to disclose to patients any error as soon as discovered that could lead to a child being born with an unintended paternity or maternity.
ÂÂ
Clinics are obliged to ensure availability of necessary written policies and procedures for making disclosure of errors to patients in such cases without nay exception.
Preventive safeguards for the couples12 - to detect genetic connection of the child with the intended parents with the child during pregnancy. Preimplantation Genetics Diagnosis (PGD): This genetic test intended for identifying genetic defects in embryos; this test carried out before implantation ensures a couple that the embryo shares the genetic match with the intended couples. Amniocentesis: This is another prenatal test using amniotic fluid around the fetus for detection of Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
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COMMUNITY MEDICINE chromosomal and genetic birth defects and identifies genetic match with the intended couples. Such early identification or determination allows the couples in consultation with clinic to decide on the continuation or termination of pregnancy or fetal reduction or otherwise. Thus, safely prevents any further IVF mix-up or birth of child with unintended genetic parentage. ISSUES FOR CONSIDERATION These cases raise a range of issues as enumerated, first and foremost these cases evince the large scale malpractice, abuse of this technology by ART Clinics, Banks. These clinics, banks as well as unregulated, unmonitored practice of these clinics, banks which are largely unregistered, lack infrastructure, expertise and function for vested or commercial gains flouting the Indian Council of Medical Research (ICMR) guidelines as these are nonbinding. Similar concerns are expressed by the ICMR, which have reported that there are some 1,200 ART Clinics in India. Only 177 of these, have enrolled with the ICMR. “While some have top-class facilities, others are really bad in terms of infrastructure and technical expertise.” Under these circumstances, with no effective law, any accountability, control or check on the functioning of these clinics is challenging. In addition to this, there are other pertinent concerns associated with the same, which are briefly mentioned as follows: ÂÂ
ÂÂ
There is need for inclusion of biomedical ethical principles, safeguards coupled with protocols, best practices to prevent ensure maximum safety, minimize any tampering, manipulation and check or control of such acts. There must be identification of onus of proof, legal presumption establishing the liability for such acts commission or omissions or any foul play on the part of ART Bank, Clinic.
ÂÂ
Legal recourse or remedial measure may be provided to redress such cases including complaint forum, procedural mechanism for the same.
ÂÂ
To specifically enlist the acts of mix-up switching, swapping of gametes, embryos as punishable act with imprisonment, fine under the list of offences as ART Bill 2014.
CONCLUSION These issue gain alarming significance in the absence of a binding legislation in India. These unresolved issues
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were submitted for consideration of law and policy makers formulating the ART Bill 2014. A list of select provisions taken after the regulations, best practices of international medical regulatory bodies for safe, desirable practice of ART technology was suggested that may be incorporate under the ART Bill as there was omission to address the same in the face of rising number of such irregularities and legal complexities. There should be inclusion of mandatory principles of biomedical ethics in the Bill seeking compliance from all banks, clinics towards ensuring safe practice of ART technology in the best interest of couples as well as towards greater good of society. REFERENCES 1. Venkat V. There are 20 million infertile couples in India. The Hindu, September 28, 2014. Available at: http://www.thehindu.com/sunday-anchor/pushpa-mbhargava-there-are-20-million-infertile-couples-in-india/ article6453374.ece. See also, Agarwal A, Mulgund A, Hamada A, Chyatte MR. A unique view on male infertility around the globe. Reprod Biol Endocrinol. 2015;13:37. 2. Government of India, Ministry of Health and Family Welfare (Department of Health Research) ART Bill 2014, 30th September 2015. Available at: http://www. prsindia.org/uploads/media/draft/Draft%20Assisted%20 Reproductive%20Technology%20(Regulation)%20 Bill,%202014.pdf. 3. ART Bill 2014 Sec. 53. (1) The highest possible standards should be followed in the storage and handling of gametes and human embryos in respect of their security, and with regard to their recording and identification. 4. Aulakh R. Couple fights federal surrogacy policy to bring their boy back to Canada. The Satr. Aug 20, 2011. Available at: http://www.thestar.com/news/gta/2011/08/20/couple_ fights_federal_surrogacy_policy_to_bring_their_boy_ back_to_canada.html. 5. OP(C).No. 2084 of 2012 (O), OS.12/2004 of Sub Court, Tirur. Available at: http://indiankanoon.org/doc/57268181/(Last visited March 1, 2016). See also, Tehelka. The invisible baby makers. Issue 50 Volume 11, 2014-12-13. Available at: http://www.tehelka.com/2014/12/the-invisible-babymakers/. 6. Woulfe C. The untold story of NZ’s surrogate babies. New Zealand Listner Current Affairs, Science. Available at: http://www.listener.co.nz/current-affairs/the-untoldstory-of-nzs-surrogate-babies/ (Last visited March 1, 2016). See also, Penfold P. Breakthrough in surrogacy mixup case. Newshub 30 Nov 2015. Available at: http://www. newshub.co.nz/tvshows/3d/breakthrough-in-surrogacymix-up-case-2015113017#ixzz44HpYYOiD. Cont'd on page 936...
2017
GASTROENTEROLOGY
A Case Report of Pancreatic Lipomatosis N JEEVA*, S ARUN KUMAR†, JOGA VEERA BALAJI‡, DEEPA JAMES#
ABSTRACT Total fat replacement of the pancreas is rare. Focal fatty replacement is the most common degenerative lesion of pancreas. Focal fatty deposits have no major clinical significance; however, extreme fat replacement is of pathologic significance, as it is associated with marked reduction in exocrine function of pancreas, resulting in malabsorption due to pancreatic enzyme insufficiency. Here we are presenting a case with nonalcoholic fatty liver disease and pancreatic lipomatosis, which is a incidental finding for which we found that aging is the only etiological factor in this case.
Keywords: Exocrine function, malabsorption, nonalcoholic fatty liver disease, pancreatic lipomatosis
I
n pancreatic lipomatosis, there will be complete replacement of pancreas by fat usually associated with pancreatic insufficiency. It is speculated that nonalcoholic fatty liver disease begets pancreatic lipomatosis. However, in this case, pancreatic lipomatosis was associated with nonalcoholic steatohepatitis in early cirrhosis. Higher incidence of pancreatic lipomatosis had been observed in obese but in our case the patient was thin.
CASE REPORT A 75-year-old woman presented with the complaints of abdominal pain on and off, bilateral lower limb swelling, generalized fatigue since 15 days. History of loss of appetite was present. Not a known-case of hypertension, diabetes mellitus, tuberculosis, coronary artery disease. Clinical examination revealed pallor and bilateral pitting pedal edema. Body mass index (BMI): 19.2. Vital signs were within normal limits. Systemic examination
revealed no abnormality. Laboratory investigations: Hemoglobin (Hb) - 6 g/dL, peripheral smear showed microcytic hypochromic anemia. Prothrombin time (PT) - 19.1, international normalized ratio (INR) - 2.02, routine blood tests, renal function tests are normal. Lipid profile - normal. Blood sugar - normal. Echo - within normal limits. USG abdomen - chronic parenchymal liver disease. CT abdomen - diffuse parenchymal liver disease with heterogeneous fatty infiltration. Mild nodular surface with complete fatty replacement of pancreas, few perigastric collaterals and degenerative changes in spine. Liver biopsy early cirrhosis. Upper gastrointestinal endoscopy - no abnormality. Serum amylase and lipase - normal. DISCUSSION Incidence of pancreatic lipomatosis is unknown. Several predisposing factors have been suggested. These include age, obesity, diabetes mellitus, chronic pancreatitis, hereditary pancreatitis, pancreatic duct obstruction by calculus or tumor and cystic fibrosis. In normal individuals, only 10% of parenchyma is sufficient for maintenance of normal exocrine function.
*Unit Chief †Assistant Professor ‡Final Year PG #Second Year PG Unit III, Dept. of General Medicine Vinayaka Missions Medical College and Hospital, Karaikal, Puducherry Address for correspondence Dr Joga Veera Balaji Final Year PG Unit III, Dept. of General Medicine Vinayaka Missions Medical College and Hospital, Karaikal, Puducherry E-mail: jogaveerabalaji@gmail.com
Even though the total parenchyma of pancreas was replaced by fat in our patient, she had no exocrine and endocrine deficiency symptoms. The subtypes are even pancreatic lipomatosis and uneven pancreatic lipomatosis. Uneven pancreatic lipomatosis may present as: ÂÂ
Type 1a: Preferential fatty replacement of head.
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GASTROENTEROLOGY ÂÂ
Type 1b: Preferential fatty replacement of head, neck and body.
ÂÂ
Type 2a: Preferential fatty replacement of head and uncinate process.
ÂÂ
Type 2b: Fatty replacement of most of pancreas except peribiliary region.
The role of ultrasound in the diagnosis of pancreatic lipomatosis is very limited. However, the CT has an important role in evaluation of pancreatic disease.
SUGGESTED READING 1. Reddy OJ, Gafoor JA, Reddy GM, Prasad PO. Total pancreatic lipomatosis: A rare presentation. J NTR Univ Health Sci. 2015;4(4):272-4. 2. Anand R, Narula MK, Chaudhary V, Agrawal R. Total pancreatic lipomatosis with malabsorption syndrome. Indian J Endocrinol Metab. 2011;15(1): 51-3. 3. Prachayakul V, Aswakul P. Pancreatic steatosis: what should gastroenterologists know? JOP. J Pancreas (Online). 2015;16(3):227-31.
■■■■ ...Cont'd from page 932
7. Morris S. Clinics urged to tighten checks after embryo mix-up. The Guardian. July 9, 2002. Available at: http://www.theguardian.com/uk/2002/jul/09/health. healthandwellbeing. 8. UK Gov. Human Fertilization and Embryology Authority. Available at: http://www.hfea.gov.uk/25.html.
10. Gianaroli L, Plachot M, van Kooij R, Al-Hasani S, Dawson K, DeVos A, et al. ESHRE guidelines for good practice in IVF laboratories. Committee of the Special Interest Group on Embryology of the European Society of Human Reproduction and Embryology. Hum Reprod. 2000;15(10):2241-6.
11. 9. UK Gov. Human Fertilization and Embryology Authority, UK HFEA, Code of Practice, Guidance notes No. 17, Use of gametes and embryos Storage of gametes and embryos. Available at: http://www.hfea.gov.uk/505.html (Last visited March 1, 2016). See also, UK Gov. Human Fertilization and Embryology Authority, UK HFEA, Press releases archive 2002, HFEA statement on the systems 12. currently in place to prevent use of the ‘wrong’ infertility treatment. 11 September 2002. Available at: http://www. hfea.gov.uk/925.html. ■■■■
American Society for Reproductive Medicine, American Society for Reproductive Medicine (ASRM). Disclosure of medical errors involving gametes and embryos: an Ethics Committee opinion. Elsevier Inc., 2015. Available at: https://www.asrm.org/uploadedFiles/ASRM_Content/ News_and_Publications/Ethics_Committee_Reports_ and_Statements/disclose_errors.pdf Katherine, IVF Mistakes: Making Sure the Baby Is Yours. March 26, 2007. Available at: http://www.foxnews.com/ story/2007/03/26/ivf-mistakes-making-sure-baby-isyours.html.
Food Insecurity Increases Risk of Stroke Recurrence A new study has linked food insecurity to increased stroke risk factors, such as diabetes and high blood pressure increasing the risk of stroke recurrence. Food insecurity is the state of being without reliable access to adequate amounts of affordable, nutritious food. The study from a Chicago Hospital presented at the American Stroke Association’s International Stroke Conference 2017, evaluated 216 patients in the outpatient neurology clinic using a standardized two-question screening tool and reviewing electronic medical records. Forty-nine (22.7%) of the participants were identified as food insecure. Sixty-four patients were diagnosed with stroke; of these, 18.8% were found to be food insecure. In the food insecure stroke group, 84.6% also had hypertension; 58.3% had diabetes and 16.7% had a previous stroke. While, among stroke survivors not labeled food insecure, 67.3% had hypertension; 28.8% had diabetes and 21.2% had a previous stroke. These findings suggest that medical treatment of risk factors like hypertension and diabetes may not be enough to prevent stroke recurrence. Food insecurity may also complicate management of these health problems. Hence, social support is also required in addition to medical management especially for high risk patients. Health policy should be framed keeping in mind the availability of nutritious food to lead a healthy life. The proposed Sustained Developments Goals (SDG) of the United Nations have included food insecurity under Goal 2 “End hunger, achieve food security and improved nutrition, and promote sustainable agriculture”. SDG 2 aims to achieve ending hunger, and ensuring access by all people, in particular the poor and people in vulnerable situations including infants, to safe, nutritious and sufficient food all year round by the year 2030.
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HEMATOLOGY
The Wide Clinical Spectrum of Raised Fetal Hemoglobin in Adults PRATIK VORA*, SAKSHI SINGH†, JEMIMA BHASKAR‡, MANISH MEHTA#, AMI TRIVEDI¥
ABSTRACT Fetal hemoglobin (HbF) is found in infants up to 6 months. It is a normal physiological phenomenon. However in adults, in the absence of hemoglobin A (HbA) in thalassemic syndromes, HbF is raised even to 98%. However, presence of HbF does not always prevent symptoms. There is a wide clinical spectrum of disease. Some patients are asymptomatic as in delta-beta-thalassemia and hereditary persistence of fetal hemoglobin (HPFH) and some have severe symptomatic disease as in beta-thalassemia.
Keywords: Beta-thalassemia, delta-beta-thalassemia, HPFH, HbF, HbA, red cell indices
T
he thalassemic syndromes are inherited disorders of globin synthesis and present as hemolytic anemia. The reduced supply of globin causes hypochromia and microcytosis. In beta-thalassemia, there is unbalanced accumulation of alpha-chain and reduction of beta-chain. This is to some extent corrected by gamma-chain (fetal hemoglobin [HbF]). However, the clinical severity varies widely even though HbF replace the hemoglobin (HbA). We are presenting two cases of raised HbF with widely varying clinical picture. CASE REPORTS
Case 1 A 13-year-old boy presented with history of fever for 3-4 days, associated with abdominal pain, along with anorexia, nausea and generalized fatigue since a week. Patient’s parents also noticed icterus and yellowish discoloration of urine since 3-4 days. On examination, patient was anemic, icteric with splenomegaly.
*Second Year Resident †Third Year Resident ‡Senior Resident #HOD and Professor, Dept. of Medicine ¥Associate Professor, Dept. of Medicine MP Shah Govt. Medical College, Jamnagar, Gujarat Address for correspondence Dr Jemima Bhaskar 404, Kings Palace, Mehul Nagar Opp. BSNL Telephone Exchange, Jamnagar - 361 006, Gujarat
Investigations Hemoglobin (Hb) - 10.1 g/dL, mean corpuscular volume (MCV) - 69.6 fl, platelet - 2.83 lakhs, erythrocyte sedimentation rate (ESR) - 40 mm/hr; Mentzer index 15.13, reticulocyte count - 0.6%. Peripheral smear - microcytic hypochromic picture along with many target cells and few elliptocytes. Hyperbilirubinemia was mainly indirect (total 5.2 mg/dL), serum glutamic pyruvic transaminase (SGPT) - 133 IU/L. USG abdomen - Splenomegaly, minimal ascites, distended gallbladder with sludge. Viral markers - negative, Coombs test - negative, NESTROFT - positive; Hb electrophoresis - 98.7% HbF, 1.3% HbA2. Past History Patient had blood transfusion three times in the last 6 years and his lowest Hb was 5 g/dL in 2009 when he took treatment for first-time. He was given 2 pints of packed cells on first occasion. Later on, after 1-2 years interval, he was again transfused when minimum Hb was 7 g/dL. Every time patient had indirect hyperbilirubinemia and predominance of HbF on Hb electrophoresis. Coombs and glucose-6-phosphate dehydrogenase (G6PD) was negative. Reticulocyte count was 3-6%. On further follow-up, Hb was 8-11 g/dL. On further analysis of patient’s parents: Father was diagnosed as thalassemia minor and mother was diagnosed as hereditary persistence of fetal hemoglobin (HPFH). Parents never required transfusion and since last 2 years patient had not required transfusion.
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HEMATOLOGY Case 2 A 33-year-old male patient presented to OPD with chief complaint of abdominal pain in left hypochondrium, low intensity in nature, nonradiating since 12 days. No complaint of nausea or vomiting or any previous blood transfusion. Patient was conscious, oriented, hemodynamically stable, nonicteric and nonanemic. On abdominal examination, mild splenomegaly without tenderness. Investigations White blood cell (WBC) - 9,400 (N62,L30,M7,E0,B0), red blood cell (RBC) - 6.09 lakhs, platelet - 2.88 lakhs, Hb - 12.4 g/dL, hematocrit - 37.5%, mean corpuscular hemoglobin (MCH) - 18.7 pg/dL, MCV - 61.6 fl/dL, mean corpuscular hemoglobin concentration (MCHC) 30.4%, red blood-cell distribution width (RDW) 45.7%, ESR - 22/hr. Reticulocyte count - 1%, Mentzer index - 12.3, NESTROFT - positive. Peripheral smear microcytic hypochromic anemia. Serum creatinine - 0.5 mg/dL, serum urea - 19 mg/dL, random blood sugar (RBS) - 89 mg/dL, SGPT - 54 mg/dL, lactate dehydrogenase - 193.8 mg/dL. Serum bilirubin (total - 1.2, indirect - 1.0, direct 0.2 mg/dL), viral markers - negative. USG - Hepatosplenomegaly liver 14.5 cm and spleen 15.3 cm.
Hb electrophoresis - 100% HbF on HPLC and capillary method. DISCUSSION Hemoglobin A is the major normal adult Hb. It consists of heme + globin. Globin consists of two alpha chains and two beta chains. HbF is the major hemoglobin of the fetus. It consists of two alpha chains and two gamma chains. HbA2 consists of two alpha chains and two delta chains. It accounts for 1.5-3.5% of normal adult Hb. Thalassemia is an inherited disease causing impairment of globin chain production. In thalassemias, globin chains of normal structure are produced at a decreased rate. The beta thalassemias and their associated biochemical and molecular defects are given in Table 1. Beta-thalassemia refers to decreased production of beta chains. This is compensated by increased production of delta chains. Hence, there is an increase in HbA2. However, it is never more than 12%. The beta thalassemias are clinically classified as beta-thalassemia major, a severe and transfusion-dependent form; betathalassemia intermedia with less severe symptoms and beta-thalassemia minor or trait without clinical symptoms but with hematological abnormalities (Table 2). With an absence (β0) or marked decreased (β+) in beta-chain production, there is an excess of
Table 1. Beta Thalassemias and their Associated Biochemical and Molecular Defects Typical DNA defect
β-chain
δ-chain
γ-chain
HbF distribution
α: Non-α-globin imbalance
β+-thalassemia
Mutation
↓
+
+
Heterocellular
+++
β0-thalassemia
Mutation
0
+
+
Heterocellular
++++
δβ-thalassemia
Deletion
0
0
+++
Heterocellular
++
HPFH
Deletion
0 or ↓
0
++++
Pancellular
+
Table 2. Major Categories of Beta-thalassemia Syndromes Syndrome
Genotype
Clinical features
Hemoglobin pattern
β+-thalassemia
β+/β+
Thalassemia major or intermedia
↓↓ HbA, ↑↑ HbF, variable HbA2
β0-thalassemia
β0/ β0
Thalassemia major
>95% HbF, rest HbA2
δβ0-thalassemia
δβ0/δβ0
Thalassemia intermedia
100% HbF
Lepore/Lepore
Thalassemia major
85% HbF, 15% Hb Lepore
β+-thalassemia
β+/β
Thalassemia minor
HbA, ↑ HbA2, ±↑ HbF
β0-thalassemia
β0/β
Thalassemia minor
HbA, ↑ HbA2, ±↑ HbF
δβ0-thalassemia
δβ0/δβ
Thalassemia minor
HbA, 5-20% HbF, ±↓ HbA2
Lepore/β
Thalassemia minor
HbA, ↑ HbF, ↓ HbA2,10% Hb Lepore
Homozygous states
Hb Lepore Heterozygous states
Hb Lepore
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HEMATOLOGY alpha chains, which precipitate and cause ineffective erythropoiesis and form toxic inclusion bodies that kill erythrocytes and cause hemolytic anemia. Thalassemias are also classified as homozygous and heterozygous states. Clinical findings include jaundice, leg ulcers, gall stones, high output cardiac failure and splenomegaly evident in early childhood. There is a prominence of frontal bones, cheek bones and jaws due to extreme bone marrow hyperplasia, presenting with characteristic chipmunk facies. X-rays findings of thinned cortex of long and flat bones and thickening of skull with osteoporosis (hair on end appearance) are seen. Growth is stunted. Most patients require regular transfusions due to profound anemia and iron over loading occurs. Unlike most hemolytic diseases, the anemia is microcytic and hypochromic. In B0 thalassemia (homozygous) HbA is absent, HbF is as high as 98% and HbA2 is 2%. In β+-thalassemia (heterozygous), HbF is 60-95%, HbA is present but HbA2 ratio to HbA is always increased. In delta-beta-thalassemia, beta and delta chains are not produced and there is a significant increase in HbF. In the homozygous state, Hb consists only of HbF. The heterozygous state is similar to mild betathalassemia trait except that HbA2 is not increased or is even reduced and HbF is increased. Clinically, homozygous delta-beta-thalassemia behaves as a mild form of beta-thalassemia intermedia with a Hb level of 10-13 g/dL, mildly thalassemic red cell indices and mild hepatosplenomegaly. The mild phenotype is the result of increased production of gamma-chain, which compensate to some degree for lack of beta chains. HPFH - In this condition, there is persistence of HbF in adults without significant hematologic abnormalities or clinical illness. The rise in HbF in adults, presents with a wide clinical spectrum. In one end of the spectrum, in β0-thalassemia, HbF may be raised to even more than 95% with the rest HbA2 and absent HbA. This presents in childhood, clinically as homozygous β0-thalassemia major, with profound anemia, microcytic hypochromic picture in peripheral smear, red cell indices of thalassemia. Target cell, poikilocytosis, Howell-Jolly bodies and anisocytosis are seen. The reticulocyte count is less elevated than expected for degree of anemia because of destruction of erythroid precursors in the marrow. Intramedullary destruction of Hb (ineffective erythropoiesis) is markedly increased. Extramedullary erythropoiesis occurs and patients die by the third decade. The raised
gamma chains do not compensate for the lack of beta chains by improving clinical outcome. The other clinical picture is that of delta-betathalassemia (homozygous), where HbF is again very high (even 100%). HbA is absent and HbA2 may be absent or present in normal range. But unlike β0thalassemia major, it presents clinically as a mild form of beta-thalassemia intermedia. Patients present with above 10 g/dL, mild thalassemic indices and minimal hepatosplenomegaly. The raised gamma chains compensate to high-degree for the lack of beta chains. At the other end of the spectrum is HPFH, where HbF is raised to nearly 100%. Hb levels are normal, red cell indices are normal and patients are asymptomatic and are apparently healthy. They are usually not diagnosed as they never need treatment and may not visit a hospital. Both our patients had raised HbF to >98%. However, 1 patient presented with severe anemia in childhood to the extent of requiring 3 blood transfusions with a clinical picture of jaundice, splenomegaly, raised reticulocyte count, Mentzer index of 15.13 and thalassemic red cell indices, HbF 98.7%, HbA2 1.3%, absent HbA and had B0-thalassemia major. The other patient was 33 years old, clinically there was no anemia, no icterus, mild splenomegaly, with mild thalassemic red cell indices, reticulocyte count of 1%, HbF 100%, absent HbA and HbA2. He had deltabeta-thalassemia, which presented clinically with mild symptoms of beta-thalassemia intermedia. CONCLUSION The carry home message of this presentation is that although HbF is elevated in the absence of HbA after birth, all is not well. The prognosis depends on the clinical picture, which can present as β0-thalassemia in childhood with early death, but it can also present as delta-beta-thalassemia and HPFH; where they are asymptomatic and lead normal lives. SUGGESTED READING 1. Harrison’s Principles of Internal Medicine. 18th Edition, Vol 1. Mc-Grawhill; 2012. 2. De Gruchy’s Clinical Haematology. 5th Edition; 2011. 3. Henry’s Clinical Diagnosis and Management Laboratory Methods. 21st Edition; 2007.
by
4. Davidson’s Principles and Practice of Medicine. 21th Edition, Churchill Livingstone; 2010.
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A Case of Kerosene Poisoning Complicated with Right-sided Pleural Effusion: An Unusual Presentation MONIKA MAHESHWARI
ABSTRACT In literature, data is scarce on complications and lethal outcomes of hydrocarbon poisoning following kerosene aspiration in adults. We, herein report a case of a right-sided pleural effusion secondary to kerosene aspiration in a 45-year-old male.
Keywords: Kerosene poisoning, pleural effusion, hydrocarbons
K
erosene poisoning, intentionally or accidentally, is toxic. Lethal dose is 30-100 mL. The most common pulmonary manifestation is aspiration pneumonia. Rarely, it may lead to complications like pneumothorax, pneumatocele, bronchiectasis, bronchopleural fistula and bilateral hemorrhagic pleural effusion. We report herein a case of unilateral (right-sided) pleural effusion following kerosene ingestion. CASE REPORT A 45-year-old male presented in casualty department with complaints of progressively increasing breathlessness associated with chest pain following accidental ingestion of kerosene (around 30 mL), about half an hour before admission. On examination, he was conscious, oriented but tachypneic with respiratory rateâ&#x20AC;&#x201D;30/min and oxygen saturation 87%. Other vital parameters were stable with pulse 88/min, regular and blood pressure 110/76 mmHg. Chest auscultation revealed diminished breath sounds in right infrascapular zone. Rest of the systemic examination revealed no abnormality.
Laboratory investigation showed normal hemoglobin with raised total leukocyte count (12,200 cells/mm3). An arterial blood gas analysis revealed arterial oxygen
tension (pO2) - 80 mmHg, pCO2 - 40 mmHg, HCO3 23 mEq/L and pH - 7.3. Chest X-ray film showed right-sided pleural effusion (Fig. 1). Pleurocentesis was done under ultrasonic guidance. Pleural effusion analysis showed transudative picture and yielded no organisms growth. The patient was treated with oxygen supplementation and corticosteroids (prednisolone 1 mg/kg body weight). The patient responded to the treatment and was discharged symptomatically better, after 7 days of treatment. DISCUSSION Kerosene oil, a petroleum product, is a mixture of hydrocarbons contaminated with organic sulfur, petrol, gasoline, vaseline and paraffin related hydrocarbons.1 The most frequent adverse effect of any hydrocarbon poisoning is aspiration. Hydrocarbons with lower
RL
LL
R PI. Effusion
Associate Professor JLN Medical College, Ajmer, Rajasthan Address for correspondence Dr Monika Maheshwari Naveen Niwas, 434/10, Bapu Nagar, Ajmer, Rajasthan E-mail: opm11@rediffmail.com
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Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
Figure 1. Chest X-ray film showing right-sided pleural effusion.
INTERNAL MEDICINE viscosity and higher volatility are associated with a greater chance of aspiration with resultant pulmonary injury. The type 2 pneumocytes are the most affected resulting in decreased surfactant production, which leads to alveolar collapse, ventilation-perfusion mismatch and hypoxemia. The end result of hydrocarbon aspiration is interstitial inflammation, intra-alveolar hemorrhage and edema, hyperemia, bronchial necrosis and vascular necrosis.2
REFERENCES
The hemorrhagic alveolitis and bronchial and vascular necrosis can result in a hemorrhagic pleural effusion, which has rarely been reported.3,4 So, treating physicians should be aware of this rare complication. Symptoms and radiological findings resolve rapidly after cessation of exposure and corticosteroid therapy as it did in our patient.
3. Prasad R, Karmakar S, Sodhi R, Karmakar S. Bilateral hemorrhagic pleural effusion due to kerosene aspiration. Lung India. 2011;28(2):130-2.
1. Bronstein AC, Spyker DA, Cantilena LR Jr, Green J, Rumack BH, Heard SE. 2006 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS). Clin Toxicol (Phila). 2007;45(8):815-917. 2. Dice WH, Ward G, Kelley J, Kilpatrick WR. Pulmonary toxicity following gastrointestinal ingestion of kerosene. Ann Emerg Med. 1982;11(3):138-42.
4. Rajashekhar P, Adinagesh, Vamshivhari, Sivunisrilatha. A rare case of kerosene poisoning with rightsided pleural effusion. Indian J Appl Res. 2015,5(8): 678-79. ■■■■
BE FAST: A Modified Assessment Tool to Identify Stroke ‘Time is brain’. A patient with suspected stroke or ‘brain attack’ should therefore be shifted to hospital at the earliest and given a clot dissolving therapy. Jeffrey L Saver reported in the journal Stroke that “every minute in which a large vessel ischemic stroke is untreated, the average patient loses 1.9 million neurons, 13.8 billion synapses and 12 km (7 miles) of axonal fibers. And, each hour in which treatment fails to occur, the brain loses as many neurons as it does in almost 3.6 years of normal aging” (Stroke. 2006;36:263-6). The American Stroke Association recommends the mnemonic FAST to recall the signs of stroke and quickly identify victims of stroke; "F" stands for Face drooping; "A" stands for Arm weakness i.e., inability to raise arms high, "S" stands for Speech difficulty - slurring of speech and "T" stands for Time - time to call for emergency medical help. A new research has devised a modified version of this simple prehospital stroke assessment tool, ‘BE FAST’ for early identification of patients with occlusion of large vessel, which was presented at the American Stroke Association’s International Stroke Conference 2017, which concludes in Houston, USA today (AHA News. February 22, 2017). The acronym ‘BE FAST’ evaluates: ÂÂ
Balance/coordination
ÂÂ
Eye deviation
ÂÂ
Facial weakness
ÂÂ
Arm/leg weakness
ÂÂ
Slurred speech/sensory deficits
ÂÂ
Time of onset
Researchers examined 455 ischemic stroke patient charts from July 2014 to June 2015, using information about patients’ symptoms and physical findings. The sensitivity i.e. positively recognizes a large vessel occlusion, for the ‘BE FAST’ score was found to be 83%. Stroke is an emergency and getting timely help and treatment is extremely important. Hence, it is very important to act fast to identify these patients. Early treatment improves the chances of recovery.
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A Study to Probe the Biological Lag of Electrolyte Imbalance Due to Diuretics SUDHAKAR M PARHATE*, ASHTAPUTRE†, RENUKA HARWANI*, KHALID INAMDAR*
ABSTRACT A total number of 453 (age 25-75 years) patients were enrolled to probe the type of serum electrolyte imbalance and the biological lag, which occurred in patients suffering from renal edema, hepatic edema, hypertension and ischemic heart diseases, who were prescribed diuretics (spironolactone, furosemide and amiloride). The adverse effects (6.8%) were hypokalemia (2.9%), followed by hyponatremia (2.4%) and hyperkalemia (1.5%). The earliest adverse effects found at 2 months lag were hyponatremia (22%), hypokalemia (13%) and hyperkalemia (3.2%). At 4-10 months lag, similar adverse drug effects were detected with variable pattern. Delayed effects, as long as at 12 months lag, were hypokalemia (furosemide-6.4%), hyperkalemia (spironolactone-3.2%). None of the angina pectoris group showed adverse effects. Maximum patients belonged to higher age 61-75 years; (37.5%) and most were sufferers of renal edema (38.7%).
Keywords: Diuretics, electrolyte imbalance, biological lag, dose-dependent dynamics, prognostic dilemma
L
ong-term administration of diuretics is known to cause adverse drug effects (ADE) such as hyperkalemia (potassium-sparing group), 1 hypokalemia and hyponatremia (loop diuretic). Serum sodium and potassium abnormalities are deleterious for cardiac and other functions, hence their detection at proper biological lag (time interval between drug administration and desired effects)1 (lag) is of utmost importance. However, there are no reports regarding lag for such ADE to be evident; also no knowledge about the complex inter-relationship between the dose of diuretic, type of ADE, diagnosis and age susceptibility. METHODS Adult male patients (25-75 years) attending Medicine OPD, who were prescribed various diuretics formed the sample. The clinical diagnosis, baseline investigations were recorded. Diuretics prescribed were targeted for studying biological lag; types of ADE and their
*Dept. of Pharmacology †Dept. of Internal Medicine Govt. Medical College and Hospital, Akola, Maharashtra Address for correspondence Dr Sudhakar M Parhate Professor and Head Dept. of Pharmacology Govt. Medical College, Akola - 444 001, Maharashtra E-mail: drsmparhate@gmail.com
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Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
relationship (if any) with diagnosis and age. The dose of diuretics was recorded.
Inclusion Criteria ÂÂ
OPD level treatment.
ÂÂ
One diagnosis.
ÂÂ
Normal baseline serum electrolyte (s. electrolyte) report, diuretics and other drugs given based on diagnosis.
Exclusion Criteria ÂÂ
Patients who needed indoor management.
ÂÂ
Polydiagnosis.
ÂÂ
Abnormal baseline electrolyte levels.
ÂÂ
Patients prescribed s. electrolytes.
ÂÂ
Diabetes mellitus subjects.
ÂÂ
Malabsorption syndrome.
ÂÂ
Chronic diarrhea/recent gastroenteritis.
ÂÂ
Hepatic/renal failure patients on drug therapy.
other
drug
affecting
The patient’s clinical protocol was pursued for clinical review, investigations, prognosis as per physician’s advice. The s. electrolytes report was noted every 2 months till 12 months. The lag of s. electrolyte imbalance was correlated with dose of diuretic, type of ADE, diagnosis and age. We also jotted down the pharmacotherapy of s. electrolyte imbalance.
INTERNAL MEDICINE serum sodium and potassium reports for assessing the electrolyte imbalance; month when detected (2-12) number of subjects affected, the related diagnosis and the age group affected. Table 3 shows the s. electrolyte changes due to diuretic therapy in above patients, after serial investigations at space of 2 months till 12 months (For abbreviations refer to Table 3 footnote).
RESULTS The present study was conducted on 453 adult male patients of age 25-75 years as per above criteria. The distribution of patients according to age and the diagnosis (renal edema, hepatic edema, hypertension, ischemic heart diseases) is shown in Table 1. Among the patients given diuretics, age-wise distribution showed that there were 27 (6%) patients belonging to the age group of 25-40 years, 106 (23.4%) to age group 41-50 years, 150 (33.1%) to age group 51-60 years and 170 (37.5%) to age group 61-75 years. As per diagnosis, 109 prescriptions were given to patients of renal edema (nephritis-24%), 97 to patients of hepatic edema (cirrhosis-21.4%), 85 to patients of hypertension (mild) (18.7%), 65 to patients of angina pectoris (14.5%) and 97 patients of post-myocardial infarction (MI) (noninterventional) (21.4%).
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Hypokalemia was seen at 2 months lag in 1 (L/d), 3 (R/d, L/a, H/c) subjects on furosemide 20 and 40 mg, respectively. At 4-12 months lag none of furosemide 20 mg receivers but 40 mg receivers were found hypokalemic as documented in 2 patients each at 4 (M/c, R/b), 6 (H/b, L/a), 8 (L/d, R/b), 12 months lag (M/d, L/a), respectively and 1 (R/c) patient at 10 months lag. Spironolactone and furosemide + amiloride did not induce hypokalemia.
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Hyponatremia: Low serum sodium was seen in patients taking furosemide 20 mg, 1 each at 2 (R/d) and 4 (R/b) months lag. Recipients of furosemide 40 mg were found hyponatremic at lag of 2 months in 4 (R/d L/d, M/d, H/c); 1 each at lag of 4 (M/c), 6 (L/b), 8 (R/a) months. In addition, low serum sodium was detected in subjects on furosemide + amiloride therapy at lag of 2 months in 2 (R/b, R/d).
Ninety-three (20.5%) patients were prescribed spironolactone 50 mg b.i.d.; furosemide 20 mg o.d. was given to 94 (20.7%); 40 mg o.d. to 73 (16.1%), and furosemide + amiloride fixed-dose combination (FDC, 20 mg +10 mg) o.d. to 193 (42.6%) patients as shown in Table 2. Following parameters were considered; the
Table 1. The Distribution of Patients According to Age and Diagnosis Age (years)
Diagnosis
Age group total
Renal edema
Hepatic edema
Hypertension AP
PMI
25-40
8
3
8
6
2
27 (6%)
41-50
26
12
14
23
31
106 (23.4%)
51-60
34
47
24
24
21
150 (33.1%)
61-75
41
35
39
12
43
170 (37.5%)
109 (24%)
97 (21.4%)
85 (18.7%)
65 (14.5%)
97 (21.4%)
453 (100%)
Diagnosis total
IHD
IHD = Ischemic heart disease; AP = Angina pectoris; PMI = Post-MI (conservative therapy)
Table 2. The Various Diuretics Prescribed as per Diagnosis Diuretic
Diagnosis Renal edema
Spironolactone (50 mg b.i.d.)
Hepatic edema
Drug-wise total
Hypertension
IHD AP
PMI
8
42
9
10
24
93 (20.5%)
12
8
40
12
22
94 (20.7%)
Furosemide 20 mg o.d.
9
6
20
20
18
73 (16.1%)
Furosemide + Amiloride (20 + 10 mg)
40 mg o.d.
80
41
16
23
33
193 (42.6%)
Total (diagnosis-wise)
109 (24%)
97 (21.4%)
85 (18.7%)
65 (14.5%)
97 (21.4%)
453 (100%)
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INTERNAL MEDICINE Table 3. Electrolyte Imbalance Due to Diuretics, Biological Lag, Diagnosis and Age Group Diuretic
Serum electrolyte reports Hypokalemia
Hyponatremia
Hyperkalemia
Month of Investigations (Diagnosis and age group; a, b, c, d) Month
2
4
6
8
10
12
2
4
6
8
10
12
2
4
6
8
10
12
Spironolactone 50 mg b.i.d. n = 93
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
0
0
1
-
-
-
-
-
-
-
-
-
-
-
-
-
R
M
-
-
L
-
-
-
-
-
-
-
-
-
-
-
-
-
(d)
(c)
-
-
(a)
Furosemide 20 mg, n = 94
1
0
0
0
0
0
1
1
0
0
0
0
0
0
0
0
0
0
L
-
-
-
-
-
R
R
-
-
-
-
-
-
-
-
-
-
(d)
-
-
-
-
-
(d)
(b)
-
-
-
-
-
-
-
-
-
-
Furosemide 40 mg, n = 73
Furosemide + Amiloride n = 193
3
2
2
2
1
2
4
1
1
1
0
0
0
0
0
0
0
0
R1
M1
H1
L1
R
M1
R1
M
L
R
-
-
-
-
-
-
-
-
(d)
(c)
(b)
(d)
(c)
(d)
(d)
(c)
(b)
(a)
-
-
L2
R2
L2
R2
-
L2
L2
-
-
-
-
-
(d)
-
-
-
-
-
(a)
(b)
(d)
(b)
-
(a)
M3(d)
H3
-
-
-
-
-
H4
(C)
-
-
-
-
-
(c)
0
0
0
0
0
0
2
0
0
0
0
0
1
2
1
0
0
0
-
-
-
-
-
-
R1
-
-
-
-
-
R
M1
L
-
-
-
(d)
(c)
(b)
-
-
-
-
L2
-
-
-
-
(b) R2
-
-
-
(d) Total (N = 453 )
13 (2.9% )
-
-
(d) 11 (2.4% )
7 (1.5%)
Note: Diagnosis: R= Renal edema, L= Hepatic edema, H = Hypertension, A = Angina pectoris, M = Post myocardial infarction; Age group: a = 25-40 years, b = 41-50 years, c = 51-60 years, d = 61-75 years.
Hyperkalemia was detected in spironolactone receivers in three subjects; one each at lag of 4 (R/d), 6 (M/c), 12 (L/a) months; furosemide + amiloride receivers too found so (n = 4) at lag of 2 months in 1 (R/d), at lag 4 months in 2 (M/c, L/d), and at lag 6 months in 1 (L/b) patient. Overall, the ADE as electrolyte imbalance was observed in 31 (6.8%) sample subjects, the break-up being hypokalemia in 13 (2.9%), hyponatremia in 11 (2.4%) and hyperkalemia in 7 (1.5%).
hyponatremia in 2, 6, 1, 0, 2 (11: 35.5%); maximum in renal edema (6/11: 54.5%) and hyperkalemia in 3, 2, 0, 0, 2 (7: 22.5%) topping in hepatic edema patients (3/7: 42.8%). Overall ADE assessed in this study was hepatic edema-10 (32.2%), renal edema-12 (38.7%), hypertension-3 (9.7%), none in angina (0%) and postMI-6 (19.4%).
The ADE of diuretics as electrolyte imbalance in context to diagnosis was seen in total 31 patients except angina pectoris (0), as shown in Table 4.
All the age groups (a, b, c, d; 25-75 years) have shown s. electrolyte imbalance in the form of hypokalemia in 3, 3, 3, 4 (n = 13); hyponatremia in 1, 3, 2, 5 (n = 11) and hyperkalemia in 1, 1, 2, 3 (n = 7), respectively (total n = 31). In a nutshell above 3 types of ADE as per age group were found: Group ‘á’ – (25-40 years) 5 (16.1%), Group ‘b’ and ‘c’ (41-50 and 51-60 years)–7 each (22.6%) and Group ‘d’ (61-75 years) - 12 (38.7%).
ÂÂ
Table 4 depicts the relationship between s. electrolyte imbalance and diagnosis in hepatic edema, renal edema, hypertension, angina pectoris, post-MI, respectively (total 31: 6.8%). Hypokalemia was seen in 5, 4, 2, 0, 2 (13: 42%); most in hepatic edema (5/13: 38.5%),
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The electrolyte imbalance as change in serum sodium and potassium level was seen in all age groups (25-75 years) is shown in Table 5.
INTERNAL MEDICINE Table 4. Exhibits Relationship of Serum Electrolyte Change and Diagnosis Electrolyte change
Diagnosis Hepatic edema Renal edema Hypertension Angina pectoris
Hypokalemia
5
4
2
Post-MI
Total electrolyte imbalance
2
13 (42%)
0
Hyponatremia
2
6
1
0
2
11 (35.5%)
Hyperkalemia
3
2
0
0
2
7 (22.5%)
10 (32.2%)
12 (38.7%)
3 (9.7%)
0 (0%)
6 (19.4%)
31 (100%)
Total ADE (Diagnosis-wise)
Table 5. Serum Electrolyte Imbalance as per Age Group a (25-40 years)
b (41-50 Years)
c (51-60 Years)
d (61-75 years)
Total (diagnosis-wise)
Hypokalemia
Electrolyte change
3
3
3
4
13
Hyponatremia
1
3
2
5
11
Hyperkalemia Age group total
1
1
2
3
7
5 (16.1%)
7 (22.6%)
7 (22.6%)
12 (38.7%)
31 (100%)
DISCUSSION Diuretics are frequently prescribed drugs in medical speciality. The pharmacotherapy may be of short or long duration; later may cause serious ADE in the form of s. electrolyte imbalance, which may affect vital cardiac function. So, monitoring these biochemical changes is the aim of ethical therapeutics. There is no data about the biological lag for ADE to be evident, moreover reports on the complex relationship between the diuretic, dose, type of s. electrolyte imbalance, clinical diagnosis and age vulnerability is lacking. The research target of present study was to make an effort to explore such information, so as to be pharmacotherapeutically vigilant regarding even marginal detection of overconcentration of serum electrolytes, thereby to advocate prompt therapy to curtail complexity of morbidity and mortality. Even if the s. electrolyte reading is within physiological but at high border level, serial estimation may signal either the declining, static, gradual or rapidly increasing concentration. In beginning, marginal overconcentration may be asymptomatic or clinically undetectable, a situation of clinically prognostic dilemma, but short spaced investigation may signal the risk; treatment at this stage may prevent further complications. The sample patient population selected as per criteria described earlier, enrolled 453 suitable adult males of different diagnosis from 25 to 75 years. Age group 61-75 years had the largest number of patients (170: 37.5%) while age group 25-40 years had the least (27: 6%). The diuretics prescribed were loop group (furosemide 20 and 40 mg) and potassium-sparing group
(spironolactone 50 mg, amiloride 10 mg). Furosemide + amiloride FDC was given most in 193 (42.6%) subjects, and most were sufferers of renal edema (24%), indicating that diuretics were mostly needed for upper age group population with reference to present clinical diagnosis in this study. It was observed that patients with high normal S. potassium level (5 mEq/dL) as baseline investigation were prescribed furosemide + amiloride combination. This is in agreement with the principles of preventing hyperkalemia.1 There are multiple indications of diuretics including lifesaving one.1 Among group of diuretic prescription, patients suffering from renal edema (nephritis) were maximum (24%), and so were those of 61-75 years (37.6%) showing the trend of renal diseases being prominent in this study, as also suggested by other authors.2 Although the mechanism of action of various diuretics is different, the ultimate effect is to eliminate sodium + water load; reduce extracellular fluid volume; vascular edema.1 Furosemide is a highly potent loop diuretic, site of action being ascending limb of loop of Henle, where it inhibits Na+-K+-2Cl- symport, thus may cause hypokalemia and hyponatremia,1 whereas spironolactone and amiloride are weak diuretics, but both are potassium-sparing one, so hypokalemia does not occur. Spironolactone by mechanism of action is a mineralocorticoid receptor (MR) antagonist, acts on late distal tubule. Amiloride interacts with the Na+K+-H+ transport mechanism at distal convoluted tubule and collecting duct.1 However, potassium-sparing diuretics may lead to hyperkalemia.1,2 These electrolyte alterations have multiple adverse functional cardiac effects,2 may lead to extended indoor stay, more cost
Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
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INTERNAL MEDICINE of therapy and also risk of mortality. Moreover, the problem with these ADE is that, in few patients they are asymptomatic and undetectable clinically - a silent risk. Therefore, fair information of biological lag, the type of electrolyte derangement that may appear early or late, which patients by age and diagnosis are vulnerable for these ADE, is very vital for a competent physician. In the present study, s. electrolyte imbalance (total 6.8%) was seen as hypokalemia (2.9%), hyponatremia (2.4%) and hyperkalemia (1.5%). The types of ADE seen earliest at 2 months lag were: ÂÂ
Hypokalemia in patients taking furosemide 20 mg (n = 1) and more with 40 mg - (n = 3) (total n = 4), showing the risky dose-dependent potential.
ÂÂ
Hyponatremia observed in furosemide receivers 20 mg (n = 1), 40 mg (n = 4), again showing the dose-dependent effect; and furosemide + amiloride FDC (n = 2) thus (total n = 7). Hypokalemia (13) and hyponatremia (11) did not show similarity of incidence and related diagnosis as well, may be due to individual variable state of electrolyte elimination kinetic.1
ÂÂ
Hyperkalemia in furosemide + amiloride FDC treated group - (n = 1). The early electrolyte imbalance seen as such in this study at 2 months lag warrants caution; it may be possible that few or more of these ADE have occurred still earlier, so investigations at short period is suggested. S. electrolyte reports at later space from 4 to 10 months also shows all three ADE with variable pattern.
At 12th months lag ADE is found as hypokalemia in furosemide 40 mg dose - (n = 2), and hyperkalemia in spironolactone (n = 1) subject, which suggests not to overlook the possibility of delayed s. electrolyte imbalance. It is noteworthy that the total ADE of furosemide are 3 with 20 mg dose, and 19 with 40 mg dose, a dose-dependent effect signalling geometric trend; this draws the attention to titrate dose cautiously so as to avoid ADE. Hyperkalemia is the principle risk of spironolactone, which can be life-threatening.1 It is also observed that at any lag, the s. electrolyte imbalance once treated appropriately, none showed recurrence, suggesting justified treatment, preventive advice and proper follow-up by physician in this hospital set-up. Overall, the s. electrolyte imbalance (6.8%) although showed variable pattern with reference to lag, age and diagnosis, the chronological relation of diagnosis and ADE (n=) was - renal edema-12 (38.7%), hepatic edema-10 (32.3%), post-MI-6 (19.3%), hypertension3 (9.7%) and none from angina pectoris group. However,
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the incidence of hypokalemia was most (42%), then hyponatremia (35.5%), followed by hyperkalemia (22.5%) out of total ASEs, overall prominently affecting in sequence patients with hepatic edema (5/13: 38.5%), renal edema (6/11: 54.5%) and hepatic edema (3/7: 43%), respectively. The diuretics interact with pathology (drug-disease interaction) of renal edema (nephritis) that involve reduced glomerular filtration rate (GFR), alteration in electrolyte kinetic; of hepatic edema (cirrhosis) causing hyperaldosteronic state; of post-MI causing hemodynamic alteration and hypertension affecting renal, vascular elements and extracellular fluid volume derangement.3 All the age groups have shown ADE as electrolyte imbalance; however, higher age group (61-75 years) were affected most (12; 38.7%), followed in equal fashion by 51-60 years, 41-50 years (7 each: 22.6%) and least were from age 25 to 40 years (5: 16.1%). The finding regarding upper age group suggests that due to declining physiological function of renal, gastrointestinal, hepatobiliary systems, the ADE in geriatric age sample corroborate maximum with reports.4 Surprisingly no patient of angina pectoris group showed any electrolyte imbalance due to diuretics. Although electrolyte imbalance seen here from 2 to 12 months lag gives fair information, the research needs large bisexual sample size, more diagnostic coverage, investigations at lesser space so as to find more informative knowledge, thereby appropriate measures can be undertaken at the right time to restrict complications, morbidity, mortality and also reduce indoor stagnation and cost of treatment. CONCLUSION In the present study, we made an attempt to find out the adverse effects of diuretics in patients pursued over a period of 12 months (spironolactone, furosemide and amiloride) prescribed to 453 patients of 25-75 years age). Most patients were of the age group 61-75 years (37.5%) and maximum were suffering from renal edema (24%). The diagnostic indications were renal edema, hepatic edema, hypertension and ischemic heart disease (stable angina pectoris, post-MI). The diuretics preferred most was furosemide + amiloride combination (42.5%). The electrolyte imbalance observed (total = 6.8%) were hypokalemia (42%), hyponatremia (35.5%) and hyperkalemia (22.5%). The early adverse effect at 2 months lag found, was hyponatremia in 7 (22.6%), hypokalemia in 4 (13%) and hyperkalemia in 1 (3.2%). At lag of 12 months, hypokalemia (6.4%) and hyperkalemia (3.2%) were observed. At lag 4-10
INTERNAL MEDICINE months, electrolyte imbalance was seen in similar way with variable pattern. Overall, patients showing electrolyte imbalance were found most of renal edema (38.7%), and least of hypertension (9.6%). No adverse effects were seen in patients of angina pectoris group, does not mean that in these patients ADE does not occur. In nutshell, the electrolyte imbalance due to diuretics may occur at any time, irrespective of diagnosis, no age bar, draws the attention when planned for prolonged or lifelong therapy. Whenever they occur, there should be no recurrence after treatment, as found in this hospital prescription model. Repeated short space investigations correlated with age, symptoms, clinical examination and diagnosis is the aim of modern ever-developing field of medical science.
REFERENCES 1. Regulation of renal function and vascular volume. In: Brunton LL, Chabner B, Knollman BC (Eds.). Goodman and Gillman: The Pharmacological Basis of Therapeutics. 2011. pp. 671-700. 2. Aging and disease. In: Walker BR, Colledge NR, Ralston SH, Penman I. Davidsons Principle and Practice of Medicine. Churchill Livingstone, Elsevier; 2014. pp. 166-78. 3. Robbins Basic Pathology. Vinay Kumar, Abbas, Aster (Eds.), Reed Elsevier India Private Limited, 2014, p: pathogenesis - nephritis 518, cirrhosis of liver 617, hypertension 333, IHD 375-77.
4. Geriatric physiology - Aging. In: Lango DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J (Eds.). Harrison's Principle and Practice of Internal Medicine. Mac-Graw Hills; 2012/1:562-69. ■■■■
Health Ministry Undertakes Largest Ever Drug Survey in the World for Determining Quality of Drugs The Ministry of Health and Family Welfare, Government of India had entrusted the work relating to carrying out a Survey of the extent of Problems of ‘Spurious and Not of Standard Quality Drugs’ to the National Institute of Biologicals (NIB), Noida, which has submitted the report to the Government. The statistical design of the Drug Survey included as many as 224 Drug molecules belonging to 15 different therapeutic categories of the National List of Essential Medicines (NLEM) 2011. As part of this survey, 47,954 drug samples relating to 23 dosage forms were drawn from 654 districts of 36 States and Union Territories from the supply chains including retail outlets, Government sources and from eight airports and sea ports. Overall, out of the 47,012 samples tested, 13 samples were found to be Spurious and 1,850 samples were found to be ‘Not of Standard Quality’ (NSQ). As such, the percentage of NSQ Drugs in India has been found to be 3.16% and that of spurious drugs 0.0245%. This is the largest ever scientifically designed and professionally executed drug survey undertaken in the world for determining the quality of drugs. The entire survey report has been uploaded in the Reports section of website of the Ministry of Health and Family Welfare viz. HYPERLINK "http://www.mohfw. gov.in/" www.mohfw.gov.in and also on the website of Central Drugs Standard Control Organisation (CDSCO) viz.HYPERLINK "http://www.cdsco.nic.in/" www.cdsco.nic.in … (Press Information Bureau, Ministry of Health and Family Welfare, 22nd February, 2017)
Nearly 1.4 Million Children at Imminent Risk of Death: UNICEF Almost 1.4 million children are at imminent risk of death from severe acute malnutrition this year, as famine looms in Nigeria, Somalia, South Sudan and Yemen, UNICEF said today. “Time is running out for more than a million children,” said UNICEF Executive Director Anthony Lake. “We can still save many lives. The severe malnutrition and looming famine are largely man-made. Our common humanity demands faster action. We must not repeat the tragedy of the 2011 famine in the Horn of Africa.” This year, UNICEF is working with partners to provide therapeutic treatment to 2,20,000 severely malnourished children in Nigeria, over 2,00,000 severely malnourished children in South Sudan, more than 200,000 severely malnourished children in Somalia, and 320,000 children in Yemen … (UNICEF, February 21, 2017)
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OBSTETRICS AND GYNECOLOGY
Bilateral Single System Ectopic Ureters with Secondary Calculi in an Adult: Case Report GOPI KISHORE M*, SUHASINI G*, PRASAD PVGS*, SAINADH AV*
ABSTRACT Bilateral single system ectopic ureter (BSSEU) is a rare entity in urology presenting typically in the pediatric age group with urinary incontinence, recurrent urinary tract infection (UTI) or ureteric obstruction. It is generally agreed that these patients require ureteric reimplantation with or without bladder augmentation depending upon bladder capacity. We herein present a case of BSSEU presenting late in adulthood with secondary ureteric calculi, which is the first of its kind to be reported in literature. It was managed endoscopically with satisfactory outcome and without a need for major reconstructive surgery.
Keywords: Ectopic ureter, secondary calculi, megaureter, hydroureteronephrosis
B
y definition, an ectopic ureter is any ureter, single or duplex, that does not enter the trigonal area of the bladder.1 It is more common among females and is usually associated with double collecting system. About one-fifth of ectopic ureters are associated with single system kidneys and are common in males. A rare entity of bilateral single-system ectopic ureters (BSSEU) occurs and may be associated with a hypoplastic bladder and bilateral renal abnormalities.2
and bladder (CT-KUB, Fig. 1) revealed bilateral hydroureteronephrosis with multiple calculi in right lower ureter and single calculus in left lower ureter. Intravenous pyelogram (IVP, Fig. 2) revealed bilateral single system gross hydroureteronephrosis
We are presenting a case of BSSEU in an adult male with secondary stones, which was managed endoscopically. CASE REPORT A 50-year-old male presented with obstructive voiding symptoms, increased frequency, dysuria, hematuria and bilateral flank pain since 2 months. General examination was unremarkable. Abdominal examination was normal except mild bladder distension. External genitalia and per rectal examination was normal. All routine investigations including kidney function tests were normal. Ultrasonography showed bilateral moderate hydroureteronephrosis with lower ureteric calculi. Plain computed tomography-kidney, ureter
*Dept. of Urology ESIC SSH, Sanath Nagar, Hyderabad, Telangana Address for correspondence Dr Gopi Kishore M Dept. of Urology, ESIC SSH, Sanath Nagar, Hyderabad - 500 038, Telangana E-mail: gkmeda@yahoo.com
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Figure 1. Reformatted coronal image of plain CT-KUB scan showing bilateral hydroureteronephrosis with lower ureter calculi.
OBSTETRICS AND GYNECOLOGY with multiple calculi in right ureter and one calculus in left ureter. With provisional diagnosis of bilateral megaureters with secondary stones or bilateral lower ureteric calculi with megaureters, cystourethroscopy was carried out under spinal anesthesia. Cystourethroscopy (Fig. 3) showed right
ureteric orifice just distal to bladder neck and left ureteric orifice distal to right ureteric orifice and 1 cm proximal to the veru with absent trigone and good capacity bladder. Bilateral retrograde pyelography showed bilateral single system ectopic megaureters with secondary calculi. Definitive diagnosis of BSSEU with secondary calculi was made. Bilateral ureteric meatotomy was done up to 1 cm proximal to bladder neck using a Collins knife and stones fragmented with help of nephroscope and lithotripsy. As stone burden was high, fragmented stones in bladder were removed by percutaneous cystolithotripsy and bilateral double-J (DJ) stenting done. Postoperative recovery was uneventful. In postoperative period, the patient was totally continent and able to void freely. DJ stent was removed after 1 month and follow-up ultrasound showed decrease in hydroureteronephrosis and patient is doing well without urinary tract infection (UTI) or flank pain. DISCUSSION
Figure 2. Post-void IVP film showing bilateral single system hydroureteronephrosis with secondary calculi.
Right ureteric orifice Left ureteric orifice
Veru
Figure 3. The cystourethroscopic picture showing both ureteric orifices in prostatic urethra.
Ectopic ureters are more common in females, 80% of them drain a duplicated kidney and are frequently associated with a poorly functioning renal unit.3 Embryologically, ectopic ureters can arise due to abnormal timing or location of the primary ureteral budding from the mesonephric ducts. That temporospatial location will determine both the character of the ureter incorporated into the emerging bladder, as well as the development of the trigone and kidney.2 It is believed that, as single system ectopic ureters (SSEU) are associated with dysplastic kidneys, the affected renal units do not function appreciably.3 Single system ureteral ectopia is due to cranial origin of ureteric bud from mesonephric duct, which results in delay in incorporation into the urogenital sinus and prevents in growth of mesenchyme, which is necessary for development of bladder neck musculature.4 As there is no formation of trigone and base plate, bladder neck is wide, poorly defined and incompetent. BSSEUs are even rarer compared to SSEU.4 It is possible that during development the abnormal origin of both ureteric buds results in poor mesenchymal induction of the urogenital structures, which results in failure of normal development of the bladder and bladder neck. Both the sphincter and reservoir functions of the bladder will be severely affected. Overall, female patients are affected twice as commonly as males, although SSEU is reported to be more common in males.3,5 Usually, BSSEU present in infants
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OBSTETRICS AND GYNECOLOGY or children with recurrent UTIs, urinary incontinence and a poor capacity of bladder, which requires ureteric reimplantation with or without bladder augmentation.6,7 In males, the posterior urethra is the most common site for insertion of the ectopic ureter.5,6 Evaluation is usually by ultrasonography, renal nuclear scan, micturating cystourethrography and retrograde pyelography. Intravenous pyelography and magnetic resonance imaging (MRI) may be used occasionally.2,6 Male patients with BSSEU in posterior urethra proximal to external sphincter may be continent with external sphincter control and have a good capacity bladder. Patients with good bladder capacity may require bilateral ureteric reimplantation alone.6,7 Our patient presented with obstructive symptoms due to stone in the right distal ureter obstructing bladder neck. As the patient presented in late adulthood with secondary stones and a good capacity bladder with normal continence, endoscopic management alone was done with ureteral meatotomy, lithotripsy and DJ stenting. Surgical management consisting of transurethral endoscopic incision of the distal ureter has previously been reported by Mathews et al.5 Ureteric reimplantation was not preferred as reflux in late age is not a worrying factor. However, the patient is kept on close follow-up for any late symptoms.
in adulthood in current English literature. As patient presented in late adulthood with only obstructive symptoms, major reconstructive surgery was avoided and patient managed endoscopically. REFERENCES 1. Glassberg KI, Braren V, Duckett JW, Jacobs EC, King LR, Lebowitz RL, et al. Suggested terminology for duplex systems, ectopic ureters and ureteroceles. J Urol. 1984;132(6):1153-4. 2. Peters CA, Schlussel RN, Mendelsohn C. Ectopic ureter, ureterocele, and ureteral anomalies. In: Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA (Eds.). Campbell-Walsh Urology. 10th Edition, Philadelphia: Saunders Elsevier; 2011. pp. 3236-66. 3. Keating MA. Ureteral duplication anomalies: ectopic ureters and ureteral anomalies. In: Belman BA, King LR, Kramer SA (Eds.). Clinical Pediatric Urology. 4th Edition, London: Martin Dunitz; 2002. pp. 677-733. 4. Redman JF, Lightfoot ML, Reddy PP. Bilateral single ureteral ectopia in a boy. Urology. 2002;60(3):514. 5. Mathews R, Jeffs RD, Maizels M, Palmer LS, Docimo SG. Single system ureteral ectopia in boys associated with bladder outlet obstruction. J Urol. 1999;161(4):1297-300. 6. Dange AS, Sen S, Zachariah N, Chacko J, Mammen KE. Single-system ureteral ectopia - Associated malformations and management in children lacking an orthotopic ureter. Pediatr Surg Int. 1994;9:377-80.
7. Kumar A, Goyal NK, Trivedi S, Dwivedi US, Singh PB. Bilateral single system ectopic ureters: case report with literature review. Afr J Paediatr Surg. 2008;5(2):99-101. ■■■■
To the best of our knowledge, this is the first case of BSSEUs with secondary ureteric calculi presenting
An Active Lifestyle Improves HRQOL in Menopausal Women A supervised, multicomponent exercise program led to positive changes in short and long-term physical and mental health, with significant enhancements in several health related quality-of-life (HRQoL) dimensions especially mental well-being and menopause-related health and subdomains, which persisted throughout the study period and follow-up at 1 year. The cardiometabolic status and fitness, including weight, body mass index, cardiorespiratory fitness and flexibility were also improved. These findings are published online in Menopause on February 15, 2017.
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2017
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
OBSTETRICS AND GYNECOLOGY
Antepartum Hemorrhage: An Obstetrician’s Nightmare SURYA MALIK*, KHUSHPREET KAUR†, PARNEET KAUR‡
ABSTRACT Background: Antepartum hemorrhage (APH) is an important cause of maternal and fetal morbidity and mortality, despite modern improvements in obstetric practice and transfusion services. Aims and objectives: To find the demographic profile, factors associated with APH, maternal and fetal outcomes in the cases presented with APH as obstetric emergency. Material and methods: The present study was conducted on a prospective basis for 1 year, from 1st February 2011 to 31st January 2012, in the Dept. of Obstetrics and Gynecology, Govt. Medical College, Patiala. All the cases of APH, presenting as obstetric emergency, major and massive hemorrhage were included in the study. A detailed history including age, parity, gestational age, antenatal care, obstetric history, risk factors, medical and surgical disorders were taken into account. Attention was paid on the management received by each case including blood transfusion, surgical interventions, ICU admissions, etc. Results: During this period, total number of patients who presented with APH as obstetric emergency were 48, equally distributed into placenta previa and abruptio placenta, 24 each. APH is more prevalent in multipara, unbooked, uneducated and in women who belonged to rural background. In the present study, LSCS rates were 66.66%. Various complications that were encountered included postpartum hemorrhage, 20.83%; coagulopathy, 6.25%; ICU stay, 8.33%. Maternal mortality was 10.42%. Fetal mortality was 59.18%. Conclusion: APH is a grave and potentially life-threatening condition for mother and fetus, which tests the limits of even best equipped obstetrical and neonatal units. Proper antenatal care and counseling aids in early diagnosis of APH, thereby reducing the maternal and fetal morbidity and mortality. And finally the complications can be reduced by early referral to a tertiary care center for management.
Keywords: Antepartum hemorrhage, postpartum hemorrhage, maternal and fetal morbidity and mortality
O
bstetric hemorrhage remains one of the major causes of maternal death in developing countries and is the cause of maternal death of up to 50% of the estimated 5,00,000 maternal deaths that occur globally each year.1 Hemorrhage emerges as the major cause of severe maternal morbidity in almost all ‘near miss’ audits in both developed and developing countries.2
Antepartum hemorrhage (APH) is an important cause of maternal and fetal morbidity and mortality, despite modern improvement in obstetric practice and transfusion service. It is defined as any vaginal bleeding from the 24th week of pregnancy till delivery.
*Junior Resident †Professor ‡Associate Professor Dept. of Obstetrics and Gynecology, Govt. Medical College, Patiala, Punjab Address for correspondence Dr Surya Malik A2A, House No-159, Janakpuri West, New Delhi E-mail: surya85.sm@gmail.com
The initial management of APH should concentrate on resuscitation and accurate diagnosis.3 The most important causes of APH are placenta previa and abruption, accounting for more than half the cases.4 Definitions that have been used to define severity of APH:5 ÂÂ
Spotting - Straining, streaking or blood spotting noted on underwear or sanitary protection.
ÂÂ
Minor hemorrhage - Blood loss <50 mL that has settled.
ÂÂ
Major hemorrhage - Blood loss of 50-1,000 mL, with no signs of clinical shock.
ÂÂ
Massive hemorrhage - Blood loss >1,000 mL and/or signs of clinical shock.
Placental abruption complicates approximately 1-2% of all pregnancies and remains a significant cause of both maternal and fetal morbidity. The key factor in the pathophysiology is hemorrhage at the decidual-placental interface. The maternal effect of such abruption depends primarily on its severity, whereas its effect on the fetus is determined both by
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OBSTETRICS AND GYNECOLOGY its severity and the gestational age at which it occurs.6 Placenta previa is still an important complication of the pregnancy. Its incidence is on rise because of the increasing number of cesarean section being performed, liberalization of abortion laws and a trend of childbearing at a later age among the women.3 The dangerous complication of placenta accreta associated with placenta previa and prior cesarean deliveries has also increased in frequency.7
interventions, amniotomy followed by delivery was done in 13 (27.08%) cases, 32 (66.66%) cases were taken up for emergency LSCS. Cesarean hysterectomy was done in 3 (6.25%) cases due to atonic postpartum hemorrhage (PPH) (Table 3). Blood was transfused Table 1. Demographic Profile of Cases No.
Percentage (%)
Age (years)
MATERIAL AND METHODS
<20
3
6.25
The present study was conducted on a prospective basis for 1 year, from 1st February 2011 to 31st January 2012, in the Dept. of Obstetrics and Gynecology, Govt. Medical College and Rajindra Hospital. All the cases of APH, presenting as obstetric emergency, major and massive hemorrhage were included in the study. A detailed history including age, parity gestational age, antenatal care during pregnancy, obstetric history, risk factors, medical or surgical disorders were taken into account. A thorough general physical examination, local examination was done in every case. Attention was paid on the management received by each case including blood transfusion, surgical interventions, ICU admissions, etc.
21-25
20
41.67
26-30
23
47.92
31-35
2
4.17
0
16
33.33
1-2
19
39.58
3-4
11
22.92
>4
2
4.17
RESULTS During this time period total no. of cases, who presented with APH as obstetric emergency were 48, equally distributed between placenta previa and abruptio placenta, 24 each. Approximately half of these patients (47.9%), belonged to the age group of 26-30 years. Only 4% patients belonged to age group of 31-35 years. Maximum cases 19 (39.58%) were of parity 1-2, followed by 16 (33.33%) cases who were nullipara. Eleven (22.92%) cases had parity between 3 to 4. Only 2 (4.17%) cases had parity >4. Majority of the patients were unbooked, uneducated and belonged to the rural background (Table 1). It was seen that 22.92% of the cases had history of previous lower segment cesarean section (LSCS) and 10.42% had history of previous curettage. More than 50% of the patients who presented with obstetric catastrophe had severe anemia. Out of 24 cases who presented with abruption placentae, 22 patients had pre-eclampsia as a predisposing factor. Only 1, (2%) patients presented with twin gestation in the present study. Malpresentations were seen in 11 (22.92%) women which included breech, transverse and oblique presentations, respectively (Table 2). Regarding
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Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
Parity
Mean
1.58
Booking status Booked
8
16.67
Unbooked
40
83.33
Rural
37
77.08
Urban
11
22.92
Educated
8
16.67
Uneducated
40
83.33
Background
Educated/Uneducated
Table 2. Other Associated Conditions No.
Percentage (%)
11
22.92
Previous curettage
5
10.42
Severe anemia <7 g/dL
26
54.2
Pre-eclampsia
22
45.83
Previous LSCS
Multiple pregnancy
1
2.08
Prematurity
33
68.75
Malpresentation
11
22.92
Table 3. Interventions Procedure
No.
Percentage (%)
Amniotomy + delivery
13
27.08
Emergency LSCS
32
66.66
Cesarean hysterectomy
3
6.25
OBSTETRICS AND GYNECOLOGY Table 4. Blood Transfusions Units of blood
No.
Percentage (%)
1-2
5
10.42
3-4
28
58.35
>4
15
31.25
Table 5. Maternal Outcomes Complications
No.
Percentage (%)
PPH
10
20.83
Coagulopathy
3
6.25
ICU stay
4
8.33
Maternal deaths
5
10.42
Table 6. Fetal Outcome Outcome
Percentage of preterm/ term
Percentage of age alive/still births
66.66
40.82
33.33
59.18
Preterm (33) Alive (14) Still births (19) Term (16) Alive (6) Still births (10) Note: There was one twin gestation, hence no. of babies were 49.
in all the patients. Maximum cases 28 (58.33%) had blood transfusion between 3 to 4 units, followed by 15 (31.25%) who had blood transfusion >4 units (Table 4). Maternal outcomes were studied in terms of morbidity and mortality. Ten (20.83%) patients had PPH due to which 3 (6.25%) were taken up for cesarean hysterectomy. Three (6.25%) had coagulopathy and 4 (8.33%) were shifted to ICU as they needed ventilator support. All 4 cases who were shifted to ICU died due to cardiorespiratory arrest. One patient died as the patient was already in moribund state with hemoglobin (Hb) - 5.5 g/dL (Table 5). Out of 49 fetuses, 33 (66.66%) were preterm, whereas 16 (33.33%) were term. Fetal mortality was 59.18% in the present study (Table 6). DISCUSSION Present study shows equal distribution of both placenta previa and abruption in 50%, which is almost similar to Oladapo et al.8 Singhal et al9 and Adekanle et al10 have mentioned unspecified as one of the causes of APH. In the present study, 33.33% of the cases were primigravida and 66.66% were multigravida, which
is almost similar to the study of Singhal et al,9 26.99% and 63.1%, respectively. Sheikh et al11 has reported less incidence of primigravida, 9%. In the present study, 27.08% cases had of vaginal delivery and 66.66% had LSCS, which is almost similar to the study by Adekanle et al10 and Sheikh et al.11 Present study had 6.25% of hysterectomy rates, which is greater than that reported by Singhal et al9 and Sheikh et al.11 There was 100% blood transfusion rates as more than half were severely anemic. Present study showed 20.83% PPH rates which is comparable to Singhal et al9 and Sheikh et al.11 Present study had 6.25% of cases complicated by coagulopathy, which is greater than Singhal et al9 and Sheikh et al.11 Survival rates of present study was 89.58% which is slightly lesser than that seen in studies by Singhal et al9 and Sheikh et al11 due to the fact, that maximum cases were severally anemic and were unstable at admission and moreover patients with major and massive hemorrhage only were included in the present study. Present study had 66.66% of preterm births, which is compared to Sheikh et al.11 Singhal et al9 had reported 42.67% of preterm births. Present study depicted 40.8% live birth rates; which is lesser than reported by Singhal et al,9 Sheikh et al11 and Adekanle et al10 as present study had greater rates of abruption as compared to others. CONCLUSIONS Antepartum hemorrhage is a grave and potentially life-threatening condition for mother and fetus, which tests the limits of even best equipped obstetric and neonatal units. Proper antenatal care and counseling aids in early diagnosis of APH, thereby reducing the maternal and fetal morbidity and mortality. And finally, the complications can be reduced by early referral to tertiary care for management. REFERENCES 1. Khan KS, Wojdyla D, Say L, GĂźlmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet. 2006;367(9516):1066-74. 2. Brace V, Kernaghan D, Penney G. Learning from adverse clinical outcomes: major obstetric haemorrhage in Scotland, 2003-05. BJOG. 2007;114(11):1388-96. 3. Sinha P, Kuruba N. Antepartum haemorrhage: an update. J Obstet Gynaecol. 2008;28(4):377-81. 4. Yang Q, Wen SW, Phillips K, Oppenheimer L, Black D, Walker MC. Comparison of maternal risk factors between placental abruption and placenta previa. Am J Perinatol. 2009;26(4):279-86.
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OBSTETRICS AND GYNECOLOGY 5. Royal College of Obstetricians and Gynaecologists. Antepartum Haemorrhage. Green–Top Guideline No 63. London: RCOG; 2011. 6. Oyelese Y, Ananth CV. Placental abruption. Obstet Gynecol. 2006;108(4):1005-16. 7. Bahar A, Abusham A, Eskandar M, Sobande A, Alsunaidi M. Risk factors and pregnancy outcome in different types of placenta previa. J Obstet Gynaecol Can. 2009;31(2):126-31.
9. Singhal SR, Nymphaea, Nanda S. Maternal and perinatal outcome in antepartum haemorrhage: A study at a tertiary care referral institute. Internet J Gynaecol Obstet. 2008;9(2). 10. Adekanle DA, Adeyemi AS, Fadero FF. Antepartum hemorrhage and pregnancy outcome in Lautech teaching hospital, South Western Nigeria. J Med Med Sci. 2011; 2(12):1243-7.
8. Oladapo OT, Sule-Odu AO, Olatunji AO, Daniel OJ. 11. Sheikh F, Khokhar SA, Sirichand P, Shaikh RB. A study “Near-miss” obstetric events and maternal deaths in of antepartum haemorrhage maternal and perinatal Sagamu, Nigeria: a retrospective study. Reprod Health. outcome. Medical Channel. 2010;16(2):268-71. 2005;2:9. ■■■■
Postmenopausal Hormone Therapy Associated with Reduced Risk of Dementia or Alzheimer’s Disease According to a study published online in the journal Neurology, the estrogen replacement therapy is not only associated with greater longevity but also linked to reduced risk of Alzheimer’s disease in postmenopausal women. Further researchers recommended to start the estrogen based therapy prior to the onset of menopause because at this stage the health status of neurons are far better than compared to years after menopause.
Regular Physical Exercise a Remedy to Menopause Problems Nonsedentary lifestyle or improved physical activity can possibly help to reduce the extra belly fat gained by postmenopausal women due to changes in hormones. Also, it was observed that the 20-week exercise program resulted not only reduced the waist-line but also reduced the body mass index and hot flashes. Further, the health promotion intervention improved the cardiovascular health, flexibility, mood and other menopause symptoms.
Reduced Thigh Muscle Endurance Linked to Increased Risk of Knee Osteoarthritis in Female Population A study published online in the journal Arthritis Care & Research, suggests that poor thigh muscle strength is significantly associated with knee osteoarthritis in women only, whereas men are not affected by low muscle strength of thigh. Further, the scientists observed that men with high body mass index (BMI) are associated with more strength in thighs, but in case of women it is vice-versa. Thus in the light of above findings Dr Adam Culvenor, lead author of the Arthritis Care & Research study commented that "our results highlight the importance of maintaining thigh muscle strength to reduce the risk of knee osteoarthritis development, particularly in women. The different relationships we observed between muscle weakness, muscle size, BMI and knee osteoarthritis development in men and women suggest that the mechanism by which BMI increases the risk of knee osteoarthritis is sex-specific and may require distinct treatment approaches."
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OPHTHALMOLOGY
To Study the Efficacy and Safety of Tacrolimus (0.1%) in Vernal Keratoconjunctivitis JITENDER PHOGAT*, SUMIT SACHDEVA†, MANISHA RATHI‡, NIKUNJ BHATT#, SHIKHA NAILWAL¥, MARISHA BISHNOI#
ABSTRACT Aim: To determine the efficacy and safety of tacrolimus eye ointment (0.1%) in the treatment of vernal keratoconjunctivitis (VKC). Material and methods: A prospective trial was conducted in 80 cases of VKC including newly diagnosed and recurrent cases. After discontinuing their previous medications, they were treated with tacrolimus eye ointment (0.1%) twice a day for a period of 1 year. Clinical signs and symptoms were recorded at the beginning of the treatment and at follow-ups done weekly for 1 month and then every month for 1 year. Results: There was marked subjective as well as objective improvement in all cases. No significant toxic effects of tacrolimus were observed during the treatment period. Conclusion: Tacrolimus eye ointment (0.1%) is an effective therapy in patients of VKC and it is a safe alternative to topical steroids.
Keywords: Tacrolimus, vernal keratoconjunctivitis, topical steroids, allergy
V
ernal keratoconjunctivitis (VKC) is a bilateral acute-on-chronic inflammatory disease of the conjunctiva and cornea, which is encountered usually in children.1 There is intense burning and itching along with lacrimation, a stringy mucoid discharge, photophobia and heaviness of eyelids due to involvement of the tarsal conjunctiva by formation of papillae. Symptoms are exaggerated in warm and humid environment. Mild cases of VKC show improvement with nonspecific, supportive therapy. But severe cases show frequent remissions and relapses, run a protracted course and if not treated properly, usually result in sight-threatening complications over a period of time.2 VKC is a type 1 (immediate) hypersensitivity reaction, which occurs when a sensitized individual comes into contact with a specific antigen resulting in degranulation of mast cells in the conjunctiva and release of histamine.3 Histamine causes acute symptoms including redness, watering with intense itching and other allergic manifestations. Later
*Assistant Professor †Associate Professor ‡Professor #Junior Resident ¥Senior Resident Regional Institute of Ophthalmology (RIO), PGIMS, Rohtak, Haryana Address for correspondence Dr Jitender Phogat 923/A-28, Bharat Colony, Rohtak, Haryana E-mail: drjitenderphogat@gmail.com
in disease process, there is super imposed involvement of T lymphocytes which results in chronicity of the disease, corneal and tarsal conjunctival signs. Involvement of both eyes occurs, which may be asymmetrical and recurrence occurs when treatment is stopped. Patients with VKC exhibit large amounts of circulating immunoglobulin E (IgE); the cross-linking of 2 adjacent IgE molecules by the antigens triggers mast cell degranulation. This releases various preformed mediators of the inflammatory cascades histamine, prostaglandins, leukotrienes, tryptase, chymase, heparin and chondritin sulfate. These mediators cause increased vascular permeability with migration of eosinophils, polymorphs, T and B lymphocytes and proliferation of fibroblasts, which lay down exuberant amount of collagen in conjunctival tissue. Conjunctiva shows cellular infiltration with epithelium hyperplasia and dilation of vessels with increased leakage. In upper tarsal area, proliferation of fibrous layer of conjunctiva and its hyalinization results in the formation of giant papillae, >0.3 mm in diameter, which gives classic ‘cobble-stone’ appearance. In severe cases, these papillae may get hypertrophied producing cauliflower-like excrescences (giant papillae), which may produce mechanical ptosis. Limbal involvement comprises of papillae which are thick, gelatinous along with multiple white spots, which are collection of degenerated epithelial cells and eosinophils called ‘Horner-Trantas dots’. These undergo rapid dissolution with the start of treatment.
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OPHTHALMOLOGY Corneal involvement shows different signs, which may be punctate epithelial keratopathy (PEK), and these fine epithelium punctate erosions may coalesce into large shield ulcers. Giant tarsal papillae can cause chronic mechanical irritation on corneal surface, which also contribute to corneal ulcer formation. Keratoconus is a frequent complication in chronic cases, due to chronic rubbing and superimposed corneal thinning by injudicious use of topical steroids. Treatment options for milder form of VKC include topical antihistamines, mast cell stabilizers, mucolytics. In severe and chronic disease, corticosteroids are required for longer duration to control symptoms. Corticosteroid withdrawal leads to clinical worsening in significant number of patients, while long-term use of corticosteroids is associated with side effects like cataract, glaucoma, corneal thinning, corneal ectasia/keratoconus and tear film abnormality.4 Hence, marked ocular morbidity and even blindness may be the result of prolonged use of topical steroids. Immunomodulators are newer class of drugs used for management of VKC used mainly as steroid-sparing drugs.5 Tacrolimus is one such immunomodulating drug, the other being cyclosporine eye drop.6 Tacrolimus is a macrolide, discovered in 1984 from the bacteria Streptomyces tsukubaensis and is known to be 10-100 times more potent than cyclosporine. It is effective in suppressing the activation and proliferation of B and T lymphocytes and formation of inflammatory mediators like cytokines especially interleukin-2. It is used as an immunosuppressant in organ transplantation and as a ointment in skin disorders like vitiligo, atopic dermatitis. According to numerous clinical studies, tacrolimus has been successfully used in the treatment of autoimmune diseases of the ocular surface such as dry eyes, Mooren’s ulcer, scleritis, cicatricial conjunctivitis, atopy and VKC.7-10 It suppresses inflammation as effectively as steroids with benefit of no severe side effects that are encountered with corticosteroid therapy. Only mild burning and itching sensations are the reported side effects of topical tacrolimus. This study is conducted to evaluate efficacy of tacrolimus 0.1% eye ointment in treatment of moderate-to-severe VKC and to look for any ocular or systemic side effect.
in this study. There were 25 newly diagnosed cases and 55 recurrent, being refractory to their previous therapy consisting of topical antihistaminics, mast-cell stabilizers and topical steroids.
Inclusion Criteria ÂÂ
Moderate-to-severe cases of VKC presenting with the symptoms of chronic, recurrent, bilateral red eyes with itching, watering and mucoid discharge and papillae found on upper tarsal conjunctiva with limbal signs.
Exclusion Criteria ÂÂ
Mild VKC with only palpebral conjunctivitis.
ÂÂ
Patients who had received subconjunctival corticosteroids.
ÂÂ
History of glaucoma, developmental cataract or any systemic illness.
systemic
or
Patient’s symptoms were graded according to severity before the start of treatment. Symptoms included itching, redness, watering, mucoid discharge and foreign body sensation. Grading of symptoms by patients were 0 (none), 1 for mild (occasional symptoms), 2 for moderate (frequent symptoms), 3 for severe (constant symptoms). Informed consent was taken from parents before starting the treatment. Previous medications of patients were discontinued and all were treated with tacrolimus 0.1% eye ointment applied into the lower conjunctival fornix twice a day for a period of 12 months (mean of 8 months). Efficacy of treatment was evaluated subjectively by assessing patient’s symptoms and objectively by noting an improvement in the clinical signs. The need for any additional therapy was noted. Any side effects of the treatment were asked and any possible ocular complications such as intraocular pressure elevation, cataract formation and secondary bacterial infection were noted. These findings were recorded at the beginning of the treatment and at follow-ups conducted weekly for 1st month and then every month for 1 year. Any recurrence of symptoms and signs after stopping all medications was also noted on follow-up.
MATERIAL AND METHODS
RESULTS
A prospective clinical trial was conducted in Regional Institute of Ophthalmology (RIO) at Postgraduate Institute of Medical Sciences (PGIMS), Rohtak, Haryana. A total of 80 patients of moderate-to-severe VKC (160 eyes) of age group from 5 to 20 years were included
The commonest presenting symptoms in all the patients in this study was itching and watering. Other associated symptoms were redness, mucoid discharge, photophobia and sensation of grittiness in eyes. The grading scales for objective clinical signs are given in Table 1. Papillary
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OPHTHALMOLOGY hypertrophy was present in all the patients while giant papillae were found in 45 patients of recurrent VKC (moderate-25 and severe-20). Giant papillae tend to form in chronic, recurrent cases of VKC. Limbitis was found in all cases (mild-10, moderate-38, severe-32), corneal involvement in form of punctate erosions was also seen in all cases (mild-12, moderate-38, severe-32). Other corneal signs noted were corneal pannus in 45 cases and shield ulcers indicating very serious disease were noted in 2 patients. Shield ulcer is responsible for decrease in vision and may lead to corneal scarring, which can cause permanent loss of vision. After starting 0.1% tacrolimus eye ointment, all the patients were followed up for 8-12 months duration (mean 10 Âą
Conjunctival injection
Limbitis
SPK
Papillae
Score
Definition
3
Impossible to distinguish individual vessels
2
Dilatation of many blood vessels
1
Dilatation of several blood vessels
0
None
3
7 or more limbal papillae
2
4-6 limbal papillae
1
1-3 limbal papillae
0
None
3
Diffusely scattered on whole cornea
2
Half of cornea spared
1
Only a few punctate erosions
0
None
3
Elevated papillae >0.3 mm
2
Elevated papillae of 0.2-0.3 mm
1
Elevated papillae <0.2 mm
0
None
After 8 weeks of treatment, the residual symptoms only included mild redness in 8 eyes (90% improvement), mild photophobia in 5 patients, mild foreign body sensation in 6 patients and mild watering and discharge each in 4 patients. All symptoms were relieved in more than 90% of patients. After further 1 month of treatment all symptoms disappeared. The patients remained mostly symptom-free during the remaining period of therapy. However, when tacrolimus was stopped after 2-3 months of continuous use, almost all of them had a recurrence of disease although mostly in milder form and only few in severe form. Hence, it was continued for a further 2 months and then tapered gradually over another 1 month. After stopping all treatment, 40 patients developed recurrence of VKC mostly milder form and few in severe form after few weeks and it was managed with antihistamine eye drop. While during treatment with tacrolimus, none of the cases needed additional medications like topical steroids, antihistamines or mast-cell stabilizers to control symptoms.
Table 1. Grading Scales for Objective Clinical Signs Signs
1.5 months). All symptoms significantly improved after treatment and itching was first symptom, which was relieved and it improved in 97.5% of patients. All other symptoms including redness, watering, discharge, photophobia and grittiness sensation also improved as shown in Table 2.
After treatment with tacrolimus, marked improvement was note objectively in all signs of VKC. Conjunctival injection was the first sign to show improvement in more than 90% cases within a short-time after start of therapy. Conjunctival papillary hypertrophy showed improvement in all cases with reduction in size of papillae and also total disappearance. All 45 cases with moderate-to-severe giant papillae, showed reduction in size of papillae within first month of therapy and
Table 2. Grading of Symptoms of VKC Patients Before and After 8-week Therapy with 0.1% Tacrolimus Eye Ointment (n = 80) Symptoms
Grade prior to treatment
Grade after 1 month of treatment
Improvement %
0
1
2
3
0
1
2
3
Itching
-
-
20
60
78
2
-
-
97.5
Redness
-
-
25
55
72
8
-
-
90
Watering
-
-
38
42
76
4
-
-
95
Discharge
-
10
50
20
76
4
-
-
95
Photophobia
-
-
36
54
75
5
-
-
93.75
Grittiness
-
25
30
15
74
6
-
-
92.5
Grade 0-none, 1-mild, 2-moderate and 3-severe.
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OPHTHALMOLOGY papillae disappeared after 3 months of treatment. Giant papillae persisted for longer duration and needed treatment for few months. Limbitis (limbal papillary hypertrophy) improved in 95% cases after 8 weeks of treatment and corneal punctate erosions disappeared in 97.5% of cases. Corneal pannus completely resolved in all cases. Shield ulcer which was present in 2 patients of VKC before treatment, also showed complete healing. Patients of shield ulcer also showed improvement in visual acuity after treatment.
a immunomodulator has emerged as a very safe and effective steroid-sparing drug which inhibits all immune reactions, which causes pathogenesis of VKC.8-10 This study shows that it is a safe and effective alternate option to steroid treatment. Effectiveness of tacrolimus has been shown in earlier numerous studies to control atopic blepharoconjunctivitis and associated ocular allergic conditions including VKC.11,12 Sengoku et al13 used 0.01-1% eye drops in an animal study for ocular allergy, while Qhashi et al14 used an 0.1% ophthalmic suspension in another clinical study. In this study, there was effective control of both symptoms (Table 2) and signs (Table 3) of VKC with treatment. The first sign which showed improvement was conjunctival injection, which occurred within 2 weeks of starting the treatment. Giant papillae also resolved either to smaller size or completely disappeared although prolonged treatment of up to 3 months was needed for complete resolution of giant papillae. This response was similar to earlier study by Kymionis et al.15 Corneal signs including punctate epithelial erosions and pannus also showed drastic improvement with treatment. Two patients who had shield ulcers which is a serious vision-threatening condition prior to the starting treatment, also showed improvement vision improving in patients with healing of ulcer. Similar results were demonstrated by another study by Vichyanond et al.16 Risk of corneal ectasia and keratoconus is higher in patients of VKC due to constant rubbing of eyes due to persistent itching. Tacrolimus does not cause corneal thinning which may occur due to chronic topical steroid therapy, and hence minimizes the risk of keratoconus.
To assess the safety of tacrolimus 0.1% eye ointment, detailed ocular examination including anterior and posterior segment was done. Patients were asked for occurrence of any new symptoms and any signs of ocular and systemic toxicity were noted. Only 4 patients complained of mild discomfort and burning sensation on instillation of ointment, remaining 76 cases did not complain of any discomfort or burning sensation. Intraocular pressure remained normal in all cases. No eczema of periorbital skin was evident in any case. No systemic side effect was seen in any patient. No patient had to discontinue tacrolimus eye ointment due to any adverse effect. DISCUSSION VKC is a chronic, recurrent ocular disease mostly occurring in children, which has marked morbidity. Since mechanism is immunemediated, the use of immuno-modulating drugs to control the debilitating symptoms in moderate-to-severe cases becomes necessary. Conventionally steroids mostly by topical route and rarely systemic route have been used, which showed drastic improvement. But prolonged use of steroidâ&#x20AC;&#x2122;s results in vision-threatening complications like glaucoma, cataract, corneal thinning and corneal ectasia in significant number of patients. They can be used safely for only a short duration with steroid-free interval to minimize side effects. Hence, tacrolimus,
In this study, there was recurrence of disease mostly in milder form when tacrolimus was discontinued after 2-3 months of use, hence therapy was continued for at least 4-6 months and it was gradually tapered off. In other studies, topical tacrolimus was
Table 3. Grading of Signs in VKC Patients Before and After 8-week Therapy with 0.1% Tacrolimus Eye Ointment (n = 80) Signs
Grade prior to treatment
Grade after 1 month of treatment
Improvement %
0
1
2
3
0
1
2
3
Conjunctival injection
-
-
24
56
72
8
-
-
Limbitis
-
10
38
32
76
4
-
-
95
PEK
-
12
38
30
78
2
-
-
97.5
Corneal pannus
-
5
32
8
80
-
-
-
100
Papillae
-
-
25
20
72
8
-
-
80
Grade 0-none, 1-mild, 2-moderate and 3-severe.
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90
OPHTHALMOLOGY stopped after 4 weeks of treatment and no recurrence was documented.13,14 In another study by Vichyanond et al,16 topical tacrolimus was continued for 7 months while in a study in patients of atopic keratoconjunctivitis (AKC) by Virtanen et al,11 it was used for a longer duration of 42 months with no side effects documented. In present study, no case needed additional medications like antihistamines, mast-cell stabilizers or steroid to control the disease. Thus, tacrolimus can be used as a prophylactic drug in less severe disease as well as to prevent its aggravation during hot, humid season of the year. When treatment was started with topical tacrolimus, a local burning sensation was reported in earlier studies in few patients.14-16
4. Carnahan MC, Goldstein DA. Ocular complications of topical, peri-ocular, and systemic corticosteroids. Curr Opin Ophthalmol. 2000;11(6):478-83.
In the present study, it was seen in 4 patients at the start of the treatment and disappeared after 2 weeks of therapy. Lubricant eye drops can be added in cases of burning sensation. During the whole period of treatment, none of the cases developed any ocular or systemic side effects. Topical tacrolimus is much safer than steroids for prolonged duration in treatment of VKC with similar efficacy.
9. Lee YJ, Kim SW, Seo KY. Application for tacrolimus ointment in treating refractory inflammatory ocular surface diseases. Am J Ophthalmol. 2013;155(5):804-13.
CONCLUSION The use of immunomodulator drug tacrolimus as topical preparation in treatment of chronic ocular allergy VKC is being studied as an alternate to steroid therapy. In present study, tacrolimus 0.1% eye ointment used twice-daily showed marked improvement in VKC after 1 month of therapy. Since VKC requires longer treatment, tacrolimus showed great efficacy for treatment duration of more than 6 months with no significant ocular or systemic side effect noted and no need of additional medication. REFERENCES 1. Bonini S, Coassin M, Aronni S, Lambiase A. Vernal keratoconjunctivitis. Eye (Lond). 2004;18(4):345-51. 2. Kumar S. Vernal keratoconjunctivitis: a major review. Acta Ophthalmol. 2009;87(2):133-47.
5. Bertelmann E, Pleyer U. Immunomodulatory therapy in ophthalmology - is there a place for topical application? Ophthalmologica. 2004;218(6):359-67. 6. Joseph MA, Kaufman HE, Insler M. Topical tacrolimus ointment for treatment of refractory anterior segment inflammatory disorders. Cornea. 2005;24(4):417-20. 7. Zhai J, Gu J, Yuan J, Chen J. Tacrolimus in the treatment of ocular diseases. BioDrugs. 2011;25(2):89-103. 8. Kheirkhah A, Zavareh MK, Farzbod F, Mahbod M, Behrouz MJ. Topical 0.005% tacrolimus eye drop for refractory vernal keratoconjunctivitis. Eye (Lond). 2011;25(7):872-80.
10. Müller GG, José NK, de Castro RS. Topical tacrolimus 0.03% as sole therapy in vernal keratoconjunctivitis: a randomized double-masked study. Eye Contact Lens. 2014;40(2):79-83. 11. Virtanen HM, Reitamo S, Kari M, Kari O. Effect of 0.03% tacrolimus ointment on conjunctival cytology in patients with severe atopic blepharoconjunctivitis: a retrospective study. Acta Ophthalmol Scand. 2006;84(5):693-5. 12. Zribi H, Descamps V, Hoang-Xuan T, Crickx B, Doan S. Dramatic improvement of atopic keratoconjunctivitis after topical treatment with tacrolimus ointment restricted to the eyelids. J Eur Acad Dermatol Venereol. 2009;23(4):489-90. 13. Sengoku T, Sakuma S, Satoh S, Kishi S, Ogawa T, Ohkubo Y, et al. Effect of FK506 eye drops on late and delayed-type responses in ocular allergy models. Clin Exp Allergy. 2003;33(11):1555-60. 14. Ohashi Y, Ebihara N, Fujishima H, Fukushima A, Kumagai N, Nakagawa Y, et al. A randomized, placebocontrolled clinical trial of tacrolimus ophthalmic suspension 0.1% in severe allergic conjunctivitis. J Ocul Pharmacol Ther. 2010;26(2):165-74. 15. Kymionis GD, Goldman D, Ide T, Yoo SH. Tacrolimus ointment 0.03% in the eye for treatment of giant papillary conjunctivitis. Cornea. 2008;27(2):228-9.
16. 3. Kumagai N, Fukuda K, Fujitsu Y, Yamamoto K, Nishida T. Role of structural cells of the cornea and conjunctiva in the pathogenesis of vernal keratoconjunctivitis. Prog Retin Eye Res. 2006;25(2):165-87. ■■■■
Vichyanond P, Tantimongkolsuk C, Dumrongkigchaiporn P, Jirapongsananuruk O, Visitsunthorn N, Kosrirukvongs P. Vernal keratoconjunctivitis: Result of a novel therapy with 0.1% topical ophthalmic FK-506 ointment. J Allergy Clin Immunol. 2004;113(2):355-8.
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ORTHOPEDICS
Study of Transverse Patellar Fractures Treated with Modified Tension Band Wiring MITHUN MOHAN*, DK GOVINDARAJU, BS JAYAKRISHNA REDDY†
ABSTRACT Background: Patellar fractures constitutes about 1% of all skeletal injuries resulting from either direct or indirect trauma. Patella is of importance for the extension of knee joint, which increases the force of quadriceps apparatus by improving the leverage. This study was directed towards the functional results and complications of modified tension band wiring for patella fractures. Any improper and inadequate treatment would inevitably lead to a greater disability especially squatting. Material and methods: The study consisted of 20 cases of displaced transverse fracture patella treated by modified tension band wiring. The patients were followed up for 6 months and the clinical and functional outcomes were evaluated using the modified scale of Bostman. Results: In this study, average age of patients was of 39.7 with male patients outnumbering the females by more than double. Right-sided patellar fractures were predominant, 70% of our patients had no pain or only mild pain. Only 20% of our patients had significant extensor lag and nearly 80% had normal quadriceps strength. We had 70% excellent, 20% good and 10% poor results according to modified scale of Bostman. Conclusion: Our study shows that modified tension band wiring is a definitive procedure in management of displaced transverse patellar fracture with least complications. This surgery helps for early mobilization postoperatively, which plays an important role in final outcome. Early and continuous physiotherapy following surgery is of paramount importance in obtaining good functional outcomes.
Keywords: Modified tension band wiring, fracture patella, knee joint
T
he patella is the largest sesamoid bone in the human body situated in front of knee in the tendon quadriceps femoris muscles. It is flattened, triangular distally and curved proximally with the thickness between 1.5 and 2 cm. The patella is of importance for the extension of knee joint. It increases the force of the quadriceps apparatus by improving the leverage. In addition, it protects the anterior articular surface of distal femur against external violence. Fractures of the patella constitute almost 1% of all skeletal injuries, resulting from either direct or indirect trauma. Most are transverse fractures involving the middle third of the patella in patients aged 20 and 50 years, and affect almost twice as many men as women. The anterior subcutaneous location of the patella makes it vulnerable to direct trauma as in dashboard
*Junior Resident (PG Student) †Professor and Head Dept. of Orthopedics Sri Siddhartha Medical College, Tumkur, Karnataka Address for correspondence Dr Mithun Mohan Junior Resident, Dept. of Orthopedics Sri Siddhartha Medical College, Tumkur, Karnataka E-mail: mithun0085@gmail.com
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injuries or fall on flexed knee. Fractures caused by indirect mechanisms result from a violent contraction of the quadriceps with the knee flexed. These fractures usually are transverse and may be associated with tears of the medial and lateral retinacular expansions. Most patellar fractures are caused by a combination of direct and indirect forces. The most significant effects of fracture of the patella are loss of continuity of extensor mechanism of the knee. Any improper and inadequate treatment inevitably lead to great deal of disability, which would be perceptibly felt in a country like India, where squatting is an important activity in daily life. Modified tension band technique is currently the most widely accepted and several studies have shown a high percentage of good results. Several methods of internal fixation of fractured patella have been advocated. This dissertation is directed towards the clinical evaluation of patellar fractures treated with modified tension band wiring. AIMS AND OBJECTIVES
Aims ÂÂ To evaluate the clinical and functional outcome of modified tension band wiring for fractures of patella.
ORTHOPEDICS Objectives ÂÂ To assess the functional results of modified tension band wiring in patellar fractures. ÂÂ To assess the complications of modified tension band wiring in patellar fractures. MATERIAL AND METHODS
superior border till lower pole of patella is reached. 18 G stainless steel wire was taken and passed deep to ligamentum patellae inferiorly and behind the quadriceps tendon superiorly making a figure of “8” in front of the patella sufficient tension is given. Tear in the quadriceps expansion was sutured with vicryl and wound closed in layers.
This study consisted of 20 cases of displaced transverse fracture patella treated by modified tension band wiring. The cases were selected based on inclusion and exclusion criteria. This prospective study was conducted at Sri Siddhartha Medical College and Research Centre, Tumkur, Karnataka.
Above knee slab or pressure bandage was given as a temporary immobilization. Check X-rays were done postoperatively. The operated knee was immobilized in extension in an above knee posterior slab, and the patient was advised to do straight leg raising and weight-bearing from third postoperative day.
Inclusion Criteria ÂÂ All closed and type 1 open displaced transverse patellar fractures. ÂÂ Age more than 16 years to less than 60 years. ÂÂ Sex: Both male and female. ÂÂ Patient who are medically fit for the surgery.
Sutures were removed from 12th to 14th day and knee flexion exercise were started with quadriceps board and with continuous passive motion machine. Patients were discharged from the hospital once they were fully mobilized and advised to do dynamic quadriceps exercise.
Exclusion Criteria ÂÂ Type 2 and type 3 compound fractures. ÂÂ Grossly comminuted, vertical or marginal fractures. ÂÂ Old fractures (more than 2-3 weeks). ÂÂ Undisplaced transverse fractures. Preoperative Procedure Once the patients were admitted, the details of the cases were recorded including name, age, sex, occupation, address, detailed clinical history, past history, family and personal history were taken. Thorough general and clinical examination was carried out. Routine blood investigations and radiological investigations were done. The limb was immobilized by an above knee plaster of Paris posterior slab.
Figure 1a. After spinal anesthesia.
Patients were explained in detail about surgery, possible complications and limitations to be followed after surgery.
Operative Procedure The fracture site was exposed through transverse incision/midline longitudinal incision in front of the knee; the fragments were reduced and held in position with the help of patellar clamp or towel clips. Two Kirschner wires of 2 mm thickness were passed parallel to each other from above downwards starting at its
Figure 1b. Parts painted and draped.
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ORTHOPEDICS
Figure 1f. Cerclage wire passing as figure of eight. Figure 1c. Skin incision.
Figure 1g. Skin closure.
Follow-up Figure 1d. Fracture reduction.
The discharged patients were advised to report for follow-up every month, for 6 months; during each follow-up the patients were examined for objective assessment including range of knee movement, extension lag, effusion, circumference of thigh, efficacy of quadriceps and questioned for subjective symptoms like pain, use of walking aid, giving away, stair case climbing, squatting, which was recorded according to Modified Bostman scale. OBSERVATIONS Table 1. Age Distribution Age group (in years)
Figure 1e. K-wire insertion.
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Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
No. of cases
Percentage (%)
16-25
2
10
26-35
6
30
36-45
4
20
46-55
6
30
>56
2
10
Total
20
100
Mean age = 39.7 (SD Âą 12.607).
ORTHOPEDICS Table 2. Sex Incidence Sex
Table 7a. Functional Outcome Knee Flexion
Distribution of cases
Percentage (%)
6
30
Female
Knee flexion (in degrees)
No. of cases
Percentage (%)
2
10
<90°
Male
14
70
90-120°
2
10
Total
20
100
>120°
16
80
Total
20
100
No. of cases
Percentage (%)
16
80
Table 3. Side of Fracture Side of fracture
No. of cases
Percentage (%)
Left
6
30
Right
14
70
Total
20
100
Table 4. Mechanism of Injury Mechanism of injury
No. of cases
Percentage (%)
Direct
8
40
Indirect
12
60
Total
20
100
Table 5. Type of Fracture Type of fracture
No. of cases
Percentage (%)
Open
5
25
Closed
15
75
Total
20
100
Table 7b. Knee Extensor Lag Extensor lag (in degrees) 0-5° 6-10°
3
15
11 -15°
1
5
Total
20
100
Table 8. Score Results Results
No. of cases
Percentage (%)
Excellent
14
70
Good
4
20
Poor
2
10
Total
20
100
Case 1
Table 6a. Complications Whether Present or Absent Complications
No. of cases
Percentage (%)
Present
5
25
Not present
15
75
Total
20
100
Table 6b. Type of Complications Complications
No. of cases
Percentage (%)
Proximal migration of K-wire with loss of complete flexion
1
5
Superficial wound infection with extension lag
1
5
Extension lag
1
5
Loss of complete flexion with extension lag
2
10
Malunion
0
0
Nonunion
0
0
No complication
15
75
Total
20
100
a
b
Figure 2 a and b. Preoperative.
c
d
Figure 2 c and d. Intraoperative and immediate postoperative.
Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
967
ORTHOPEDICS ÂÂ
Seventy percent of our patients had no pain or only mild pain.
ÂÂ
Only 4 (20%) of our patients had significant extensor lag.
ÂÂ
Nearly 80% of our patients had normal quadriceps strength.
ÂÂ
In our study, 90% had >90 of knee flexion.
Figure 2 e-g. Complications.
ÂÂ
The fixation technique did not affect the function of walking.
Case 5
ÂÂ
Seventy percent cases had excellent results and 20% had good results.
e
f
g
CONCLUSION
a
b
Figure 3 a and b. Final follow-up - Extension lag and loss of complete flexion.
Case 16
a
b
Figure 4 a and b. Superficial wound infection.
DISCUSSION ÂÂ
In this study, incidence of patients in the age groups 26-35 and 46-55 years was more with the mean of 39.7.
ÂÂ
In our study, male patients outnumbered the females by more than double.
ÂÂ
Right-sided patellar fractures were predominant.
ÂÂ
All fractures selected were of transverse type.
ÂÂ
Ten percent of our patients had associated injury with extensor lag.
ÂÂ
Modification with longitudinal K wires was the preferred tension band wiring technique.
ÂÂ
Longitudinal midline skin incision was used in all cases.
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Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
The study was conducted on 20 fresh patellar fractures, which occurred during the period September 2013 to February 2015 with age group varying from 16 to 60 years and treated by modified tension band wiring technique. In patellar fractures, the most significant effect is loss of continuity of extensor mechanism of the knee. The study shows that the treatment of patella fractures with modified tension band wiring is a definitive treatment with minimal complications and good functional outcome. The surgery helps for early mobilization postoperatively. Modified tension band wiring technique, eventually results in a favorable outcome in terms of satisfactory return of knee function. Early and continuous physiotherapy following the surgery is a paramount importance in obtaining good functional end results. This study favors modified tension band wiring as a better choice for treatment of transverse patella fracture. SUGGESTED READING 1. Terry S, Beaty JH (Eds.). Campell’s Operative Orthopaedics”. Chapter 54. 12th Edition, Vol. 3, 2013. pp. 2681-8. 2. Bucholz RW, Heckman JD, Court-Brown CM. Rockwood & Green’s Fractures in Adults. Chapter 49. 6th Edition, Vol. 1, 2006. pp. 1970, 1978-80. 3. Insall and Scott Surgery of the Knee. Chapter 67. 4th Edition. 4. Vatansever M, Kuyurtar F, Sadiogler M. Surgical management of patellar fractures. Acta Orthop Trauma Turc. 1996:30(3):290-3. 5. Böstman O, Kiviluoto O, Nirhamo J. Comminuted displaced fractures of the patella. Injury. 1981;13(3): 196-202. 6. Chang JH. Sohn JM, Bank WJ, Song JH. Pattelar fractures treated by modified tension band wiring. J Korean Fract Soc. 1993;6(2):262-70.
ORTHOPEDICS 7. Smith ST, Cramer KE, Karges DE, Watson JT, Moed BR. Early complications in the operative treatment of patella fractures. J Orthop Trauma. 1997;11(3):183-7. 8. John J, Wagner WW, Kuiper JH. Tension-band wiring of transverse fractures of patella. The effect of site of wire twists and orientation of stainless steel wire loop: a biomechanical investigation. Int Orthop. 2007;31(5): 703-7. 9. Heusinkveld MH, den Hamer A, Traa WA, Oomen PJ, Maffulli N. Treatment of transverse patellar fractures: a comparison between metallic and non-metallic implants. Br Med Bull. 2013;107:69-85.
screw technique in transverse patella fracture. Chin J Traumatol. 2014;17(4):208-13. 11. Jabshetty AB. A comparative study of modified tension brand wiring and cerclage wiring in management of transverse fractures of patella. Indian J Sci Technol. 2011;4(10):1314-21. 12. Sudheendra PR, Krishnaprasad S. Functional outcome of patellar fractures treated by internal fixation: a retrospective study. J Evolut Med Dent Sci. 2014;3(29):8126-41.
13. Attique Ur Rehman Qureshi. Postoperative functional outcome of modified tension band wiring in patients with transverse fracture of patella [internet]. DHQ Hospital, Bhakkar: Department of Orthopaedic Surgery; 2011 June 10. Wang CX, Tan L, Qi BC, Hou XF, Huang YL, Zhang HP, [Cited 2013]. Available at: http://HYPERLINK “http:// et al. A retrospective comparison of the modified tension pjmhsonline.com/”pjmhsonline.com. band technique and the parallel titanium cannulated lag ■■■■
Discovery of a Novel Blood Test to Detect Early Stages of Arthritis A new blood test that assesses changes in oxidized, nitrated and sugar-modified amino acids in the bloodstream of an individual can significantly classify and predict the early stages of arthritis, suggests a study published online in the journal Arthritis Research & Therapy. According to the authors the new test classifies and detects the early stages of arthritis with “relatively high sensitivity and specificity.” Hence by early detection of the diseased condition by means of this test, health professionals can start the treatment early and prevent painful and debilitating disease.
Targeting Serotonin System for Developing Therapies for Alzheimer’s Associated Bone Disorders A study published online in the Journal of Alzheimer's Disease, observed a reduced bone mineral density at an early stage in the tau-based mouse models of Alzheimer's disease. Further, it was suggested that modifications in tau protein is a result of serotonin-producing cells of the brainstem of such mice models. Thus, by carefully exploring the serotonin system, new therapeutic targets can be developed for the treatment of Alzheimer’s associated bone disorders.
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RHEUMATOLOGY
Effect of Adjuvant Atorvastatin Therapy on Disease Activity in Active Rheumatoid Arthritis: A Tertiary Care Center Study in India H SINGH*, REKHA MATHUR*, A SINGHANIA*, KIRAN B*
ABSTRACT Introduction: In current practice, rheumatoid arthritis (RA) patients are being treated with combinations of different diseasemodifying antirheumatic drugs (DMARDs). This early aggressive approach halts the progression of disease. Among different drugs being used for treatment of RA, statins provide cardiovascular safety but its role as immunomodulatory drug in RA is still being studied. In our study, we studied the effect of atorvastatin on disease activity in RA patients. Material and methods: An open-label, prospective, comparative clinical study was conducted with 100 patients. After baseline evaluation, subjects selected for the study were categorized into two groups of 50 each. Subjects in Group I received tablet atorvastatin (20 mg/day) along with their pre-existing DMARD therapy. Group II were those subjects who continued their pre-existing DMARDs, but didn’t receive atorvastatin so was considered as control group. Results: The study results showed that Group I had higher level (6.20 ± 1.2) of Disease Activity Score-28 (DAS28) at baseline than Group II (5.50 ± 1.24), which was statistically insignificant (p 0.06). At 4 weeks, DAS28 was improved significantly from baseline in both groups. There was significant improvement in DAS28 by 2.52 and 1.53 from baseline to 12 weeks in Group I and Group II, respectively (p < 0.001). Similarly, the Clinical Disease Activity Index (CDAI) was higher in Group I (35.48 ± 16.72) than in Group II (27.56 ± 14.45). At 4 weeks, CDAI was improved significantly from baseline in both groups. There was significant reduction in CDAI by 23.32 and 12.84 from baseline to 12 weeks in Group I (p < 0.001). Conclusion: In our study, the results showed that atorvastatin, when used as adjuvant therapy with DMARDs had beneficial effects on parameters of disease activity in RA patients and also was well-tolerated when given in combination with DMARDs.
Keywords: Atorvastatin, CDAI, DAS28, rheumatoid arthritis
R
heumatoid arthritis (RA) is associated with increase cardiovascular mortality and morbidity.1 In well-established RA, the median life expectancy is less than in control populations.2,3 Infection, renal disease and respiratory failure traditionally have been the primary factors contributing to excess mortality in RA patients, although it has been belatedly recognized that congestive heart failure, ischemic heart disease and peripheral atherosclerosis deserve the appellation as the prime killers of rheumatoid patients.4 It may be that chronic systemic inflammation in RA contributes to excess cardiovascular disease (CVD) in this
*Dept. of Medicine and Rheumatology PGIMS, Rohtak, Haryana Address for correspondence Dr Rekha Mathur Dept. of Medicine and Rheumatology PGIMS, Rohtak - 124 001, Haryana E-mail: drrekhamathur04@gmail.com
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Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
population either by potentiating and/or accelerating atherosclerosis or by other mechanisms such as diffuse subclinical vasculitis.5 Parallels between the inflammatory and immunological mechanisms operating in atherosclerotic plaque and rheumatoid synovitis have been highlighted and atherosclerosis is widely considered to be an inflammatory disease.6 Arterial stiffness is a marker of vascular dysfunction and an independent risk factor for CVD.7 Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have demonstrated benefit in the primary and secondary prevention of CVD.8,9 The protective effect of statins appears to be greater than can be explained by their cholesterol reduction property10 and the benefit of statins appear to be even greater in the presence of higher C-reactive protein (CRP) levels.11 Statins are known to have a number of immunomodulatory effects, which may affect vascular function, plaque stability and thrombosis.12 These immunomodulatory effects of statins may be especially
RHEUMATOLOGY important in patients with RA who have systemic immune activation. Statins have been demonstrated to reduce disease activity and inflammatory responses in a murine model of inflammatory arthritis and in patients with RA.13 Many data indicate effects for statins in innate immune response include effects on endothelial function,14 macrophage, natural killer cell and neutrophil effect or functions.15 Similar effects on acquired immune responses via suppression of antigen presentation16 and T-cell polarization have been shown in vitro and in vivo. Synovial inflammation in RA is characterized by activated components of both innate and acquired immune responses. Thus, postulated effects for statins might reasonably operate within the synovial membrane. Findings of in vitro study17 showed suppression of synovial T-cell and fibroblastlike synoviocyte cytokine release, which tends support to this notion. Data suggest that modulation of inflammation can be achieved by atorvastatin in a proportion of patients with RA, suggesting that some of the above pathways may indeed be tractable to HMG-CoA reductase inhibition.18 Moreover, in vitro cytokine release by RA synovial mononuclear cells and by synovial fibroblasts was also reduced by statins.17 Statins have a satisfactory safety profile and relatively few adverse effects. In the absence of side effect and contraindications it may be reasonable to consider statin use in selected cases particularly in patients with a long history of active RA that are at increased cardiovascular risk. A previous study “Trial of Atorvastatin in Rheumatoid Arthritis18 (TARA)” showed significant improvement in Disease Activity Score-28 (DAS28) (-0.5, 95% confidence interval [CI] - 0.75 to -0.25) compared with placebo (0.03, -0.23 to 0.28; difference between groups -0.52, 95% CI -0.87 to -0.17, p = 0.004). CRP and erythrocyte sedimentation rate (ESR) declined, swollen joint counts also fell (-2.69 vs. -0.53; mean difference -2.16, 95% CI -3.67 to -0.64, p = 0.0058). Although, authors found only modest change but the significant reduction in DAS28 provides proof of concept that pathways targeted by atorvastatin offer therapeutic opportunity in inflammatory disease. A double-blind trial, studied the effect of either increased dose of methotrexate (MTX) from 7.5 mg to 15 mg (Group A) or 7.5 mg MTX plus 40 mg atorvastatin (Group B). This study showed a significant reduction in DAS28, CRP, ESR and swollen joint count in atorvastatin group compared to placebo in patients with
RA presenting with active disease despite undergoing disease-modifying antirheumatic drug (DMARD) therapy. Although not indicative for first-line use, this effect of atorvastatin could prove beneficial in the context of DMARD combination design, in which a statin offers both vascular protective and adjunctive immunomodulatory potential. Based on the above literature, we planned to study the effect of atorvastatin on disease activity of RA as there is scant Indian data available in this regard. MATERIAL AND METHODS Patients with diseases like (known or detected on baseline investigations) hepatic, renal diseases, heart failure, endocrinological disorders, hematological disorders, uncontrolled hypertension, coronary heart disease, pregnant or lactating mothers, those belonging to reproductive age group, not willing to practice contraception and who were taking lipid-lowering therapy (statin or fibrate), had hypersensitivity to statin, were excluded from the study. The study was approved by Ethical Committee. After giving the informed consent, we recruited 100 patients, meeting the 1987 American College of Rheumatology criteria, with high activity disease (DAS28 >5.5 and Clinical Disease Activity Index [CDAI] >22) despite ongoing DMARD therapy. All participants were informed about all possible side effects of drugs. A detailed history and clinical examination was done in all subjects included in the study. They underwent routine laboratory investigations like serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), blood urea, ESR and baseline radiograph of hands. After baseline evaluation, subjects selected for the study were categorized into two groups of 50 each by Random No. Table. Subjects in Group I received tablet atorvastatin (20 mg/day) along with their preexisting DMARD therapy. Group II were those subjects who continued their pre-existing DMARDs but didn’t receive atorvastatin, who were considered as control group. Disease activity using DAS28 and CDAI in each of the subjects of either group was evaluated at baseline and every 4 weeks for 3 months by the same observer at each visit. Patients were also observed for adverse effects in both the groups. All data collected in the study were analyzed statistically at the end of study using Independent t-test, Paired t-test and Chi-square
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RHEUMATOLOGY test. Improvement in disease activity was measured by subtraction from baseline value. RESULTS Baseline variable were comparable in both groups (Table 1). There was statistically significant improvement in DAS28 in both groups with the therapy of DMARDs including adjuvant atorvastatin in Group I at 4, 8 and 12 weeks (Table 2). The DAS28 score was comparable (i.e., statistically insignificant) in both groups at 4, 8 and 12 weeks (Table 3). When both groups were analyzed by CDAI, significant improvement in disease activity was observed at 4, 8 and 12 weeks (Table 4). The comparison of CDAI between groups was comparable (i.e., statistically insignificant) at baseline, 4, 8 and 12 weeks (Table 5). Both DAS28 and CDAI showed Table 1. Baseline Variables in Both Groups
Table 3. Analysis and Comparative Assessment of DAS28 Between Two Groups Duration
Group I
Group II
P value
Baseline
6.20 ± 1.2
5.50 ± 1.2
0.00
4 weeks
4.74 ± 1.3
4.67 ± 1.1
0.77
8 weeks
4.49 ± 1.2
4.34 ± 1.4
0.59
12 weeks
3.68 ± 1.0
3.97 ± 1.3
0.24
Table 4. Analysis and Improvement in CDAI Over 12 Weeks
Group I
Group II
P value
42.56 ± 13.3
43.12 ± 9.96
0.237
Male
10
10
1.00
Female
40
40
1.00
2.08 years ± 1.3
2.00 years ± 1.2
0.590
60.45%
61.33%
0.745
ESR (mm Ist hour)
44.2 ± 19.4
31.92 ± 11.87
0.001
CDAI
35.48 ± 16.7
27.56 ± 14.4
0.01
Table 5. Analysis and Comparative Assessment of CDAI Between Two Groups
6.20 ± 1.2
5.50 ± 1.2
0.006
Duration
TJC
10.88 ± 8.96
11.48 ± 8.41
0.730
SJC
3.2 ± 3.07
2.08 ± 2.13
0.037
PGA
3.2 ± 1.51
3.24 ± 1.22
0.884 0.559
Age (years)
Disease (mean) Duration RF
DAS28
EGA
2.96 ± 1.44
ESR
3.12 ± 1.28
28.36 ± 16.09 23.72 ± 10.24
GH
32 ± 15.11
32 ± 12.45
Group II
4 weeks
1.46
0.83
8 weeks
1.71
1.16
12 weeks
2.52
1.53
<0.001
<0.001
P value
972
Group II
4 weeks
15.24
7.64
8 weeks
17.36
9.68
12 weeks
23.32
12.84
P value
<0.001
<0.001
Group I
Group II
P value
Baseline
35.48 ± 16.7
27.56 ± 14.45
0.012
4 weeks
20.24 ± 12.9
19.92 ± 10.59
0.892
8 weeks
18.12 ± 11.9
17.88 ± 14.30
0.927
12 weeks
12.16 ± 10.3
14.72 ± 10.27
0.217
1
Table 2. Analysis and Improvement in DAS28 Over 12 Weeks in Both Groups Group I
Group I
0.088
CDAI = Clinical Disease Activity Index; DAS28 = Disease Activity Score-28; ESR = Erythrocyte sedimentation rate; EGA = Evaluator global assessment; PGA = Patient global assessment; RF = Rheumatoid factor; TJC = Tender joint counts; SJC = Swollen joint counts; GH = Patient’s general health; P = P value (<0.05 = significant).
Duration
Duration
Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
6
5.9
Group I (Atorvastatin) Group II (Control)
5.5
5
Mean DAS28
Variables
gradual and significant improvement from high disease activity to moderate disease activity in both groups (Figs. 1 and 2). No clinical, hematological adverse events were noted. Atorvastatin when given as adjuvant therapy in active RA patients was well-tolerated. No significant liver function or muscle abnormality was detected in those given atorvastatin.
4.74
4.67
4.49
4.34
4
3.68
3.97
3 2 1 0
Baseline
4 weeks 8 weeks Duration
12 weeks
Figure 1. Comparative assessment of DAS28 between two groups from baseline to 12 weeks.
RHEUMATOLOGY 30
28.48
Group I (Atorvastatin) Group II (Control)
27.56
25 20.24
Mean CDAI
20
19.92 17.12
17.88
15
14.72 12.16
10 5 0
Baseline
4 weeks
8 weeks
12 weeks
Duration
Figure 2. Comparative assessment of CDAI between two groups from baseline to 12 weeks.
DISCUSSION RA is a chronic disease with more predispositions to atherosclerosis owing to its inflammatory state. This increased prevalence of atherosclerosis RA has made the ischemic heart disease, the most common cause of death, followed by infection in RA, thus increasing its mortality two times greater than the general population. Also in RA, the median life expectancy is shortened by an average of 7 years for men and 3 years for women compared to control populations. In the studies, DMARDs to some extent reduced the cardiovascular mortality in RA. Statins have been demonstrated to reduce disease activity and inflammatory responses in a murine model of inflammatory arthritis and in patients with RA.13,17,18 In present study, Group I had higher level (6.20 ± 1.2) of DAS28 at baseline than Group II (5.50 ± 1.24), which was insignificant (p 0.06). At 4 weeks, DAS28 was improved significantly from baseline in both groups but the improvement in DAS28 score in Group I (1.46) was more than the Group II (0.83) (Table 2). There was significant improvement in DAS28 by 2.52 and 1.53 from baseline to 12 weeks in Group I and Group II, respectively (p < 0.001) (Table 2). Similarly, CDAI was higher in Group I (35.48 ± 16.72) than in Group II (27.56 ± 14.45) (Table 4). At 4 weeks, CDAI was improved significantly from baseline in both groups but the improvement in CDAI score in Group I (15.24) was more than the Group II (7.64) (Table 5). There was significant reduction in CDAI by 23.32 and 12.84 from baseline to 12 weeks in Group I (p < 0.001) (Table 5). This study showed a significant reduction in various variables of disease activity of RA-like tender joint count (TJC), swollen joint count (SJC), patient global
assessment (PGA), evaluator global assessment (EGA), ESR, patient’s general health (GH) over a period of 12 weeks in both groups (atorvastatin and control), similar finding was observed for 40 mg atorvastatin in TARA study.18 In our study, the results showed that atorvastatin when used as adjuvant therapy with DMARDs had beneficial effects on parameters of disease activity and also, was well-tolerated when given in combination with DMARDs. Since, the improvement in diseases activity was numerically higher in the atorvastatin adjuvant therapy group when compared with DMARD alone group, but this was statistically insignificant; hence, it is suggested that larger and longer trails are needed so as to evaluate the modest but beneficial effect of welltolerated atorvastatin therapy in patients of RA. But thanks to good safety profile, easy administration and the existence of a broad experience regarding their use in clinical practice, statins are particularly attractive therapeutic agents, so that even a modest efficacy in the treatment of RA in association with the reduction of cardiovascular risk can lead to a beneficial therapeutic ratio. This can make statins become particularly useful as adjuvant therapy associated with other conventional therapeutic methods used in RA, especially in patients with dyslipidemia, where they should be the first choice of treatment. REFERENCES 1. Van Doornum S, McColl G, Wicks IP. Accelerated atherosclerosis: an extraarticular feature of rheumatoid arthritis? Arthritis Rheum. 2002;46(4):862-73. 2. Pinals RS. Survival in rheumatoid arthritis. Arthritis Rheum. 1987;30(4):473-5. 3. Vandenbroucke JP, Hazevoet HM, Cats A. Survival and cause of death in rheumatoid arthritis: a 25-year prospective follow-up. J Rheumatol. 1984;11(2):158-61. 4. Reilly PA, Cosh JA, Maddison PJ, Rasker JJ, Silman AJ. Mortality and survival in rheumatoid arthritis: a 25year prospective study of 100 patients. Ann Rheum Dis. 1990;49(6):363-9. 5. Bacon PA, Raza K, Banks MJ, Townend J, Kitas GD. The role of endothelial cell dysfunction in the cardiovascular mortality of RA. Int Rev Immunol. 2002;21(1):1-17. 6. Pasceri V, Yeh ET. A tale of two diseases: atherosclerosis and rheumatoid arthritis. Circulation. 1999;100(21): 2124-6. 7. Arnett DK, Evans GW, Riley WA. Arterial stiffness: a new cardiovascular risk factor? Am J Epidemiol. 1994;140(8):669-82. 8. Van Doornum S, McColl G, Jenkins A, Green DJ, Wicks IP. Screening for atherosclerosis in patients with rheumatoid Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
973
RHEUMATOLOGY arthritis: comparison of two in vivo tests of vascular function. Arthritis Rheum. 2003;48(1):72-80.
modulatory effects of atorvastatin in rheumatoid arthritis. Arthritis Rheum. 2003;48:666.
9. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333(20):1301-7.
14. Palinski W, Napoli C. Unraveling pleiotropic effects of statins on plaque rupture. Arterioscler Thromb Vasc Biol. 2002;22(11):1745-50.
10. Vaughan CJ, Murphy MB, Buckley BM. Statins do more than just lower cholesterol. Lancet. 1996;348(9034): 1079-82. 11. Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, et al; Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med. 2001;344(26):1959-65. 12. Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy3-methylglutaryl coenzyme a reductase inhibitors. Arterioscler Thromb Vasc Biol. 2001;21(11):1712-9.
15. Choi M, Rolle S, Rane M, Haller H, Luft FC, Kettritz R. Extracellular signal-regulated kinase inhibition by statins inhibits neutrophil activation by ANCA. Kidney Int. 2003;63(1):96-106. 16. Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nat Med. 2000;6(12):1399-402. 17. Leung BP, Sattar N, Crilly A, Prach M, McCarey DW, Payne H, et al. A novel anti-inflammatory role for simvastatin in inflammatory arthritis. J Immunol. 2003;170(3):1524-30.
18. McCarey DW, McInnes IB, Madhok R, Hampson R, Scherbakov O, Ford I, et al. Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised 13. McCarey DW, Satter N, Hampson R, Madhok R, Capell placebo-controlled trial. Lancet. 2004;363(9426): HA, McInnes IB. A randomised, placebo controlled trial comparing the anti-inflammatory and vascular risk 2015-21. ■■■■
SLE may Present as Lupus Myocarditis Lupus myocarditis is a severe manifestation of systemic lupus erythematosus (SLE). It can either be the first manifestation of the disease or it can occur during follow-up, in particular in untreated patients, says a multicentric retrospective study in the January 2017 issue of the Journal of Rheumatology. The long-term prognosis is typically positive. Patients with less severe disease exhibited good left ventricular ejection fraction recovery without cyclophosphamide.
Abatacept in Combination with Prednisone Decreases the Relapse-rate in Patients with Giant Cell Arteritis A study published online in the journal Arthritis & Rheumatology, suggests that abatacept when added to treatment regimen with prednisone diminished the rate of relapse, significantly. Also, it was observed that abatacept in combination with prednisone did not resulted in toxicity, compared to prednisone alone. Moreover, between the treatment arms there was no difference in frequency of adverse drug effects.
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Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
EXPERT’S VIEW
How can One Reduce Cardiovascular Mortality in Patients with Hypertension? NANDINI MUKHERJEE, KOLKATA
C
ardiovascular disease (CVD) including coronary heart disease (CHD) is the commonest cause of death in hypertensive patients. In elderly hypertensive, notably the diuretic-treated group in the Medical Research Council (MRC) elderly trial and in two trials of isolated systolic hypertension (SHEP and SYST-EUR), there was significant reduction (30%) in coronary disease events with reduction of blood pressure (BP). There is no doubt that to reduce the level of systolic and diastolic BP is essential to prevent cardiovascular (CV) mortality, but there are many pros and cons. These are: when to intervene- at any particular level of BP or in presence of any particular clinical feature?
WHAT ASSOCIATED RISK FACTORS NEED SPECIAL ATTENTION? How to intervene, when first detected? By pharmacological agents or by nonpharmacological means? Which agents are most helpful? Recent attempts have been made to find out most effective drug treatment strategies. Systolic and diastolic thresholds of 160 and 100 mmHg, respectively are clear indicators of drug treatment. Nonpharmacological methods fail. Systolic pressure in the range of 140-159 mmHg and diastolic pressure in the range of 90-99 mmHg indicate treatment under following situations. It is remarkable from different observational studies that international guidelines are inconsistent in their recommendations on thresholds for intervention to prevent CHD and CVD. In recent years; however, the following recommendations have been made. ÂÂ
When there is evidence of end-organ damage, like left ventricular hypertrophy (LVH).
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When coexistent clinical situation, like diabetes, may increase the risk of CV mortality.
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When dyslipidemia adds to the risk factor; premature mortality from hypertension among first-degree relatives.
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In elderly hypertensives: Most elderly people exceed the threshold for intervention both on BP
and lipid-lowering. In contrast, younger people, notably women, may have high levels of BP or cholesterol which, when projected through their life time, would reduce life expectancy, but under current guidelines, would not warrant therapeutic intervention. ÂÂ
An estimated 10-year coronary risk of 15% (equivalent to a CVD risk of 20%).
PHARMACOLOGICAL AGENTS USED VARY IN THEIR ABILITY TO PREVENT CV MORTALITY Antihypertensive agents, which achieve similar reduction of level of BP, differ in their ability to prevent CV mortality, due to the differences of their mechanism of action or their effect on central or peripheral pulse pressure. It is found that central pulse pressure i.e., mean aortic pressure, which is the chief determinant of arterial wall stiffness, is the predictor of all-cause mortality including CV mortality. Very stiff arteries cause increase in circumferential arterial wall stress, and this is likely to cause breakdown of medial elastic tissue and it increases possibility of endothelial damage and development of atherosclerosis. So, antihypertensive drugs need to be effective not only in reducing brachial artery BP but also in reducing central arterial wall stiffness. Calcium channel blockers though may have very little effect on large central elastic arteries, through their effect on peripheral muscular arteries, they reduce wave reflection amplitude and markedly lower systolic and pulse pressure, hence ventricular afterload. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study failed to identify any treatment benefit attributable to a particular class of agent, but the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) study shows BP reduction with b-blockers and diuretics as the best recorded intervention for prevention of CV mortality. The Losartan Intervention For Endpoint reduction (LIFE) in hypertension study and recent clinical trial, Perindopril pROtection aGainst REcurrent Stroke
Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
975
EXPERT’S VIEW Study (PROGRESS) clearly showed that angiotensinconverting enzyme (ACE) inhibitors prevent CV mortality more than b-blockers for a similar reduction of BP. ‘Pressure-independent’ effect of ACE inhibitors and receptor blockers may be explained by their optimal effects on arterial stiffness, augmentation of aortic pressure, left ventricular wasted energy, all of which should be reduced to lowest possible level to prevent CV mortality. LIPID-LOWERING DRUGS These drugs, formerly set at a higher threshold for global risk of intervention, are brought down by current joint British guidelines. With introduction of statin, the West of Scotland Coronary Prevention Study (WOSCOPS) and ASCOT-Lipid-Lowering Arm (ASCOT-LLA) studies showed that a 20% reduction in cholesterol was associated with a 30-40% reduction of the incidence of CHD. The issue relating to treatment of patients with lower levels of cholesterol becomes an economic argument rather than one demanding an evidence base.
Hypertension (DASH) done to investigate the effects of diet on hypertension has recommended: ÂÂ
A diet with decreased content of dairy produce
ÂÂ
A diet with increased fruit and vegetable content
ÂÂ
A diet avoiding salty and processed food
ÂÂ
A diet rich in starchy food (which promotes weight loss by flat glycemic response, reduces BP and protects against atherosclerosis by providing phytoestrogens, helpful for raising high-density lipoprotein (HDL): total cholesterol ratio).
SALT RESTRICTION Studies on salt restriction show that a reduction in salt intake by 76 mmol/day (4.6 g/day) results in 5.0 mmHg and 2.7 mmHg falls in systolic and diastolic BP, respectively. There is evidence of additive effect of salt restriction in hypertensive patients when used in conjunction with drugs which block the reninangiotensin-aldosterone system (RAAS). SMOKING CESSATION Smoking cessation may reduce CHD by about 25%.
ANTIOXIDANTS
MODERATION OF ALCOHOL INTAKE
In hypertensives, endothelial dependent dilatation is impaired. This dilatation is mediated largely by release of nitric oxide (NO), which plays an important role in maintaining vascular integrity by modulating vascular tone, inhibiting thrombosis and leukocyte adhesion and influencing smooth muscle proliferation. So, reduced endothelial NO may contribute to vascular injury and hence increase CV mortality. Despite the plausibility for antioxidant therapy in CVD risk reduction, there is no evidence of benefit in prospective placebo-controlled trials.
Moderation in alcohol intake shows a significant fall in both systolic and diastolic BP, though relationship of alcohol intake and CHD is more complex due to beneficial effect of alcohol on HDL cholesterol. Therefore, preventive strategies for CV mortality in essential hypertension include:
LIFESTYLE MODIFICATIONS Lifestyle modifications produce important effect in lowering BP and prevention of CV mortality. In obese patients, a 10 kg loss of weight might well normalize the BP. Short-term studies of physical exercise program demonstrated a 10% fall in mean arterial pressure, a 25% fall in total peripheral resistance and a 20% rise in cardiac index. Epidemiological studies demonstrated that potassium intake, given as potassium chloride tablets, brings about a significant fall in BP. Potassium intake, as potassium chloride tablet, is not recommend but intake may be increased as fruits and vegetables. A major American study, Dietary Approaches to Stop
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Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
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Early detection
ÂÂ
Lifestyle modification
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Timely therapeutic intervention
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Appropriate choice of therapeutic agents
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Adoption of preventive program not only at personal and clinical level, but also at national level.
SUGGESTED READING 1. Hanson L, Hedner T, Lund-Johnasen P, Kjeld SE, Lindholm LH, Syvertsen Jo, et al. Lancet. 2000;356(9227):359-65. 2. Yusuf S, Sleight P, Pogue J, Bosch J, Davies K, Dagenais G. N Engl J Med. 2000;342(3):145-53. 3. du Cailar G, Ribstein J, Mimran A. Am J Hypertens. 2002;15(3):222-9. 4. Frolich ED, Varagic J. Nat Clin Pract Cardiovasc Med. 2004;1:24-30. 5. He FJ, MacGregor GA. BMJ. 2001;323(7311):497-501.
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CONFERENCE PROCEEDINGS
69th Annual National Conference of Indian Psychiatric Society (ANCIPS 2017) CHALLENGING UNITARY PSYCHOSIS
ÂÂ
Prevalence of child psychiatric illnesses is around 10% and the likelihood of continuation into adult life is high. Behavioral problems typically precede a mental disorder by 2-4 years. Early therapeutic intervention can be highly effective at limiting the severity and/or progression of problems.
ÂÂ
For public health purposes, mental health promotion; universal, selective and indicated prevention; early intervention and relapse prevention are some of the issues that need to be understood and implemented.
ÂÂ
In the field of mental health promotion of children ASHA (Accredited Social Health Activist), ANM (Auxiliary Nurse Midwife) and AWW (Anganwadi Worker) can do wonders if they are sensitized and trained.
ÂÂ
The situation demands early action because mental health problems experienced by infants and families during the perinatal period are a major public health concern as they can have serious, long-lasting and potentially intergenerational consequences.
ÂÂ
We have very limited number of child psychiatrists. So, including general psychiatrists, pediatricians, family physicians, health workers and teachers would be the most suited public health strategy for India.
ÂÂ
Parenting training of would-be-parents, early detection of vulnerable children and timely intervention are some of the efforts that will give large dividends. Early intervention may be important because there may be critical periods when the developing brain is relatively more plastic and thus offers more opportunity for change.
ÂÂ
Cohesiveness between healthcare settings, schools, social agencies and even juvenile justice system is needed. Divided system responsibilities for children make it difficult to deliver prevention programs. Interaction meetings of all concerned should be organized to have an idea of greater landscape. No one person/profession has or can have all the knowledge/skills.
RS-fMRI Differences Between Psychotic and Nonpsychotic Bipolar Disorder Dr Rashmin Mansukh Achalia, Aurangabad ÂÂ
Bipolar disorder reflects a clinically and etiologically heterogeneous entity. This may explain the difficulties in forming clinically homogeneous patient groups leading to only partial effectiveness of treatments and difficulties identifying neuropathophysiological mechanisms.
ÂÂ
Studies have reported psychotic symptoms to be associated with poorer prognosis, aggregation within family and poorer cognitive functions.
ÂÂ
We examined the association between psychotic symptoms and ReHo abnormalities in three ways: Comparison of psychotic bipolar patients with controls; comparison of patients without a history of psychosis with controls and comparison of patients with and without a history of psychosis.
ÂÂ
All three comparisons indicated that psychotic bipolar patients exhibit a more severe pattern of prefrontal - subcortical aberrant synchronization.
ÂÂ
Preliminary data suggest that specific neuroimaging-based markers could characterize some subgroups of bipolar disorder (mostly for psychotic bipolar disorder).
ÂÂ
Our findings are important in the background of growing recognition of shared psychopathology and neurobiology between schizophrenia and bipolar disorder.
ÂÂ
Valid subgrouping could allow a more targeted approach to disease in terms of diagnostic precision, vulnerability assessment, evolution and therapeutic response prediction.
PREVENTIVE PSYCHIATRY IN INDIA ON CHILD PSYCHIATRIC FRONT Dr Devashish Konar, Kolkata “The landscape is huge, problems are myriad, task looks next to impossible and yet we must act and deliver. Even a small dent made will have huge impact.”
Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
979
CONFERENCE PROCEEDINGS ÂÂ
ÂÂ
Age of the parents, maternal nutrition, smoking, alcohol and exposure to other substance abuse during pregnancy are some of the awareness issues that need to be taken up urgently. Vulnerable groups like children of financially and socially marginalized section and also children from parents with mental illness need extra attention. Public policies for poverty alleviation, neighborhood unity, quality of education, play situations and other extracurricular activities, good housing, employment of parents, marital and family support, accident prevention and protection from abuse are some of the important strategies for prevention in child psychiatry.
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THE JOURNEY OF OPIOID SUBSTITUTION THERAPY IN INDIA: ACHIEVEMENTS AND CHALLENGES Dr Ravindra Rao, New Delhi ÂÂ
Global figure of opioid users is around 33 million with 12 million injecting drug users. Similar figures in India are 2 million and 1.7 million, respectively. These figures are of high importance considering the fact that opioid use contributes to the highest number of drug-related deaths and is associated with high prevalence of HIV and hepatitis C.
ÂÂ
Opioid substitution therapy (OST) is an integral part of opioid dependence management and treatment guidelines strictly recommend OST in the absence of any contraindications.
ÂÂ
OST has been implemented in 80 countries as of 2016, with methadone being the most commonly used OST medicine.
ÂÂ
The journey of OST in India can be demonstrated into three phases:
STRESS AMONG MEDICAL STUDENTS Dr Vipul Singh, Kanpur ÂÂ
MBBS study is the toughest course among all the study courses including, BCA, IAS, Engineering or any other technical courses as quoted in the Guinness Book of World Records in May 2011.
ÂÂ
It is usually observed that medical students undergo tremendous stress during various stages of the MBBS course.
ÂÂ
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Steps should be evolved to prevent stress. In view of the potential long-term benefits of managing stress in a more effective way, it may be important for students to develop such stress coping skills early in their medical career.
ÂÂ
In susceptible cases or obvious cases of stress, counseling may be started at an appropriate stage integrated with medical curriculum and extracurricular activities, yoga, etc. in close association with parents, wherever required.
ÂÂ
980
Contemplation Phase (1989-2004): Establishment
of de-addiction centers and use of OST in the form of buprenorphine
Studies that have tried to identify the sources of stress among medical students generally pointed to four main areas: Academic pressures, emotional factors, social issues and financial problems. Distress has been found to be associated with anxiety and depression, interpersonal conflict, sleep problems, lower academic and clinical performance. It can also decrease attention, concentration, hamper decision-making and affect the ability of students to establish good relationships with peers and patients resulting in feeling of inadequacy and dissatisfaction with clinical practice in the future.
Interaction between students and faculties should be encouraged, so that the signs of stress can be detected and addressed at the earliest.
Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
There is also a need to bring about academic changes in the quality of teaching and evaluation system.
Preparation Phase (2005-2007): Projects initiated
to support OST in India, pharmacological development including buprenorphine-naloxone, slow-release oral morphine
Action plan (2007-till date): Buprenorphine
uses established in few medical college hospitals, expansion of OST for HIV prevention, collaborative OST models.
ÂÂ
Challenges for OST program in India: Low threshold approach; outpatient-based treatment, easier entry and re-entry, no mandatory urine analysis, etc.; Gap in demand and supply of OST; Unfair practices and use due to local availability of OST; Legal complications; Need of adequate training, guidelines and adherence to ethical standards.
ÂÂ
Achievements of OST program in India: Established Quality assurance system, Significant expansion from handful to more than 225 NGOs centers and Availability of local OST medicines with cheaper price.
CONFERENCE PROCEEDINGS NEUROIMAGING OF TRANSCENDENTAL MEDITATION
ÂÂ
Comparison of cervical vertebrae of both patient and control groups showed that, there was no significant difference in between the patient and control groups.
ÂÂ
Reduction of intervertebral disc was found to be significantly high at the level of C4-5 (p = 0.033) and C5-6 (p = 0.012) in patient group vs. control group.
ÂÂ
Scalp dysesthesia does not seem to follow a dermatomal distribution given that the most common location in the present study was C5-C6.
ÂÂ
Symptoms of scalp dysesthesia may be related to chronic tension placed on the occipitofrontalis muscle and scalp aponeurosis (galea aponeurotica).
ÂÂ
It may be secondary to underlying cervical spine disease, rather than psychiatric causes.
Dr Paolo Nucifora, Dr Murali Rao; Chicago ÂÂ
ÂÂ
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New models are emerging with a clinical focus on brain circuits, as opposed to focal lesions or clinical syndromes. For scientists and clinicians alike, it is and will become increasingly important to have an understanding of the different levels of biological resolution and how they influence each other in health, in disease and in therapy. Particularly for clinicians treating disorders of affect, behavior and cognition, it will be particularly important to understand the circuit level, as this is where mental states, including the pathological affective, behavioral and cognitive states that we treat, are computed. Our study is expected to show that subjects will undergo regional changes in functional connectivity after using the Transcendental Meditation (TM) technique, most likely involving increased strength of the networks commonly active during rest.
ÂÂ
Furthermore, it is expected that the beneficial effects of TM on clinical measures will be correlated to the degree of change in functional connectivity.
ÂÂ
Finally, it is expected that the degree of change in functional connectivity will be partly explained by intrinsic variability in structural brain connectivity, indicating the existence of white matter networks that mediate the effect of TM.
RELATION OF CERVICAL SPINE DISEASE IN PATIENTS OF SCALP DYSESTHESIA
PSYCHOLOGICAL DISTRESS IN SURVIVORS OF FARMERS’ SUICIDES IN DRAUGHT-HIT MARATHWADA REGION OF MAHARASHTRA, INDIA Dr Manik Bhise, Aurangabad ÂÂ
Due to consecutive 3 years of draught, there was a sharp rise in number of farmer suicides in Marathawada region of Maharashtra.
ÂÂ
This is in contrast to previous years when the Vidarbha region was the hotspot for this phenomenon. Thus, changing farm environment causes geographical shifting of farmer suicides.
ÂÂ
Often the psychological needs of suicide survivors (family members left behind) are not addressed.
ÂÂ
Our prior study on farmers’ suicide survivors had found that almost 60% survivors were in severe distress and 20% had suicidal ideas. We planned to evaluate survivors from this region to further strengthen the scarce literature in the country.
ÂÂ
In present study, we found that 81.7% of survivors had significant psychological distress after suicide by a family member; 28% of survivors had thought of ending their life in past 1 month. Most commonly distress was expressed through somatic symptoms and depressed mood. There was no significant correlation of psychological distress and age, sex, occupation and residence of survivors. There was no significant correlation of psychological distress and relation of survivors with suicide victim.
ÂÂ
We conclude that survivors of farmers’ suicides suffer from significant distress. A systematic psychological approach is needed to alleviate their suffering.
Dr Ranjan Bhattacharyya, Dr Supriya Kumar Mondal, Dr Barindranath Mallick, Dr Utpal Ray, Dr Madhab Kumar Mondal, Dr Sumita Bhattacharyya; Kolkata ÂÂ
Scalp dysesthesia is a common mode of presentation in rural India.
ÂÂ
Most of these cutaneous pain symptoms are not attributed to any pathophysiology. The range of complaints vary widely from tingling, stinging to severe itching leading to scratch-itch cycle.
ÂÂ
The study aimed at finding radiological correlation of imaging of cervical spine with the presenting symptoms. A cross-sectional, case-control design was used with sample size n = 40 with healthy volunteers (n = 40) included for comparison.
ÂÂ
The loss of curvature was significantly high among patient group (p = 0.011).
Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
981
CONFERENCE PROCEEDINGS GIVING A DIGNIFIED LIFE TO PATIENTS WITH DEMENTIA: MEANING OF A DIGNIFIED LIFE
ÂÂ
Future aspects of neuroimaging in psychiatry: The use of neuroimaging in psychiatry may be expanded considering the potential these diagnostic modalities have. In future it may be useful in validity of psychiatric diagnosis, predicting disease prognosis and accurate diagnosis. Additionally, it may also be of great use in improving the power of research to develop better treatments, by elimination erroneous inclusion. Further, in future it may prove helpful in the selection of drugs and doses and predicting side effects. Thus, minimizing adverse outcomes. Another aspect that neuroimaging may explore in psychiatry is the prediction of treatment response, and disease onset in asymptomatic patients.
ÂÂ
Limitation of neuroimaging in psychiatry: Neuroimaging, when considered for psychiatric syndromes such as schizophrenia, may not be of high specificity as imaging findings from different psychiatric disorders often overlap. Additionally, high-degree of variability exists even within the groups of healthy and ill subjects. Next, the knowledge of using imaging techniques in psychiatric syndromes is very limited, which can lead to inaccurate diagnosis or treatment plan. The heterogeneous nature of a psychiatric disorder, as in the case of schizophrenia, makes it difficult to extrapolate the findings from one group of patients to others.
Dr Shailendra Mohan Tripathi, Lucknow ÂÂ
Dignity is an important aspect of life, be it a healthy individual or a person with dementia. Just as with normal people, patients of dementia also expect respect.
ÂÂ
There is a gradual role reversal in patient with dementia that often results in a “child like state” of dependency.
ÂÂ
Also, these patients lose their “sense of self” and personal unique identity, which negatively affects their dignity and respect in the society.
ÂÂ
The central focus of care in patients with dementia should be quality-of-life and dignity.
ÂÂ
Care providers should give special emphasis on the patient’s needs, wishes and values.
ÂÂ
The ultimate goal of care must be to provide a sense of well-being for that person.
NEUROIMAGING IN SCHIZOPHRENIA: POTENTIAL AND LIMITATIONS Dr Sushil Gawande, Dr Vivek Kirpekar, Dr Abhijeet Faye, Dr Rahul Takde, Dr Sudhir Bhave; Nagpur ÂÂ
Present approach of neuroimaging in psychiatry: In current scenario, neuroimaging in psychiatric disorders is used as an assessment tool to rule out “organic” causes of psychiatric syndromes like tumors or traumatic brain injuries. It is also used as a real time procedure to measure the regional brain activity i.e., in biofeedback. Also, it sometimes guides the psychiatrists to modify the treatment approach and use of new treatments such as deep brain stimulation.
Even with great advancements in neuroimaging, its utility in psychiatry is still very much unexplored and untouched. Today neuroimaging is not considered as an effective diagnostic tool in psychiatry. But, in future this may change considering the potentials of neuroimaging, though this needs to be established by more rigorous researches.
■■■■
982
Indian Journal of Clinical Practice, Vol. 27, No. 10, March 2017
CONFERENCE PROCEEDINGS
72nd Annual Conference of the Association of Physicians of India (APICON 2017) DIABETES WITH HYPERTENSION: A DOUBLE WHAMMY
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LDL-C is a simple molecule, easy to modulate; HDL-C on the other hand is a complex molecule and a ‘hard nut’ to crack. HDL modulation is a slow process.
ÂÂ
All HDL trials on top of optimum statin therapy have flopped. This does not mean that HDL has become dysfunctional as to declare HDL as nonfunctional, sufficient lipids have to be demonstrated in the plaque.
Dr Siddharth N Shah, Mumbai ÂÂ
About 50-60% of diabetic patients are hypertensive; about 70% of hypertensives have diabetes ‘double trouble’.
ÂÂ
Many patients are unaware that they have diabetes and hypertension.
ÂÂ
CV events are more prevalent in hypertensive diabetic vs. normontensive diabetic.
ÂÂ
TGs are a barometer of metabolic health and levels >200 mg/dL in spite of statins need to be treated.
ÂÂ
In diabetics, BP should be lowered to as low as can be achieved without side effects. A diabetic hypertensive, if neglected, is a double whammy.
ÂÂ
It is time to look beyond LDL-C…look at nonHDL-C and TGs.
ÂÂ
Saroglitazar is a glitazar but its different from all other glitazars. It is the world’s first dual PPAR α/γ agonist.
ÂÂ
Saroglitazar has been shown to improve glycemic control as well as lipid abnormalities in Indian patients with diabetic dyslipidemia.
ÂÂ
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Hence, periodic surveillance, early detection and intervention, delaying disease progression and follow-up is important. The most effective therapy prescribed by the most careful clinician will control HT only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator.
DIABETIC DYSLIPIDEMIA: INDIAN PERSPECTIVE
Prevention Mantra: “Eat less, Eat on time, Eat Right, Walk more, Sleep well and on time & Smile”. DIABETES AND TECHNOLOGY Dr Banshi Saboo, Ahmedabad ÂÂ
Diabetes is a chronic metabolic disease the treatment of which is very complex with a good majority of patients developing debilitating complications.
ÂÂ
Newer technologies and therapies are developed to address the major challenges such as hypoglycemia, weight gain and progressive loss of b-cell function and lipid abnormalities.
ÂÂ
Continuous glucose monitoring (CGM) is emerging as a routine investigation in all subjects with diabetes.
ÂÂ
The revolutionary new insulin pump 640 G comes with predictive low glucose suspend mechanism.
ÂÂ
Recent advances in technology makes it possible to combine three technologies—continuous glucose monitors, insulin pumps and a computerized control algorithm. This forms the basis of a closed loop system, sometimes termed as artificial pancreas.
Dual PPAR Agonist: The Journey So Far Dr Shashank R Joshi, Mumbai ÂÂ
Dyslipidemia is the single most important CV risk factor for MI.
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The onset of CVD is earlier in South Asians because risk factors are prevalent at a younger age.
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Almost 9 out of 10 diabetics in India have dyslipidemia.
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In the ICMR-INDIAB study, the overall prevalence, in 4 regions, of at least one lipid abnormality was 79%.
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Indian dyslipidemia is atherogenic in nature; low HDL, high TG, high Lp(a).
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Statins take care of only 40%, but a residual atherogenic risk of 60% still remains.
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CONFERENCE PROCEEDINGS DRUG-DRUG INTERACTIONS: AN UNDERRATED PHENOMENON Dr KM Prasanna Kumar, Bengaluru Polypharmacy is inevitable in certain circumstances, especially in chronic conditions like diabetes, given the varied treatment options and the multiple comorbidities involved. Its consequences could range from adverse drug events to drug interactions, lowered compliance, increased hospitalizations and finally a decreased QoL.1 Drug-drug interactions are a preventable cause of morbidity and mortality.2-5 Pharmacodynamic drug interactions can be either beneficial or detrimental to patients. An example of beneficial interaction is the addition of an antihypertensive drug like an ACEI and a CCB like amlodipine or cilnidipine.2 While an example of disadvantage is combination of clarithromycin, a CYP3A4 inhibitor with warfarin, which can increase the anticoagulant effect.3 Most persons with diabetes will also be taking medications for dyslipidemia, HT and/or antiplatelet drugs along with antihyperglycemic drugs. Many medicines, including several cholesterollowering agents (e.g., simvastatin), antihypertensives (e.g., diltiazem, nifedipine, verapamil) and antifungals (e.g., ketoconazole) are metabolized by and/or inhibit the CYP3A4 metabolic pathway. These drugs are commonly co-prescribed to treat comorbidities in patients with T2DM and the potential for drug-drug interactions of these medicines with new medicines for T2DM must be carefully evaluated.2,3 For example, in a study, hypoglycemia was 6 times more likely in elderly persons with diabetes receiving glyburide when combined with trimethoprim/ sulfamethoxazole. Another example of drug-drug interaction in persons with diabetes is combination of ACEI and potassium-sparing diuretic, which increases the chances of hyperkalemia by 20 times.5 Emphasis should also be given to antidiabetic drugs that involve inhibition/potentiation/substrate of the CYP3A4 enzyme, apart from other less commonly involved CYP450 isoenzymes like CYP2C8 and CYP2C9.3 For example, it is well known that erythromycin derivatives and antifungal agents (azole) inhibit CYP3A4, which in turn enhances the hypoglycemic effect of repaglinide.4 Similarly, saxagliptin is a CYP3A4 substrate. With saxagliptin, up to 145% increase in exposure is observed when co-administered with potent CYP3A4 inhibitors like ketoconazole, thus requiring dose reduction of 2.5 mg.6 Along the same lines, teneligliptin is also metabolized through CYP3A4; teneligliptin lacks
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evidence on drug-drug interaction and its effects in Indian patients,7 thus precaution should be taken with these medications. Notably, sitagliptin and vildagliptin, established medications from the same class, have not reported any such significant interactions.8,9 Although physicians need to simultaneously manage a plethora of illnesses and symptoms, especially while prescribing a drug regimen for a person with diabetes,10 certain factors must be kept in mind to avoid the ill-effects of drug-drug interactions.11 ÂÂ
Work out a best possible option for treatment of each patient to avoid ADRs as far as possible.
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Encourage patients to update you on all the possible treatments that they are undergoing.
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Prescribe medications that have robust evidence and a proven safety profile.
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Periodically check the drug for efficacy of treatment.
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Eliminate all medications that are without therapeutic benefit, goal or indication.
It is the responsibility of the physician to keep in mind the consequences of inappropriate polypharmacy, particularly for elderly patients, because ADRs affect not only the well-being and financial security of the patient, but also the ability to adhere to prescribed therapy, which is ultimately the key to successful treatment.7
References 1. Austin RP. Diabetes Spectrum. 2006;19(1):13-6. 2. Dresser GK, et al. Clin Pharmacokinet. 2000;38(1):41-57. 3. Triplitt C. Diabetes Spectrum. 2006;19(4):202-11. 4. Sharma SG, et al. Int J Pharmacol Clin Sci. 2015;4(4): 98-105. 5. Juurlink DN. JAMA. 2003;289(13):1652-8. 6. Patel CG, et al. Clin Pharmacol. 2011;3:13-25. 7. Product monograph of teneligliptin. 8. Product monograph of sitagliptin. 9. Product monograph of vildagliptin. 10. Freeman JS, et al. Expert Rev Clin Pharmacol. 2012;5(1): 31-42. 11. Rambhade S, et al. Toxicol Int. 2012;19(1):68-73.
PERSONALIZED MEDICINE: MAKING EFFECTIVE THERAPY SAFE FOR THE INDIVIDUAL PATIENT Dr RD Lele, Mumbai ÂÂ
About 10,000 deaths occurred annually in the US alone due to adverse effects of therapy (IOM, 1999 “To Err is Human”).
CONFERENCE PROCEEDINGS ÂÂ
The IOM in 2006 recommended that all prescriptions should be written electronically with built in warning about drug-drug interactions and side effects. This has yet to happen.
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The main indications of FFP are bleeding due to warfarin excess, vitamin K deficiency, CLD with increased INR and bleeding, DIC and in massive transfusion.
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About 10-20% of hospitalized patients and 2-5% of outpatients develop adverse effects of medications.
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Most adverse drug reactions occur soon after the administration, while some may be seen after a month or more and still some, may take years.
Cryoprecipitate contains factor VIII, fibrinogen, fibronectin, factor XIII and VWF and is indicated in fibrinogen and factor XIII deficiency and sometimes in uremic bleeding.
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Platelets are available for transfusion as RDP (random donor or pooled platelets) and SDP (single donor platelets by apheresis). One SDP is equal to 5 RDP and will increase the platelet count by about 30 to 50,000.
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Indications for platelet transfusion are therapeutic (when there is clinical bleeding) and prophylactic to prevent spontaneous bleeding. In therapeutic transfusion, the platelet count is maintained above 50,000. In DIC and CNS bleeding, the count is maintained above 1,00,000. Platelet transfusion is given prophylactically, if the count is <10,000.
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There is a new interest in granulocytic transfusion.
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“Every individual is different from another and hence should be considered as a different entity. As many variations are there in the universe, all are seen in human beings” (Charaka Samhita).
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Personalized medicine has been a part of Ayurveda, Unani and homeopathic practice medicine. Dr Lele had observed in his book (Homeopathy and Modern Medicine in 2015) that the safety record of homeopathy is 100%.
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It is essential to understand the mechanisms of drug-drug interactions: Pharmacological incompatibility, pharmacokinetics and metabolism.
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It is possible to analyze the drug metabolizing enzymes using pharmacogenomics and determine the individual patient’s genotype.
ICMR-INDIAB STUDY: A COMPENDIUM OF T2DM IN INDIA
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The future of healthcare lies in preventive genetic testing. The challenge is how to make it available and affordable for Indian citizens.
Clinical Practical Message & Practice Points Dr V Mohan, Chennai
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CRISPR, a very precise gene editing technique, is a new and very exciting development.
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The diabetes epidemic in India is still spiraling upwards.
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A checklist makes the entire team working towards solving problems. Despite its benefits, checklists are met with resistance from doctors.
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The prevalence of diabetes in India varies widely in different states, from 4.3% in Jharkhand to 13.6% in Chandigarh.
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There are large numbers of undiagnosed diabetes in India.
Prof Dr Mathew Thomas, Trivandrum
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The common blood components used in clinical practice are whole blood, PRBC, FFP, cryoprecipitate and platelets.
The prevalence of prediabetes in India varies widely in different states from 6.0% in Mizoram to 14.6% in Chandigarh.
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There is a shift of the diabetes epidemic from urban to rural areas and from older to younger people.
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We are able to see a clear epidemiological transition with the more developed states in India having higher prevalence of diabetes.
BLOOD COMPONENT THERAPY
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As anemia leads to adverse clinical outcomes, PRBC is indicated in chronic anemia and to replace losses after acute bleeding. The Hb threshold for transfusion now is 7. PRBC is indicated only if the Hb is <7 and not indicated if it is above 10.
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The notable exception to this rule is myocardial ischemia where the Hb is kept around 10.
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The common plasma component is FFP, which contains coagulation factors.
MANAGING BLOOD PRESSURE IN ACUTE STROKE: A DILEMMA Dr (Prof) Bhupendra Chaudhary, Meerut, UP ÂÂ
HT is the most important modifiable risk factor for stroke in around 25% of cases.
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CONFERENCE PROCEEDINGS ÂÂ
Lowering DBP was once the main target to achieve reduction in stroke and other CV events, but SBP has now become the target.
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A ‘U’ shaped association b/w baseline SBP at admission and stroke outcome has been identified.
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In an ICH patient, immediate reduction of BP is required if BP >180/105 mmHg to get the target BP of 160/90 mmHg (MAP: 110 mmHg).
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In thrombolysis eligible ischemic patient, BP must be <185/110 mmHg prior to initiating thrombolysis therapy and it must be maintained up to next 24 hours. In nonthrombolysis patient, immediate reduction is required, if SBP >220 mmHg or DBP >120 mmHg. IV labetalol is the preferred agent but target of BP-lowering is more important than the agent used.
APPROACH TO SEPSIS
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Linagliptin ameliorates diabetic kidney fibrosis by inhibiting TGF-b in preclinical studies and has shown 16% significant reduction in composite renal outcome in a large meta-analysis.
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Linaglipitin does not require dose modification irrespective of stage of renal and hepatic impairment.
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CARMELINA and CAROLINA are two ongoing CVOTs with linagliptin, both of which are unique from the already completed DPP4i CVOTs.
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Side effects and difficulty in remembering the doses are most important factors for low adherence to prescribed treatment.
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Linagliptin demonstrated the highest adherence among all DPP4i and other therapies as per a nationwide US health insurance database.
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DPP4i simplify the management of T2D, both for patients and physicians.
Dr Gurinder Mohan, Amritsar Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is persisting hypotension requiring vasopressors to maintain MAP 65 mmHg and serum lactate level >2 mmol/L (18 mg/dL) despite adequate volume resuscitation. Early goal-directed therapy includes following: CVP 8-12 cm H2O, MAP ≥65 mmHg, urine output ≥0.5 mL/kg/hr and central venous oxygen (ScvO2) saturation >70%. Sepsis is a time critical illness. Remember the dictum “Speed is life” for management of sepsis.
MY DIET PLAN FOR DIABETIC CKD Dr Sanjay Dash, Bhubaneswar ÂÂ
Kidney disease attributable to diabetes is referred to as diabetic kidney disease (DKD), which is the leading cause of ESRD.
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Interim analysis report (2015) of START-INDIA suggests over 40% of T2DM patients have CKD.
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Key diet components to slowing progression of DKD are: Controlling BP by reducing sodium intake, reducing protein intake, if excessive, glycemic control and maintaining good nutritional status all the time.
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Low protein, low potassium, low phosphorous, moderate carbohydrate and high fiber diet have been recommended to DKD patients to control blood sugar levels and delay CKD progression.
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The diet of every patient needs to be individualized depending on the tendency to retain or lose salt and the serum levels of protein, potassium, phosphorus and lipids and finally the overall nutritional status and daily urine output of the patient.
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For most DKD patients, the optimal diet is one similar to the DASH diet, consisting of fruits, vegetables, legumes, fish, poultry and whole grains.
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A skilled dietician will incorporate a patient’s food preferences, adequate calories and a proper distribution of foods while encouraging compliance.
SIMPLIFYING T2D MANAGEMENT: DPP4i PERSPECTIVE Dr Sanjay Kalra, Karnal ÂÂ
DPP4i cover significant aspects of the egregious eleven (of pathophysiology of T2D).
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DPP4i significantly improve the glycemic pentad comprising of HbA1c, FPG, PPG, glycemic variability and lack of hypoglycemia.
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DPP4i have demonstrated superior efficacy in the Asian counterparts as compared to the Caucasians.
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Linagliptin is the only DPP4i to have shown significant glycemic control irrespective of the TCF7L2 gene polymorphism (common in Indian population).
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DPP4i also reduce hypoglycemia, probably due to dual action of GIP, which facilitates a-cell sensitivity to hypoglycemia.
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MEDILAW
Doctors are Required to Provide Emergency Medical Care without Waiting for the Police Report
I have the right to treat my patient without a police/court order in any medico-legal case.
Proceed
The Police have filed against this doctor who treated a patient of road traffic accident without waiting for the Police.
Yes, medical practitioners are required to provide emergency medical care without waiting for the Police report.
Lesson: Doctors have the right to practice unencumbered in the best interest of patients even in medico-legal cases. In Pt. Parmanand Katara vs Union Of India & Ors on 28 August, 1989 AIR 2039, 1989 SCR (3) 997, the Supreme Court of India, in the context of medico-legal cases, has emphasized the need for rendering immediate medical aid to injured persons to preserve life and the obligations of the State as well as doctors in that regard. The Court observed: “Every doctor whether at a Government Hospital or otherwise has the professional obligation to extend his services with due expertise for protecting life. No law or State action can intervene to avoid/delay the discharge of the paramount obligation cast upon members of the medical profession.” Regulation 13 of the Code of Medical Ethics framed by the Medical Council of India also says that the patient must not be neglected. “A physician is free to choose whom he will serve. He should, however, respond to any request for his assistance in an emergency or whenever temperate public opinion expects the service…”
CASE SUMMARY Mr P, a human rights activist, filed a writ petition in the Supreme Court under Article 32 of the Constitution of India on the basis of a newspaper report titled ‘‘Law helps the injured to die”. According to the story, a bystander picked up an injured scooterist who had been hit by a speeding car. He took the injured to the hospital nearby, but the doctors refused to attend to the victim and instead asked him to take the injured person to another hospital located, 20 km away, that was authorised to handle medico-legal cases. The victim succumbed to his injuries before he could reach the hospital. Mr ‘P’ asked that every citizen brought to the hospital should be promptly administered treatment and the procedural criminal law should be allowed to operate after that. And,
suitable compensation should be allowed in addition to any action taken for negligence in contravention of this directive. SOME SALIENT COURT OBSERVATIONS ÂÂ
The Counsel for Medical Council of India (MCI) stated that there is no prohibition in law justifying the attitude of the doctors as complained. The affidavit filed on behalf of the MCI mentioned ‘Clause 10 - Obligations to the sick and Clause 13 – The patient must not be neglected’ of the Code of Medical Ethics Regulations and further stated: “… It should be the duty of a doctor in each and every casualty department of the hospital to attend such person first and thereafter take care of the formalities under the Criminal Procedure Code. The life of a person is far more important than the legal formalities.”
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MEDILAW ÂÂ
The affidavit filed on behalf of the Union of India on 3rd August, 1989 also said: “There are no provisions in the Indian Penal Code, Criminal Procedure Code, Motor Vehicles Act, etc. which prevent Doctors from promptly attending seriously injured persons and accident case before the arrival of Police and their taking into cognisance of such cases, preparation of F.I.R. and other formalities by the Police.”
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“There can be no second opinion that preservation of human life is of paramount importance. This is so on account of the fact that once life is lost, the status quo ante cannot be restored, as resurrection is beyond the capacity of man.”
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“Every doctor whether at a Government hospital or otherwise has the professional obligation to extend his services with due expertise for protecting life. No law or State action can intervene to avoid/delay the discharge of the paramount obligation cast upon members of the medical profession. The obligation being total, absolute and paramount, laws of procedure whether in statutes or otherwise which would interfere with the discharge of this obligation cannot be sustained and must, therefore, give way.”
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“There is also no doubt that the effort to save the person should be the top priority not only of the medical professional but even of the Police or any other citizen who happens to be connected with the matter or who happens to notice such an incident or a situation.”
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The Court observed that there is an apprehension among doctors that he/she would be called as witness in medico-legal cases and also that they would be interrogated by the Police, which prevents them from helping such cases. It said, “…, the policy, the members of the legal profession, our law courts and everyone concerned will also keep in mind that a man in the medical profession should not be unnecessarily harassed for purposes of interrogation or for any other formality and should not be dragged during investigations at the Police station and it should be avoided as far as possible. We also hope and trust that our law courts will not summon a medical professional to give evidence unless the evidence is necessary and even if he is summoned, attempt should be made to see that the men in this profession are not made to wait and waste time unnecessarily…”
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“We have no hesitation in saying that it is expected of the members of the legal profession which is the other honourable profession to honour the persons in the medical profession and see that they are not called to give evidence so long as it is not necessary… where the
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facts are so clear it is expected that necessary harassment of the members of the medical profession either by way of requests for adjournments or by cross examination should be avoided so that the apprehension that the men in the medical profession have which prevents them from discharging their duty to a suffering person who needs their assistance utmost, is removed and a citizen needing the assistance of a man in the medical profession receives it.” ÂÂ
“…if he finds that whatever assistance he could give is not sufficient really to save the life of the person but some better assistance is necessary-it is also the duty of the man in the medical profession so approached to render all the help which he could and also see that the person reaches the proper expert as early as possible.”
COURT ORDER The Court ordered that the guidelines indicated in the 1985 decision of the Committee under the Chairmanship of the Director-General of Health Services should become operative. 1. “Whenever any medico-legal case attends the hospital, the medical officer on duty should inform the Duty Constable, name, age, sex of the patient and place and time of occurrence of the incident, and should start the required treatment of the patient. It will be the duty of the Constable on duty to inform the concerned Police Station or higher police functionaries for further action. Full medical report should be prepared and given to the Police, as soon as examination and treatment of the patient is over. The treatment of the patient would not wait for the arrival of the Police or completing the legal formalities. 2. Zonalisation as has been worked out for the hospitals to deal with medico-legal cases will only apply to those cases brought by the Police. The medico-legal cases coming to hospital of their own (even if the incident has occurred in the zone of other hospital) will not be denied the treatment by the hospital where the case reports, nor the case will be referred to other hospital because the incident has occurred in the area which belongs to the zone of any other hospital. The same police formalities as given in para 1 above will be followed in these cases.
All Government Hospitals, Medical Institutes should be asked to provide the immediate medical aid to all the cases irrespective of the fact whether they are medico-legal cases or otherwise. The practice of certain Government institutions to refuse even the primary medical aid to the patient and referring them to other hospitals simply because they are medico-legal cases is not desirable. However, after providing
MEDILAW the primary medical aid to the patient, patient can be referred to the hospital if the expertise facilities required for the treatment are not available in that Institution.”
Reference 1. Pt. Parmanand Katara vs Union of India & Ors on 28 August, 1989; 1989 AIR 2039, 1989 SCR (3) 997.
SUPREME COURT APPROVES CENTRE’S GUIDELINES TO PROTECT GOOD SAMARITANS ÂÂ
The Supreme Court of India has approved the Centre’s guidelines to protect Good Samaritans, who help road accident victims, from being unnecessarily harassed by police or any other authority.
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A bystander, including an eyewitness to a road mishap, shall be allowed to leave immediately after taking the injured to the nearest hospital without furnishing his address.
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They (good Samaritans) will also be exempted from any criminal and civil liability.
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A bench comprising justices V Gopala Gowda and Arun Mishra has asked the Central Government to give wide publicity to these guidelines.
Police cannot compel people to reveal their identity even if they are the informers or complainants in the case.
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The person can give his or her name voluntarily.
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All registered public and private hospitals will not detain a Good Samaritan or demand payment for registration and admission costs.
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No police official shall ask him any questions and he would be later given a choice to record his statement before the Court through video conferencing.
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Departmental or disciplinary action shall be initiated against the officer who coerces or intimidates the informer.
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If the witness volunteers to go before the Court to depose in the case, the trial judge shall complete his examination in one sitting.
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The bench also took on record the guidelines placed by the Ministry of Road Transport and Highways, based on the recommendations of the three-member committee headed by former judge KS Radhakrishnan. The 2014 Committee had given 12 major recommendations including setting up of State Road Safety Councils, evolving a protocol for identification of black spots, their removal and monitoring to see the effectiveness of the action taken and strengthening of enforcement relating to drunken driving, over-speeding, red light jumping and helmet or seat belt laws. With the Court’s approval, the government guidelines are law of the land today and binding to all states.
Source: eMedinewS, 1st April, 2016
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AROUND THE GLOBE
News and Views Four Pivotal NIH-funded Artificial Pancreas Research Efforts Begin
Hair Analysis may Help Diagnose Cushing Syndrome: NIH
The first of several major research efforts to test and refine artificial pancreas systems is now underway. Four separate projects, funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), are designed to be the potential last steps between testing the fully automated devices and requesting regulatory approval for permanent use. A successful artificial pancreas would be a life-changing advance for many people with type 1 diabetes. NIDDK is part of the National Institutes of Health (NIH). The artificial pancreas is an integrated system that monitors blood glucose levels automatically and provides insulin or a combination of insulin and a second hormone. The closed-loop system would replace reliance on testing by fingerstick or continuous glucose monitoring systems and separate, non-integrated delivery of insulin by shots or a pump… (NIH, February 7, 2017)
Analyzing a hair sample may help with the diagnosis of Cushing syndrome, a rare and potentially fatal disorder in which the body overproduces the stress hormone cortisol, according to researchers at the National Institutes of Health (NIH). The researchers found that measuring cortisol levels in hair samples tracked closely with standard techniques for diagnosing Cushing syndrome. The findings appear in Endocrine: International Journal of Basic and Clinical Endocrinology.
Mission XI Million, the Biggest School Sports Outreach Program Launched Driven by the Prime Minister, Shri Narendra Modi´s vision of making football the sport of choice in India, Mission XI Million, the biggest school sport outreach program was launched by the Minister of State (I/C) for Youth Affairs and Sports, Shri Vijay Goel in the presence of President of AIFF, Shri Praful Patel. A first of its kind, the program will encourage children to play the beautiful game of football, gain healthy habits and learn important life lessons in teamwork and sportsman spirit. The approach is to work with school principals and sports teachers and encourage and incentivize them to make children play football games on regular basis… (Press Information Bureau, Ministry of Youth Affairs and Sports, 10th February, 2017)
FDA Approves Drug to Treat Duchenne Muscular Dystrophy The U.S. Food and Drug Administration today approved Emflaza (deflazacort) tablets and oral suspension to treat patients age 5 years and older with Duchenne muscular dystrophy (DMD), a rare genetic disorder that causes progressive muscle deterioration and weakness. Emflaza is a corticosteroid that works by decreasing inflammation and reducing the activity of the immune system.
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Disorder-specific Psychotherapy More Effective Than Nonspecific Therapy in Depression In a randomized clinical trial of 268 adults with early-onset chronic depression, patients not taking antidepressant medication who were treated with the Cognitive Behavioral Analysis System of Psychotherapy reported significantly less severe depressive symptoms after 20 weeks than those who received nonspecific psychotherapy. These findings were published online February 1, 2016 in JAMA Psychiatry.
Retina Recovers Quickly After Surgically-induced Detachment In a prospective interocularly controlled study of 5 patients who underwent gene therapy for choroideremia, structural recovery occurred within 1 week of iatrogenic retinal detachment, while functional recovery occurred within 1 month. However, subtle functional changes to color matching—consistent with reduced cone photopigment optical density—persisted at 1 month in 1 patient. These findings are published online February 2, 2017 in JAMA Ophthalmology.
Complications of Diabetes Associated with Declining Balance in Older Persons with Diabetes The presence of multiple diabetic complications, lower Mini-Mental State Examination (MMSE), Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) score were associated with declining balance function in the older persons with diabetes. According to the study published January 26, 2017 in the journal Clinical Interventions in Aging, these findings can alert physicians to detect and intervene earlier on declining balance in older persons with diabetes.
AROUND THE GLOBE Fractional CO2 Laser Safe and Effective for Menopausal Genitourinary Syndrome One-year outcomes of a study reported February 6, 2017 in the journal Menopause show that fractional CO2 laser may be an effective and safe treatment for women suffering from symptoms of genitourinary syndrome of menopause such as pain, burning, itching, dryness, dyspareunia and dysuria. About 92% were satisfied or extremely satisfied with the treatment at 1 year.
FSSAI Issues Clarification Regarding Use of FSSAI Logo and Name In an order dated February 3, 2017, the Food Safety and Standards Authority of India (FSSAI) has clarified that the FSSAI logo is only allowed to be used as per Food Safety and Standards (Packaging and Labelling) Regulations 2.2.1 (7) “License number shall be displayed on the principal display panel …” It further directs that the display of FSSAI logo and name in label and/or advertisements in any form should not be used to misrepresent the Authority or to suggest that FSSAI endorses any particular Food Business Operator, Company, Organization, Product etc…(FSSAI, 3rd February, 2017).
Central Government Clarification on Service Tax on Healthcare Services The Central Government has clarified that there is NO proposal in the Union Budget 2017-18 to levy 5% Service Tax on Healthcare Services, as reported in certain Social Media circles… (Press Information Bureau, Ministry of Finance, 13th February, 2017).
About 50 Million People Worldwide have Epilepsy Epilepsy is a chronic disorder of the brain that affects people worldwide. It is characterized by recurrent seizures. The estimated proportion of the general population with active epilepsy at a given time is between 4 and 10 per 1,000 people. As an initiative established in 1997, WHO and partners are carrying out a global campaign—“Out of the Shadows”—to provide better information and raise awareness about epilepsy and strengthen public and private efforts to improve care and reduce the disorder’s impact... (WHO, 13th February, 2017).
Epinephrine is the Drug of Choice for the Anaphylaxis First-aid In a clinical report published February 13, 2017 in the journal Pediatrics, the American Academy of Pediatrics (AAP) has recognized the lifesaving role of Epinephrine
as soon as anaphylaxis is recognized. Have a written anaphylaxis emergency action plan. Inject epinephrine (adrenaline) IM in the mid-outer aspect of the thigh by using an EA. If needed, give a second injection 5-15 minutes after the first. Education of children and supervising adults about anaphylaxis recognition and first-aid treatment is also important.
Consensus Guidelines to Address Maternal Perinatal Mental Health Perinatal mood and anxiety disorders, if not treated in time, can have profound adverse effects on women and their children, ranging from increased risk of poor adherence to medical care, exacerbation of medical conditions, loss of interpersonal and financial resources, smoking and substance use, suicide and infanticide. Recognizing them as a significant patient safety issue, the Council on Patient Safety in Women’s Health Care has published a Consensus Bundle on Maternal Mental Health with focus on perinatal depression and anxiety in the March 2017 issue of Obstetrics & Gynecology.
Radiotherapy may Improve QOL in Painful Bone Metastases A secondary analysis of the NCIC Clinical Trials Group Symptom Control Trial SC.23 published online February 9, 2017 in JAMA Oncology concluded that a single 8-Gy dose of radiotherapy for painful bone metastases should be offered to all patients, even those with poor survival. Forty percent of patients experienced pain reduction and better quality of life (QOL) at Day 10 after radiotherapy with further improvements in QOL at Day 42 in responders.
FDA Issues Alert About Potential Risks with Fluid-filled Intragastric Balloons The US Food and Drug Administration has cautioned about two adverse events associated with fluidfilled intragastric balloons used to treat obesity and recommends close monitoring of patients with these devices for these adverse events. The first type of adverse event involves the fluid-filled intragastric balloon overinflating with air or with more fluid (spontaneous hyperinflation) in patients’ stomachs, resulting in the need for premature device removal. The second type of adverse event is the development of acute pancreatitis, which has also resulted in the need for premature device removal. Dietary Protein may Improve Muscle Health Dietary protein from any source is associated with musculoskeletal health independently of dietary pattern,
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AROUND THE GLOBE according to the results of the Framingham Third Generation Study published February 8, 2017 in The American Journal of Clinical Nutrition. Individuals in the lowest quartile of total protein intake had significantly lower quadriceps strength and appendicular lean mass.
quality improvement, improving data collection and increasing access to medicines, supplies, equipment and clean water… (WHO, 14th February, 2017).
Type 2 Diabetes and Obesity Affect Left Ventricular Remodeling in Normotensive Patients
In a randomized clinical trial of 182 women with breast cancer receiving chemotherapy with a taxane, anthracycline, or both, those who underwent scalp cooling were significantly more likely to have less than 50% hair loss compared with no scalp cooling (50.5% vs. 0%). These results of the SCALP randomized clinical trial were published February 14, 2017 in JAMA.
Findings of a study published February 8, 2017 in the journal Cardiovascular Diabetology concluded that the metabolically nonhealthy obese, type 2 diabetes and obese/type 2 diabetes patients can develop left ventricular hypertrophy (LVH) independent of hypertension. LVPWd, a traditional index of LVH may underestimate LV remodeling in these patient groups and that pulse pressure can be used as convenient predictor of hypertrophy status.
Cardiovascular Disease Costs will Exceed $1 Trillion by 2035, Warns AHA A new study, released by the American Heart Association (AHA), projects that by 2035, cardiovascular disease (CVD), the most costly and prevalent killer, if left unchecked, will place a crushing economic and health burden on the nation’s financial and healthcare systems. According to the study, in the next two decades, the number of Americans with CVD will rise to 131.2 million — 45% of the total US population — with costs expected to reach $1.1 trillion. The new projections are an update of those made by the association in 2011 that estimated around 100 million Americans would suffer from CVD by 2030. Unfortunately, that predication came true in 2015 — almost 15 years sooner than anticipated… (AHA, 14th February, 2017).
Nine Countries Commit to Halve Maternal and Newborn Deaths in Health Facilities Nine countries—Bangladesh, Cote d’Ivoire, Ethiopia, Ghana, India, Malawi, Nigeria, Tanzania and Uganda— committed to halving preventable deaths of pregnant women and newborns in their health facilities within the next 5 years. Through a new Network for Improving Quality of Care for Maternal, Newborn and Child Health, supported by WHO, UNICEF and other partners, the countries will work to improve the quality of care mothers and babies receive in their health facilities. This Network aims to strengthen national efforts to end preventable deaths by 2030, as envisioned by the Every Woman Every Child Global Strategy for Women’s, Children’s and Adolescents’ Health. Countries will do that for example, by strengthening capacity and motivation of health professional to plan and manage
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Scalp Cooling Devices may Reduce Chemotherapyinduced Alopecia
Shock from ICD Often Triggers Further Healthcare Needs A shock from an implantable cardioverter defibrillator (ICD) may trigger an increase in healthcare needs for many people, regardless whether the shock was medically necessary, according to a new study published in Circulation: Cardiovascular Quality and Outcomes, an American Heart Association journal. Programming strategies that reduce ICD shocks may reduce healthcare costs and improve patient health.
Bictegravir, the New Integrase Inhibitor, Shows Promise as HIV Therapy According to a study presented at the annual Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, USA, the investigational integrase inhibitor bictegravir worked as well as dolutegravir (Tivicay) and caused no serious side effects when used as part of a three-drug antiretroviral therapy regimen.
Study Suggests Longer Duration of Immunotherapy in Allergic Rhinitis According to the results of the GRASS randomized clinical trial published in the February 14, 2017 issue of JAMA, among patients with moderate-to-severe seasonal allergy to grass pollen, 2 years of sublingual grass pollen immunotherapy was not significantly different from placebo in improving the nasal response to allergen challenge at 3-year follow-up.
A Prediction Rule to Identify Children in Whom CT can be Avoided Post-blunt Abdominal Trauma According to a prospective study published online January 24, 2017 in the Journal of the American College of Surgeons, a prediction rule using history and physical examination, chest X-ray, and laboratory evaluation at the time of presentation after blunt abdominal trauma
AROUND THE GLOBE identifies children at very low risk for intra-abdominal injury for whom CT can be avoided. The prediction rule consisted of (in descending order of significance): aspartate aminotransferase >200 U/L, abnormal abdominal examination, abnormal chest X-ray, report of abdominal pain and abnormal pancreatic enzymes.
FSSAI Constitutes a Scientific Panel on “Food Fortification and Nutrition” The Food Safety and Standards Authority of India (FSSAI), which is addressing the nutritional gap in the population through fortification of various foods, has now constituted a Scientific Panel on “Food Fortification and Nutrition” to take the program further. The Panel will identify critical nutritional gaps in the Indian diet in general as well as in specific target groups based on diet surveys and credible scientific evidence, define strategies to address nutritional needs of the general population and vulnerable groups, and review the standards for all suitable food fortifying vehicles, in addition to the healthy dietary intake of fat, sugar and salt. It will also address regulatory and related technological issues, review proposals from industry using modern risk assessment methods, and prescribe standard sampling and test methods for effective monitoring, surveillance and enforcement of the relevant regulations… (Press Information Bureau, Ministry of Health and Family Welfare, 14th February, 2017)
Kayakalp Awards Felicitate Public Health Facilities for Maintaining High Standards of Sanitation and Hygiene “We want to change the image of the public health facilities. The thrust of Kayakalp is to inculcate culture of cleanliness for gaining the trust and confidence of community in these facilities.” This was stated by Shri JP Nadda, Union Minister for Health and Family Welfare during the national felicitation ceremony of Kayakalp Awardees (2016-17) for their work in maintaining high standards of sanitation and hygiene in public health facilities. Shri Nadda congratulated the awardees and said that many good practices have been initiated like emphasis on good cleaning practices, pest control, measuring infection control, etc. and healthy competition amongst healthcare facilities is motivating them to go an extra mile in pursuit of excellence. He further added that the zest and zeal shown by the hospitals and their collective efforts in improving cleanliness, hygiene and infection control practices should continue unabated… (Press Information Bureau, Ministry of Health and Family Welfare, 15th February, 2017)
FDA Approves a New Psoriasis Drug The US Food and Drug Administration has approved Siliq (brodalumab) to treat adults with moderate-tosevere plaque psoriasis. Siliq is administered as an injection to patients who are candidates for systemic therapy (treatment using substances that travel through the bloodstream, after being taken by mouth or injected) or phototherapy (ultraviolet light treatment) and have failed to respond, or have stopped responding to other systemic therapies.
Antibody Treatment Leads to Sustained Remission of HIV-like Virus Scientists at the National Institutes of Health have found that the presence of the protein alpha-4 beta-7 integrin on the surface of HIV and its monkey equivalent, simian immunodeficiency virus, or SIV may help explain why an antibody protected monkeys from SIV in previous experiments. It was found that maturing HIV and SIV particles acquire alpha-4 beta-7 as they emerge from an infected cell, presenting researchers with a new target for HIV prevention and treatment and shedding light on how HIV disease develops. These findings suggest that this protein is critical to the initial phase of infection, which has a major influence on the subsequent development of HIV disease.
Study Links Nodding Syndrome to Parasitic Protein Researchers at the National Institutes of Health (NIH) have uncovered new clues to the link between Nodding syndrome, a devastating form of pediatric epilepsy found in specific areas of East Africa, and Onchocerca volvulus, a parasitic worm that can cause river blindness. The study, published in Science Translational Medicine, suggests that the mysterious neurological disease may be caused by an autoimmune response to the parasitic proteins.
AAP Offers Customizable Allergy and Anaphylaxis Emergency Plan to Guide Effective Management Reaffirming the importance of epinephrine in first-aid treatment for anaphylaxis and written plans for when and how to use it, the American Academy of Pediatrics (AAP) has released a new, written action plan “Guidance on Completing a Written Allergy and Anaphylaxis Emergency Plan” to help patients, families, schools and communities best respond to life-threatening allergic reactions. The customizable plan is published in the March 2017 issue of the journal Pediatrics.
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AROUND THE GLOBE Sleep-disordered Breathing Increases as Menopause Progresses, Says Study
7. Women and newborns who need referrals can obtain them without delay.
Progression through menopause is associated with greater sleep-disordered breathing severity. And, this association was found to be independent of aging and changes in body habitus. The prevalence of apnea-hypopnea index (AHI) was 21% higher among perimenopausal women, 31% higher among postmenopausal women versus premenopausal women and it was 41% higher among participants whose menopausal stage could not be distinguished between peri- and postmenopause. These findings of the study which included participants in the Wisconsin Sleep Cohort Study is published in the February 2017 issue of the journal Menopause.
8. No woman should be subjected to harmful practices during labor, childbirth and the early postnatal period.
Study Supports Aripiprazole as the First Longacting Injectable Antipsychotic for Bipolar Patients A long-acting, injectable form of aripiprazole 400 mg given once a month is safe and effective as maintenance therapy for bipolar I disorder in adults, according to results of a placebo-controlled, 52-week randomized withdrawal study published online January 31, 2017 in the Journal of Clinical Psychiatry. Aripiprazole 400 mg delayed the time to and reduced the risk of recurrence of mood episodes.
10 Ways to Improve the Quality of Care in Health Facilities: WHO The World Health Organization (WHO) has given recommendations on how countries can improve quality of care in their health facilities and prevent maternal and newborn deaths, based on its Standards for improving quality of maternal and newborn care in health facilities. 1. Pregnant women should receive the right care, at the right times. 2. Newborns should receive essential care immediately after birth. 3. Small and sick babies should be well cared for in a facility. 4. All women and newborns must receive care that prevents hospital-acquired infections. 5. Health facilities must have an appropriate physical environment. 6. Communication with women and their families must be effective and respond to their needs.
9. Health facilities need well-trained and motivated staff consistently available to provide care. 10. Every woman and newborn should have a complete, accurate and standardized medical record.
Vitamin D may Prevent Acute Respiratory Infections A new study has added to the beneficial effects of vitamin D. According to a systematic review and meta-analysis of individual participant data from randomized-controlled trials published online February 15, 2017 in the BMJ, vitamin D supplements protected against acute respiratory tract infections. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.
EMA Cautions Against Lower Limb Amputation with Sodium Glucose Cotransporter 2 Inhibitors A European Medicines Agency (EMA) panel has recommended that a warning on the risk of lower limb amputation (mostly affecting the toes) should be included in the prescribing information for sodium glucose cotransporter 2 (SGLT2) inhibitors, highlighting the importance of routine preventative foot care. For canagliflozin, lower limb amputation should be listed as an uncommon side effect. Doctors should consider stopping treatment with canagliflozin if patients develop significant foot complications such as infection or skin ulcers.
A New Score Predicts Suitability of HCC Patients for Liver Transplant Researchers have devised a “Model Of Recurrence After Liver transplant” (MORAL) score for hepatocellular carcinoma (HCC) as a simple, highly accurate tool for predicting recurrence and risk-stratification preand postoperatively. The score measures neutrophillymphocyte ratio (NLR), alpha-fetoprotein (AFP) level and tumor size. The findings are published in the March 2017 issue of Annals of Surgery.
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COFFEE DILEMMA A man and his wife were having an argument about who should brew the coffee each morning. The wife said, “You should do it, because you get up first, and then we don’t have to wait as long to get our coffee”. The husband said, “You are in charge of the cooking around here and you should do it, because that is your job, and I can just wait for my coffee.” Wife replies, “No you should do it, and besides it is in the Bible that the man should do the coffee.” Husband replies, “I can’t believe that, show me.” So she fetched the Bible, and opened the New Testament and shows him at the top of several pages, that it indeed says: “HEBREWS” SALES PRACTICE The out-of-work newlywed took a temporary job as a vacuum cleaner salesman to make ends meet. After 3 days of intensive training, the sales manager told him to go home and practice his pitch on his wife. The next morning, the manager asked the novice how he made out. “Well,” the man began, “I did what you said, and after I finished, I asked her if she would buy the vacuum cleaner from me. She said ‘Yes.’ Then I asked her ‘Why?’ She replied, ‘Because I love you.’” COMMUNICATION TECHNICIAN A communication technician drafted by the army was at a firing range. At the range, he was given some instructions, a rifle and 50 rounds. He fired several shots at the target. The report came from the target area that all attempts had completely missed the target. The technician looked at his weapon, and then at the target. He looked at the weapon again, and then at the target again. He then put his finger over the end of the rifle barrel and squeezed the trigger with his other hand. The end of his finger was blown off, whereupon
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he yelled toward the target area: “It’s leaving here just fine, the trouble must be at your end!” SLOW MOM, FAST MOM! Little Freddie’s mother was in the hospital, and he was paying a visit to see his new brother. He wandered into an adjoining room which was occupied by a woman with a broken leg. “Hello,” he said. “How long have you been here?” “Oh, about a month.” “Let me see your baby,” he then asked. “Why, I haven’t a baby,” the woman replied. “Gee, you’re slow,” said Freddie. “My mama’s been here just 2 days and she’s got one.” GET ME A BATTLESHIP After lunching at the Algonquin Hotel, Robert walked through the lobby, out the front door, and said to the uniformed man on the sidewalk, “My good man, would you please get me a taxi?” The man immediately took offense and replied indignantly, “I’m not a doorman! I happen to be a rear admiral in the United States Navy.” Robert instantly quipped: “All right then, get me a battleship.”
Dr. Good and Dr. Bad SITUATION: A patient was found to have high triglycerides
Stop fat intake.
Reduce refined carbohydrates.
© IJCP Academy
HUMOR
Lighter Side of Medicine
LESSON: Triglycerides are refined carbohydrates dependent and not fat.
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). –
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. –
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.
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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. –
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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The legend must include enough information to permit interpretation of the figure without reference to the text.
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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
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