Vitamin D in Clinical Practice: Current Perspectives

India is a heliophobic country; despite ample sunshine, almost 490 million people are vitamin D deficient in the country. Additionally, the Indian diet has not been successful in providing the daily need for vitamin D, leading to a vitamin D deficiency. The need to fortifying food with vitamin D has been raised several times. Besides, there have been discussions about whether vitamin D is a hormone or a vitamin? In this review, the authors have reviewed vitamin D deficiency and its status in India, assessment and screening, the role of vitamin D in various disease conditions, dosage recommendation and regimen

Vitamin D in Clinical Practice: Current Perspectives

India is a heliophobic country; despite ample sunshine, almost 490 million people are vitamin D deficient in the country. Additionally, the Indian diet has not been successful in providing the daily need for vitamin D, leading to a vitamin D deficiency. The need to fortifying food with vitamin D has been raised several times. Besides, there have been discussions about whether vitamin D is a hormone or a vitamin? In this review, the authors have reviewed vitamin D deficiency and its status in India, assessment and screening, the role of vitamin D in various disease conditions, dosage recommendation and regimen

A Pan-India, Knowledge, Attitudes and Practices (KAP) Study of Healthcare Practitioners in India Regarding Immunomodulatory Role of Vitamin D Supplementation in COVID-19

Introduction: Vitamin D has immunomodulatory effects and vitamin D deficiency has been associated with autoimmune responses and increased risk of infections. Vitamin D-mediated antimicrobial and anti-inflammatory responses play an effective role in the prevention of various respiratory tract infections including coronavirus disease 2019 (COVID-19). Aims and objective: To evaluate the therapeutic role of vitamin D via immunomodulation in COVID-19 through a Knowledge, Attitudes and Practices (KAP) study of pan India healthcare practitioners (HCPs) to arrive at a common consensus statement regarding dosage and duration of vitamin D for immune-modulatory function. Methods: A pan-India, online, questionnaire-based, KAP survey was conducted on vitamin D and its role in immunomodulation in COVID-19 from April 2021 to January 2022 followed by polling obtained from 2,338 HCPs through round table meetings (RTMs). Results: Approximately 64% of HCPs considered the use of vitamin D in COVID-19 patients for various reasons including prevention of illness, reduced ICU stay, reduction in morbidity and mortality along with decrease in the levels of inflammatory markers in COVID-19 patients. For the dosage regime, 47% of HCPs preferred vitamin D 60,000 IUweekly while 45% of HCPs preferred both 60,000 IU weekly and 2,000 IU daily dose for boosting immune system in their patients. Conclusion: The panel agreed that vitamin D levels of 40 ng/mL and above appear to confer better immune-protective response to several infections including COVID-19

HIV infection predominantly affecting children in Sindh, Pakistan, 2019: a cross-sectional study of an outbreak.

BACKGROUND: In April 2019, an HIV screening camp for all ages was established in response to a report of an unusually large number of paediatric HIV diagnoses in Larkana, Pakistan. We aimed to understand the clinical profile of the children who registered for HIV care. METHODS: In this cross-sectional study, we review the outbreak response from the government, academia, and UN agencies in Larkana, Sindh, Pakistan. We report age-stratified and sex-stratified HIV prevalence estimated among individuals screened. For children who registered for HIV care, clinical history of previous injections and blood transfusions, HIV disease stage, hepatitis B and hepatitis C status, and CD4 count was abstracted from clinical records from Sindh AIDS Control Program HIV Clinic (Shaikh Zayed Childrens Hospital, Larkana, Pakistan) and analysed using percentages, χ2 tests, and weight-for-age Z scores. We also analysed data for parents who were tested for HIV. FINDINGS: Between April 24, and July 15, 2019, 31 239 individuals underwent HIV testing, of whom 930 (3%) tested positive for HIV. Of these, 763 (82%) were younger than 16 years and 604 (79%) of these were aged 5 years and below. Estimated HIV prevalence was 3% overall; 7% (283 of 3803) in children aged 0-2 years, 6% (321 of 5412) in children aged 3-5 years, and 1% (148 of 11 251) in adults aged 16-49 years. Of the 591 children who registered for HIV care, 478 (81%) were 5 years or younger, 379 (64%) were boys, and 315 (53%) of 590 had a weight-for-age Z score of -3·2. Prevalence of hepatitis B surface antigen was 8% (48 of 574) and hepatitis C antibody positivity was 3% (15 of 574). Of children whose mothers tested for HIV, only 39 (11%) of 371 had HIV-positive mothers. Most children (404 [89%] of 453) reported multiple previous injections and 40 (9%) of 453 reported blood transfusions. INTERPRETATION: This HIV outbreak is unprecedented among children in Pakistan: a 54% increase in paediatric HIV diagnoses over the past 13 years. The outbreak was heavily skewed towards young children younger than 5 years, with a predominance of boys. Epidemiological and molecular studies are needed to understand the full extent of the outbreak and its drivers to guide HIV control strategies. FUNDING: None

HIV infection predominantly affecting children in Sindh, Pakistan, 2019: A cross-sectional study of an outbreak

Background: In April 2019, an HIV screening camp for all ages was established in response to a report of an unusually large number of paediatric HIV diagnoses in Larkana, Pakistan. We aimed to understand the clinical profile of the children who registered for HIV care.Methods: In this cross-sectional study, we review the outbreak response from the government, academia, and UN agencies in Larkana, Sindh, Pakistan. We report age-stratified and sex-stratified HIV prevalence estimated among individuals screened. For children who registered for HIV care, clinical history of previous injections and blood transfusions, HIV disease stage, hepatitis B and hepatitis C status, and CD4 count was abstracted from clinical records from Sindh AIDS Control Program HIV Clinic (Shaikh Zayed Childrens Hospital, Larkana, Pakistan) and analysed using percentages, χ2 tests, and weight-for-age Z scores. We also analysed data for parents who were tested for HIV.Findings: Between April 24, and July 15, 2019, 31 239 individuals underwent HIV testing, of whom 930 (3%) tested positive for HIV. Of these, 763 (82%) were younger than 16 years and 604 (79%) of these were aged 5 years and below. Estimated HIV prevalence was 3% overall; 7% (283 of 3803) in children aged 0-2 years, 6% (321 of 5412) in children aged 3-5 years, and 1% (148 of 11 251) in adults aged 16-49 years. Of the 591 children who registered for HIV care, 478 (81%) were 5 years or younger, 379 (64%) were boys, and 315 (53%) of 590 had a weight-for-age Z score of -3·2. Prevalence of hepatitis B surface antigen was 8% (48 of 574) and hepatitis C antibody positivity was 3% (15 of 574). Of children whose mothers tested for HIV, only 39 (11%) of 371 had HIV-positive mothers. Most children (404 [89%] of 453) reported multiple previous injections and 40 (9%) of 453 reported blood transfusions.Interpretation: This HIV outbreak is unprecedented among children in Pakistan: a 54% increase in paediatric HIV diagnoses over the past 13 years. The outbreak was heavily skewed towards young children younger than 5 years, with a predominance of boys. Epidemiological and molecular studies are needed to understand the full extent of the outbreak and its drivers to guide HIV control strategies

Odanacatib for the treatment of postmenopausal osteoporosis : Results of the LOFT multicentre, randomised, double-blind, placebo-controlled trial and LOFT Extension study

Background Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. Methods The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between −2·5 and −4·0 if no previous radiographic vertebral fracture, or between −1·5 and −4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than −4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). Findings Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43–40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45–60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40–0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39–0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68–0·87; all p<0·0001. Combined results from LOFT plus LOFT Extension for cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 4·9% (341/6909) versus 9·6% (675/7011), HR 0·48, 95% CI 0·42–0·55; hip fractures 1·1% (86/8043) versus 2·0% (162/8028), 0·52, 0·40–0·67; non-vertebral fractures 6·4% (512/8043) versus 8·4% (675/8028), 0·74, 0·66–0·83; all p<0·0001. In LOFT, the composite cardiovascular endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 273 (3·4%) of 8043 patients in the odanacatib group versus 245 (3·1%) of 8028 in the placebo group (HR 1·12, 95% CI 0·95–1·34; p=0·18). New-onset atrial fibrillation or flutter occurred in 112 (1·4%) of 8043 patients in the odanacatib group versus 96 (1·2%) of 8028 in the placebo group (HR 1·18, 0·90–1·55; p=0·24). Odanacatib was associated with an increased risk of stroke (1·7% [136/8043] vs 1·3% [104/8028], HR 1·32, 1·02–1·70; p=0·034), but not myocardial infarction (0·7% [60/8043] vs 0·9% [74/8028], HR 0·82, 0·58–1·15; p=0·26). The HR for all-cause mortality was 1·13 (5·0% [401/8043] vs 4·4% [356/8028], 0·98–1·30; p=0·10). When data from LOFT Extension were included, the composite of cardiovascular death, myocardial infarction, or stroke occurred in significantly more patients in the odanacatib group than in the placebo group (401 [5·0%] of 8043 vs 343 [4·3%] of 8028, HR 1·17, 1·02–1·36; p=0·029, as did stroke (2·3% [187/8043] vs 1·7% [137/8028], HR 1·37, 1·10–1·71; p=0·0051). Interpretation Odanacatib reduced the risk of fracture, but was associated with an increased risk of cardiovascular events, specifically stroke, in postmenopausal women with osteoporosis. Based on the overall balance between benefit and risk, the study's sponsor decided that they would no longer pursue development of odanacatib for treatment of osteoporosis