Dapsone for paediatric chronic immune thrombocytopenia: Short report from a tertiary centre in South India.

Immune thrombocytopenia (ITP) resolves in most children within 3-12 months of diagnosis. Chronic ITP affects 10%-20% of patients, some of whom require treatment. Several second-line agents are efficacious in this group of patients. This paper describes our experience of using dapsone as a single second-line agent in children with chronic ITP. One hundred and three children with chronic ITP were seen at our centre from January 2012 to December 2016. Forty-five children met the inclusion criteria and received dapsone; 17 (37.8%) were boys; and 28 (62.2%) were girls. Early response to dapsone was seen in 37.8% of patients. The median duration of long-term follow-up was 50 months, and at least a partial response was seen in 64.4% of the patients. Dapsone offers good initial response rates and sustained remission in paediatric chronic ITP, comparable to other therapeutic agents available.

Early diagnosis of lupus: A possibilty. A multicentric study from SLE Special Interest Group (SIG) of Indian Rheumatology Association (IRA).

INTRODUCTION: Systemic Lupus Erythematosus (SLE) warrants an early diagnosis and prompt management. Delay in diagnosis can result in repeated flares, permanent damage, and even death. There is a large variability in the time taken to diagnose SLE across the world. We undertook this study to determine the time taken for diagnosis of SLE in India and to identify the factors associated. METHODS: Patients with SLE diagnosed within the previous 1 year as per Systemic Lupus Erythematosus International Collaborating Clinics criteria (SLICC) 2012 criteria were included in a cross-sectional multicentre questionnaire-based survey. Demographic profile, self-reported socioeconomic status as per Kuppuswamy classification of socioeconomic status (version 2022) (SES), and several healthcare related parameters including referral pattern were recorded. Median time taken for diagnosis was used to demarcate early or late diagnosis and associated factors were explored. RESULTS: We included 488 patients with SLE from 10 rheumatology centres. The median time to diagnosis was 6 months Interquartile Range (IQR 3,14.7) and within 3 months in about one third [150(30.7%)]. Very early diagnosis (<1 month) was established in 78(16.0%) patients. The mean SLE Disease Activity Index (SLEDAI) at diagnosis was 10.28+7.24. In univariate analysis, an older age, lower SES, non-southern state of residence and larger family size were significantly associated with late diagnosis. In the multivariate analysis, higher SES (AOR 0.95, 95% CI: 0.92-0.98), multiple organ system involvement at initial presentation (AOR1.75 95%CI: 1.08-2.84) and place of residence in south Indian states (AOR1.92 95%CI: 1.24-2.97) had lesser odds of being associated with late diagnosis. Distance from the closest medical centre/professional did not influence the time to diagnosis. Majority of patients had first consulted a medical graduate (42.5%) or postgraduate doctor (48.2%), and referral to rheumatologist was largely done by postgraduate (65%) doctors. More than half of our patients (61%) self-finance their treatment. CONCLUSION: Median time to diagnosis of SLE was 6 months, 1/3rd being diagnosed within 3 months and 78(16.0%) with 1 month of symptom onset. Delay in diagnosis was noted in those belonging to lower socioeconomic strata and those with single organ disease. Distance to the health care facility did not influence time to diagnosis.

Pattern of disease expression in SLE patients with antiphospholipid antibodies: data from Indian Systemic Lupus Erythematosus Inception cohort (INSPIRE).

Antiphospholipid antibodies (APLA) are present in one-third of systemic lupus erythematosus (SLE) patients, and they are associated with both criteria and non-criteria manifestations. We studied the prevalence, clinical associations, and impact on mortality of APLA in SLE patients from India. Among the Indian SLE inception cohort (INSPIRE), patients who had data on all five routinely performed APLAs [lupus anticoagulant (LA), IgG and IgM anticardiolipin antibody (aCL) and anti-ß2-glycoprotein I(ß2GPI)] at enrolment were selected. Patients were divided into four categories based on the presence/absence of APLA associated manifestations and presence/absence of the APLA viz SLE-APS, SLE-APLA, SLE: events but no APLA, and SLE: no events, no APLA (reference group). 1035 SLE patients at least 1 APLA antibody was detected in 372 (35.9%). LA was present in 206 (19.9%), aCL in 126 (12.2%) and ß2-GPI in 178 (17.2%). There were 88 thrombotic events in 83 patients (8.0%); 73 (82.9%) being arterial; APLA positivity was present in 37 (44.6%) [AOR 1.70 (1.054, 2.76)]. SLE-APS patients were younger and had higher mortality [AOR 4.11 (1.51, 11.3)], neuropsychiatric and hematologic disease. SLE-APLA also had a higher mortality rate [AOR 2.94 (1.06, 8.22)] than the reference group. The mortality was highest in the subset of patients with thrombotic events in the presence of APLA [AOR 7.67 (1.25, 46.9)]. The mere presence of APLA also conferred higher mortality even in the absence of thrombotic events [AOR 3.51 (1.43, 8.63)]. Hematologic manifestations (36.1%) were the most common non-criteria-manifestation. One-third of SLE patients have APLA and its presence is associated with non-criteria hematologic manifestations, arterial thrombosis and higher mortality rate.

Nutritional Prescription in ICU Patients: Does it Matter?

Background: The nutritional status of the patients before critical illness and nutrition support given during the critical illness play an important role in the recovery. We aimed to evaluate the nutritional prescription and its effect on ICU mortality. Materials and methods: This was a prospective observational study conducted after institutional ethical committee approval (IEC 94/2018, CTRI/2018/06/014625) in a case-mixed (medical and surgical) ICU. Patients admitted to the ICU were enrolled within 24 hours of admission. The amount of calories and proteins prescribed and received by the patients was collected for 7 days. The primary outcome was ICU mortality. Results: A total of 100 patients were included. The mean age was 48.63 (16.25) years, and 62% were males. The acute physiology and chronic health evaluation (APACHE II), sequential organ failure assessment (SOFA), and modified Nutric (mNUTRIC) scores were comparable between the two groups. The ICU mortality was 30%. The calorie and protein deficits were comparable between survivors and non-survivors. Among the secondary outcomes, a significant time effect (p = 0.013) and interaction effect (p = 0.004) were noted for maximum glucose levels. The glucose variability calculated by coefficient of variation (CV) was significantly higher in non-survivors than survivors (p = 0.031). Conclusion: The calorie and protein deficits did not affect ICU mortality. The maximum glucose variability and CV were significant parameters associated with ICU mortality. How to cite this article: Havaldar AA, Selvam S. Nutritional Prescription in ICU Patients: Does it Matter? Indian J Crit Care Med 2024;28(7):657-661.

Low-dose rituximab is efficacious in refractory idiopathic inflammatory myopathies.

OBJECTIVES: Rituximab (RTX) use early in the course of refractory idiopathic inflammatory myopathy (IIM) is not well studied. This study sought to determine the short-term efficacy of RTX in a registry-based cohort of refractory IIM. METHODS: Registry-based observational data about IIM patients receiving RTX between 2018 and 2021 were included. Total improvement score was calculated from the core set measures as per International Myositis Assessment and Clinical Studies group (IMACS) at baseline, 6 months and 12 months of follow-up. RESULTS: Forty-two patients (F:M, 29:13), with a mean (s.d.) age of 39.5 (11.5) years were studied. Majority of patients received RTX for refractory myositis, after a median (interquartile range) duration of 8 (4,18) months. Twenty-eight received RTX at a dosage of 1 g × two doses, while 14 received 500 mg × two doses with an interval of 15 days. At 6 months and 12 months post-RTX, the improvement was recorded in manual muscle testing (MMT-8) scores, physician global assessment (PGA), patient global assessment (PtGA) and median steroid dosage as compared with the baseline (P < 0.01 for all). A mean (s.d.) improvement of 44.5 (16) and 48.7 (19.2) in total improvement score was recorded at 6 and 12 months, respectively. The change in MMT-8, PGA and PtGA scores from baseline between the two dosage regimens of RTX were comparable at 6 and 12 months. Severe lower respiratory tract infections requiring hospitalization occurred in three patients of the cohort. CONCLUSION: RTX improved IMACS core set measures and had steroid sparing efficacy at 6 and 12 months in patients with IIM in this registry-based study. Rituximab as an induction regimen of two doses of 500 mg can be as efficacious as 1 g at 6 months and 12 months of follow-up.

Estimation of Hydration and Density of Fat-Free Mass in Indian Children Using a 4-Compartment Model: Implications for the Estimation of Body Composition Using 2-Compartment Models.

BACKGROUND: Accurate methods are needed to measure body fat mass (FM), particularly in South Asian children who are thought to have greater adiposity for a given body size. The accuracy of simple 2-compartment (2C) models of measuring FM depends on the primary measurement of the fat free mass (FFM) and the validity of assumed constants for FFM hydration and density. These have not been measured in this particular ethnic group. OBJECTIVES: To measure FFM hydration and density in South Indian children using a 4-compartment (4C) model and to compare FM estimates from this 4C-model with 2C-model-based estimates from hydrometry and densitometry, using literature-reported FFM hydration and density in children. METHODS: This study included 299 children (45% boys), aged 6-16 y from Bengaluru, India. Total body water (TBW), bone mineral content (BMC), and body volume were measured using deuterium dilution, dual-energy X-ray absorptiometry, and air displacement plethysmography, respectively, to calculate the FFM hydration and density, and the FM using 4C and 2C models. The agreement between FM estimates from 2C and 4C models was also evaluated. RESULTS: Mean FFM hydration and density were 74.2% ± 2.1% and 71.4% ± 2.0% and 1.095 ± 0.008 kg/L and 1.105 ± 0.008 kg/L in boys and girls respectively, which were significantly different from published values. Using the presently estimated constants, the mean hydrometry-based FM (as % body weight) estimates decreased by 3.5% but increased by 5.2% for densitometry-based 2C methods. When 2C-FM (using previously reported FFM hydration and density) were compared with 4C-FM estimates, the mean difference was -1.1 ± 0.9 kg for hydrometry and 1.6 ± 1.1 kg for densitometry. CONCLUSIONS: Previously published constants of hydration and density of FFM may induce errors of -12% to +17% in FM (kg) when using different 2C models in comparison to the 4C models in Indian children. J Nutr 20xx;x:xx.

Changes in bone biomarkers in response to different dosing regimens of cholecalciferol supplementation in children with chronic kidney disease.

BACKGROUND: The effect of different dosing regimens of cholecalciferol supplementation on bone biomarkers has not been studied in children with chronic kidney disease (CKD). METHODS: This is a post hoc analysis of a multi-center randomized controlled trial which included children with CKD stages 2-4 with vitamin D deficiency (25-hydroxy vitamin D (25OHD) < 30 ng/ml) randomized 1:1:1 to receive an equivalent dose of oral cholecalciferol as daily, weekly or monthly treatment. Markers of bone formation (bone alkaline phosphatase (BAP), procollagen I N terminal peptide (PINP)), bone resorption (tartarate-resistant acid phosphatase 5b (TRAP), C terminal telopeptide (CTX)), and osteocyte markers (intact fibroblast growth factor 23 (iFGF23), sclerostin) and soluble klotho were measured at baseline and after 3 months of intensive replacement therapy. The change in biomarkers and ratio of markers of bone formation to resorption were compared between treatment arms. BAP and TRAP were expressed as age- and sex-specific z-scores. RESULTS: 25OHD levels increased with cholecalciferol supplementation, with 85% achieving normal levels. There was a significant increase in the BAP/TRAP ratio (p = 0.04), iFGF23 (p = 0.004), and klotho (p = 0.002) with cholecalciferol therapy, but this was comparable across all three therapy arms. The BAPz was significantly higher in the weekly arm (p = 0.01). The change in 25OHD (Δ25OHD) inversely correlated with ΔPTH (r = - 0.4, p < 0.001). CONCLUSIONS: Although cholecalciferol supplementation was associated with a significant increase in bone formation, the three dosing regimens of cholecalciferol supplementation have a comparable effect on the bone biomarker profile, suggesting that they can be used interchangeably to suit the patient's needs and optimize adherence to therapy. A higher resolution version of the Graphical abstract is available as Supplementary information.

Identifying phenotypes of obstructive sleep apnea using cluster analysis.

PURPOSE: Over the last decade, advances in understanding the pathophysiology, clinical presentation, systemic consequences and treatment responses in obstructive sleep apnea (OSA) have made individualised OSA management plausible. As the first step in this direction, this study was undertaken to identify OSA phenotypes. METHODS: Patients diagnosed with OSA on level 1 polysomnography (PSG) were included. Clinical and co-morbidity profile, anthropometry and sleepiness scores were compiled. On PSG, apnea-hypopnea index, positional indices, sleep stages and desaturation indices (T90) were tabulated. Cluster analysis was performed to identify distinct phenotypes among included patients with OSA. RESULTS: One hundred patients (66 males) with a mean age of 49.5 ± 13.3 years were included. Snoring was reported by 94% subjects, and 50% were excessively sleepy. Two-thirds of subjects had co-morbidities, the most frequent being hypertension (55%) and dyslipidemia (53%). Severe OSA was diagnosed on PSG in 42%, while 29% each had mild and moderate OSA, respectively. On cluster analysis, 3 distinct clusters emerged. Cluster 1 consisted of older, obese subjects with no gender predilection, higher neck circumference, severe OSA with more co-morbidities and higher T90. Cluster 2 comprised of younger, less obese males with snoring, witnessed apnea, moderate and supine predominant OSA. Cluster 3 consisted of middle-aged, obese males with lesser co-morbidities, mild OSA and lower T90. CONCLUSIONS: This study revealed three OSA clusters with distinct demographic, anthropometric and PSG features. Further research with bigger sample size and additional parameters may pave the way for characterising distinct phenotypes and individualising OSA management.

Determining the optimal cholecalciferol dosing regimen in children with CKD: a randomized controlled trial.

BACKGROUND: The optimal treatment regimen for correcting 25-hydroxyvitamin D (25OHD) deficiency in children with chronic kidney disease (CKD) is not known. We compared cholecalciferol dosing regimens for achieving and maintaining 25OHD concentrations ≥30 ng/mL in children with CKD stages 2-4. METHODS: An open-label, multicentre randomized controlled trial randomized children with 25OHD concentrations <30 ng/mL in 1:1:1 to oral cholecalciferol 3000 IU daily, 25 000 IU weekly or 100 000 IU monthly for 3 months (maximum three intensive courses). In those with 25OHD ≥30 ng/mL, 1000 IU cholecalciferol daily (maintenance course) was given for up to 9 months. Primary outcome was achieving 25OHD ≥30 ng/mL at the end of intensive phase treatment. RESULTS: Ninety children were randomized to daily (n = 30), weekly (n = 29) or monthly (n = 31) treatment groups. At the end of intensive phase, 70/90 (77.8%) achieved 25OHD ≥30 ng/mL; 25OHD concentrations were comparable between groups (median 44.3, 39.4 and 39.3 ng/mL for daily, weekly and monthly groups, respectively; P = 0.24) with no difference between groups for time to achieve 25OHD ≥30 ng/mL (P = 0.28). There was no change in calcium, phosphorus and parathyroid hormone, but fibroblast growth factor 23 (P = 0.002) and klotho (P = 0.001) concentrations significantly increased and were comparable in all treatment groups. Irrespective of dosing regimen, children with glomerular disease had 25OHD concentrations lower than non-glomerular disease (25.8 versus 41.8 ng/mL; P = 0.007). One child had a 25OHD concentration of 134 ng/mL, and 5.5% had hypercalcemia without symptoms of toxicity. CONCLUSION: Intensive treatment with oral cholecalciferol as daily, weekly or monthly regimens achieved similar 25OHD concentrations between treatment groups, without toxicity. Children with glomerular disease required higher doses of cholecalciferol compared with those with non-glomerular disease.

Population pharmacokinetics and dose optimisation of colecalciferol in paediatric patients with chronic kidney disease.

AIMS: The prevalence of vitamin D deficiency is high in children with chronic kidney disease (CKD). However, current dosing recommendations are based on limited pharmacokinetic (PK) data. This study aimed to develop a population PK model of colecalciferol that can be used to optimise colecalciferol dosing in this population. METHODS: Data from 83 children with CKD were used to develop a population PK model using a nonlinear mixed effects modelling approach. Serum creatinine and type of kidney disease (glomerular vs. nonglomerular disease) were investigated as covariates, and optimal dosing was determined based on achieving and maintaining 25-hydroxyvitamin D (25(OH)D) concentration of 30-48 ng/mL. RESULTS: The time course of 25(OH)D concentrations was best described by a 1-compartment model with the addition of a basal concentration parameter to reflect endogenous 25(OH)D production from diet and sun exposure. Colecalciferol showed wide between-subject variability in its PK, with total body weight scaled allometrically the only covariate included in the model. Model-based simulations showed that current dosing recommendations for colecalciferol can be optimised using a weight-based dosing strategy. CONCLUSION: This is the first study to describe the population PK of colecalciferol in children with CKD. PK model informed dosing is expected to improve the attainment of target 25(OH)D concentrations, while minimising the risk of overdosing.

Demographics and Clinical Characteristics of COVID-19-vaccinated Patients Admitted to ICU: A Multicenter Cohort Study from India (PostCoVac Study-COVID Group).

Background: Emergency authorization and approval were given for the coronavirus disease-19 (COVID-19) vaccines. The efficacy reported after phase III trials were 70.4% and 78% for Covishield and Covaxin, respectively.In this study, we aim to analyze the risk factors, which were associated with mortality in critically ill COVID-19-vaccinated patients admitted into intensive care unit (ICU). Materials and methods: This study was conducted from April 1, 2021 to December 31, 2021 across five centers in India. Patients who had received either one or two doses of any of the COVID vaccines and developed COVID-19 were included. The ICU mortality was a primary outcome. Results: A total of 174 patients with COVID-19 illness were included in the study. The mean age was 57 years standard deviation (SD 15). Acute physiology, age and chronic health evaluation (APACHE II) score and the sequential organ failure assessment (SOFA) score were 14 (8-24.5) and 6 (4-8), respectively. Multiple variable logistic regression showed patients who have received a single dose [odds ratio (OR): 2.89, confidence interval (CI): 1.18, 7.08], neutrophil:lymphocyte (NL) ratio (OR: 1.07, CI: 1.02,1.11), and SOFA score (OR: 1.18, CI: 1.03,1.36) were associated with higher mortality. Conclusion: The mortality in the vaccinated patients admitted to the ICU was 43.68% due to COVID illness. The mortality was lower in patients who had received two doses. How to cite this article: Havaldar AA, Prakash J, Kumar S, Sheshala K, Chennabasappa A, Thomas RR et al. Demographics and Clinical Characteristics of COVID-19-vaccinated Patients Admitted to ICU: A Multicenter Cohort Study from India (PostCoVac Study-COVID Group). Indian J Crit Care Med 2022;26(11):1184-1191.

Identification of subclinical tuberculosis in household contacts using exposure scores and contact investigations.

BACKGROUND: The goal of tuberculosis elimination put forward in the End TB Strategy prioritizes diagnosis and treatment of incipient and subclinical TB, recently defined by key stakeholders as "asymptomatic, early pre-clinical disease during which pathology evolves". Regarded as indicative of a high risk of TB progression, considerable efforts have been made to identify these cases through exploration of biomarkers. The present study aimed to evaluate simple scoring systems for TB exposure as screening tools for subclinical TB, the only identifiable of the incipient and subclinical disease states, in a contact investigation (CI) setting of low HIV-prevalence. METHODS: Nested within a large prospective study in household contacts (HHCs) of smear positive pulmonary TB cases in South-India conducted 2010-2012, we assessed 1) the association between the Tuberculosis Contact Score (TCS) and the Infectivity Score, with established tools for Mycobacterium tuberculosis (Mtb) infection, corrected for established TB risk factors, and 2) the capability of the TB exposure scores to identify subclinical TB defined by Mtb-culture positivity in sputum or gastric aspirate (subjects < 5 years) specimen. RESULTS: Of 525 HHCs, 29 were Mtb-culture positive and 96.6% of these asymptomatic. The TCS and the Infectivity Score associated with positive Tuberculin Skin Test and QuantiFeron TB-Gold In-tube assay (QFT) results in multivariate analyses (TCS: ORTST 1.16, 95% CI: 1.01, 1.33; ORQFT 1.33 95% CI: 1.16, 1.51. Infectivity Score: ORTST 1.39, 95% CI: 1.10, 1.76; ORQFT 1.41 95% CI: 1.16, 1.71). The Infectivity Score showed a moderate capability to identify subclinical TB (AUC of 0.61, 95% CI: 0.52, 0.70). CONCLUSIONS: Although our results did not identify an easily applicable screening tool for subclinical TB, the present study indicates that focusing on TB-related symptoms in CI settings may be of limited value for early identification of HHCs with high risk for TB progression.

Incidence of tuberculosis among school-going adolescents in South India.

BACKGROUND: Tuberculosis (TB) incidence data in vaccine target populations, particularly adolescents, are important for designing and powering vaccine clinical trials. Little is known about the incidence of tuberculosis among adolescents in India. The objective of current study is to estimate the incidence of pulmonary tuberculosis (PTB) disease among adolescents attending school in South India using two different surveillance methods (active and passive) and to compare the incidence between the two groups. METHODS: The study was a prospective cohort study with a 2-year follow-up period. The study was conducted in Palamaner, Chittoor District of Andhra Pradesh, South India from February 2007 to July 2010. A random sampling procedure was used to select a subset of schools to enable approximately 8000 subjects to be available for randomization in the study. A stratified randomization procedure was used to assign the selected schools to either active or passive surveillance. Participants who met the criteria for being exposed to TB were referred to the diagnostic ward for pulmonary tuberculosis confirmation. A total number of 3441 males and 3202 females between the ages 11 and less than 18 years were enrolled into the study. RESULTS: Of the 3102 participants in the active surveillance group, four subjects were diagnosed with definite tuberculosis, four subjects with probable tuberculosis, and 71 subjects had non-tuberculous Mycobacteria (NTM) isolated from their sputum. Of the 3541 participants in the passive surveillance group, four subjects were diagnosed with definite tuberculosis, two subjects with probable tuberculosis, and 48 subjects had non-tuberculosis Mycobacteria isolated from their sputum. The incidence of definite + probable TB was 147.60 / 100,000 person years in the active surveillance group and 87 / 100,000 person years in the passive surveillance group. CONCLUSION: The incidence of pulmonary tuberculosis among adolescents in our study is lower than similar studies conducted in South Africa and Eastern Uganda - countries with a higher incidence of tuberculosis and human immunodeficiency virus (HIV) than India. The study data will inform sample design for vaccine efficacy trials among adolescents in India.

Real-time feedback for improving compliance to hand sanitization among healthcare workers in an open layout ICU using radiofrequency identification.

The aim of this study is to increase hand sanitizer usage among healthcare workers by developing and implementing a low-cost intervention using RFID and wireless mesh networks to provide real-time alarms for increasing hand hygiene compliance during opportune moments in an open layout Intensive Care Unit (ICU). A wireless, RFID based system was developed and implemented in the ICU. The ICU beds were divded into an intervention arm (n = 10) and a control arm (n = 14). Passive RFID tags were issued to the doctors, nurses and support staff of the ICU. Long range RFID readers were positioned strategically. Sensors were placed beneath the hand sanitizers to record sanitizer usage. The system would alert the HCWs by flashing a light if an opportune moment for hand sanitization was detected. A significant increase in hand sanitizer use was noted in the intervention arm. Usage was highest during the early part of the workday and decreased as the day progressed. Hand wash events per person hour was highest among the ancilliary staff followed by the doctors and nurses. Real-time feedback has potential to increase hand hygiene compliance among HCWs. The system demonstrates the possibility of automating compliance monitoring in an ICU with an open layout.

The tuberculin skin test in school going adolescents in South India: associations of socio-demographic and clinical characteristics with TST positivity and non-response.

BACKGROUND: India has generally used 1 TU purified protein derivative (PPD) as opposed to 2 TU PPD globally, limiting comparisons. It is important to assess latent TB infection in adolescents given that they may be a target group for new post-exposure TB vaccines. The aim of this study is to describe the pattern and associations of tuberculin skin test (TST) responses (0.1 ml 2 TU) in adolescents in South India. METHODS: 6643 school-going adolescents (11 to <18 years) underwent TST. Trained tuberculin reader made the reading visit between 48 and 96 hours after the skin test RESULTS: Of 6608 available TST results, 9% had 0 mm, and 12% ≥10 mm responses. The proportion of TST positive (≥10 mm) was higher among older children, boys, those with a history of TB contact and reported BCG immunization Those with no TST response (0 mm) included younger participants (<14 years), those whose mothers were illiterate and those with a recent history of weight loss. Those of a higher socio-economic status (houses with brick walls, LPG gas as cooking fuel) and those with a visible BCG scar were less likely to be non-responders. CONCLUSION: Proportion of non-responders was lower than elsewhere in the world. Proportion of TST positivity was higher in those already exposed to TB and in children who had been BCG immunized, with a zero response more likely in younger adolescents and those with recent weight loss.

Estimation of the effect of vaccination in critically ill COVID-19 patients, analysis using propensity score matching.

BACKGROUND: Vaccination helped in reducing mortality and disease severity due to COVID-19. Some patients can develop breakthrough infections. The effect of vaccination in critically ill patients admitted with breakthrough infections is not well studied. We designed a study to estimate the effect of vaccination on ICU mortality in critically ill COVID-19 patients by using propensity score matching. METHODS: We included patients from 15th June 2020 to 31st December 2021. Inclusion criteria were unvaccinated and vaccinated COVID-19 patients requiring intensive care unit (ICU) admission. The institutional ethics committee approval was obtained (institutional ethics committee, IEC 08/2023, Clinical trial registry, India CTRI/2023/01/049142). The primary outcome was ICU mortality. The secondary outcomes were the length of ICU stay and duration of mechanical ventilation. We used multivariable logistic regression (MLR) and propensity score matching (PSM) for the statistical analysis. RESULTS: Total of 667 patients (79.31%) were unvaccinated and 174 (20.68%) vaccinated. The mean age was 57.11 [standard deviation (SD) 15.13], and 70.27% were males. The ICU mortality was 56.60% [95% confidence interval (CI) 53.24-60%]. The results of MLR and PSM method showed that vaccinated patients were less likely to be associated with mortality [adjusted odds ratio (AOR), 95% CI using logistic regression: 0.52 (0.29, 0.94), and by propensity score matching: 0.83 (0.77, 0.91)]. CONCLUSION: The findings of this study support COVID-19 vaccination as an effective method for reducing case fatality not only in the general population but also in critically ill patients, and it has important public health implications.

Vitamin B12 status and skeletal muscle function among elderly: A literature review and pilot study on the effect of oral vitamin B12 supplementation in improving muscle function.

Objectives: The objective of this study is to understand the role of vitamin B12 supplementation in improving skeletal muscle function among the elderly. Methods: A literature review in the Medline database was conducted to understand the association between vitamin B12 and muscle function in Section A. In Section B, 28 healthy elderly participants aged ≥60 years were recruited in a cross-sectional design for estimation of plasma vitamin B12 status and assessment of upper limb muscle strength Maximal voluntary contraction (MVC) and muscle quality (expressed as MVC/total muscle mass). Participants were grouped based on vitamin B12 status into vitamin B12-depleted (<148 pmol/L) and replete (≥148 pmol/L) groups. In a quasi-experimental study design, the vitamin B12-depleted group (n = 14) received daily oral vitamin B12 supplementation of 100 µg for 3 months. All the study measures were repeated post-supplementation. Results: Vitamin B12 deficiency was identified to contribute adversely to muscle strength, quality, and physical performance among older people in the extensive literature review. The pilot intervention study showed significant improvement in MVC and muscle quality (p < 0.050) post-vitamin B12 supplementation, comparable to the vitamin B12-replete group. Conclusions: Vitamin B12 may have a crucial role in the maintenance of muscle function. 3-month oral vitamin B12 supplementation among subclinical vitamin B12 deficient elderly improved muscle strength and quality and reached levels similar to the vitamin B12 replete group.

The Effect of 8-Week Protein Supplementation with a Simple Exercise Program on Body Composition, Muscle Strength, and Amino Acid OMICS among Healthy Sedentary Indians: A Randomized, Double-Blind, Placebo-Controlled Trial.

Dietary protein plays a crucial role in the modulation of several physiological processes to sustain health and well-being. There is robust evidence of enhanced muscle protein synthesis, improved physical fitness, body composition, and performance contributed by protein supplementation combined with exercise among trained individuals or athletes. Evidence of the efficacy of such intervention on healthy adults having a sedentary lifestyle is limited. The objective of this study was to evaluate the impact of 12 g of additional protein in the form of a protein supplement compared to a placebo combined with a simple exercise program on plasma amino acid level, body composition, and muscle strength among healthy Indian adults having a relatively sedentary lifestyle. This double-blinded, randomized controlled trial was conducted on sedentary healthy adults 20-45 years of age, with a body mass index (BMI) between 18.5 and 27.9 kg/m2. Eighty-two participants were randomized into either the protein (intervention) or placebo (control) group. The exercise regime was the same for both groups. Out of 82 randomized participants, 58 completed the intervention. Blood tests were conducted for the amino acid OMICS measurement followed by dual-energy X-ray absorptiometry (DXA) for body composition and isokinetic dynamometry for muscle strength. A significant improvement was observed in the lean mass (kg) and appendicular muscle mass (AMM) adjusted for weight in the intervention group compared to the control group (p < 0.05). The muscle strength and contractile quality were comparable in the 2 groups. Plasma BCAA showed a significant negative association with body fat % (r = -0.43, p < 0.05 for the intervention group and r = -0.33, p = 0.07 for the control group) and a positive association with lean body mass % (r = 0.56, p < 0.01 in the intervention group vs r = 0.29, p = 0.10 in the control group) in the intervention group compared to control. In conclusion, this study highlighted the value of incorporating a lifestyle intervention including protein supplementation with simple exercises to optimize body composition in sedentary healthy individuals. This trial is registered with CTRI/2018/12/016777.

Development and evaluation of the Indian Sleepiness Scale to assess excessive daytime sleepiness in patients with Obstructive Sleep Apnea.

Background: Excessive daytime sleepiness (EDS), a cardinal symptom of obstructive sleep apnea (OSA) is assessed using Epworth Sleepiness Scale (ESS). Some limitations of ESS include graded responses, inapplicable situations and equal scores for active and passive situations. To overcome these limitations, we developed a novel sleepiness scale and evaluated its performance in patients with OSA. Methods: The study was executed in multiple phases. After determining applicability of items in the ESS, a 6-item questionnaire was developed comprising OSA symptoms and self-reported 'sleepy' situations, dichotomized responses and weighted scoring. After content and face validation by experts, the scale was tested for applicability and its performance was compared with ESS in patients with suspected OSA. Results: In phase I, applicability of ESS was tested in 189 participants, of whom 98 (51.8 %) participants found multiple items inapplicable.In phase II, 34 self-reported sleepy situations from 200 participants were narrowed down to a 6-item questionnaire, based on expert validation. This scale was named the Indian Sleepiness Scale (ISS) and was tested for applicability in phase III in 226 participants from diverse literacy backgrounds, who found all situations applicable.In phase IV, ISS and ESS were administered to 335 patients with suspected OSA. OSA was confirmed on polysomnography in 294 (87.7 %) patients. A cut-off score of ≥6 was derived for ISS; at this cut-off score, the ISS which was more sensitive than ESS (71.1 % vs 43.2 %). Conclusions: The Indian Sleepiness Scale was found to be widely applicable and more sensitive than ESS for sleepiness evaluation in patients with OSA.

Do cardiometabolic risk factors mediate the relationship between body composition and bone mineral content in South Indian children aged 5 to 16 years?

BACKGROUND/OBJECTIVE: The complex interplay between adiposity, bone health and cardiometabolic risk (CMR) factors is unclear in Indian children. We aimed to investigate the mediating role of number of CMR factors on the relationship between fat % and bone mineral content (BMC) % in South Indian children aged 5-16 years. SUBJECTS AND METHODS: Healthy children (n = 317), from India, underwent anthropometric, blood biochemistry, blood pressure, along with body composition and BMC assessments using Dual-energy X-ray absorptiometry. Based on the number of CMR factors, children were categorised into three groups: 0, 1 and ≥ 2. Analysis of variance was used to compare the parameters between the CMR groups and mediation analysis was performed to examine if the number of CMR factors mediated the relationship between fat % and BMC %. RESULTS: The prevalence of 0, 1 and ≥ 2 CMR factors was 42.3%, 33.9% and 23.9% respectively; mean BMC % was lowest in ≥ 2 CMR group. In the whole group, BMC % had significant negative correlation with fat % (r = -0.68, p < 0.0001) and positive correlation with lean % (r = 0.64, p < 0.0001). Adjusted for age and sex, results suggested significant mediating effect of number of CMR factors on the relationship between fat % and BMC % (Average Causal Mediation Effects =-0.002, bootstrapped 95% CI: -0.0039, -0.0001, p < 0.01), but losing significance when adjusted for co-variates. CONCLUSION: Number of CMR factors mediates the relationship between fat % and BMC % in Indian children. Further studies are needed to confirm these findings, understand mechanisms and plan appropriate strategies.