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.

Exploratory clinical subgroup clustering in systemic sclerosis: Results from the Indian Progressive Systemic Sclerosis Registry.

Objective: To conduct an exploratory cluster analysis of systemic sclerosis patients from the baseline data of the Indian systemic sclerosis registry. Methods: Patients satisfying American College of Rheumatology-European League Against Rheumatism classification criteria for systemic sclerosis were included. The clusters formed using clinical and immunological parameters were compared. Results: Of the 564 systemic sclerosis registry participants, 404 patients were included. We derived four clusters of which three were anti-topoisomerase I predominant and one was anti-centromere antibody 2 dominant. Cluster 1 (n-82 (20.3%)) had diffuse cutaneous systemic sclerosis patients with the most severe skin disease, anti-topoisomerase I positivity, males, younger age of onset and high prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 2 (n-141 (34.9%)) was also diffuse cutaneous systemic sclerosis and anti-topoisomerase I predominant but with less severe skin phenotype than cluster 1 and a lesser prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 3 (n-119 (29.5%)) had limited cutaneous systemic sclerosis patients with anti-topoisomerase I positivity along with other antibodies. The proximal muscle weakness was higher and digital pitting scars were lower, while other organ involvement was similar between clusters 2 and 3. Cluster 4 (n-62 (15.30%)) was the least severe group with limited cutaneous systemic sclerosis and anti-centromere antibody predominance. Age of onset was higher with low musculoskeletal disease and a higher presence of upper gastrointestinal features. The prevalence of interstitial lung disease was similar in the three anti-topoisomerase I predominant clusters. Conclusion: With exploratory cluster analysis, we confirmed the possibility of subclassification of systemic sclerosis along a spectrum based on clinical and immunological characteristics. We also corroborated the presence of anti-topoisomerase I in limited cutaneous systemic sclerosis and the association of interstitial lung disease with anti-topoisomerase I.

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.

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.

Comparison of Risk Factors During First and Second Wave of COVID-19 in Patients with Autoimmune Rheumatic Diseases (AIRD): Results from KRACC Subset.

Background: The differential influence and outcome of various risk factors on occurrence of COVID-19 among patients with autoimmune rheumatic diseases (AIRD) during different COVID-19 peaks is underreported. Aim: To assess the impact and outcome of conventional risk factors, immunosuppressants, and comorbidities on the risk of COVID-19 among AIRD patients during the first two COVID-19 peaks. Design: Prospective, non-interventional longitudinal cohort study. Methods: This is a subset of the KRA COVID19 cohort undertaken during the initial wave of COVID-19 (W1) (Apr-Dec2021); and the 2nd-wave (W2) (Jan-Aug2021). Data collected included description of AIRD subsets, treatment characteristics, comorbidities, and COVID-19 occurrence. Risk factors associated with mortality were analysed. The incidence rate was compared with that of the general population in the same geographic region. Results: AIRD patients (n=2969) had a higher incidence of COVID-19 in the W2 (7.1%) than in the W1 (1.7%) as compared to the general population (Government bulletin). Age (p<0.01) and duration of AIRD (p<0.001) influenced COVID-19 occurrence in W2 while major disease subsets and immunosuppressants including glucocorticoids did not. The W2 had lower HCQ usage (Adjusted Odds Ratio [AOR]-0.81) and comorbidities like hypertension (AOR -0.54) and pre-existing lung disease (AOR -0.38;0.19-0.75) compared to W1. Older age (1.11) and coexistent diabetes mellitus (AOR 6.74) were independent risk factors associated with mortality in W2. Conclusions: We report 1.7 times higher occurrence, and no influence of major disease subsets or immunosuppressants including glucocorticoids on COVID-19. Age and diabetes were independent risk factors for mortality.

Effect of collaborative care intervention on productivity losses among people with comorbid common mental disorders and cardiovascular disease in rural Karnataka.

Introduction: Common mental disorders (CMD) and cardiovascular diseases (CVD), common health problems among patients seeking primary healthcare, contribute to high economic productivity losses. Collaborative care programs for CMDs and CVDs have shown improvement in clinical outcomes for both conditions; however, data on productivity outcomes are scarce. Objective: Effect of integrated collaborative care on productivity among people with comorbid CMD and CVD in rural Karnataka primary health clinics. Methods: Participants were recruited within a randomized trial in rural South India, where patients received either collaborative or enhanced standard care. In this substudy, 303 participants were followed for 3 months and assessed with the iMTA Productivity Cost Questionnaire (iPCQ). Results: We found a reduction in the proportion of individuals reporting productivity loss at 3 months (66%) compared to baseline (76%; P = 0.002). Productivity losses decreased from INR 30.3 per person per day at baseline to 17.7 at 3 months. Reductions were similar in the two treatment conditions. Conclusion: Medical intervention may foster reduced productivity losses among patients with CMD and CVD. Collaborative care did not translate into higher reductions in productivity losses than "enhanced standard care."

Comparison of Anthropometry and Body Composition Using Air Displacement Plethysmography in Term Small for Gestational Age and Appropriate for Gestational Age Neonates.

BACKGROUND: Small for gestational age (SGA) neonates are prone to growth deficits in early life, which may be associated with later life metabolic abnormalities. OBJECTIVES: To compare anthropometry and body composition using air-displacement plethysmography (ADP) in term SGA and appropriate for gestational age (AGA) neonates, and assess if sexual dimorphism existed in estimates of body composition. STUDY DESIGN: Cross-sectional analytical study. PARTICIPANTS: 413 term neonates (91 SGA and 322 AGA) at birth (≤7days). METHODS: Neonatal anthropometry and body composition were measured using ADP. Length corrected fat mass index (FMI) and fat free mass index (FFMI) were calculated. OUTCOME: Anthropometry and body composition estimates of SGA and AGA neonates, segregated by sex. RESULTS: The mean (SD) birth weight of SGA and AGA neonates was 2.5 (0.2) kg and 3.1 (0.3) kg, respectively. SGA neonates had significantly lower % body fat (BF) (2.0%), fat mass (94.4 g), fat free mass (FFM) (349.7 g), FMI (0.34 kg/m2), and FFMI (0.76 kg/m2), but higher %FFM (2.0%) compared to AGA neonates (P<0.001). Males had significantly higher %FFM [91.2 (3.1) vs 90.2 (3.5); P=0.001], FFM [2604 (280) vs 2442 (233) g; P<0.001], and FFMI [11.1 (0.8) vs 10.8 (0.8) kg/m2; P=0.005], but lower % BF [8.8 (3.1) vs 9.8 (3.5); P=0.001] and FMI [1.1(0.4) vs 1.2 (0.5) kg/m2; P=0.008], compared to females. CONCLUSIONS: Accurate estimates of body composition in neonates at birth suggest significantly lower body fat and fat free mass in SGA compared to AGA, with sexual dimorphism.

Echocardiographic parameters in COVID-19 patients and their association with ICU mortality: a prospective multicenter observational study.

BACKGROUND: Echocardiography has become an integral part of the management of critically ill patients. It helps to diagnose and treat various conditions. COVID-19 patients can develop cardiac dysfunction. We planned to study the echocardiographic parameters in COVID-19 patients. METHODS: We conducted a prospective observational multicenter study after institutional ethical committee approval. COVID-19 pneumonia patients admitted to the intensive care unit (ICU) were enrolled. The echocardiographic evaluation was done within 24-48 hours of admission. Assessment of the left and right heart with systolic and left ventricular diastolic function evaluation was done. The primary outcome was ICU mortality. The secondary outcomes were the length of ICU stay and duration of mechanical ventilation. RESULTS: Among 573 patients mean age was 57.17 (14.67) with 68.60% being males. On day 1 of ICU, invasive mechanical ventilation was used in 257 (45%) patients. One hundred and forty-eight (25.83%) patients were on vasopressors when echocardiography was performed. Severe left ventricle (LV) systolic dysfunction was seen in 8.7% of patients and had higher odds of mortality [2.48(1.058-5.807), p = 0.037] followed by E and e' with odds ratio of [0.984(0.971-0.998), p = 0.021] and 0.897 (0.805-0.998), p = 0.046], respectively. E/e' indicative of filling pressure of the LV was not found to be significant. Troponin I, E/A, and RV dilatation were similar among survivors and non-survivors. CONCLUSION: Echocardiographic evaluation in COVID-19 patients showed severe LV systolic dysfunction was associated with ICU mortality. E/e' was not found to be significant but lower e' was associated with higher mortality. Trial registration IEC 131/2020, CTRI/2020/06/025858 date 13th June 2020.

Cardiac findings in multisystem inflammatory syndrome in children: Short term follow up in a large Indian series.

Background: We present a large Indian series of Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) infection. The aim of the study is to present the incidence and pattern of cardiac involvement in children with MIS-C and their short-term follow-up. Methods and Results: Consecutive 144 children younger than 18 years of age diagnosed with MIS-C referred for cardiac evaluation between June 1 and November 30, 2021, were included and were followed up till February 2022. In addition to the demographics, details of COVID-19 infection, and biomarkers, their cardiovascular assessment (echocardiogram and electrocardiogram) was documented at baseline and on follow-up. The median age of children with MIS-C was 60 (24-104) months. Abnormal cardiac imaging was noted in 59% of children. Ventricular dysfunction was noted in 13.9% and coronary abnormalities were noted in 25.7% of children. The median duration when the first cardiac abnormality was reported was 7 (5-10) days. The distribution of age categories between children with and without cardiac abnormality was comparable. Children with cardiac abnormalities were followed up for a median duration of 47 (30-58) days. Complete resolution was documented in 92% of children after a median duration of 20 (9-38) days. There were no readmissions or deaths during follow-up. Conclusion: Cardiac involvement in children with MIS-C is frequent with coronary abnormalities and ventricular dysfunction being the most common manifestations. Most children exhibit complete clinical and myocardial recovery with appropriate anti-inflammatory therapy. Studies on long-term outcome of these children are needed.

The Effect of Soy and Whey Protein Supplementation on Glucose Homeostasis in Healthy Normal Weight Asian Indians.

Milk and legumes are good source of protein foods used to sustain muscle mass, but their effects on postprandial glucose homeostasis and energy metabolism may be different. This is relevant, for example, in the dietetic response to obesity or diabetes, where the intake of high-quality protein is often increased significantly. The objective of this study was to characterize the acute effect of whey and soy protein (15% vs. 30%) on glucose homeostasis, energy metabolism, and satiety. Healthy, normal body mass index (BMI) Indian adult males aged 20-35 years (n = 15) received 4 test meals (2 proteins (soy vs. whey) and 2 doses (15% vs. 30% protein: energy ratio)). Blood samples were collected serially after the meal to calculate the incremental area under the curve for plasma glucose and insulin. Energy expenditure and substrate oxidation were measured after the meal. Satiety was measured with a visual analogue scale. The insulin response, represented by the incremental area under the curve, was significantly higher for the 30% whey compared to the 30% soy protein meal (p < 0.01) but was not significantly different between the 15% protein doses. There were no differences in the plasma glucose response across protein sources or doses. The mean peak fat and carbohydrate oxidation, satiety, and energy expenditure did not differ between the protein sources and doses. In conclusion, at higher doses, whey protein has a greater insulinogenic response, compared to soy protein, and exhibits a dose-response effect. However, at lower doses, whey and soy protein elicit similar insulinogenic responses, making them equally effective protein sources in relation to glucose homoeostasis.

Determinants of Kangaroo Mother Care Uptake for Small Babies Along the Health Facility to Community Continuum in Karnataka, India.

INTRODUCTION: Kangaroo mother care (KMC) scale-up is a proposed strategy to accelerate reduction in neonatal mortality rates. We aimed to identify determinants of KMC uptake for small babies (less than 2,000 g birth weight) along the health facility to community continuum in Karnataka, India. METHODS: From June 2017 to March 2020, data on characteristics of health facilities and health care workers (HCWs) from 8 purposively selected health facilities were assessed. Knowledge, attitude, and support the mothers received for KMC uptake were assessed once between 4 weeks and 8 weeks unadjusted age of the cohort of babies. Secondary data on KMC were obtained from the district-wide implementation research project database. Bivariate analysis was used to assess the association of characteristics of health facilities, HCWs, mothers, and small babies with the day of KMC initiation and its duration. Log-binomial regression analysis was then computed to identify determinants of KMC. RESULTS: We recruited 227 (91.5%) of 248 babies eligible to participate with a mean unadjusted age of 35.6 days (±7.5) and 1,693.9 g (±263.1 g) birth weight. KMC was initiated for 95.2% of 227 babies at the health facility; initiated at 3 days or earlier of life for 59.6% of 226 babies; and babies continued to receive KMC for more than 4 weeks (30.2 days [±8.4]) at home. Determinants of KMC initiation were HCWs' attitudes, initiation support at the health facility, and place of hospitalization. Determinants of KMC maintenance at the health facility were HCWs' skills and support the mother received at the facility after initiating KMC. Place of hospitalization and HCWs' knowledge determined KMC duration at home 1 week after discharge. CONCLUSION: These findings emphasize the importance of competent HCWs and support for mothers at the health facility for initiation and maintenance of KMC within the health facility and 1 week after discharge.

Severe thrombocytopenia is associated with high mortality in systemic lupus erythematosus-analysis from Indian SLE Inception cohort for Research (INSPIRE).

Thrombocytopenia in patients with systemic lupus erythematosus (SLE) is associated with higher morbidity and mortality. We report frequency, associations and short-term outcome of moderate-severe thrombocytopenia in a prospective inception cohort from India (INSPIRE). We evaluated consecutive SLE patients classified per SLICC2012 for the occurrence of thrombocytopenia and its associations. The outcomes assessed included bleeding manifestations, kinetics of thrombocytopenia recovery, mortality and recurrence of thrombocytopenia. Among a total of 2210 patients in the cohort, 230 (10.4%) had incident thrombocytopenia, of whom moderate (platelet count [PC] 20-50 × 109/L) and severe thrombocytopenia (PC < 20 × 109/L) were noted in 61 (26.5%) and 22 (9.5%), respectively. Bleeding manifestations were generally limited to the skin. Compared to controls, cases had a higher proportion of autoimmune haemolytic anaemia (p < 0.001), leukopenia (p < 0.001), lymphopenia (p < 0.001), low complement (p < 0.05), lupus anticoagulant (p < 0.001), higher median SLEDAI 2 K (p < 0.001) and lower proportion of anti-RNP antibody (p < 0.05). There was no significant difference in these variables between moderate and severe thrombocytopenia. There was a sharp rise in PC by 1 week that was sustained in the majority through the period of observation. There was three times higher mortality in the severe thrombocytopenia group as compared to moderate thrombocytopenia and controls. The thrombocytopenia relapse and lupus flare rates were similar across categories. We report a low occurrence of major bleeds and higher mortality in those with severe thrombocytopenia as compared to moderate thrombocytopenia and controls. Key Points • Severe thrombocytopenia occurs in 1% of patients with SLE; however, major bleeds are uncommon. • Thrombocytopenia has a strong association with other lineage cytopenias and lupus anticoagulants. • Response to initial glucocorticoids therapy is quick and is well sustained with additional immunosuppressants. • Severe thrombocytopenia increases mortality threefold in SLE.

A comparative analysis of clinicopathological features and survival between pre and postmenopausal breast cancer from an Indian cohort.

Breast cancer (BC) among premenopausal women is an aggressive disease associated with poor outcome despite intensive treatment. Higher burden is observed in southeast Asian countries attributed to younger population structure. We compared the reproductive and clinicopathological characteristics, distribution of subtypes and survival between pre and postmenopausal women from a retrospective cohort of BC patients with median follow up over 6 years to examine the differences. In our cohort of 446 BC patients, 162/446 (36.3%) were premenopausal. Parity and age at last childbirth were significantly different between pre and postmenopausal women. Premenopausal BC had a higher proportion of HER2 amplified and triple negative breast cancer (TNBC) tumors (p = 0.012). Stratified analysis by molecular subtypes showed TNBC had significantly better disease free (DFS) and overall survival (OS) among premenopausal group (mean survival, pre vs. post, DFS = 79.2 vs. 54.0 months, OS = 72.5 vs. 49.5 months, p = 0.002 for both). Analysis on external datasets (SCAN-B, METABRIC) confirmed this finding for overall survival. Our data confirmed the previously observed association of clinical and pathological features between pre and postmenopausal BC. Exploration of better survival among premenopausal TNBC tumors is warranted in larger cohorts with long term 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.

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.

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.

Assessment of Bone Health Using Dual-Energy X-Ray Absorptiometry (DEXA) And Its Association with Dietary Intakes, Serum Vitamin D Levels, and Anthropometric Measures in Healthy Urban Preschool Children.

OBJECTIVES: To generate reference data for bone mineral content (BMC) and bone mineral density (BMD) measures among apparently healthy children aged 4-5 y and to study the relationship of BMC and BMD with age, sex, anthropometric measures, dietary intakes, and serum vitamin D levels. METHODS: This cross-sectional study was conducted among 219 urban preschool children, aged 4.0-5.11 y. Bone health (BMC and BMD) was measured using dual energy X-ray absorptiometry (DEXA). Anthropometric parameters were measured using standard methodology. The 24-h dietary recall method was used to assess the dietary intake of the children. Serum vitamin D levels were assessed using the ELISA kit method. Percentiles for BMC and BMD for each age and sex were constructed using the lambda-mu-sigma (LMS) method. RESULTS: The mean BMD and BMC among children was 0.75 ± 0.04 g/cm2 and 544.9 ± 87.6 g, respectively, and were significantly different by age and sex category. The BMC and BMD values of boys and girls increased with age, with boys having significantly higher values. A significant positive correlation was observed for BMC and BMD with anthropometric measures and dietary intake of calcium, phosphorous, protein, zinc, and B vitamins. CONCLUSION: This study developed smoothed percentile curves for BMC and BMD in preschool children, which could be used as reference values for children from India.

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.

Timing of tofacitinib therapy is critical to improving outcomes in severe-critical COVID-19 infection: A retrospective study from a tertiary care hospital.

Describe the use of tofacitinib in severe and critical coronavirus disease-2019 (COVID-19), and explore the association of drug initiation time with survival. A retrospective study of inpatients with severe or critical COVID-19 at a tertiary care hospital, who were prescribed generic tofacitinib for at least 48 hours, was conducted. Baseline demographics, comorbidities, illness severity, treatment, adverse effects and outcomes were analyzed. Patients were grouped based on median duration of symptomatic illness prior to tofacitinib administration, as early or late initiation groups. Forty-one patients ([85.4% males], mean age 52.9 ±â€…12.5 years), were studied. 65.9% (n = 27) had severe COVID-19, while 34.1% (n = 14) were critically ill. Death occurred in 36.6% patients (n = 15). The median time to prescription of tofacitinib was 13 (9.50, 16.0) days of symptom onset. Tofacitinib was initiated early (8-13 days) in 56.1% of patients (n = 23), while the remaining received it beyond day 14 of symptom onset (late initiation group). Multivariate logistic regression adjusted for age, presence of diabetes mellitus and illness duration prior to hospitalization demonstrated higher odds of survival (adjusted odds ratio 19.3, 95% confidence interval 2.57, 145.2) in the early initiation group, compared to the late initiation group. Early initiation of tofacitinib in severe and critical COVID-19 has potential to improve survival odds.

Circulating C-Terminal Agrin Fragment: A Potential Marker for Sarcopenia Among Type 2 Diabetes.

Background: Undetected onset of sarcopenia among individuals with chronic diseases especially Type 2 Diabetes Mellitus (T2D) makes it important to be evaluated. The feasibility of diagnosing sarcopenia in a clinical setup might be a difficult task. Circulating markers including C-terminal agrin fragment (CAF) are emerging as an alternative. Hence, the objectives of the study were to compare circulating CAF levels between T2D, prediabetes (PD) and healthy controls and to study its association with sarcopenic index, muscle mass, strength and quality. Methods: Ninety-nine participants (n = 42, T2D; n = 33, PD; n = 24, healthy controls) aged 18 to 60 yrs were recruited. HOMA (homeostatic model assessment) indices were derived using plasma glucose and insulin. All participants underwent lipid profiling, muscle strength including quality (isokinetic dynamometer), body composition (Dual energy X-ray Absorptiometry (DXA)) and sarcopenic index (appendicular skeletal muscle mass/body weight) assessment. Serum samples were used to estimate CAF levelsusing enzyme-linked immunosorbent assay (ELISA). Results: Median CAF level was significantly higher among T2D group compared to PD and control groups (P < 0.0001). Circulating CAF levels correlated positively with age and glycated haemoglobin (HbA1c) (both, P < 0.001) and negatively with HOMA-B and muscle quality (both, P < 0.001), and sarcopenic index (P = 0.07). Multivariable analysis demonstrated that the odds of being in the highest tertile category was 7.67, 95% C.I. (2.10, 29.3) among T2D. Conclusion: Circulating CAF levels were significantly higher among T2D compared to PD and control study groups along with reduced skeletal muscle quality. This suggests that the circulating CAF level has the potential to be considered as a clinical marker to evaluate sarcopenia among T2D.