Development and Prospective Validation of the Levothyroxine Dose Prediction Model in Primary Hypothyroidism.

Multiple visits are needed to achieve euthyroidism on levothyroxine in newly detected primary hypothyroidism. We aimed to develop a levothyroxine dose estimation algorithm for primary hypothyroidism. Adults with newly diagnosed hypothyroidism were enrolled prospectively, first in the training cohort, followed by the validation cohort separated by time and person. We developed a predictive algorithm from Training Cohort and validated the model in Validation Cohort. Training Cohort: In this cohort, 358 subjects (259 women and 99 men) were enrolled. The median duration needed to achieve euthyroidism was 4±0.5 months. The mean levothyroxine daily dose was 60.5±34.1 µg. Data of euthyroid subjects within 6 months of treatment initiation and age range 18-65 years were used for algorithm development. In the multivariable linear regression algorithm, pretreatment serum thyrotropin level, and sex formed the best-fit predictive model (adjusted R2 0.73, p-value <0.001). Validation Cohort: Eighty-four subjects (61 women and 23 men) were enrolled and started on an estimated levothyroxine dose derived from the developed prediction model. On the first follow-up on treatment, 34/50 participants achieved euthyroidism (68%) at 1.5 months. In conclusion, the proposed prediction model for levothyroxine dose estimation effectively achieves early euthyroidism in two-third subjects in the age range of 18-65 years.

Burden of injury along the development spectrum: associations between the Socio-demographic Index and disability-adjusted life year estimates from the Global Burden of Disease Study 2017.

BACKGROUND: The epidemiological transition of non-communicable diseases replacing infectious diseases as the main contributors to disease burden has been well documented in global health literature. Less focus, however, has been given to the relationship between sociodemographic changes and injury. The aim of this study was to examine the association between disability-adjusted life years (DALYs) from injury for 195 countries and territories at different levels along the development spectrum between 1990 and 2017 based on the Global Burden of Disease (GBD) 2017 estimates. METHODS: Injury mortality was estimated using the GBD mortality database, corrections for garbage coding and CODEm-the cause of death ensemble modelling tool. Morbidity estimation was based on surveys and inpatient and outpatient data sets for 30 cause-of-injury with 47 nature-of-injury categories each. The Socio-demographic Index (SDI) is a composite indicator that includes lagged income per capita, average educational attainment over age 15 years and total fertility rate. RESULTS: For many causes of injury, age-standardised DALY rates declined with increasing SDI, although road injury, interpersonal violence and self-harm did not follow this pattern. Particularly for self-harm opposing patterns were observed in regions with similar SDI levels. For road injuries, this effect was less pronounced. CONCLUSIONS: The overall global pattern is that of declining injury burden with increasing SDI. However, not all injuries follow this pattern, which suggests multiple underlying mechanisms influencing injury DALYs. There is a need for a detailed understanding of these patterns to help to inform national and global efforts to address injury-related health outcomes across the development spectrum.

District level inequality in reproductive, maternal, neonatal and child health coverage in India.

BACKGROUND: As India already missed maternal and child health related millennium development goals, the maternal and child health outcomes are a matter of concern to achieve sustainable development goals (SDGs). This study is focused to assess the gap in coverage and inequality of various reproductive, maternal, neonatal and child health (RMNCH) indicators in 640 districts of India, using data from most recent round of National Family Health Survey. METHODS: A composite index named Coverage Gap Index (CGI) was calculated, as the weighted average of eight preventive maternal and child care interventions at different administrative levels. Bivariate and spatial analysis were used to understand the geographical diversity and spatial clustering in districts of India. A socio-economic development index (SDI) was also derived and used to assess the interlinkages between CGI and development. The ratio method was used to assess the socio-economic inequality in CGI and its component at the national level. RESULTS: The average national CGI was 26.23% with the lowest in Kerala (10.48%) and highest in Nagaland (55.07%). Almost half of the Indian districts had CGI above the national average and mainly concentrated in high focus states and north-eastern part. From the geospatial analysis of CGI, 122 districts formed hotspots and 164 districts were in cold spot. The poorest households had 2.5 times higher CGI in comparison to the richest households and rural households have 1.5 times higher CGI as compared to urban households. CONCLUSION: Evidence from the study suggests that many districts in India are lagging in terms of CGI and prioritize to achieve the desired level of maternal and child health outcomes. Efforts are needed to reduce the CGI among the poorest and rural resident which may curtail the inequality.

Hypertension screening, awareness, treatment, and control in India: A nationally representative cross-sectional study among individuals aged 15 to 49 years.

BACKGROUND: Evidence on where in the hypertension care process individuals are lost to care, and how this varies among states and population groups in a country as large as India, is essential for the design of targeted interventions and to monitor progress. Yet, to our knowledge, there has not yet been a nationally representative analysis of the proportion of adults who reach each step of the hypertension care process in India. This study aimed to determine (i) the proportion of adults with hypertension who have been screened, are aware of their diagnosis, take antihypertensive treatment, and have achieved control and (ii) the variation of these care indicators among states and sociodemographic groups. METHODS AND FINDINGS: We used data from a nationally representative household survey carried out from 20 January 2015 to 4 December 2016 among individuals aged 15-49 years in all states and union territories (hereafter "states") of the country. The stages of the care process-computed among those with hypertension at the time of the survey-were (i) having ever had one's blood pressure (BP) measured before the survey ("screened"), (ii) having been diagnosed ("aware"), (iii) currently taking BP-lowering medication ("treated"), and (iv) reporting being treated and not having a raised BP ("controlled"). We disaggregated these stages by state, rural-urban residence, sex, age group, body mass index, tobacco consumption, household wealth quintile, education, and marital status. In total, 731,864 participants were included in the analysis. Hypertension prevalence was 18.1% (95% CI 17.8%-18.4%). Among those with hypertension, 76.1% (95% CI 75.3%-76.8%) had ever received a BP measurement, 44.7% (95% CI 43.6%-45.8%) were aware of their diagnosis, 13.3% (95% CI 12.9%-13.8%) were treated, and 7.9% (95% CI 7.6%-8.3%) had achieved control. Male sex, rural location, lower household wealth, and not being married were associated with greater losses at each step of the care process. Between states, control among individuals with hypertension varied from 2.4% (95% CI 1.7%-3.3%) in Nagaland to 21.0% (95% CI 9.8%-39.6%) in Daman and Diu. At 38.0% (95% CI 36.3%-39.0%), 28.8% (95% CI 28.5%-29.2%), 28.4% (95% CI 27.7%-29.0%), and 28.4% (95% CI 27.8%-29.0%), respectively, Puducherry, Tamil Nadu, Sikkim, and Haryana had the highest proportion of all adults (irrespective of hypertension status) in the sampled age range who had hypertension but did not achieve control. The main limitation of this study is that its results cannot be generalized to adults aged 50 years and older-the population group in which hypertension is most common. CONCLUSIONS: Hypertension prevalence in India is high, but the proportion of adults with hypertension who are aware of their diagnosis, are treated, and achieve control is low. Even after adjusting for states' economic development, there is large variation among states in health system performance in the management of hypertension. Improvements in access to hypertension diagnosis and treatment are especially important among men, in rural areas, and in populations with lower household wealth.

Variation in health system performance for managing diabetes among states in India: a cross-sectional study of individuals aged 15 to 49 years.

BACKGROUND: Understanding where adults with diabetes in India are lost in the diabetes care cascade is essential for the design of targeted health interventions and to monitor progress in health system performance for managing diabetes over time. This study aimed to determine (i) the proportion of adults with diabetes in India who have reached each step of the care cascade and (ii) the variation of these cascade indicators among states and socio-demographic groups. METHODS: We used data from a population-based household survey carried out in 2015 and 2016 among women and men aged 15-49 years in all states of India. Diabetes was defined as a random blood glucose (RBG) ≥ 200 mg/dL or reporting to have diabetes. The care cascade-constructed among those with diabetes-consisted of the proportion who (i) reported having diabetes ("aware"), (ii) had sought treatment ("treated"), and (iii) had sought treatment and had a RBG < 200 mg/dL ("controlled"). The care cascade was disaggregated by state, rural-urban location, age, sex, household wealth quintile, education, and marital status. RESULTS: This analysis included 729,829 participants. Among those with diabetes (19,453 participants), 52.5% (95% CI, 50.6-54.4%) were "aware", 40.5% (95% CI, 38.6-42.3%) "treated", and 24.8% (95% CI, 23.1-26.4%) "controlled". Living in a rural area, male sex, less household wealth, and lower education were associated with worse care cascade indicators. Adults with untreated diabetes constituted the highest percentage of the adult population (irrespective of diabetes status) aged 15 to 49 years in Goa (4.2%; 95% CI, 3.2-5.2%) and Tamil Nadu (3.8%; 95% CI, 3.4-4.1%). The highest absolute number of adults with untreated diabetes lived in Tamil Nadu (1,670,035; 95% CI, 1,519,130-1,812,278) and Uttar Pradesh (1,506,638; 95% CI, 1,419,466-1,589,832). CONCLUSIONS: There are large losses to diabetes care at each step of the care cascade in India, with the greatest loss occurring at the awareness stage. While health system performance for managing diabetes varies greatly among India's states, improvements are particularly needed for rural areas, those with less household wealth and education, and men. Although such improvements will likely have the greatest benefits for population health in Goa and Tamil Nadu, large states with a low diabetes prevalence but a high absolute number of adults with untreated diabetes, such as Uttar Pradesh, should not be neglected.

Hypertension prevalence as a function of different guidelines, India.

OBJECTIVE: To determine the effect of different hypertension management guidelines and of basing diagnosis on a single reading of blood pressure on the hypertension prevalence in the Indian population. METHODS: We performed a secondary analysis of data acquired as part of the Fourth national family health survey, 2015 to 2016, over all districts in India. We calculated the proportion of the population within three different age groups (18 to 34, 35 to 49 and 18 to 49 years of age) with raised blood pressure according to six different guidelines, and how prevalence changed if diagnoses were based on a single blood pressure measurement. FINDINGS: We observed that the Government of India and the American College of Cardiology/American Heart Association guidelines consistently yielded the lowest and highest prevalence of raised blood pressure; in the combined age group, we calculated the proportion of the population categorized as having raised blood pressure as 7.5% (95% confidence interval (CI): 7.4 to 7.7) and 40.1% (95% CI: 39.7 to 40.7), respectively. When basing diagnosis on a single reading of blood pressure only, a total of 56 million individuals would be erroneously categorized as hypertensive following the Government of India guidelines. We also showed that prevalence of hypertension in India varies with guidelines adhered to; in the combined age group, the national hypertension prevalence was three times higher when following the American College of Cardiology/American Heart Association compared with the Government of India guidelines. CONCLUSION: To optimize current clinical practice, health-care providers need to follow universally agreed, evidence-based methods of diagnosing hypertension.

Geographic and sociodemographic variation of cardiovascular disease risk in India: A cross-sectional study of 797,540 adults.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality in India. Yet, evidence on the CVD risk of India's population is limited. To inform health system planning and effective targeting of interventions, this study aimed to determine how CVD risk-and the factors that determine risk-varies among states in India, by rural-urban location, and by individual-level sociodemographic characteristics. METHODS AND FINDINGS: We used 2 large household surveys carried out between 2012 and 2014, which included a sample of 797,540 adults aged 30 to 74 years across India. The main outcome variable was the predicted 10-year risk of a CVD event as calculated with the Framingham risk score. The Harvard-NHANES, Globorisk, and WHO-ISH scores were used in secondary analyses. CVD risk and the prevalence of CVD risk factors were examined by state, rural-urban residence, age, sex, household wealth, and education. Mean CVD risk varied from 13.2% (95% CI: 12.7%-13.6%) in Jharkhand to 19.5% (95% CI: 19.1%-19.9%) in Kerala. CVD risk tended to be highest in North, Northeast, and South India. District-level wealth quintile (based on median household wealth in a district) and urbanization were both positively associated with CVD risk. Similarly, household wealth quintile and living in an urban area were positively associated with CVD risk among both sexes, but the associations were stronger among women than men. Smoking was more prevalent in poorer household wealth quintiles and in rural areas, whereas body mass index, high blood glucose, and systolic blood pressure were positively associated with household wealth and urban location. Men had a substantially higher (age-standardized) smoking prevalence (26.2% [95% CI: 25.7%-26.7%] versus 1.8% [95% CI: 1.7%-1.9%]) and mean systolic blood pressure (126.9 mm Hg [95% CI: 126.7-127.1] versus 124.3 mm Hg [95% CI: 124.1-124.5]) than women. Important limitations of this analysis are the high proportion of missing values (27.1%) in the main outcome variable, assessment of diabetes through a 1-time capillary blood glucose measurement, and the inability to exclude participants with a current or previous CVD event. CONCLUSIONS: This study identified substantial variation in CVD risk among states and sociodemographic groups in India-findings that can facilitate effective targeting of CVD programs to those most at risk and most in need. While the CVD risk scores used have not been validated in South Asian populations, the patterns of variation in CVD risk among the Indian population were similar across all 4 risk scoring systems.

High Prevalence of Osteoporosis and Morphometric Vertebral Fractures in Indian Males Aged 60 Years and Above: Should Age for Screening Be Lowered?

Current guidelines recommend bone mineral density (BMD) measurement in asymptomatic men above age 70 years and vertebral fracture (VF) assessment above 80 years with T-score <-1.0 with risk factors. We studied the prevalence of osteoporosis and morphometric VF in asymptomatic males aged 60 years and above in North India. Free-living community-dwelling men (n = 241, age: mean ± standard deviation 68.0 ± 6.2 years) underwent a detailed history, physical examination, biochemical evaluation, and BMD measurements at 3 sites: lumbar spine, total hip (TH), and femoral neck (FN). Morphometric VF were assessed by instant vertebral assessment using Genant et al's semiquantitative method. We observed osteoporosis, osteopenia, and normal BMD in 19%, 56%, and 25% of subjects, respectively. The decade wise prevalence of osteoporosis in the age groups 60-70 years, 71-80 years, and >80 years was 16.9%, 17%, and 50%, respectively. Mean serum 25OHD levels were 17.2 ± 10.3 ng/mL. Vitamin D deficiency (<20 ng/mL) and secondary hyperparathyroidism (plasma intact parathyroid hormone >65 ng/mL) were present in 68.8% and 45.4%, respectively. VF were present in 29.6% subjects (grade I: 58%, grade II: 32.4%, and grade III: 8.8%). Age and iPTH had significant negative correlation with BMD at FN and TH. Serum 25OHD had no correlation with BMD at any site. The prevalence of VF was positively associated with age (p = 0.018) and negatively associated with BMD at FN (p = 0.002) and TH (p = 0.013). Osteoporosis and VF are common in asymptomatic Indian males aged 60 years and above. Screening for osteoporosis and instant vertebral assessment may be recommended earlier than currently existing guidelines.

Global Mortality From Firearms, 1990-2016.

Importance: Understanding global variation in firearm mortality rates could guide prevention policies and interventions. Objective: To estimate mortality due to firearm injury deaths from 1990 to 2016 in 195 countries and territories. Design, Setting, and Participants: This study used deidentified aggregated data including 13 812 location-years of vital registration data to generate estimates of levels and rates of death by age-sex-year-location. The proportion of suicides in which a firearm was the lethal means was combined with an estimate of per capita gun ownership in a revised proxy measure used to evaluate the relationship between availability or access to firearms and firearm injury deaths. Exposures: Firearm ownership and access. Main Outcomes and Measures: Cause-specific deaths by age, sex, location, and year. Results: Worldwide, it was estimated that 251 000 (95% uncertainty interval [UI], 195 000-276 000) people died from firearm injuries in 2016, with 6 countries (Brazil, United States, Mexico, Colombia, Venezuela, and Guatemala) accounting for 50.5% (95% UI, 42.2%-54.8%) of those deaths. In 1990, there were an estimated 209 000 (95% UI, 172 000 to 235 000) deaths from firearm injuries. Globally, the majority of firearm injury deaths in 2016 were homicides (64.0% [95% UI, 54.2%-68.0%]; absolute value, 161 000 deaths [95% UI, 107 000-182 000]); additionally, 27% were firearm suicide deaths (67 500 [95% UI, 55 400-84 100]) and 9% were unintentional firearm deaths (23 000 [95% UI, 18 200-24 800]). From 1990 to 2016, there was no significant decrease in the estimated global age-standardized firearm homicide rate (-0.2% [95% UI, -0.8% to 0.2%]). Firearm suicide rates decreased globally at an annualized rate of 1.6% (95% UI, 1.1-2.0), but in 124 of 195 countries and territories included in this study, these levels were either constant or significant increases were estimated. There was an annualized decrease of 0.9% (95% UI, 0.5%-1.3%) in the global rate of age-standardized firearm deaths from 1990 to 2016. Aggregate firearm injury deaths in 2016 were highest among persons aged 20 to 24 years (for men, an estimated 34 700 deaths [95% UI, 24 900-39 700] and for women, an estimated 3580 deaths [95% UI, 2810-4210]). Estimates of the number of firearms by country were associated with higher rates of firearm suicide (P < .001; R2 = 0.21) and homicide (P < .001; R2 = 0.35). Conclusions and Relevance: This study estimated between 195 000 and 276 000 firearm injury deaths globally in 2016, the majority of which were firearm homicides. Despite an overall decrease in rates of firearm injury death since 1990, there was variation among countries and across demographic subgroups.

Utility of Osteoporosis Self-Assessment Tool as a Screening Tool for Predicting Osteoporosis in Indian Men.

The osteoporosis self-assessment tool (OSTA) predicts the risk of osteoporosis in an individual. It is a simple calculation-based tool [wt (kg) - age (yr)/5] and can be used for measuring bone mineral density (BMD). However, OSTA is influenced by ethnicity. We studied the performance of OSTA index as a screening tool for osteoporosis in 257 community-dwelling North Indian men above 50 yr age. Each subject underwent a detailed clinical, dietary, anthropometric, and biochemical assessment and bone density measurement using dual-energy X-ray absorptiometry. As per World Health Organization criteria, osteoporosis, osteopenia, and normal BMD were observed in 17.9%, 58.8%, and 23.3%, respectively. OSTA index ranged between -6.4 and 8.8. OST index ≤2 predicted osteoporosis with a sensitivity of 95.7% and a specificity of 33.6% and an area under the curve for a receiver operating characteristic curve of 0.702. The OSTA index is an effective screening tool for measuring BMD in elderly Indian men and can be used by primary care physicians.

Arterial spin labeling magnetic resonance perfusion study to evaluate the effects of age and gender on normal cerebral blood flow.

PURPOSE: Arterial spin labeling (ASL) is a noninvasive magnetic resonance (MR) perfusion technique to detect changes in blood flow. This study was undertaken to obtain a reference set of normal values of cerebral blood flow (CBF) in different age groups using three-dimensional pseudocontinuous ASL (3D PCASL) technique. The existence of an age-related decline in the gray matter (GM) and white matter (WM) CBF was evaluated. The gender-related CBF was also analyzed. MATERIALS AND METHODS: One hundred and sixty normal volunteers of varying age (6-72 years), arranged in 4 age groups, underwent MR perfusion imaging using 3D PCASL technique at 3 Tesla (T). Mean CBF values in global and regional GM and WM in different age groups were extracted from the quantitative perfusion map. RESULTS: A significant negative correlation was observed between the age and mean GM and WM CBF values (r = -0.80, P = 0.001; r = -0.59, P = 0.001, respectively). Similar results were also observed between age and various regional mean GM and WM CBF values (P = 0.001). No significant effect of gender on the GM CBF and WM CBF was found in any age group (P > 0.05). CONCLUSION: PCASL technique provides reliable quantitative parameters for the precise mapping of age-related perfusion changes occurring in the normal brain.

Trends in the incidence, mortality and clinical outcomes in patients with ventricular septal rupture following an ST-elevation myocardial infarction.

BACKGROUND: Despite improvements in outcomes of ST elevation myocardial infarction (STEMI), ventricular septal rupture (VSR) remains a known complication, carrying high mortality. The contemporary incidence, mortality, and management of post-STEMI VSR remains unclear. METHODS: The National Inpatient Sample database (2009-2020) was used to study trends in admissions and outcomes of post-STEMI VSR over time. Survey estimation commands were used to determine weighted national estimates. RESULTS: There were 2 315 186 ±â€…22 888 visits for STEMI with 0.194 ±â€…0.01% experiencing VSR during 2009-2020 in the USA. Patients with VSR were more often older, white, female, and presented with an anterior STEMI; there was no difference in the rates of fibrinolysis. In-hospital mortality was 73.6 ±â€…1.8%, but only 29.2 ±â€…1.9 and 10 ±â€…1.2% received surgical repair and transcatheter repair (TCR), respectively. TCR was associated with higher and surgical repair with lower mortality. Days to surgery were longer for those who survived (5.9 ±â€…2.75) compared with those who died (2.44 ±â€…1). In a multivariable analysis, surgical repair at greater than or equal to day 4 was associated with lower in-hospital mortality (odds ratio = 0.39, 95% confidence interval: 0.17-0.88). CONCLUSION: Mortality in post-STEMI VSR remains high with no improvement over time. Most patients are managed conservatively, and the frequency of surgical repair has decreased, while TCR has increased over the study period. Despite design limitations and survival bias, surgical repair at greater than or equal to 4 days was associated with a lower mortality.

Evaluating bias with loss to follow-up in a community-based cohort: empirical investigation from the CARRS Study.

BACKGROUND: Retention of participants is a challenge in community-based longitudinal cohort studies. We aim to evaluate the factors associated with loss to follow-up and estimate attrition bias. METHODS: Data are from an ongoing cohort study, Center for cArdiometabolic Risk Reduction in South Asia (CARRS) in India (Delhi and Chennai). Multinomial logistic regression analysis was used to identify sociodemographic factors associated with partial (at least one follow-up) or no follow-up (loss to follow-up). We also examined the impact of participant attrition on the magnitude of observed associations using relative ORs (RORs) of hypertension and diabetes (prevalent cases) with baseline sociodemographic factors. RESULTS: There were 12 270 CARRS cohort members enrolled in Chennai and Delhi at baseline in 2010, and subsequently six follow-ups were conducted between 2011 and 2022. The median follow-up time was 9.5 years (IQR: 9.3-9.8) and 1048 deaths occurred. Approximately 3.1% of participants had no follow-up after the baseline visit. Younger (relative risk ratio (RRR): 1.14; 1.04 to 1.24), unmarried participants (RRR: 1.75; 1.45 to 2.11) and those with low household assets (RRR: 1.63; 1.44 to 1.85) had higher odds of being lost to follow-up. The RORs of sociodemographic factors with diabetes and hypertension did not statistically differ between baseline and sixth follow-up, suggesting minimal potential for bias in inference at follow-up. CONCLUSION: In this representative cohort of urban Indians, we found low attrition and minimal bias due to the loss to follow-up. Our cohort's inconsistent participation bias shows our retention strategies like open communication, providing health profiles, etc have potential benefits.

Disparities in Drug-Eluting Stent Utilization in Patients With Acute ST-Elevation Myocardial Infarction: An Analysis of the National Inpatient Sample.

The superiority of drug-eluting stents (DES) compared with bare-metal stents (BMS) is well-established, but data regarding DES use in ST-elevation myocardial infarction (STEMI) as a function of race is limited. Our goal was to examine stent utilization patterns and disparities based on race, sex, and insurance status in patients with STEMI undergoing percutaneous coronary intervention. The National Inpatient Sample database was used to retrospectively compare DES vs BMS use in patients admitted with STEMI from 2009 to 2018. Multivariable logistic regression was performed to assess the independent predictors of DES use. DES utilization increased significantly from 62.8% in 2009 to 94.0% in 2018. However, African Americans were less likely to receive a DES (odds ratio [OR] .82, 95% confidence interval [CI] .77-.87) compared with Caucasians. Women were more likely to undergo DES implantation (OR 1.07, 95% CI 1.05-1.10). Patients insured by Medicaid (OR .84, 95% CI .80-.89) and those classified as Self-pay (OR .63, 95% CI .61-.66) were less likely to undergo DES implantation compared to those with private insurance (OR 1.33, 95% CI 1.29-1.38). Disparities based on race and insurance status continue to persist despite a significant increase in DES utilization in STEMI patients across the identified subgroups.

Eight versus twelve weeks of sofosbuvir-velpatasvir in treatment-naïve non-cirrhotic patients with chronic hepatitis C virus infection: Study protocol for a multicentric, open labelled, randomized, non-inferiority trial (RESOLVE trial).

BACKGROUND: Hepatitis C virus (HCV) is a common cause of liver cirrhosis and hepatocellular carcinoma. Globally, nearly 71 million people have chronic HCV infection, and approximately 399,000 dies annually. In patients without cirrhosis, HCV infection is treated with 12 weeks of sofosbuvir/velpatasvir combination. Results from available small, single-centre observational studies suggest that the sofosbuvir/velpatasvir combination given for 8 weeks may be as effective as the standard 12 weeks of treatment. We propose to compare the treatment response of 12 weeks versus 8 weeks of sofosbuvir/velpatasvir in non-cirrhotic people with chronic HCV infection. METHODS: This multicentric, randomized, open-label, non-inferiority trial will include 880 (2 arms x 440) treatment naïve, viraemic (HCV RNA >10,000 IU/mL), non-cirrhotic adults (age >18 years) with chronic hepatitis C. People who are at high-risk for HCV reinfection such as haemophiliacs, people who inject drugs, those on maintenance hemodialysis or having HIV will be excluded. The presence or absence of cirrhosis will be determined with a combination of history, examination, ultrasound, liver stiffness measured with transient elastography, APRI, FIB-4, and esophagogastroduodenoscopy. Participants will be randomized to receive either 8- or 12-week sofosbuvir/velpatasvir treatment. A blood specimen will be collected before starting the treatment (to determine the HCV genotype), after 4 weeks of treatment (for early virological response), and at 12 weeks after treatment discontinuation for SVR12. DISCUSSION: The study will provide data on the efficacy of 8 weeks of treatment as compared to the standard of care (12 weeks) in non-cirrhotic patients with chronic HCV infection. Treatment for a shorter duration may improve treatment compliance, reduce the cost of treatment, and ease the treatment implementation from a public health perspective. TRIAL REGISTRATION: Registered with Clinical Trial Registry of India (http://ctri.nic.in) Registration No. CTRI/2022/03/041368 [Registered on: 24/03/2022]-Trial Registered Prospectively.

Discriminant analysis to classify glioma grading using dynamic contrast-enhanced MRI and immunohistochemical markers.

INTRODUCTION: The purpose of the present study was to look for the possible predictors which might discriminate between high- and low-grade gliomas by pooling dynamic contrast-enhanced (DCE)-perfusion derived indices and immunohistochemical markers. METHODS: DCE-MRI was performed in 76 patients with different grades of gliomas. Perfusion indices, i.e., relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), permeability (k (trans) and k (ep)), and leakage (v (e)) were quantified. MMP-9-, PRL-3-, HIF-1α-, and VEGF-expressing cells were quantified from the excised tumor tissues. Discriminant function analysis using these markers was used to identify discriminatory variables using a stepwise procedure. To look for correlations between immunohistochemical parameters and DCE metrics, Pearson's correlation coefficient was also used. RESULTS: A discriminant function for differentiating between high- and low-grade tumors was constructed using DCE-MRI-derived rCBV, k (ep), and v (e). The form of the functions estimated are "D (1) = 0.642 × rCBV + 0.591 × k (ep) - 1.501 × v (e) - 1.550" and "D (2) = 1.608 × rCBV + 3.033 × k (ep) + 5.508 × v (e) - 8.784" for low- and high-grade tumors, respectively. This function classified overall 92.1% of the cases correctly (89.1% high-grade tumors and 100% low-grade tumors). In addition, VEGF expression correlated with rCBV and rCBF, whereas MMP-9 expression correlated with k (ep). A significant positive correlation of HIF-1α with rCBV and VEGF expression was also found. CONCLUSION: DCE-MRI may be used to differentiate between high-grade and low-grade brain tumors non-invasively, which may be helpful in appropriate treatment planning and management of these patients. The correlation of its indices with immunohistochemical markers suggests that this imaging technique is useful in tissue characterization of gliomas.

Serum Level of Alanine- and Aspartate-Aminotransferase Levels in Newborns in India.

Background: Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤40 IU/L is normal. This cutoff, although determined in adults, is widely used for newborns. We studied the reference ranges for ALT and AST in newborns in India. Methods: We prospectively included babies with gestational age (GA) between 34 and 41weeks and birth weight (BW) ≥ 1500 g. We excluded the babies who either themselves or their mother had risk factors, which could cause elevation of serum levels of liver enzymes. Serum ALT and AST were measured in venous cord blood. The estimated percentile curves for ALT and AST, for BW and GA covariates, were drawn with General Additive Model for Location Scale and Shape (GAMLSS) with Box-Cox Power Exponential (BCPE). Results: Five-hundred thirty-seven babies (Boys 53.3%; GA 34-36 wks 19.7%; appropriate for GA 74.9%; BW < 2500 g 20.5%) were included. Overall, mean [SD] serum ALT and AST were 4412 IU/L and 5218 IU/L, respectively. The serum AST was significantly higher than the ALT level, regardless of gender, BW, GA, or fetal growth categories. The percentile curve against GA remained flat for ALT, although it showed a slight rise for AST. Serum levels of ALT and AST plotted against BW were also similar and showed an increase up to 2000 g and then remained stationary after that. Conclusion: The serum levels of ALT and AST up to 44 IU/L and 52 IU/L, respectively, can be taken as normal in newborns with BW ≥ 2000 g or GA ≥34 weeks.

Kidney disease burden in an Asian Indian population: Effect of the new 2021 serum creatinine CKD-EPI equation.

AIMS: CKD-EPI (chronic kidney disease-epidemiological) serum creatinine equation is widely accepted for calculating estimated glomerular filtration rate (eGFR). The effect of transitioning from the older 2009 to the newer race-independent 2021 CKD-EPI equation on the estimated kidney disease burden (eKDB) was studied in an Asian-Indian population. METHODS: The study included 1156 adults, the two equations were compared for agreement (Bland-Altman and Cohen's kappa) and concordance (Lin's correlation and test for proportions). RESULTS: The 2021 CKD-EPI increased the eGFR (positive-bias), independent of age-group, gender or presence of type 2 diabetes mellitus (T2DM) and hypertension (HTN). Thus, the eKDB was significantly decreased by 2021 CKD-EPI equation. The agreement was highest for the age-group 31-40 years (95.8 % versus 87.5 % for > 50 years). Besides, the eGFR category was shifted from G3 to G1 in 8.2 % (95 % CI: 6.8-9.9) individuals by 2021 CKD-EPI. The effect of transition on eKDB was greater in individuals > 50 years (7.4 %) or with HTN (6.3 %). CONCLUSION: In comparison to the old equation, the 2021 CKD-EPI equation increased the eGFR, lowering the eKDB in this Asian-Indian cohort. The degree of lowering was affected by age-group, and presence of T2DM /HTN, but independent of gender.

Patterns of multimorbidity in India: A nationally representative cross-sectional study of individuals aged 15 to 49 years.

There is a dearth of evidence on the epidemiology of multimorbidity in low- and middle-income countries. This study aimed to determine the prevalence of multimorbidity in India and its variation among states and population groups. We analyzed data from a nationally representative household survey conducted in 2015-2016 among individuals aged 15 to 49 years. Multimorbidity was defined as having two or more conditions out of five common chronic morbidities in India: anemia, asthma, diabetes, hypertension, and obesity. We disaggregated multimorbidity prevalence by condition, state, rural versus urban areas, district-level wealth, and individual-level sociodemographic characteristics. 712,822 individuals were included in the analysis. The prevalence of multimorbidity was 7·2% (95% CI, 7·1% - 7·4%), and was higher in urban (9·7% [95% CI, 9·4% - 10·1%]) than in rural (5·8% [95% CI, 5·7% - 6·0%]) areas. The three most prevalent morbidity combinations were hypertension with obesity (2·9% [95% CI, 2·8% - 3·1%]), hypertension with anemia (2·2% [95% CI, 2·1%- 2·3%]), and obesity with anemia (1·2% [95% CI, 1·1%- 1·2%]). The age-standardized multimorbidity prevalence varied from 3·4% (95% CI: 3·0% - 3·8%) in Chhattisgarh to 16·9% (95% CI: 13·2% - 21·5%) in Puducherry. Being a woman, being married, not currently smoking, greater household wealth, and living in urban areas were all associated with a higher risk of multimorbidity. Multimorbidity is common among young and middle-aged adults in India. This study can inform screening guidelines for chronic conditions and the targeting of relevant policies and interventions to those most in need.