High failure rate of ChAdOx1-nCoV19 immunization against asymptomatic infection in healthcare workers during a Delta variant surge.

Immunization is expected to confer protection against infection and severe disease for vaccines while reducing risks to unimmunized populations by inhibiting transmission. Here, based on serial serological studies of an observational cohort of healthcare workers, we show that during a Severe Acute Respiratory Syndrome -Coronavirus 2 Delta-variant outbreak in Delhi, 25.3% (95% Confidence Interval 16.9-35.2) of previously uninfected, ChAdOx1-nCoV19 double vaccinated, healthcare workers were infected within less than two months, based on serology. Induction of anti-spike response was similar between groups with breakthrough infection (541 U/ml, Inter Quartile Range 374) and without (342 U/ml, Inter Quartile Range 497), as was the induction of neutralization activity to wildtype. This was not vaccine failure since vaccine effectiveness estimate based on infection rates in an unvaccinated cohort were about 70% and most infections were asymptomatic. We find that while ChAdOx1-nCoV19 vaccination remains effective in preventing severe infections, it is unlikely to be completely able to block transmission and provide herd immunity.

COVID-19 Risk Stratification and Mortality Prediction in Hospitalized Indian Patients: Harnessing clinical data for public health benefits.

The variability of clinical course and prognosis of COVID-19 highlights the necessity of patient sub-group risk stratification based on clinical data. In this study, clinical data from a cohort of Indian COVID-19 hospitalized patients is used to develop risk stratification and mortality prediction models. We analyzed a set of 70 clinical parameters including physiological and hematological for developing machine learning models to identify biomarkers. We also compared the Indian and Wuhan cohort, and analyzed the role of steroids. A bootstrap averaged ensemble of Bayesian networks was also learned to construct an explainable model for discovering actionable influences on mortality and days to outcome. We discovered blood parameters, diabetes, co-morbidity and SpO2 levels as important risk stratification features, whereas mortality prediction is dependent only on blood parameters. XGboost and logistic regression model yielded the best performance on risk stratification and mortality prediction, respectively (AUC score 0.83, AUC score 0.92). Blood coagulation parameters (ferritin, D-Dimer and INR), immune and inflammation parameters IL6, LDH and Neutrophil (%) are common features for both risk and mortality prediction. Compared with Wuhan patients, Indian patients with extreme blood parameters indicated higher survival rate. Analyses of medications suggest that a higher proportion of survivors and mild patients who were administered steroids had extreme neutrophil and lymphocyte percentages. The ensemble averaged Bayesian network structure revealed serum ferritin to be the most important predictor for mortality and Vitamin D to influence severity independent of days to outcome. The findings are important for effective triage during strains on healthcare infrastructure.

The iHealth-T2D study, prevention of type 2 diabetes amongst South Asians with central obesity and prediabetes: study protocol for a randomised controlled trial.

BACKGROUND: People from South Asia are at increased risk of type 2 diabetes (T2D). There is an urgent need to develop approaches for the prevention of T2D in South Asians that are cost-effective, generalisable and scalable across settings. HYPOTHESIS: Compared to usual care, the risk of T2D can be reduced amongst South Asians with central obesity or raised HbA1c, through a 12-month lifestyle modification programme delivered by community health workers. DESIGN: Cluster randomised clinical trial (1:1 allocation to intervention or usual care), carried out in India, Pakistan, Sri Lanka and the UK, with 30 sites per country (120 sites total). Target recruitment 3600 (30 participants per site) with annual follow-up for 3 years. ENTRY CRITERIA: South Asian, men or women, age 40-70 years with (i) central obesity (waist circumference ≥ 100 cm in India and Pakistan; ≥90 cm in Sri Lanka) and/or (ii) prediabetes (HbA1c 6.0-6.4% inclusive). EXCLUSION CRITERIA: known type 1 or 2 diabetes, normal or underweight (body mass index < 22 kg/m2); pregnant or planning pregnancy; unstable residence or planning to leave the area; and serious illness. ENDPOINTS: The primary endpoint is new-onset T2D at 3 years, defined as (i) HbA1c ≥ 6.5% or (ii) physician diagnosis and on treatment for T2D. Secondary endpoints at 1 and 3 years are the following: (i) physical measures: waist circumference, weight and blood pressure; (ii) lifestyle measures: smoking status, alcohol intake, physical activity and dietary intake; (iii) biochemical measures: fasting glucose, insulin and lipids (total and HDL cholesterol, triglycerides); and (iv) treatment compliance. INTERVENTION: Lifestyle intervention (60 sites) or usual care (60 sites). Lifestyle intervention was delivered by a trained community health worker over 12 months (5 one-one sessions, 4 group sessions, 13 telephone sessions) with the goal of the participants achieving a 7% reduction in body mass index and a 10-cm reduction in waist circumference through (i) improved diet and (ii) increased physical activity. Usual care comprised a single 30-min session of lifestyle modification advice from the community health worker. RESULTS: We screened 33,212 people for inclusion into the study. We identified 10,930 people who met study entry criteria, amongst whom 3682 agreed to take part in the intervention. Study participants are 49.2% female and aged 52.8 (SD 8.2) years. Clinical characteristics are well balanced between intervention and usual care sites. More than 90% of follow-up visits are scheduled to be complete in December 2020. Based on the follow-up to end 2019, the observed incidence of T2D in the study population is in line with expectations (6.1% per annum). CONCLUSION: The iHealth-T2D study will advance understanding of strategies for the prevention of diabetes amongst South Asians, use approaches for screening and intervention that are adapted for low-resource settings. Our study will thus inform the implementation of strategies for improving the health and well-being of this major global ethnic group. IRB APPROVAL: 16/WM/0171 TRIAL REGISTRATION: EudraCT 2016-001350-18 . Registered on 14 April 2016. ClinicalTrials.gov NCT02949739 . Registered on 31 October 2016, First posted on 31/10/2016.

Effects of a lifestyle intervention programme after 1 year of follow-up among South Asians at high risk of type 2 diabetes: a cluster randomised controlled trial.

INTRODUCTION: South Asians are at high risk of type 2 diabetes (T2D). We assessed whether intensive family-based lifestyle intervention leads to significant weight loss, improved glycaemia and blood pressure in adults at elevated risk for T2D. METHODS: This cluster randomised controlled trial (iHealth-T2D) was conducted at 120 locations across India, Pakistan, Sri Lanka and the UK. We included 3684 South Asian men and women, aged 40-70 years, without T2D but with raised haemoglobin A1c (HbA1c) and/or waist circumference. Participants were randomly allocated either to the family-based lifestyle intervention or control group by location clusters. Participants in the intervention received 9 visits and 13 telephone contacts by community health workers over 1-year period, and the control group received usual care. Reductions in weight (aim >7% reduction), waist circumference (aim ≥5 cm reduction), blood pressure and HbA1C at 12 months of follow-up were assessed. Our linear mixed-effects regression analysis was based on intention-to-treat principle and adjusted for age, sex and baseline values. RESULTS: There were 1846 participants in the control and 1838 in the intervention group. Between baseline and 12 months, mean weight of participants in the intervention group reduced by 1.8 kg compared with 0.4 kg in the control group (adjusted mean difference -1.10 kg (95% CI -1.70 to -1.06), p<0.001). The adjusted mean difference for waist circumference was -1.9 cm (95% CI -2.5; to 1.3), p<0.001). No overall difference was observed for blood pressure or HbA1c. People who attended multiple intervention sessions had a dose-dependent effect on waist circumference, blood pressure and HbA1c, but not on weight. CONCLUSION: An intensive family-based lifestyle intervention adopting low-resource strategies led to effective reduction in weight and waist circumference at 12 months, which has potential long-term benefits for preventing T2D. A higher number of attended sessions increased the effect on waist circumference, blood pressure and HbA1c. TRIAL REGISTRATION NUMBER: EudraCT: 2016-001350-18; ClinicalTrials.gov: NCT02949739.

Respiratory Co-Infections: Modulators of SARS-CoV-2 Patients' Clinical Sub-Phenotype.

Co-infection with ancillary pathogens is a significant modulator of morbidity and mortality in infectious diseases. There have been limited reports of co-infections accompanying SARS-CoV-2 infections, albeit lacking India specific study. The present study has made an effort toward elucidating the prevalence, diversity and characterization of co-infecting respiratory pathogens in the nasopharyngeal tract of SARS-CoV-2 positive patients. Two complementary metagenomics based sequencing approaches, Respiratory Virus Oligo Panel (RVOP) and Holo-seq, were utilized for unbiased detection of co-infecting viruses and bacteria. The limited SARS-CoV-2 clade diversity along with differential clinical phenotype seems to be partially explained by the observed spectrum of co-infections. We found a total of 43 bacteria and 29 viruses amongst the patients, with 18 viruses commonly captured by both the approaches. In addition to SARS-CoV-2, Human Mastadenovirus, known to cause respiratory distress, was present in a majority of the samples. We also found significant differences of bacterial reads based on clinical phenotype. Of all the bacterial species identified, ∼60% have been known to be involved in respiratory distress. Among the co-pathogens present in our sample cohort, anaerobic bacteria accounted for a preponderance of bacterial diversity with possible role in respiratory distress. Clostridium botulinum, Bacillus cereus and Halomonas sp. are anaerobes found abundantly across the samples. Our findings highlight the significance of metagenomics based diagnosis and detection of SARS-CoV-2 and other respiratory co-infections in the current pandemic to enable efficient treatment administration and better clinical management. To our knowledge this is the first study from India with a focus on the role of co-infections in SARS-CoV-2 clinical sub-phenotype.

Low uptake of COVID-19 prevention behaviours and high socioeconomic impact of lockdown measures in South Asia: Evidence from a large-scale multi-country surveillance programme.

BACKGROUND: South Asia has become a major epicentre of the COVID-19 pandemic. Understanding South Asians' awareness, attitudes and experiences of early measures for the prevention of COVID-19 is key to improving the effectiveness and mitigating the social and economic impacts of pandemic responses at a critical time for the Region. METHODS: We assessed the knowledge, behaviours, health and socio-economic circumstances of 29,809 adult men and women, at 93 locations across four South Asian countries. Data were collected during the national lockdowns implemented from March to July 2020, and compared with data collected prior to the pandemic as part of an ongoing prospective surveillance initiative. RESULTS: Participants were 61% female, mean age 45.1 years. Almost half had one or more chronic disease, including diabetes (16%), hypertension (23%) or obesity (16%). Knowledge of the primary COVID-19 symptoms and transmission routes was high, but access to hygiene and personal protection resources was low (running water 63%, hand sanitisers 53%, paper tissues 48%). Key preventive measures were not widely adopted. Knowledge, access to, and uptake of COVID-19 prevention measures were low amongst people from disadvantaged socio-economic groups. Fifteen percent of people receiving treatment for chronic diseases reported loss of access to long-term medications; 40% reported symptoms suggestive of anxiety or depression. The prevalence of unemployment rose from 9.3% to 39.4% (P < 0.001), and household income fell by 52% (P < 0.001) during the lockdown. Younger people and those from less affluent socio-economic groups were most severely impacted. Sedentary time increased by 32% and inadequate fruit and vegetable intake increased by 10% (P < 0.001 for both), while tobacco and alcohol consumption dropped by 41% and 80%, respectively (P < 0.001), during the lockdown. CONCLUSIONS: Our results identified important knowledge, access and uptake barriers to the prevention of COVID-19 in South Asia, and demonstrated major adverse impacts of the pandemic on chronic disease treatment, mental health, health-related behaviours, employment and household finances. We found important sociodemographic differences for impact, suggesting a widening of existing inequalities. Our findings underscore the need for immediate large-scale action to close gaps in knowledge and access to essential resources for prevention, along with measures to safeguard economic production and mitigate socio-economic impacts on the young and the poor.

HCQ prophylaxis in COVID-19 did not show any QTc prolongation in Healthcare workers.

BACKGROUND: HCQ is a commonly recommended drug for the prophylaxis of COVID-19. One of its rare side-effect includes QTc prolongation. METHODS: This was a prospective, cross sectional and observational study conducted on Hydroxychloroquine (HCQ) among Healthcare Workers (HCWs) at Max Super Speciality Hospital, Saket, New Delhi, India. A 3-lead ECG (only limb leads, it does not require chest leads) was performed. The QTc cut offs were pre decided, QTC < 470 ms for males and <480 ms for females was considered within the normal limits and anything above this was regarded as QTc prolongation. RESULTS: There were 274 HCWs enrolled into the study, including 175 males and 99 females. Majority of the HCWs were young and had a mean age of 32.19 ± 9.29 years. Out of these, 218 were taking HCQ as per the Indian Council of Medical Research (ICMR) guidelines. The median cumulative dose being taken was 1600 mg and the median QTc of these participants was 390 ms in males and 391.5 ms in females. Subsequently, 33 participants were followed-up and found to have a median QTc of 389 ms and a cumulative dose of HCQ as 2000 mg. CONCLUSION: In conclusion, ours is a first study in the middle of the pandemic which showed that HCQ prophylaxis in young HCWs without comorbidities did not show any QTc prolongation.

Effectiveness of Pregabalin Compared to Duloxetine in Diabetic Peripheral Neuropathic Pain: An Observational Study.

INTRODUCTION: Neuropathy is a comorbid complication of diabetes and Pregabalin and Duloxetine are the two most common drugs used for the treatment of neuropathic pain. AIM: To determine the effectiveness and side effects of Pregabalin and Duloxetine in patients with diabetic peripheral neuropathic pain. MATERIALS AND METHODS: This prospective observational study was conducted at Max Super Speciality Hospital. Patients attending the endocrinology department, above 18 years of age who were prescribed with Pregabalin or Duloxetine were screened and included in this study. The data was collected for all study participants using a specially designed case record form by conducting personal interviews. SF-MPQ, Mc-Gill, NRS and DN-4 questionnaires were used to assess the extent of pain and the side-effects associated with the drugs. RESULTS: Based on the responses from the Numerical Rating Scale and McGill Pain Questionnaire, Pregabalin was seen to be less effective compared to Duloxetine. The only side effect observed with Pregabalin was drowsiness, which was observed in 4% cases at 50 mg dose whereas those reported with Duloxetine were drowsiness (22.2% at 20 mg and 33.3% at 30 mg), vomiting (11.1% at 20mg and 30mg), headache (11.1% at 20 mg and 30 mg), and dizziness (0% at 20mg and 11.1% at 30 mg). CONCLUSION: Pregabalin has a better safety profile and tolerability compared to Duloxetine but the latter is more effective in treating Diabetic Peripheral Neuropathic Pain. However, further studies with a larger sample size and longer duration are required to be conducted for finding the effectiveness of these drugs, specifically in the Indian population.

Augmentation of IL-6 production contributes to development of gestational diabetes mellitus: An Indian study.

AIM: Inflammatory mediators like interleukin-6 (IL-6) and acute phase protein like C-reactive protein (CRP) are supposed to contribute to development of GDM, however clinical data supporting this hypothesis is limited. This study was designed to analyze the association of IL-6 and CRP with development of GDM in Indian females. METHODS: This case control study included pregnant women diagnosed as GDM (n = 53) and those having normal glucose tolerance (n = 50). Serum levels of IL-6 and CRP were analysed and correlated with various clinical parameters. RESULTS: Serum IL-6 levels were significantly high (p < 0.05) in GDM females as compared to control females. IL-6 levels correlated with pre-pregnancy body mass index (BMI), fasting blood sugar (FBS) and postprandial sugar (PPBS). Unlike IL-6, CRP levels did not show significant differences between GDM and control females. However, positive correlation of CRP levels with BMI, FBS and PPBS was observed. CONCLUSION: High IL-6 levels in gestational diabetes may indicate a possible role for inflammation in pathophysiology of GDM.

Role of immunological markers in gestational diabetes mellitus-a brief review.

Gestational Diabetes Mellitus (GDM) is a condition which develops due to insulin resistance. There are a number of immunological markers (IL-6, TNF-α, IL-10, etc), which play significant role during normal pregnancy and their irregular levels could likely cause some level of insulin resistance. There are studies which have compared the levels of different immunological mediators in GDM affected females and their healthy controls, but their findings are little controversial. Some of the studies have reported increased levels of IL-6, TNF-α, adiponectin, leptin, in females affected with GDM, while others do not confirm this. We have tried to summarize, in this short review, the findings of research studies being conducted globally, which have reported the association of insulin resistance, GDM and immunological markers. Our review suggests that there is a need for high quality data on the immunological parameters associated with GDM, especially from India.

GCK Gene Screening and Association of GCK Variants With Gestational Diabetes in North Indian Population.

BACKGROUND: GCK gene variants have been reported to be associated with gestational diabetes mellitus (GDM) in the Caucasian population. There are no reports exploring this association in the Indian population. METHODS: This cross-sectional study included subjects from Max Super Speciality Hospital, New Delhi, India, over a span of 6 months. Females diagnosed with GDM as per the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria were enrolled. Direct gene sequencing was performed to screen all 10 exons and promoter region of GCK gene. RESULTS: Out of the total 1000 females screened, 154 subjects had any degree of hyperglycemia. GCK gene screening was done and we observed 11 variants in 80.4% (41/51) of the GDM subset and 89.6% (43/48) of the controls. Allele frequencies of observed variants were not different between the control subjects (12.5%) and those diagnosed with GDM (8.4%). CONCLUSION: To the best of our knowledge, this is the first report from north India exploring association of GCK variants with GDM and we do not observe any association of GCK variants with GDM in our study population.CTRI Registration No: CTRI/2017/07/008964.

Psychological Insulin Resistance in Patients with Type 2 Diabetes.

AIMS/HYPOTHESIS: To identify risk factors associated with psychological insulin resistance (PIR) in Indian type 2 diabetes (T2DM) population. METHODS: Patients with T2DM, aged 18 years, undergoing treatment with oral hypoglycaemic agents and providing written informed consent were considered eligible for the study. Patient's data was collected by face-to-face interaction using 5 validated diabetes questionnaires--Diabetes Attitude Scale, Diabetes Knowledge Test, Diabetes Self-Efficacy Scale, Interpersonal Processes of Care Survey-29, and Barriers to Insulin Treatment scale. Demographic variables, categories of patients based on their annual family income, education, glycosylated haemoglobin (HbA1c), occupation and type of healthcare setup were correlated with overall scores of validated questionnaires. Statistical analyses were performed using Pearson correlation coefficients, analysis of variance, two-group t-test and hierarchical multiple regression. RESULTS: One hundred ninty-eight patients with T2DM were enrolled where 63% were males, 52% had HbA1c <7% (<53 mmol/mol), 32% were in service, 35% had the annual family income between Rs 100,000-500,000, 50% were graduates and 81% were enrolled from private healthcare set ups. Significant high opposition to use insulin was observed in females, patients based at home, patients with insufficient education, and patients visiting government set-ups compared to males, service-class patients, graduates, and patients approaching private set-ups, respectively. CONCLUSIONS: In India, major factors contributing to PIR were fear of injection or fear of pain during injection, fear of hypoglycemia, social stigma and lack of education. Effective interpersonal interactions with healthcare providers could help to counteract PIR, especially in patients who are not sufficiently literate highlighting the need of skilled healthcare staffs in Indian public hospitals.

Prevalence of depression in patients with type 2 diabetes attending an outpatient clinic in India.

BACKGROUND: Clinical studies have suggested that depression is common among patients with type 2 diabetes (T2D). Depression is an important factor which affects the management and complications of diabetes. However, the available data regarding its prevalence in India are limited. OBJECTIVES: To estimate the prevalence of depression in patients in India with T2D and to compare it with a non-diabetic group; and to determine the association of depression with glycaemic control and complications of diabetes in patients with T2D. METHODS: This case-control study was carried out over 5 months from May to September 2012 at a tertiary care hospital in India. Cases were patients with T2D and controls were individuals without diabetes. Depression was assessed using the Patient Health Questionnaire (PHQ)-9. The sociodemographic profile, duration of diabetes, presence of complications and other medical variables were also analysed. RESULTS: 260 subjects of Indian origin (162 men and 98 women; 130 with known T2D and 130 controls without T2D) were evaluated. The prevalence of depression in subjects with T2D was almost twice that in control subjects (46/130 (35.38%) vs 26/130 (20%); p=0.006). A statistically significant difference was found in the fasting blood glucose levels of subjects with depression and those without depression among the patients with T2D (145.70±53.92 vs 130.61±42.39; p=0.022), but depression was not found to be associated with any of the diabetic complications and glycaemic control. CONCLUSIONS: Our findings demonstrate that there is a higher prevalence of depression in Indian patients with T2D, which is almost twice that in those without T2D. Since patients with T2D are at higher risk of developing depression, assessment of depression should be performed as part of the routine practice in India. TRIAL REGISTRATION NUMBER: CTRI/2012/06/002747.

Thyroid storm due to inappropriate administration of a compounded thyroid hormone preparation successfully treated with plasmapheresis.

BACKGROUND: Thyroid storm (TS) is a rare life-threatening condition that is characterized by fever and altered mental status precipitated by endogenous or exogenous critical events, illness/injury, acute iodine load, and thyroid or non thyroid surgery. A large number of thyroid extracts are available and extensively used, even though they are not recommended clinically in hypothyroid or euthyroid patients. Consumption of such products can be dangerous and result in life-threatening TS. Here, we report a case of TS caused by inadvertent intake of very high dosages of triiodothyronine (T3) and thyroxine (T4) in compounded thyroid extracts. Plasmapheresis may be considered an option for the management of exogenous TS. PATIENT FINDINGS: A 62-year-old woman with no significant past medical history presented with severe myalgia, fever, tachycardia, and blood pressure of 170/80 mmHg, which precipitated to an altered mental state within 24 hours. Neurological examination did not reveal any focal deficit or any signs of meningeal irritation. Further investigation revealed that she had been taking thyroid supplements. The patient had accidentally been supplied with a batch of thyroid extract pills that had an inadvertently high content of T4. Her free T3 (FT3) and free T4 (FT4) levels were found to be very high beyond the laboratory readable range (FT3>30 pg/mL; FT4>6.06 ng/dL; thyrotropin [TSH]=0.07 IU/mL). SUMMARY: Three days post commencement of standard conservative management of TS, the patient developed posterior reversible encephalopathy syndrome, resulting in a seizure. She remained unresponsive and in a poor mental state. The confirmed exogenous etiology for TS led to a decision to conduct plasmapheresis. Plasmapheresis conducted for two consecutive days proved successful as a therapeutic measure for TS and improved her thyroid profile as well as her mental state. CONCLUSIONS: The inappropriate use of thyroid extracts in euthyroid and hypothyroid patients can result in life-threatening TS. Plasmapheresis is probably a life-saving treatment in patients who are exposed to amounts of thyroid hormone far in excess of that usually produced by the thyroid gland.

Accuracy of physical signs for detecting meningitis: a hospital-based diagnostic accuracy study.

OBJECTIVES: To evaluate accuracy of physical signs for detecting meningitis. PATIENTS AND METHODS: We enrolled patients aged 12 years or more, admitted with acute encephalitis syndrome (fever, headache, altered mental status, vomiting, seizures, neurodeficit) to a rural teaching hospital. The design was a double-blind, cross-sectional analysis of consecutive patients, independently comparing signs of meningeal inflammation (nuchal rigidity, head jolt accentuation of headache, Kernig's sign and Brudzinski's sign) elicited by internal medicine residents against an established reference standard (cerebrospinal fluid white cell count >5 white cells/µL). Diagnostic accuracy was measured by computing sensitivity, specificity and likelihood ratios (LRs) and their 95% confidence interval (CI) values. RESULTS: Of 190 patients (119 men, 71 women; ages 13-81 years; mean 38(SD 18) years) CSF analysis identified meningitis in 99 (52%; 95% CI 44, 59%) patients. No physical sign of meningeal irritation could accurately distinguish those with and without meningitis: nuchal rigidity (LR+ 1.33 (0.89, 1.98) and LR- 0.86 (0.70, 1.06)), head jolt accentuation of headache (LR+ 5.52 (0.67, 44.9) and LR- 0.95(0.89, 1.00)), Kernig's sign (LR+ 1.84 (0.77, 4.35) and LR- 0.93(0.84, 1.03)) and Brudzinski's sign (LR+ 1.69 (0.65, 4.37) and LR- 0.95 (0.87, 1.04)). CONCLUSION: Physical signs of meningeal inflammation do not help clinicians rule in or rule out meningitis accurately. Patients suspected to have meningitis should undergo a lumbar puncture regardless of the presence or absence of physical signs.