Association of hyperglycaemia with hospital mortality in nondiabetic COVID-19 patients: A cohort study.

OBJECTIVE: Diabetes is a known risk factor for mortality in Coronavirus disease 2019 (COVID-19) patients. Our objective was to identify prevalence of hyperglycaemia in COVID-19 patients with and without prior diabetes and quantify its association with COVID-19 disease course. RESEARCH DESIGN AND METHODS: This observational cohort study included all consecutive COVID-19 patients admitted to John H Stroger Jr. Hospital, Chicago, IL from March 15, 2020 to May 3, 2020 and followed till May 15, 2020. The primary outcome was hospital mortality, and the studied predictor was hyperglycaemia [any blood glucose ≥7.78 mmol/L (140 mg/dL) during hospitalization]. RESULTS: Of the 403 COVID-19 patients studied, 51 (12.7%) died; 335 (83.1%) were discharged while 17 (4%) were still in hospital. Hyperglycaemia occurred in 228 (56.6%) patients; 83 of these hyperglycaemic patients (36.4%) had no prior history of diabetes. Compared to the reference group no-diabetes/no-hyperglycaemia patients the no-diabetes/hyperglycaemia patients showed higher mortality [1.8% versus 20.5%, adjusted odds ratio 21.94 (95% confidence interval 4.04-119.0), P < 0.001]; improved prediction of death (P = 0.01) and faster progression to death (P < 0.01). Hyperglycaemia within the first 24 and 48 h was also significantly associated with mortality (odds ratio 2.15 and 3.31, respectively). CONCLUSIONS: Hyperglycaemia without prior diabetes was common (20.6% of hospitalized COVID-19 patients) and was associated with an increased risk of and faster progression to death. Development of hyperglycaemia in COVID-19 patients who do not have diabetes is an early indicator of progressive disease.

Waist circumference is genetically correlated with incident Type 2 diabetes in Mexican-American families.

AIMS: We aimed to determine the genetic and environmental correlation between various anthropometric indexes and incident Type 2 diabetes with a focus on waist circumference. METHODS: We used the data on extended Mexican-American families (808 subjects, 7617.92 person-years follow-up) from the San Antonio Family Heart Study and estimated the genetic and environmental correlations of 16 anthropometric indexes with the genetic liability of incident Type 2 diabetes. We performed bivariate trait analyses using the solar software package. RESULTS: All 16 anthropometric indexes were significantly heritable (range of heritabilities 0.24-0.99). Thirteen indexes were found to have significant environmental correlation with the liability of incident Type 2 diabetes. In contrast, only anthropometric indexes consisting of waist circumference (waist circumference, waist-hip ratio and waist-height ratio) were significantly genetically correlated (genetic correlation coefficients: 0.45, 0.55 and 0.44, respectively) with the liability of incident Type 2 diabetes. We did not observe such a correlation for BMI. CONCLUSIONS: Waist circumference as a predictor of future Type 2 diabetes is supported by the finding that they share common genetic influences.

Efficacy trial of Camouflage Syringe to reduce dental fear and anxiety.

AIM: Dental fear and anxiety in early childhood are widely prevalent and contribute to dental problems and behaviour in adulthood. Novel ways to reduce dental fear and anxiety in children are needed. Our aim was to conduct an efficacy trial of a novel Camouflage Syringe to reduce dental fear and anxiety in children. STUDY DESIGN: randomised controlled trial of efficacy of the Camouflage Syringe. We designed a Camouflage Syringe with a toy-like appearance that veils the conventional syringe to permit topical application and injection of local anaesthesia and ensure more involvement of the patient in the treatment process. We conducted a concurrent parallel, randomised controlled trial (NCT01398007) on the efficacy of this Camouflage Syringe to reduce the dental fear and anxiety in children seeking dental treatment who required the use of local anaesthesia. RESULTS: Using Venham's clinical rating scale, Venham's picture test, parental stress questionnaire and recall questionnaire, the efficacy of the Camouflage Syringe to reduce dental fear and anxiety ranged from 82% to 97% for various outcomes and from 60% to 100% for prevention of related adverse outcomes. For all outcomes, the number needed to treat was close to unity. CONCLUSION: Our results strongly favour the use of Camouflage Syringe to reduce dental fear and anxiety in children.

Weak or absent evidence for the association of HLA-DR antigens with risk of thyroid carcinoma: a meta-analysis of observational studies.

Inconsistent reports of associations between human leukocyte antigen (HLA)-DR and thyroid cancers exist. We conducted a comprehensive search of the PubMed, Scopus and Web of Science databases. Using random-effects modeling, subgroup analyses, meta-regression and prediction interval (PI) estimation, we combined the existing evidence from 13 studies (977 cases of thyroid cancer and 3735 controls). Only HLA-DR1 and HLA-DR11 were significantly associated; however, the evidence for HLA-DR11 came from only three studies while that for HLA-DR1 had large between-study heterogeneity. All the PIs estimated in the study straddled unity. Therefore, current evidence for the studied association is incomplete as well as uncertain. Attempts to include HLA-DR typing as a prognostic or therapeutic marker may be premature at this time.

Bone recovery after zoledronate therapy in thalassemia-induced osteoporosis: a meta-analysis and systematic review.

UNLABELLED: Zoledronate is a promising bisphosphonate that improves the bone mineral density by 0.69 standard deviations in thalassemia-induced osteoporosis, but the entire range of its actions and side effects is currently not fully understood. INTRODUCTION: Zoledronate is a promising bisphosphonate for the treatment of thalassemia-induced osteoporosis; however, a quantitative summary of its beneficial effect and its effects on the markers of bone turnover are not established. METHODS: We conducted a meta-analysis of the published randomized controlled trials using standardized mean difference and a random effects model for improvement in bone mineral density (BMD). We also conducted a systematic review for the influence of zoledronate on markers of bone turnover and bone pain. RESULTS: We found that zoledronate improves the baseline BMD by 0.69 (95% confidence interval 0.47-0.90) standard deviations-an effect that was more pronounced when BMD was measured at the lumbar spine. However, the mechanistic interpretations of the effects on the markers of bone turnover are not completely clear. CONCLUSION: Sufficient evidence exists to demonstrate that 4 mg zoledronate given every 3 months markedly improves the BMD; however, more qualitative and quantitative evidence is required to understand the mechanisms of its action and the potential side effects.

Association of copy number variation in the FCGR3B gene with risk of autoimmune diseases.

Copy number variation (CNV) in the human genome is an important determinant of susceptibility to autoimmune diseases. Many autoimmune diseases share similar clinical and pathogenic features. Thus, CNVs of genes involved in immunity may serve as shared determinants of multiple autoimmune diseases. Here, we determined the association between CNV in the gene encoding FCGR3B with the risk of developing autoimmune diseases and whether the observed associations are modified by the CNV in CCL3L1 (CC chemokine ligand 3-like 1), a gene encoding a potent chemokine. In a cross-sectional study of 774 subjects, we estimated FCGR3B and CCL3L1 gene copy number in 146, 158 and 61 subjects with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and primary Sjögren's syndrome (SS), respectively, and 409 healthy controls. The median gene dose of FCGR3B in the study population was two. FCGR3B copy number < or >2 was associated with an increased risk of SLE and primary SS but not RA. This association was mostly evident in subjects who also had two copies of CCL3L1. Thus, our data suggest that epistatic interactions between CNV of FCGR3B and CCL3L1, two immune response genes, may influence phenotypically related autoimmune diseases.

Value of chest radiography in predicting treatment response in children aged 3-59 months with severe pneumonia.

SETTING: International multicentric study at nine tertiary care centres. OBJECTIVE: The World Health Organization (WHO) currently does not recommend chest radiographs (CXRs) for routine management of pneumonia. We evaluated the use of CXR for the prediction of treatment failure in children with severe pneumonia. DESIGN: We used WHO vaccine trials radiographic assessment, clinical and nasopharyngeal microbiological data from 1121 3-59-month-old children recruited using the WHO definition of severe pneumonia in the Amoxicillin Penicillin Pneumonia International Study (APPIS). Using Poisson regression, we estimated the relative risk of developing clinical treatment failure and predictive preventive benefit of the CXR and examined the concordance of the CXR findings with the nasopharyngeal microbiological data. RESULTS: A CXR with 'significant pathology' (defined by the WHO algorithm as end-point consolidation, pleural fluid and other infiltrates) was associated with a high risk of treatment failure, especially in children who received penicillin as compared to oral amoxicillin. Significant pathology was also associated with nasopharyngeal isolation of penicillin-resistant Streptococcus pneumoniae. Children with a normal CXR had a reduced risk of clinical treatment failure. CONCLUSIONS: CXR with significant pathology independently and additively predicts clinical treatment failure. If CXR and the WHO tool are available, they can be used in the management of severe pneumonia.

Use of the QuantiFERON-TB Gold In-Tube test to monitor treatment efficacy in active pulmonary tuberculosis.

SETTING: Cohort study at a tertiary care hospital. OBJECTIVE: To assess the potential use of QuantiFERON-TB Gold In-Tube (QFT-G) in monitoring clinical response to anti-tuberculosis treatment. DESIGN: We conducted a cohort study of 76 active pulmonary tuberculosis patients with serial testing by QFT-G at baseline and after 2 and 6 months of treatment. At these time points, we compared the performance of QFT-G with sputum culture status of the study subjects. RESULTS: Compared to baseline, 59 (77.6%) cases showed a decline whereas 17 (22.4%) showed persistent or stronger interferon-gamma (IFN-gamma) responses at 2 months. Using robust statistical methods, we observed that QFT-G assessment at 2 months independently and significantly predicted the likelihood of remaining sputum culture-positive at the end of the intensive phase of anti-tuberculosis treatment. A higher IFN-gamma concentration by 1 international unit (IU)/ml corresponded to a 45% (95%CI 8-97) higher likelihood of failing to convert to a negative culture, whereas a rising or persistent IFN-gamma response was associated with a 17.3 (P = 0.007) times higher likelihood of remaining culture-positive at 2 months. CONCLUSIONS: Our results suggest that QFT-G can potentially be used as a tool to monitor the efficacy of anti-tuberculosis treatment.

A randomised controlled trial of high-dose isoniazid adjuvant therapy for multidrug-resistant tuberculosis.

SETTING: Tertiary care hospital in Kanpur, India. BACKGROUND: The need for a standardised treatment protocol for multidrug-resistant tuberculosis (MDR-TB) in resource-limited countries is being increasingly recognised. OBJECTIVE: To assess the effectiveness of high-dose isoniazid (INH) (16-18 mg/kg) adjuvant to second-line therapy in documented cases of MDR-TB. DESIGN: The present study is a double blind, randomised controlled trial with three treatment arms, high-dose INH, normal-dose INH and placebo, in addition to second-line drugs. Primary outcomes of the study were time to sputum culture conversion and proportion with sputum culture negative 6 months after treatment initiation. Secondary outcomes were radiological improvement at 1 year post treatment and development of toxicity. RESULTS: After adjustment for potential confounders, subjects who received high-dose INH became sputum-negative 2.38 times (95%CI 1.45-3.91, P = 0.001) more rapidly than those who did not receive it, and had a 2.37 times (95%CI 1.46-3.84, P < 0.001) higher likelihood of being sputum-negative at 6 months. These subjects showed significantly better radiological improvement without an increased risk of INH toxicity. CONCLUSION: In low-resource scenarios where a standardised therapeutic protocol is used for MDR-TB, the protocol can be significantly improved by including high-dose INH as an adjuvant.

CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus.

OBJECTIVES: There is an enrichment of immune response genes that are subject to copy number variations (CNVs). However, there is limited understanding of their impact on susceptibility to human diseases. CC chemokine ligand 3 like-1 (CCL3L1) is a potent ligand for the HIV coreceptor, CC chemokine receptor 5 (CCR5), and we have demonstrated previously an association between CCL3L1-gene containing segmental duplications and polymorphisms in CCR5 and HIV/AIDS susceptibility. Here, we determined the association between these genetic variations and risk of developing systemic lupus erythaematosus (SLE), differential recruitment of CD3+ and CD68+ leukocytes to the kidney, clinical severity of SLE reflected by autoantibody titres and the risk of renal complications in SLE. METHODS: We genotyped 1084 subjects (469 cases of SLE and 615 matched controls with no autoimmune disease) from three geographically distinct cohorts for variations in CCL3L1 and CCR5. RESULTS: Deviation from the average copy number of CCL3L1 found in European populations increased the risk of SLE and modified the SLE-influencing effects of CCR5 haplotypes. The CCR5 human haplogroup (HH)E and CCR5-Delta32-bearing HHG*2 haplotypes were associated with an increased risk of developing SLE. An individual's CCL3L1-CCR5 genotype strongly predicted the overall risk of SLE, high autoantibody titres, and lupus nephritis as well as the differential recruitment of leukocytes in subjects with lupus nephritis. The CCR5 HHE/HHG*2 genotype was associated with the maximal risk of developing SLE. CONCLUSION: CCR5 haplotypes HHE and HHG*2 strongly influence the risk of SLE. The copy number of CCL3L1 influences risk of SLE and modifies the SLE-influencing effects associated with CCR5 genotypes. These findings implicate a key role of the CCL3L1-CCR5 axis in the pathogenesis of SLE.

Prevalence of beta-thalassaemia in subcastes of Indian Sindhis: Results from a two-phase survey.

OBJECTIVE: To estimate the prevalence of beta-thalassaemia in different subcastes of the Indian Sindhi population who, in general, have a high prevalence of this disease. STUDY DESIGN: A two-phase, community-based survey. METHODS: Asymptomatic, Sindhi volunteers from Nagpur, central India, were recruited into the present study over a 7-year period. The first phase included the use of the Naked Eye Single Tube Red cell Osmotic Fragility Test (NESTROFT). Those positive for NESTROFT or those volunteering for haemoglobin A(2) (HbA(2)) quantification entered the second phase of the survey. Appropriate statistical methods for estimating prevalence from two-phase surveys were used. RESULTS: The prevalence of beta-thalassaemia carriers across the five major Sindhi subcastes varied substantially in the study population. Larkana Sindhis had the highest (17%) whereas Dadu Sindhis had the lowest (8%) frequency of the beta-thalassaemia allele. As a corollary, the projected incidence of beta-thalassaemia major in newborn babies greatly varied by the subcastes of the parents. CONCLUSION: Ethnic subgroups within populations known to commonly carry the beta-thalassaemia gene provide further information that is useful from epidemiological and public health perspectives.

Radioactivity studies along fracture zones in areas around Galudih, East Singhbhum, Jharkhand, India.

The application of radon to delineate geological processes like faulting and deformation, groundwater flow and contamination have assumed considerable significance over the last decade due to low-level detection capabilities and long-distance time migration. Suitable modeling procedures have helped in quantification of radon emanation and migration along active and passive faults. In the present study, we have attempted to correlate the radionuclide content and the extent of fracturing. For this purpose, quartzites occurring around Galudih, Jharkhand State, India, have been investigated. The study includes fracture density measurements at selected outcrops and joint analyses to evaluate the relationship between radionuclides and mesoscopic fractures. Moreover, microstructural studies have also been performed to decipher any existing relationship between radionuclides and microscale deformation mechanisms. It has been found that the microstructural phenomena are more important than mesoscopic scale processes and the former controls the concentration of radionuclides in rocks.