Alcohol state markers- facility and utility for clinical management of alcohol use disorders: study from a tertiary care centre in South India

Background: Alcoholism is broadly any drinking of alcohol resulting in significant psychological and physiological health problems. As alcoholism is not a recognized diagnostic entity the detection and monitoring of the clinical manifestations of alcoholism is of great importance in the alcohol use disorders (AUD) treatment. Hence, the use of alcohol biomarkers plays a vital role in the diagnosis, treatment and prognosis of AUDs.Methods: This study aimed to understand the utility of state markers in alcohol related distress, both for diagnosis and prognosis in a tertiary care centre. The relative number and the frequency of the alcohol biomarker tests such as AST (aspartate aminotransferase), ALT (alanine aminotransferase), MCV (mean corpuscular volume) and GGT (gamma-glutamyl transferase) investigated in the hospital departments (32 departments) were collected. Test requests and results in January to March on five consecutive years from 2016 to 2020 were analyzed, by comparing psychiatry department with all other departments and AUD with non-AUD cases.Results: The study findings revealed that, the tests AST, ALT and MCV were well utilized for the AUD treatment procedure in the tertiary care centre, irrespective of the department the patient got admitted. Since GGT was the least preferred test, the figures of GGT could not be analysed because of the exceptionally low number.Conclusions: The utility of the commonly available alcohol biomarker tests is especially useful for the clinical management of AUD patients and these are well utilized in an appreciable manner in the study centre. Development of more accurate, specific, and sensitive panel of biomarker tests may further motivate clinicians to better monitor individuals who suffer from alcoholism

Assessment of knowledge and awareness among the pregnant women about their medication use in a tertiary care hospital

Background: Pregnancy is a physiological state where drug therapy is of particular concern. The pertinent use of drugs during pregnancy is beneficial as it affects not only the health of the pregnant woman but also the developing fetus. The study was carried out to access the knowledge and awareness regarding the drug use among pregnant women.Methods: Cross sectional descriptive study was conducted among 150 pregnant women for six-month duration. All the information was acquired through direct interview with the subjects and from treatment chart of subjects which were then recorded in a data collection form.Results: Majority of the subjects were under the age group of 18-28 years (50%). Most of the subjects predominantly has tertiary level of education (69%). Furthermore, 57% of the subjects were at the third trimester of their pregnancy. Knowledge regarding use of their own medications were significantly high (95%), which suggest that the subjects were well aware of their medications. Besides, 82% of the subjects had knowledge about the medications that were not to be consumed during pregnancy. In addition, 89% of the pregnant women did not take any over the counter medications and about 92% of the subjects did not treat themselves with any ayurvedic or homeopathic medications.Conclusions: Significant number of subjects were aware about their medication use. They ensured themselves and their developing fetus a better health.

Public Health Service Project Py 71-1, National Institutes of Health Projects HE 11829 and HE 12536

SUMMARY Entrance block of an atrial premature beat (APB) into the atrioventricular node is demonstrated by its lack of effect on the A-V nodal conduction of a subsequent beat which is introduced before the full recovery time of the A-V node. This phenomenon was demonstrated in five patients by using programmed atrial stimulation and His bundle recordings. Entrance block into the A-V node occurred in a narrow range (28-33%) of the basic cycle length and concealed conduction occurred at coupling intervals longer than this range. It appears that entrance block of these early APBs is due to a "functional block" between the atrium and the A-V node

Performance and genetic assessment of rubber tree clones in Southern Thailand

Thailand is the world leader in the production of latex extracted from the rubber tree (Hevea brasiliensis). However, the most cultivated clone RRIM 600, is highly susceptible to diseases, and there is economic incentive to develop new rubber tree clones. Four rubber tree clones (T2, SK1, NK1 and SK3) that have high latex yield potential from plantations in Southern Thailand were selected for this study. Yield performance, latex biochemical parameters and anatomical characteristics of bark were monitored for two years, using RRIM 600 clones in the same fields as paired controls. The average yields of the clones SK1, NK1 and SK3 were 129.3, 74.2 and 53.9 g per tree per tapping, respectively, surpassing the paired RRIM 600 controls (94.3, 49.9 and 43.9 g per tree per tapping in matching order). There was a difference in girth increment of SK1, SK3 and T2 clones when compared with RRIM 600, whereas the clones SK1 and T2 had higher renewed bark thickness than the paired RRIM 600. The anatomical measurements showed that the diameter of the latex vessels and density of latex vessels mm−2 were the highest in clone NK1, which also had the best latex biochemical parameters. This indicates NK1 is superior, and supports its use in Hevea breeding programs to improve latex yield. Our genetic characterization and assessment of the four clones selected used Random Amplified Polymorphic DNA (RAPD) and Simple Sequence Repeats (SSR). Seventeen recommended rubber clones were included as references. The clones SK3 and SK1 were closely related to RRIM 600 with similarity coefficients of 0.891 and 0.809, while NK1 and T2 were closely related to RRIT 250 (0.836) and RRIC 110 (0.864), respectively

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years