Genetic Variants Associated with the Risk of Stroke in Sickle Cell Anemia: Systematic Review and Meta-Analysis.

Sickle cell anemia (SCA) is the most common cause of stroke in children. As it is a rare disease, studies investigating the association with complications like stroke in SCD have small sample sizes. Here, we performed a systematic review and meta-analysis of the studies exploring an association of genetic variants with stroke to get a better indication of their association with stroke. PubMed and Google Scholar were searched to identify studies that had performed an association analysis of genetic variants for the risk of stroke in SCA patients. After screening of eligible studies, summary statistics of association analysis with stroke and other general information were extracted. Meta-analysis was performed using the fixed effect method on the tool METAL and forest plots were plotted using the R program. The random effect model was performed as a sensitivity analysis for loci where significant heterogeneity was observed. 407 studies were identified using the search term and after screening 37 studies that cumulatively analyzed 11,373 SCA patients were included. These 37 studies included a total of 2,222 SCA patients with stroke, predominantly included individuals of African ancestry (N = 16). Three of these studies performed whole exome sequencing while 35 performed single nucleotide-based genotyping. Though the studies reported association with 132 loci, meta-analyses could be performed only for 12 loci that had data from two or more studies. After meta-analysis we observed that four loci were significantly associated with risk for stroke: -α3.7 kb Alpha-thalassemia deletion (P = 0.00000027), rs489347-TEK (P = 0.00081), rs2238432-ADCY9 (P = 0.00085), rs11853426-ANXA2 (P = 0.0034), and rs1800629-TNF (P = 0.0003396). Ethnic representation of regions with a high prevalence of SCD like the Mediterranean basin and India needs to be improved for genetic studies on associated complications like stroke. Larger genome-wide collaborative studies on SCD and associated complications including stroke need to be performed.

Computed tomography severity score as a predictor of disease severity and mortality in COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND: Prediction of outcomes in severe COVID-19 patients using chest computed tomography severity score (CTSS) may enable more effective clinical management and early, timely ICU admission. We conducted a systematic review and meta-analysis to determine the predictive accuracy of the CTSS for disease severity and mortality in severe COVID-19 subjects. METHODS: The electronic databases PubMed, Google Scholar, Web of Science, and the Cochrane Library were searched to find eligible studies that investigated the impact of CTSS on disease severity and mortality in COVID-19 patients between 7 January 2020 and 15 June 2021. Two independent authors looked into the risk of bias using the Quality in Prognosis Studies (QUIPS) tool. RESULTS: Seventeen studies involving 2788 patients reported the predictive value of CTSS for disease severity. The pooled sensitivity, specificity, and summary area under the curve (sAUC) of CTSS were 0.85 (95% CI 0.78-0.90, I2 =83), 0.86 (95% CI 0.76-0.92, I2 =96) and 0.91 (95% CI 0.89-0.94), respectively. Six studies involving 1403 patients reported the predictive values of CTSS for COVID-19 mortality. The pooled sensitivity, specificity, and sAUC of CTSS were 0.77 (95% CI 0.69-0.83, I2 = 41), 0.79 (95% CI 0.72-0.85, I2 = 88), and 0.84 (95% CI 0.81-0.87), respectively. DISCUSSION: Early prediction of prognosis is needed to deliver the better care to patients and stratify them as soon as possible. Because different CTSS thresholds have been reported in various studies, clinicians are still determining whether CTSS thresholds should be used to define disease severity and predict prognosis. CONCLUSION: Early prediction of prognosis is needed to deliver optimal care and timely stratification of patients.  CTSS has strong discriminating power for the prediction of disease severity and mortality in patients with COVID-19.

A Comparative Study of Sublingual Misoprostol Versus Intramuscular Oxytocin in the Active Management of Third Stage of Labor.

Objective Misoprostol has attracted low-income low-resource countries for the active management of the third stage of labor. The objective of this study was to compare the efficacy of sublingual misoprostol and intramuscular oxytocin in the active management of the third stage of labor. Study design This was a prospective randomized controlled trial in which a total of 407 healthy pregnant women having singleton pregnancy, cephalic presentation, and normal vaginal delivery were divided into two groups. In the first group (n=203), women received 600 µg misoprostol tablet sublingually, and in the second group (n=204), women received 10 IU of intramuscular oxytocin, within 1 minute of the delivery of the baby during the third stage of labor. Three patients from the first group and four patients from the second group were excluded from the analysis due to traumatic postpartum hemorrhage (PPH). The primary outcome was an incidence of PPH. Secondary outcomes were the duration of the third stage of labor, amount of blood loss, fall in hemoglobin concentration after 48 hours of delivery, need for additional uterotonics, and side effects of the drugs. Data were compared using the chi-square and independent samples t-test. Results The incidence of PPH was 6.5% in the misoprostol group as compared to 2% in the oxytocin group (p=0.026). The misoprostol group also had significantly higher blood loss (293.75±125.8 mL) and a greater fall in hemoglobin level (0.58±0.25 g/dL) as compared to that in the oxytocin group (226.13±98.44 mL and 0.45±0.20 g/dL) (p<0.001). The mean duration of the third stage of labor was significantly higher in the misoprostol group (5.31±2.1 min) as compared to that in the oxytocin group (3.65±1.75 min) (p<0.001). The additional need for uterotonics was recorded in 15% of the study participants in the misoprostol group as compared to 8% in the oxytocin group (p=0.028). The incidence of side effects such as shivering and fever was significantly higher in the misoprostol group as compared to the oxytocin group. No significant difference between the two groups was observed concerning the incidence of nausea, vomiting, diarrhea, and headache. Conclusion Intramuscular oxytocin is a safe and useful alternative to sublingual misoprostol in facilitating the third stage of labor with minimal blood loss, fewer incidences of hemorrhage, and fewer adverse effects.

Drivers for COVID 19 vaccine hesitancy among breastfeeding women in Eastern tribal state, India.

Background: In the COVID-19 pandemic age, vaccination hesitancy also known as vaccine refusal is a cause for worry since it hinges on the five Cs of confidence, complacency, convenience, calculation, and shared responsibility. The current study was to pinpoint the elements that contribute to breastfeeding women's hesitation to receive the coronavirus disease-19 (COVID-19) vaccine. Materials and Methods: A cross-sectional observational study was carried out at the Department of Obstetrics and Gynaecology, Tertiary Care Hospital, Ranchi, Jharkhand. Result: Out of 365 nursing mothers, 242 (66.3%) were hesitant to get the COVID-19 vaccination. Those who chose not to receive the COVID-19 vaccination mostly belong to those aged 18 to 25 (38.1%), living in rural regions (44.9%), and belonging to non-tribal ethnic groups (41.1%). On application of logistic regression, it was found that rural areas had 3 times higher rate of vaccine hesitancy than urban residents, and that husbands' education levels up to the 12th grade had a 3.55 times higher rate and 5 times agriculture by husband's occupation, which was statistically significant (P value less than 0.05) The most prevalent grounds for rejection were fear of side effects (85.8%) and worry of adverse effects on newborns (83.48%). Conclusion: Both husband and wife, who had completed high school and were aware of the vaccination, were fearful of the COVID-19 vaccine. Concerns about the side effects and undesirable effects of vaccination on their newborns were the main reasons for refusal.

Procalcitonin as a predictive marker in COVID-19: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 has emerged as a global pandemic causing millions of critical cases and deaths. Early identification of at-risk patients is crucial for planning triage and treatment strategies. METHODS AND FINDINGS: We performed this systematic review and meta-analysis to determine the pooled prognostic significance of procalcitonin in predicting mortality and severity in patients with COVID-19 using a robust methodology and clear clinical implications. DESIGN: We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane Handbook for Systematic Reviews of Interventions guidelines. We included thirty-two prospective and retrospective cohort studies involving 13,154 patients. RESULTS: The diagnostic odds ratio of procalcitonin for predicting mortality were estimated to be 11 (95% CI: 7 to 17) with sensitivity, specificity, and summary area under the curveof 0.83 (95% CI: 0.70 to 0.91), 0.69 (95% CI: 0.58 to 0.79), and 0.83 (95% CI: 0.79 to 0.86) respectively. While for identifying severe cases of COVID-19, the odds ratio was 8.0 (95% CI 5.0 to 12.0) with sensitivity, specificity, and summary area under the curve of 0.73 (95% CI 0.67 to 0.78), 0.74 (0.66 to 0.81), and 0.78 (95% CI 0.74 to 0.82) respectively. CONCLUSION: Procalcitonin has good discriminatory power for predicting mortality and disease severity in COVID-19 patients. Therefore, procalcitonin measurement may help identify potentially severe cases and thus decrease mortality by offering early aggressive treatment.

Updated meta-analysis on the diagnostic accuracy of serum anti-Mullerian hormone in poly cystic ovary syndrome involving 13 509 subjects.

AIM: To determine the diagnostic accuracy of anti-Mullerian hormone (AMH) in the diagnosis of polycystic ovary syndrome (PCOS). METHODS: Two independent reviewers searched the electronic databases and search engines using PubMed, Cochrane library, and Google Scholar systematically to retrieve relevant articles published from inception to September 2021. The diagnostic efficacy of AMH was computed using the random-effects model in terms of pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence interval (CI). A meta-regression and subgroup analysis were performed to check for any source which could explain possible heterogeneity. Risk of bias assessment was conducted using the QUADAS-2 tool recommended by Cochrane Library. RESULTS: This meta-analysis included a total of 41 studies involving 13 509 subjects. We observed promising pooled sensitivity 0.78 (95% CI 0.74 to 0.81), specificity 0.87 (95% CI 0.84 to 0.90), and diagnostic odds ratio (DOR) 24 (95% CI 15 to 37), for AMH in detecting PCOS and discriminatory power (summary receiver operating characteristic [SROC] curves, 0.89 [95% CI 0.86-0.92]). The most prominent bias was noted in the patient selection and index test assessment. CONCLUSIONS: With the findings of this current meta-analysis, we conclude serum AMH to be a promising biomarker for the diagnosis of PCOS, however, substantial heterogeneity among studies needs individual patient data analysis in order to identify an optimal cut-off value and homogenous findings. REGISTRATION NUMBER AND GUIDELINES: This meta-analysis was performed according to constructed protocol registered in the PROSPERO database with registration number CRD42021246910.

Aminoacid Profiling of Children with Severe Acute Malnutrition Pre and Post Nutritional Rehabilitation.

Malnutrition is a significant comorbidity in nearly one-third of the 8 million deaths in children under five years of age worldwide. Children with severe acute malnutrition have severely disturbed physiology and metabolism. Considering the vital importance of amino acids and the likely changes with the therapeutic diet, we aimed at evaluating these changes in children with SAM at baseline and after rehabilitation with a therapeutic diet at 14 days. Severe acute malnutrition defined as per WHO, for children between 6 months and 5 years with weight for height/length < -3SD of WHO charts, bilateral pitting edema, and mid-upper arm circumference (MUAC) < 1.5 cm. A total of 38 children were enrolled as cases, whereas the control group comprised of 37 children. Anthropometric measurement and estimation of amino acids in the blood were done at the baseline and after dietary rehabilitation. The individual levels of the essential and non-essential amino acids were significantly lower in the cases as compared to the controls, except for Aspartate and Threonine. The levels of amino acids increased significantly after dietary rehabilitation except for arginine, however not to the levels of those in controls. Most of the metabolites were reflective of maladaptation in SAM. Though nutritional rehabilitation of children with SAM improved the levels of amino acids, these levels were still low when compared to the controls, stipulating that complete metabolic recovery may take a longer duration of time. This necessitates the continuation of nutritional rehabilitation for a longer time and regular follow up of these children to ensure better compliance.

Study of platelet indices and their role in evaluation of thrombocytopenia.

Background: Thrombocytopenia may result from mechanisms such as marrow hypoplasia, increased destruction of platelets, and splenic sequestration. The gold standard method for discriminating the causes of thrombocytopenia is bone marrow examination, but it is invasive and expensive. Therefore, an alternative method should be introduced as a first-line diagnostic procedure. Of late, the automated blood cell analyzer has made it possible to assess the cause of thrombocytopenia through various machine-derived parameters, known as platelet indices, which include the mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT), which are provided as a part of routine complete blood count. Objectives: The objectives of the present study are to study the variation and effectiveness of platelet indices in establishing the etiology of thrombocytopenia. Method: An observational, prospective, and comparative study was conducted on 134 patients with thrombocytopenia, and 67 cases were taken as the normal group. The study group was classified into two groups: hypo-productive and hyper-destructive. Platelet indices were recorded and compared in the two groups along with the normal group. Results: The mean platelet count (10^3 µL) in the normal, hypo-productive, and hyper-destructive groups was 232.03 ± 74.84, 73.00 ± 36.52, and 68.28 ± 38.24, respectively. The MPV and mean PCT in the normal, hypo-productive, and hyper-destructive groups were 9.46 ± 1.68fL, 8.99 ± 1.49fL, and 11.35 ± 1.35fL and 0.22 ± 0.06%, 0.07 ± 0.04%, and 0.08 ± 0.05%, respectively. The mean PDW in the normal, hypo-productive, and hyper-destructive groups was 15.66 ± 1.76fL, 17.63 ± 1.01fL, and 18.32 ± 1.10fL, respectively. Conclusion: In the present study, platelet indices such as MPV, PCT, and PDW are higher in the hyper-destructive group and may discriminate hyper-destructive from hypo-productive causes of thrombocytopenia.

Evaluation of the Utility of Amino Acid Citrulline as a Surrogate Metabolomic Biomarker for the Diagnosis of Celiac Disease.

INTRODUCTION: Citrulline is regarded as a biomarker for celiac disease (CD). Its utility for assessment and evaluation of additive predictive value for latent, potential CD and first degree relatives (FDRs) needs exploration. METHOD: Consecutive 558 index cases diagnosed as per European Society for Pediatric Gastroenterology and Nutrition (ESPGHAN) 2012 guidelines and their 1565 FDRs were evaluated over five and half year period. Serology negative FDRs at initial visit and follow ups were served as controls. HLA typing for DQ2 and DQ8 genotypes, along with plasma and dried blood spot (DBS) filter paper citrulline were evaluated. RESULTS: Median plasma citrulline values were 20.1 and 37.33 µMol/l in cases and controls (P < .001). Cut off values for Marsh grade 3a, 3b, and 3c were 35.0, 32.8, 25.26 µMol/l in CD patients and 36.51, 30.10, 25.26 µMol/l in biopsy proven FDR. Increasing trends of plasma citrulline levels with decreasing tTG-IgA levels were observed on follow up. Low plasma citrulline levels were observed with HLA DQ 2.5 genotype (P < .05). Agreement between DBS and plasma citrulline was 94.8%. CONCLUSION: Citrulline is a good surrogate biomarker for identification of histopathological grade of damage, extent of mucosal recovery and has negative correlation with tTG-IgA. It identifies the silent and latent phase of CD. DBS citrulline provides adequate information and can be used for monitoring CD patients at remote locations.

Lack of Association between Poor Glycemic Control in T2DM and Subclinical Hypothyroidism.

BACKGROUND: Hypothyroidism is a highly prevalent and multifactorial disorder and has been implicated in the causation of dyslipidemia, dermatological diseases, atherosclerosis, and myocardial dysfunction, as well as endothelial dysfunction. The relationship between subclinical hypothyroidism and type 2 diabetes mellitus is not well established. In the present study, we attempt to find out the prevalence of subclinical hypothyroidism in type 2 diabetes mellitus and its association with glycemic control. MATERIALS AND METHODS: This was an observational study in which 205 consecutive patients of T2DM visiting the outpatient department of medicine were recruited. Serum TSH, free thyroxine, free triiodothyronine, and lipid profile, as well as HbA1c assays, were done in the study participants, and they were categorized into three groups by HbA1c: <7%, 7-9%, and >9%. RESULTS: There is a high prevalence of subclinical hypothyroidism in type 2 DM patients. Mean HbA1c in diabetics without SCH was 7.89%, whereas it was 8.33% in diabetics with SCH. This difference was statistically not significant. TSH was not found to be significantly associated with HbA1c. CONCLUSION: High prevalence of SCH in T2DM patients suggests that there is a need for regular follow-up to check the progression of SCH to overt hypothyroidism. High serum TSH is not a predictor of poor glycemic control.