Effects of almond consumption compared with the consumption of traditional isocaloric cereal/pulse-based snacks on glycaemic control and gut health in adults with pre-diabetes in rural India: protocol for a 16-week, parallel-arm, cluster randomised controlled trial.

INTRODUCTION: Almonds have prebiotic potential to maintain gut health and regulate glycaemia. Western studies have shown their positive effects on preventing non-communicable diseases like diabetes and cardiovascular diseases. However, there is a lack of research involving Asian Indians, who have a higher predisposition to diabetes due to their unique 'Asian phenotype'. Therefore, this study aims to evaluate the impact of almond supplementation on glycaemic control and gut health in adults with pre-diabetes in rural India through a randomised clinical trial. METHODS AND ANALYSIS: A parallel cluster randomised controlled trial with 178 participants with pre-diabetes (assigned 1:1) aged 20-50 years, of both genders, with a body mass index of 18.9-25 kg/m2, will be conducted in rural areas of Chikkaballapur, Kolar and Rural Bangalore districts in India. The intervention group will receive 56 g of almonds as mid-morning snacks for 16 weeks, while the control group will receive cereal/pulse-based traditional isocaloric snacks under the closed supervision of the study investigators. The primary outcome of the study is HbA1c measured at the 16th week. The secondary outcomes-anthropometry, clinical and other biochemical parameters-will be measured at 0th, 8th and 16th weeks, and a subgroup of 120 participants will undergo gut health analysis. Glucagon-like peptide 1 analysis will be conducted on 30 participants at 0th and 16th weeks. Statistical analysis will be performed using SPSS for Windows V.27.0, and both intention-to-treat and per-protocol analyses will be conducted. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Institutional Ethics Committee at Ramaiah Medical College, Bangalore, Karnataka, India (DRPEFP7672021). We will obtain the informed written consent of the participants prior to screening and enrolling them in the study. Results from this trial will be disseminated through publication in peer-reviewed journals and scientific gatherings. TRIAL REGISTRATION NUMBER: Clinical Trial Registry of India (CTRI/2023/03/050421).

Feeding styles and adiposity in children of 6 months- 5 years of age: Protocol for a systematic review and meta- analysis.

Obesity in children is a major public health concern due to the increased risk of developing adverse health outcomes in their future, and disability in adulthood. The existing systematic reviews on the topic are limited in scope, focusing solely on high-income countries and children aged 4-12 years. Hence, we propose to conduct a systematic review and meta-analysis to understand, how exposure to authoritative feeding style versus authoritarian, indulgent, uninvolved compare in terms of its association with adiposity in children aged 6 months to 5 years. Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines were followed for ensuring the completeness of the protocol. Case-control and cohort studies will be included. Searches will be done using electronic databases viz. PubMed, Ovid EMBASE, PsycINFO and Web of Science. Grey literature will be searched using OpenGrey and Grey Literature Report. We will only include quantitative studies using the developed search strategy. For categorical outcomes, relative risks, odds ratios, and hazard ratios with confidence intervals and for continuous outcomes mean difference with confidence intervals will be used. Risk of Bias In Non-randomized Studies- of Exposure (ROBINS-E) will be used for the evaluation of risk of bias in the individual observational studies. Considering the inherent variability in the observational studies, random effects meta-analysis will also be conducted. If between-study heterogeneity exists, a subgroup analysis based on low and middle-income countries vs. high income countries will be conducted. If the data is not suitable for combining quantitatively, a narrative synthesis will be undertaken. We propose to identify publication bias by using contour-enhanced funnel plots and "trim and fill" method. Outcome reporting bias will be ascertained by comparing the outcomes published in the protocol and the published report. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system will be used to understand the confidence we can have on the effect estimates. Registration: This protocol has been registered in International Prospective Register of Systematic Reviews (PROSPERO) on 13 March 2023 with registration number CRD42023356014.

External validation of prediction models for vaginal delivery after the trial of labour among women with previous one caesarean section - A cohort study.

OBJECTIVE: To externally validate three predictive models (the Grobman model (2007), the Zhang model (2020), and the Grobman model (2021)) for identifying women with increased chances of a successful trial of labour after caesarean section (TOLAC). METHODS: This retrospective observational cohort study was conducted in a tertiary teaching hospital from 2018 to 2021. Individual probabilities were calculated for women with previous one caesarean section who underwent TOLAC at term, using the predicted probabilities from the logistic regression models. The primary outcome of this study was vaginal delivery following attempted TOLAC. The predictive ability of the models was assessed using the area under the receiver operative characteristics curves (AUC) and a calibration graph. RESULTS: Of 1515 eligible women who underwent TOLAC, we found an overall rate of successful TOLAC of 60.3 %. No significant difference was noticed in adverse scar outcome and neonatal morbidity while comparing successful and failed TOLAC. The discriminative ability of Grobman-2007 and Grobman-2021 and the Zhang model were fair to poor with the AUC of 0.54(95 % CI 0.51-0.57), 0.62(95 % CI 0.59-0.65) and 0.66(95 % CI 0.63-0.69) respectively. The agreement between the observed rates of TOLAC success and the predicted probabilities for all three models was poor. CONCLUSION: The performance of all three models predicting success after TOLAC was poor in the study population. A population-specific model may be needed, with the addition of factors influencing the labour, such as the methods of induction, which may aid in predicting the outcome.

Effects of Vitamin D on Migraine: A Meta-Analysis.

Objective: The aim of this study was to evaluate the difference in mean serum 25-hydroxy vitamin D level between migraineurs and nonmigraineurs, the association between hypovitaminosis D and migraine, and the effects of oral vitamin D supplementation on migraine-related symptoms as compared to placebo. Methods: Relevant databases were searched for observational studies and randomized-controlled trials (RCTs) which evaluated the difference in mean serum 25-hydroxy vitamin D level between migraineurs and nonmigraineurs; the association between hypovitaminosis D and migraine; and the effects of vitamin D supplementation on migraine-frequency, duration, and severity. Pooled mean difference and odds ratio were calculated (random-effects model, RevMan version 5.3). Results: Ten observational studies and two RCTs were included. The serum 25-hydroxy vitamin D level in the migraineurs was significantly lower than that in the nonmigraineurs [mean difference - 4.44 ng/mL (95% CI: -6.11, -2.77)] (low-GRADE evidence). Hypovitaminosis D was found to be significantly associated with migraine [OR: 1.95 (95% CI: 1.07, 3.58)] (low-GRADE evidence). As compared to placebo, oral vitamin D supplementation significantly reduced the monthly migraine-frequency [mean difference: -2.20 (95% CI: -3.04, -1.36)]. ,: although it did not reduce the migraine-duration [mean difference: -16.00 hours per month (95% CI: -42.77, 10.76)] and migraine-severity score [standardized mean difference: -0.23 (95% CI: -0.79, 0.32)] (moderate-GRADE evidence). Conclusion: Serum 25-hydroxy vitamin D level was significantly lower in the migraineurs than that in the nonmigraineurs, and hypovitaminosis D was significantly associated with migraine. Oral vitamin D supplementation significantly reduced migraine-frequency, but not its duration and severity.

Interventions for dialysis patients with hepatitis C virus (HCV) infection.

BACKGROUND: Hepatitis C virus (HCV) infection is common in chronic kidney disease (CKD) patients on dialysis, causes chronic liver disease, may increase the risk of death, and impacts kidney transplant outcomes. Direct-acting antivirals have replaced interferons because of better efficacy and tolerability. This is an update of a review first published in 2015. OBJECTIVES: We aimed to look at the benefits and harms of interventions for HCV in CKD patients on dialysis: death, disease relapse, treatment response/discontinuation, time to recovery, quality of life (QoL), cost-effectiveness, and adverse events. We aimed to study comparisons of available interventions, compared with placebo, control, with each other and with newer treatments. SEARCH METHODS: We searched the Cochrane Kidney and Transplant's Specialised Register to 23 February 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE and EMBASE, handsearching conference proceedings, and searching the International Clinical Trials Register Portal (ICTRP) and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs, first period of randomised cross-over studies on interventions for HCV in CKD on dialysis were considered. DATA COLLECTION AND ANALYSIS: Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Three studies were included in this update, therefore 13 studies (997 randomised participants) met our inclusion criteria. Overall, the risk of bias was judged low in seven studies, unclear in four, low to unclear in one, and high in one study. Interventions included standard interferon, pegylated (PEG) interferon, standard or PEG interferon plus ribavirin; direct-acting antivirals, and direct-acting antivirals plus PEG interferon plus ribavirin. Compared to placebo or control, standard interferon may make little or no difference to death (5 studies, 134 participants: RR 0.89, 95% CI 0.06 to 13.23) or relapse (low certainty evidence), probably improves end-of-treatment response (ETR) (5 studies, 132 participants: RR 8.62, 95% CI 3.03 to 24.55; I² = 0%) (moderate certainty evidence), and probably makes little or no difference to sustained virological response (SVR) (4 studies, 98 participants: RR 3.25, 95% CI 0.81 to 13.07; I² = 53%), treatment discontinuation (4 studies, 116 participants: RR 4.59, 95% CI 0.49 to 42.69; I² = 63%), and adverse events (5 studies, 143 participants: RR 3.56, 95% CI 0.98 to 13.01; I² = 25%) (moderate certainty evidence). In low certainty evidence, PEG interferon (1 study, 50 participants) may improve ETR (RR 1.53, 95% CI 1.09 to 2.15) but may make little or no difference to death (RR 0.33, 95% CI 0.01 to 7.81), SVR (RR 2.40, 95% CI 0.99 to 5.81), treatment discontinuation (RR 0.11, 95% CI 0.01 to 1.96), adverse events (RR 0.11, 95% CI 0.01 to 1.96) and relapses (21/38 relapsed) (RR 0.72, 95% CI 0.41 to 1.25) compared to standard interferon. In moderate certainty evidence, high-dose PEG interferon (alpha-2a and alpha-2b) may make little or no difference to death (2 studies, 97 participants: RR 4.30, 95% CI 0.76 to 24.33; I² = 0%), ETR (RR 1.42, 95% CI 0.51 to 3.90; I² = 20%), SVR (RR 1.19, 95% CI 0.68 to 2.07; I² = 0%), treatment discontinuation (RR 1.20, 95% CI 0.63 to 2.28; I² = 0%) or adverse events (RR 1.05, 95% CI 0.61 to 1.83; I² = 27%) compared to low-dose PEG interferon. High-dose PEG interferon may make little or no difference to relapses (1 study, 43 participants: RR 1.11, 95% CI 0.45 to 2.77; low certainty evidence). There were no significant subgroup differences. Standard interferon plus ribavirin may lead to higher treatment discontinuation (1 study, 52 participants: RR 2.97, 95% CI 1.19 to 7.36; low certainty evidence) compared to standard interferon alone.  In low certainty evidence, PEG interferon plus ribavirin (1 study, 377 participants) may improve SVR (RR 1.80, 95% CI 1.46 to 2.21), reduce relapses (RR 0.33, 95% CI 0.23 to 0.48), slightly increase the number with adverse events (RR 1.10, 95% CI 1.01 to 1.19), and may make little or no difference to ETR (RR 1.01, 95% CI 0.94 to 1.09) compared to PEG interferon alone. The evidence is very uncertain about the effect of PEG interferon plus ribavirin on treatment discontinuation (RR 1.71, 95% CI 0.69 to 4.24) compared to PEG interferon alone. One study reported grazoprevir plus elbasvir improved ETR (173 participants: RR 174.99, 95% CI 11.03 to 2775.78; low certainty evidence) compared to placebo. It is uncertain whether telaprevir plus ribavirin (high versus low initial dose) plus PEG interferon for 24 versus 48 weeks (1 study, 35 participants) improves ETR (RR 1.02, 95% CI 0.67 to 1.56) or SVR (RR 1.02, 95% CI 0.67 to 1.56) because the certainty of the evidence is very low.  Data on QoL, cost-effectiveness, cardiovascular outcomes and peritoneal dialysis were not available. AUTHORS' CONCLUSIONS: In dialysis patients with HCV infection grazoprevir plus elbasvir probably improves ETR. There is no difference in ETR or SVR for combinations of telaprevir, ribavirin and PEG interferon given for different durations and doses. Though no longer in use, PEG interferon was more effective than standard interferon for ETR but not SVR. Increasing doses of PEG interferon did not improve responses. The addition of ribavirin to PEG interferon may result in fewer relapses, higher SVR, and higher numbers with adverse events.

Comparison of diagnostic accuracy of models combining the renal biomarkers in predicting renal scarring in pediatric population with vesicoureteral reflux (VUR).

INTRODUCTION: Renal scarring is prominently observed in children with vesicoureteral reflux (VUR) and can lead to complicated renal outcomes. Although biopsy is the gold standard to detect renal scarring, it is an invasive procedure. There are established renal biomarkers which can help detect renal scarring. Individual biomarkers have not shown to have extensively good discriminatory ability for this. AIM: This paper aims at combining the values of multiple biomarkers in models to detect renal scarring. METHODOLOGY: Secondary data with the values of renal biomarkers like kidney injury molecule-1, neutrophil gelatinase-associated lipocalin (NGAL), and urinary creatinine along with the renal scarring status was considered. Logistic regression, discriminant analysis, Bayesian logistic regression, Naïve Bayes, and decision tree models were developed with these markers. The discriminatory ability of individual biomarkers along with the models was assessed using the area under the curve from ROC curve. Sensitivity, specificity, and misclassification rates were estimated and compared. RESULTS: NGAL was the most predominant renal biomarker in classifying the patients with renal scarring (AUC: 0.77 (0.67, 0.87); p value < 0.001). Each of the model performed better than individual biomarkers. Decision tree (AUC: 0.83 (0.74, 0.91); p value < 0.001) and Naïve Bayes model (misclassification rate = 20.2%) performed the best amongst the models. CONCLUSION: Combining the values of renal biomarkers through a statistical or machine learning model to detect renal scarring is a better approach as compared to considering individual renal biomarkers.

Maternal and perinatal outcome in pregnancies complicated with portal hypertension: a systematic review and meta-analysis.

BACKGROUND: Portal hypertension is secondary to either cirrhotic or non-cirrhotic causes, and complicating pregnancy poses a challenge to the treating team. A systematic review was performed to determine maternal and perinatal outcomes in women with portal hypertension. Outcomes were compared among those with cirrhotic (CPH) with non-cirrhotic portal hypertension (NCPH) as well as non-cirrhotic portal fibrosis (NCPF) with extra-hepatic portal vein obstruction (EHPVO). METHODS: Medline and EMBASE databases were searched for studies reporting outcomes among pregnant women with portal hypertension. Reference lists from relevant papers and reviews were hand-searched for appropriate citations. Data were extracted to describe maternal complications, obstetric and neonatal outcomes. A random-effects model was used to derive pooled estimates of various outcomes, and final estimates were reported as percentages with a 95% confidence interval (CI). Cumulative, sequential and sensitivity analysis was studied to assess the temporal trends of outcomes over the period. RESULTS: Information on 895 pregnancies among 581 patients with portal hypertension was included from 26 studies. Portal hypertension was diagnosed during pregnancy in 10% (95% CI 4-24%). There were 22 maternal deaths (0%, 95% CI 0-1%), mostly following complications from variceal bleeding or hepatic decompensation. Variceal bleeding complicated in 14% (95% CI 9-20%), and endoscopic interventions were performed in 12% (95% CI 8-17%) during pregnancy. Decompensation of liver function occurred in 7% (95% CI 3-12%). Thrombocytopenia was the most common complication (41%, 95% CI 23-60%). Miscarriages occurred in 14% (95% CI 8-20%), preterm birth in 27% (95% CI 19-37%), and low birth weights in 22% (95% CI 15-30%). Risk of postpartum hemorrhage was higher (RR 5.09, 95% CI 1.84-14.12), and variceal bleeding was lower (RR 0.51, 95% CI 0.30-0.86) among those with CPH compared to NCPH. Risk of various outcomes was comparable between NCPF and EHPVO. CONCLUSION: One in ten pregnancies complicated with portal hypertension is diagnosed during pregnancy, and thrombocytopenia is the most common complication. Hepatic decompensation and variceal bleeding remain the most common cause of maternal deaths, with reduced rates of bleeding and its complications reported following the introduction of endoscopic procedures during pregnancy. CPH increases the risk of postpartum hemorrhage, whereas variceal bleeding is higher among NCPH.

Efficacy of pharmacological interventions in COVID-19: A network meta-analysis.

AIMS: To perform network meta-analysis for a head-to-head comparison of various interventions used in coronavirus disease 2019 (COVID-19) on mortality, clinical recovery, time to clinical improvement and the occurrence of serious adverse events. METHODS: Systematic search was performed using online databases with suitable MeSH terms including coronavirus, COVID-19, randomized controlled trial, hydroxychloroquine, lopinavir/ritonavir, tocilizumab, remdesivir, favipiravir, dexamethasone and interferon-ß. Data were independently extracted by 2 study investigators and analysed. RESULTS: Out of 1225 studies screened, 23 were included for qualitative and quantitative analysis. Among the drugs studied, dexamethasone reduces mortality by 10%, with a relative risk of 0.90 (95% confidence interval [0.82-0.97]) and increases clinical recovery by 6% (relative risk 1.06, 95% confidence interval [1.02-1.10]) compared to standard of care. Similarly, remdesivir administered for 10 days increased clinical recovery by 10%, reduced time to clinical improvement by 4 days and lowered the occurrence of serious adverse events by 27% as compared to standard of care. CONCLUSION: In comparison to standard of care, dexamethasone was found to increase clinical recovery and lower mortality; remdesivir was significantly associated with a lower risk of mortality as compared to tocilizumab and higher clinical recovery and shorter time to clinical improvement as compared to hydroxychloroquine and tocilizumab; remdesivir followed by tocilizumab were found to have lesser occurrence of serious adverse events in patients with moderate to severe COVID-19.

Factors Associated With Neonatal Pneumonia and its Mortality in India: A Systematic Review and Meta-Analysis.

BACKGROUND: Neonatal pneumonia remains a significant contributor to infant mortality in India and responsible for increased prevalence of infant deaths globally. OBJECTIVE: To identify risk factors associated with neonatal pneumonia and its mortality in India. STUDY DESIGN: A systematic review was conducted including both analytic study designs and descriptive study designs, which reported a quantitative analysis of factors associated with all the three types of pneumonia among neonates. The search was conducted from August to December, 2016 on the following databases; CINAHL, EMBASE, Ovid MEDLINE, PubMed, ProQuest, SCOPUS, Web of Science, WHO IMSEAR and IndMED. The search was restricted to Indian setting. PARTICIPANTS: The population of interest was neonates. OUTCOMES: The outcome measures included risk factors for incidences and mortality predictors of neonatal pneumonia. These could be related to neonate, maternal and pregnancy, caregiver, family, environment, healthcare system, iatrogenic and others. RESULTS: A total of three studies were included. For risk factors, two studies on ventilator-associated pneumonia were included with 194 neonates; whereas for mortality predictors, only one study with 150 neonates diagnosed with pneumonia was included. 11 risk factors were identified from two studies: duration of mechanical ventilation, postnatal age, birth weight, prematurity, sex of the neonate, length of stay in NICU, primary diagnosis, gestational age, number of re-intubation, birth asphyxia, and use of nasogastric tube. Meta-analysis with random-effects model was possible only for prematurity (<37 week) and very low birth weight (<1500 g) and very low birth weight was found to be significant (OR 5.61; 95% CI 1.76, 17.90). A single study was included on predictors of mortality. Mean alveolar arterial oxygen gradient (AaDO2) >250 mm Hg was found to be the single most significant predictor of mortality due to pneumonia in neonates. CONCLUSION: The study found scant evidence from India on risk factors of neonatal pneumonia other than ventilator-associated pneumonia.

Development and validation of a clinical score to predict the probability of successful procedure in women undergoing external cephalic version.

INTRODUCTION: External Cephalic Version (ECV) reduces breech presentation at term and thus contribute to the reduction of cesarean section. This study was done to determine the factors associated with the successful ECV in women with breech presentation after 36 weeks' gestation and also to develop and validate a clinical score which could be utilized for individual patient counseling in future. METHODS: This was a retrospective cohort study conducted in a tertiary care center and teaching hospital in south India. Prospectively collected data from the register maintained for all ECVs performed on pregnant women with breech presentation at or more than 36 weeks' gestation. Clinical and ultrasound parameters at the time of performing the procedure were used in the analysis. Multiple logistic regression with a stepwise backward selection procedure was used selecting potential variable to construct the model and internal validation was done with bootstrapping. Primary outcome was successful ECV defined as cephalic presentation at the end of the procedure. RESULTS: Among 611 women who underwent ECV, it was successful in 70.4%. In the multiple logistic regression model, multiparity (OR4.48), AFI ≥ 7 (OR = 3.06), type of breech, posterior placental location (OR = 1.57), sacro-anterior position of breech (OR = 2.83), normal uterine tone (OR = 1.82) and fetal pole not engaged (OR = 2.82) were found to be predictive of successful ECV with good discrimination (AUC = 0.782) and acceptable calibration. Combining these factors from the model a predictive score (score 0-13) is proposed for clinical utility. CONCLUSIONS: Combining clinical and ultrasound parameters into a predictive score, which is simple and effective, could be utilized in the clinical practice, once validated externally.

Atomoxetine Does Not Improve Complex Attention in Idiopathic Parkinson's Disease Patients with Cognitive Deficits: A Meta-Analysis.

OBJECTIVES: To evaluate the effects of atomoxetine on complex attention and other neurocognitive domains in idiopathic Parkinson's disease (PD). METHODS: Interventional trials reporting changes in complex attention and other neurocognitive functions (Diagnostic and Statistical Manual of Mental Disorders-5) following administration of atomoxetine for at least 8 weeks in adults with idiopathic PD were included. Effect sizes (Cohen's d), the standardized mean difference in the scores of each cognitive domain, were compared using a random-effects model (MetaXL version 5.3). RESULTS: Three studies were included in the final analysis. For a change in complex attention in PD with mild cognitive impairment (MCI), the estimated effect size was small and nonsignificant (0.16 (95% CI: -0.09, 0.42), n = 42). For changes in executive function, perceptual-motor function, language, social cognition, and learning and memory, the estimated effect sizes were small and medium, but nonsignificant. A deteriorative trend in executive function was observed after atomoxetine treatment in PD with MCI. For a change in global cognitive function in PD without MCI, the estimated effect size was large and significant. CONCLUSION: In idiopathic PD with MCI, atomoxetine does not improve complex attention. Also, a deteriorative trend in the executive function was noted.

Interventions for Addressing Anemia Among Children and Adolescents: An Overview of Systematic Reviews.

Context: Anemia is a public health problem that can lead to growth, cognitive, and motor impairments. Objective: To collate evidence on interventions for addressing childhood and adolescent anemia. Methods: In this overview of systematic reviews, we included Cochrane as well as non-Cochrane systematic reviews (SRs) irrespective of language and publication status. Two sets of review authors independently screened articles for eligibility and extracted data from relevant SRs. We present data in a tabular format and summarize results based on outcome reported, age of participants, and type of interventions. We also adopt a "measurement for change" approach to assess the utility of measurement for development of interventions in childhood and adolescent anemia. Results: Our search yielded 2,601 records of which 31 SRs were found eligible for inclusion. Results were favorable for fortification and supplementation with clear reduction in the risk of anemia and increase in hemoglobin levels across all age groups. Other interventions reported by the SRs were inconclusive and suggest further research. Conclusions: Current evidence suggests that fortification or supplementation with iron and micronutrients leads to better reduction in the risk of anemia and improvements in hemoglobin levels among children and adolescents. Results of this overview can help decision makers in informing selection of interventions to address childhood and adolescent anemia. Review Registration: PROSPERO CRD42016053687.

Fortification of rice with vitamins and minerals for addressing micronutrient malnutrition.

BACKGROUND: Rice fortification with vitamins and minerals has the potential to increase the nutrition in rice-consuming countries where micronutrient deficiencies exist. Globally, 490 million metric tonnes of rice are consumed annually. It is the dominant staple food crop of around three billion people. OBJECTIVES: To determine the benefits and harms of rice fortification with vitamins and minerals (iron, vitamin A, zinc or folic acid) on micronutrient status and health-related outcomes in the general population. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and 16 other databases all up to 10 December 2018. We searched ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (ICTRP) on 10 December 2018. SELECTION CRITERIA: We included randomised and quasi-randomised trials (with either individual or cluster randomisation) and controlled before-and-after studies. Participants were populations older than two years of age (including pregnant women) from any country. The intervention was rice fortified with at least one micronutrient or a combination of several micronutrients (iron, folic acid, zinc, vitamin A or other vitamins and minerals) compared with unfortified rice or no intervention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently screened studies and extracted data. MAIN RESULTS: We included 17 studies (10,483 participants) and identified two ongoing studies. Twelve included studies were randomised-controlled trials (RCTs), with 2238 participants after adjusting for clustering in two cluster-RCTs, and five were non-randomised studies (NRS) with four controlled before-and-after studies and one cross-sectional study with a control (8245 participants). Four studies were conducted in India, three in Thailand, two in the Philippines, two in Brazil, one each in Bangladesh, Burundi, Cambodia, Indonesia, Mexico and the USA. Two studies involved non-pregnant, non-lactating women and 10 involved pre-school or school-age children. All 17 studies reported fortification with iron. Of these, six studies fortified rice with iron only; 11 studies had other micronutrients added (iron, zinc and vitamin A, and folic acid). One study had one arm each with vitamin A alone and carotenoid alone. Elemental iron content ranged from 0.2 to 112.8 mg/100 g uncooked rice given for a period varying from two weeks to 48 months. Thirteen studies did not clearly describe either sequence generation or allocation concealment. Eleven studies had a low attrition rate. There was no indication of selective reporting in the studies. We considered two RCTs at low overall risk of bias and 10 at high overall risk of bias. One RCT was at high or unclear risk of bias for most of the domains. All controlled before-and-after studies had a high risk or unclear risk of bias in most domains. The included studies were funded by Government, private and non-governmental organisations, along with other academic institutions. The source of funding does not appear to have altered the results. We used the NRS in the qualitative synthesis but we excluded them from the quantitative analysis and review conclusions since they provided mostly contextual information and limited quantitative information. Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added) Fortification of rice with iron (alone or in combination with other micronutrients) may make little or no difference in the risk of having anaemia (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.54 to 0.97; I2 = 74%; 7 studies, 1634 participants; low-certainty evidence) and may reduce the risk of iron deficiency (RR 0.66, 95% CI 0.51 to 0.84; 8 studies, 1733 participants; low-certainty evidence). Rice fortification may increase mean haemoglobin (mean difference (MD) 1.83, 95% CI 0.66 to 3.00; I2 = 54%; 11 studies, 2163 participants; low-certainty evidence) and it may make little or no difference to vitamin A deficiency (with vitamin A as one of the micronutrients in the fortification arm) (RR 0.68, 95% CI 0.36 to 1.29; I2 = 37%; 4 studies, 927 participants; low-certainty evidence). One study reported that fortification of rice (with folic acid as one of the micronutrients) may improve serum or plasma folate (nmol/L) (MD 4.30, 95% CI 2.00 to 6.60; 215 participants; low-certainty evidence). One study reported that fortification of rice with iron alone or with other micronutrients may slightly increase hookworm infection (RR 1.78, 95% CI 1.18 to 2.70; 785 participants; low-certainty evidence). We are uncertain about the effect of fortified rice on diarrhoea (RR 3.52, 95% CI 0.18 to 67.39; 1 study, 258 participants; very low-certainty evidence). Rice fortified with vitamin A alone or in combination with other micronutrients versus unfortified rice (no micronutrients added) One study had one arm providing fortified rice with vitamin A only versus unfortified rice. Fortification of rice with vitamin A (in combination with other micronutrients) may increase mean haemoglobin (MD 10.00, 95% CI 8.79 to 11.21; 1 study, 74 participants; low-certainty evidence). Rice fortified with vitamin A may slightly improve serum retinol concentration (MD 0.17, 95% CI 0.13 to 0.21; 1 study, 74 participants; low-certainty evidence). No studies contributed data to the comparisons of rice fortification versus no intervention. The studies involving folic acid and zinc also involved iron in the fortification arms and hence we reported them as part of the first comparison. AUTHORS' CONCLUSIONS: Fortification of rice with iron alone or in combination with other micronutrients may make little or no difference in the risk of having anaemia or presenting iron deficiency and we are uncertain about an increase in mean haemoglobin concentrations in the general population older than 2 years of age. Fortification of rice with iron and other micronutrients such as vitamin A or folic acid may make little or no difference in the risk of having vitamin A deficiency or on the serum folate concentration. There is limited evidence on any adverse effects of rice fortification.

Fortification of staple foods with vitamin A for vitamin A deficiency.

BACKGROUND: Vitamin A deficiency is a significant public health problem in many low- and middle-income countries, especially affecting young children, women of reproductive age, and pregnant women. Fortification of staple foods with vitamin A has been used to increase vitamin A consumption among these groups. OBJECTIVES: To assess the effects of fortifying staple foods with vitamin A for reducing vitamin A deficiency and improving health-related outcomes in the general population older than two years of age. SEARCH METHODS: We searched the following international databases with no language or date restrictions: Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library; MEDLINE and MEDLINE In Process OVID; Embase OVID; CINAHL Ebsco; Web of Science (ISI) SCI, SSCI, CPCI-exp and CPCI-SSH; BIOSIS (ISI); POPLINE; Bibliomap; TRoPHI; ASSIA (Proquest); IBECS; SCIELO; Global Index Medicus - AFRO and EMRO; LILACS; PAHO; WHOLIS; WPRO; IMSEAR; IndMED; and Native Health Research Database. We also searched clinicaltrials.gov and the International Clinical Trials Registry Platform to identify ongoing and unpublished studies. The date of the last search was 19 July 2018. SELECTION CRITERIA: We included individually or cluster-randomised controlled trials (RCTs) in this review. The intervention included fortification of staple foods (sugar, edible oils, edible fats, maize flour or corn meal, wheat flour, milk and dairy products, and condiments and seasonings) with vitamin A alone or in combination with other vitamins and minerals. We included the general population older than two years of age (including pregnant and lactating women) from any country. DATA COLLECTION AND ANALYSIS: Two authors independently screened and assessed eligibility of studies for inclusion, extracted data from included studies and assessed their risk of bias. We used standard Cochrane methodology to carry out the review. MAIN RESULTS: We included 10 randomised controlled trials involving 4455 participants. All the studies were conducted in low- and upper-middle income countries where vitamin A deficiency was a public health issue. One of the included trials did not contribute data to the outcomes of interest.Three trials compared provision of staple foods fortified with vitamin A versus unfortified staple food, five trials compared provision of staple foods fortified with vitamin A plus other micronutrients versus unfortified staple foods, and two trials compared provision of staple foods fortified with vitamin A plus other micronutrients versus no intervention. No studies compared staple foods fortified with vitamin A alone versus no intervention.The duration of interventions ranged from three to nine months. We assessed six studies at high risk of bias overall. Government organisations, non-governmental organisations, the private sector, and academic institutions funded the included studies; funding source does not appear to have distorted the results.Staple food fortified with vitamin A versus unfortified staple food We are uncertain whether fortifying staple foods with vitamin A alone makes little or no difference for serum retinol concentration (mean difference (MD) 0.03 µmol/L, 95% CI -0.06 to 0.12; 3 studies, 1829 participants; I² = 90%, very low-certainty evidence). It is uncertain whether vitamin A alone reduces the risk of subclinical vitamin A deficiency (risk ratio (RR) 0.45, 95% CI 0.19 to 1.05; 2 studies; 993 participants; I² = 33%, very low-certainty evidence). The certainty of the evidence was mainly affected by risk of bias, imprecision and inconsistency.It is uncertain whether vitamin A fortification reduces clinical vitamin A deficiency, defined as night blindness (RR 0.11, 95% CI 0.01 to 1.98; 1 study, 581 participants, very low-certainty evidence). The certainty of the evidence was mainly affected by imprecision, inconsistency, and risk of bias.Staple foods fortified with vitamin A versus no intervention No studies provided data for this comparison.Staple foods fortified with vitamin A plus other micronutrients versus same unfortified staple foods Fortifying staple foods with vitamin A plus other micronutrients may not increase the serum retinol concentration (MD 0.08 µmol/L, 95% CI -0.06 to 0.22; 4 studies; 1009 participants; I² = 95%, low-certainty evidence). The certainty of the evidence was mainly affected by serious inconsistency and risk of bias.In comparison to unfortified staple foods, fortification with vitamin A plus other micronutrients probably reduces the risk of subclinical vitamin A deficiency (RR 0.27, 95% CI 0.16 to 0.49; 3 studies; 923 participants; I² = 0%; moderate-certainty evidence). The certainty of the evidence was mainly affected by serious risk of bias.Staple foods fortified with vitamin A plus other micronutrients versus no interventionFortification of staple foods with vitamin A plus other micronutrients may increase serum retinol concentration (MD 0.22 µmol/L, 95% CI 0.15 to 0.30; 2 studies; 318 participants; I² = 0%; low-certainty evidence). When compared to no intervention, it is uncertain whether the intervention reduces the risk of subclinical vitamin A deficiency (RR 0.71, 95% CI 0.52 to 0.98; 2 studies; 318 participants; I² = 0%; very low-certainty evidence) . The certainty of the evidence was affected mainly by serious imprecision and risk of bias.No trials reported on the outcomes of all-cause morbidity, all-cause mortality, adverse effects, food intake, congenital anomalies (for pregnant women), or breast milk concentration (for lactating women). AUTHORS' CONCLUSIONS: Fortifying staple foods with vitamin A alone may make little or no difference to serum retinol concentrations or the risk of subclinical vitamin A deficiency. In comparison with provision of unfortified foods, provision of staple foods fortified with vitamin A plus other micronutrients may not increase serum retinol concentration but probably reduces the risk of subclinical vitamin A deficiency.Compared to no intervention, staple foods fortified with vitamin A plus other micronutrients may increase serum retinol concentration, although it is uncertain whether the intervention reduces the risk of subclinical vitamin A deficiency as the certainty of the evidence has been assessed as very low.It was not possible to estimate the effect of staple food fortification on outcomes such as mortality, morbidity, adverse effects, congenital anomalies, or breast milk vitamin A, as no trials included these outcomes.The type of funding source for the studies did not appear to distort the results from the analysis.

Risk factors of neonatal sepsis in India: A systematic review and meta-analysis.

BACKGROUND: The incidence of neonatal sepsis in India is the highest in the world. Evidence regarding its risk factors can guide clinical practice and prevention strategies. OBJECTIVE: To review, assess and synthesize the available literature from India on the risk factors of sepsis among neonates. METHODOLOGY: A systematic review was conducted. We searched PubMed, CINAHL, Scopus, Web of Science, Popline, IndMed, Indian Science Abstracts and Google Scholar from inception up to March 23, 2018 to identify observational analytical studies reporting on risk factors of laboratory-confirmed neonatal sepsis in India. Two authors independently screened studies (title, abstract and full-text stages), extracted data, and assessed quality. A random-effects meta-analysis was performed as substantial heterogeneity was anticipated. Subgroup and sensitivity analyses were additionally performed. Effect size in our review included odds ratio and standardized mean difference. RESULTS: Fifteen studies were included from 11,009 records, of which nine were prospective in design. Birthweight and gestational age at delivery were the most frequently reported factors. On meta-analyses, it was found that male sex (OR: 1.3, 95% CI: 1.02, 1.68), out born neonates (OR: 5.5, 95% CI: 2.39, 12.49), need for artificial ventilation (OR: 5.61; 95% CI: 8.21, 41.18), gestational age <37 weeks (OR: 2.05; 95% CI:1.40, 2.99) and premature rupture of membranes (OR:11.14, 95% CI: 5.54, 22.38) emerged as risk factors for neonatal sepsis. Included studies scored lowest on exposure assessment and confounding adjustment, which limited comparability. Inadequacy and variation in definitions and methodology affected the quality of included studies and increased heterogeneity. CONCLUSIONS: Male neonates, outborn admissions, need for artificial ventilation, gestational age <37 weeks and premature rupture of membranes are risk factors for sepsis among neonates in India. Robustly designed and reported research is urgently needed to confirm the role of other risk factors of neonatal sepsis in India.

Desmopressin acetate (DDAVP) for preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders.

BACKGROUND: Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate (DDAVP) is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of DDAVP in these groups of pregnant women should be evaluated.This is an update of a Cochrane Review first published in 2013 and updated in 2015. OBJECTIVES: To evaluate the efficacy and safety of DDAVP in preventing and treating acute bleeding in pregnant women with bleeding disorders. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched several clinical trial registries and grey literature (27 August 2017).Date of most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register: 01 October 2018. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials investigating the efficacy of DDAVP versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible. DATA COLLECTION AND ANALYSIS: No trials matching the selection criteria were eligible for inclusion. MAIN RESULTS: No trials matching the selection criteria were eligible for inclusion. AUTHORS' CONCLUSIONS: No randomised controlled trials were identified investigating the relative effectiveness of DDAVP for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high-quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with DDAVP.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high-quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using DDAVP in this population are needed.Given that there are unlikely to be any trials published in this area, this review will no longer be regularly updated.

Evaluating Sanitization of Toothbrushes Using Various Decontamination Methods: A Meta-Analysis.

Toothbrushes play an essential role in personal oral hygiene by effective plaque removal.However, they get heavily contaminated by bacteria, viruses, yeasts, and fungi which may originate from the oral cavity after every use as well as from the environment where they are stored. This systematic review was conducted to identify various decontamination interventions attempted scientifically and it summarizes the efficacy of each. Meta-analysis illustrated that the use of Ultra-violet rays and Microwave had a significant effect on reduction of the microbial count of a used toothbrush with a mean difference of -2.61 and CI (-4.66,-0.76) with I2=98%. When compared with non-active treatment group, the natural agents (garlic, green tree and tea-tree oil) proved to sterilize the toothbrushes effectively with mean difference of -483.34, CI (-914.79, -51.88) and I2=100%.In contrast, chlorhexidine showed the insignificant result with a mean difference of -347.55 and CI (-951.90, 256.80) with I2=100%. The evidence from this review suggests that decontaminating toothbrush reduces bacterial load. Toothbrushes exposed to radiation and natural agents proved to sanitize them effectively but chlorhexidine rendered insignificant results. Keywords: Chemical agent; disinfection; radiation; microbial load; natural agent; toothbrush.

Completeness of reporting in Indian qualitative public health research: a systematic review of 20 years of literature.

BACKGROUND: This study reviewed the completeness of reporting in Indian qualitative public health research (QPHR) studies using the 'Consolidated Criteria for Reporting Qualitative Research' (COREQ) checklist. METHODS: Search results from five electronic databases were screened by two independent reviewers. We included English-language, primary QPHR studies from India, which were assessed for their compliance with the COREQ checklist. Each COREQ item was noted as either reported or unreported. Descriptive statistics for the number of COREQ items reported by each study, and the number of studies that reported each COREQ item were reported, as were the items reported in each year, and in pre- and post-COREQ time periods. RESULTS: Of 537 citations, 246 articles were included. Trends demonstrated an increasing number of Indian QPHR studies being published annually, and an overall increase in reporting completeness since 1997. Only two COREQ items were reported in all studies. 52.4% of articles reported between 16 and 21 items, corresponding to 43-57% of items being reported. Six items were reported in fewer than 10% of studies. COREQ domain 1 was least frequently reported. CONCLUSIONS: Despite improving trends, the reporting of QPHR in India is incomplete. Authors and journals should ensure adherence to reporting guidelines.

Effect of metformin on exercise capacity: A meta-analysis.

AIMS: To evaluate the effect of metformin on various parameters of exercise capacity [oxygen consumption (VO2), peak oxygen consumption (VO2peak), heart rate (HR), exercise test duration, respiratory exchange ratio (RER), rating of perceived exertion (RPE), lactate and ventilatory anaerobic threshold (VAT)]. METHODS: Studies reporting change in VO2 or VO2peak after metformin administration were included. Subgroup analyses were performed as applicable. Mean difference with 95% CIs were pooled using random-effects model [RevMan (v5.3)]. RESULTS: There were no changes in VO2 and VO2peak in the overall population [VO2: n = 388, mean difference: -0.12 ml/kg/min, 95% CI: -0.74, 0.51, p = 0.71 (i2 = 0%, p = 0.99); VO2peak: n = 345, mean difference: 0.41 ml/kg/min, 95% CI: -0.51, 1.33, p = 0.38 (i2 = 0%, p = 0.89)], healthy volunteers and patients (type 2 diabetes mellitus, insulin resistance, impaired glucose tolerance/impaired fasting glucose and metabolic syndrome). For patients with insulin resistance, there was a decrease in VO2peak, but not VO2. In the overall population, there was a significant decrease in HR and RER, a significant increase in RPE, and no changes in exercise test duration and VAT. In addition, there was an increased VAT in the healthy volunteers. CONCLUSIONS: In the overall population, metformin did not affect VO2, VO2peak, exercise test duration and VAT, although it significantly decreased HR, RER and increased RPE.

Economic impact of chronic obstructive pulmonary disease: A cross-sectional study at teaching hospital in South India.

BACKGROUND: Chronic obstructive pulmonary disease continues to be the important contribution toward disability, death, and burden in the costs of health care globally. Economic impact of COPD is attributed with substantial direct and indirect costs. COPD affects the productivity of work that poses a burden on the employers and also on individuals in terms of loss of pay, limitation of activities, and related disability. MATERIALS AND METHODS: Hospital-based cross-sectional study among 24 respondents in selected hospital in Udupi Taluk. Respondents were identified by purposive sampling technique and data were collected in respondent's mother tongue. An interviewer administered questionnaire was used to collect data related to patient's demographic status, disease history, and direct and indirect costs of COPD. Data were analyzed using SPSS software version 15. RESULTS: The mean total direct medical cost that was observed among 24 respondents was Rs. 29,885 ± 11,995.33 and the mean total direct nonmedical cost was Rs. 7,441.25 ± 2,228.90. The mean total direct medical costs of COPD patients with comorbidity were Rs. 28,148.2353 ± 2,578.01580 and for those without comorbid illness was Rs. 13,460.0000 ± 1,255.33528. The observed mean absenteeism in the past 28 days was 193.50 ± 33.62 h. The mean absolute presenteeism of respondents is 72.05 ± 7.55. CONCLUSIONS: The major drivers of the total cost were cost of hospitalizations and medication costs. Acknowledging the costs and economic impact of COPD is therefore extremely important in the management of COPD and in reducing the mortality and morbidity related to COPD and in improving adherence to treatment.