Effect of preconception multiple micronutrients vs. iron-folic acid supplementation on maternal and birth outcomes among women from developing countries: a systematic review and meta-analysis.

Background: Maternal malnutrition affects the somatic growth of the fetus and subsequent adverse events during infancy and childhood period. Though trials have been conducted on multiple micronutrient (MMN) supplements initiated during the preconception period, there is no collated evidence on this. Materials and methods: We performed a systematic review of published trials with the application of Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The searches were conducted until 30 September 2023. Meta-analysis was performed using Review Manager 5 software. The primary objective was to compare the effect of preconception MMN vs. iron-folic acid (IFA) supplementation on newborn anthropometric parameters at birth. Results: Of the 11,832 total citations retrieved, 12 studies with data from 11,391 participants [Intervention = 5,767; Control = 5,624] were included. For the primary outcome, there was no significant difference in the birth weight [MD, 35.61 (95% CI, -7.83 to 79.06), p = 0.11], birth length [MD, 0.19 (95% CI, -0.03 to 0.42), p = 0.09], and head circumference [MD, -0.25 (95% CI, -0.64 to -0.14), p = 0.22] between the MMN and control groups. For all the secondary outcomes [except for small for gestational age (SGA) and low birth weight (LBW)], the difference between the MMN and control groups was not significant. The GRADE evidence generated for all the outcomes varied from "very low to moderate certainty." Conclusion: A "very low certainty" of evidence suggests that MMN supplementation may not be better than routine IFA supplementation in improving newborn anthropometric parameters (weight, length, and head circumference). The adverse events resulting from the supplementation were not significant. We need better quality uniformly designed RCTs before any firm recommendation can be made.Systematic review registration: identifier (CRD42019144878: https://www.crd.york.ac.uk/prospero/#searchadvanced).

The Novel Technique of Reconstruction of Neglected Distal Radioulnar Joint Dislocation in a Case of Two Months Old Midshaft Galeazzi Fracture Dislocation without Use of Tendon Graft - A Case Report.

Introduction: The Galeazzi fracture is a fracture of the middle to distal one-third of the radius associated with dislocation or subluxation of the distal radioulnar joint (DRUJ) associated with high energy trauma. Injury to the dynamic and static stabilizers of DRUJ if unnoticed or poorly treated may lead to chronic instability which in turn can cause chronic pain and disability due to stiffness, decreased grip strength, forearm rotation, and symptomatic osteoarthritis. Case Report: A 35-year-old gentleman sustained trauma after fall from a motorcycle presented after 2 months with radiology suggestive of midshaft radius fracture with dorsal DRUJ dislocation treated with open reduction, internal fixation with DRUJ reconstruction using a novel technique not described before in any literature. After 3 months, the patient had significant pain relief at the wrist joint and regained painless, near normal range of motion at the wrist joint with good hand grip. The patient showed improvement in radiological and functional scores. Conclusion: Reconstruction of DRUJ using this novel technique provides good functional outcome including pain relief, improvement in hand grip and movements at the wrist and elbow joint similar to conventional techniques of intra as well as extra-articular tenodesis without causing donor site morbidity to the patient with lesser instrumentations and significantly reduced operating time.

Central Venous Access Devices for the Delivery of Systemic Anticancer Therapy: An Economic Evaluation.

OBJECTIVES: Patients undergoing long-term anticancer therapy typically require one of 3 venous access devices: Hickman-type device (HICK), peripherally inserted central catheter (PICC), or implantable chest wall port (PORT). Recent evidence has shown PORT is safer and improves patient satisfaction. However, PORT did not show improvement in quality-adjusted life-years and was more expensive. Decisions regarding cost-effectiveness in the United Kingdom are typically informed by a cost-per-quality-adjusted life-year metric. However, this approach is limited in its ability to capture the full range of relevant outcomes, especially in the context of medical devices. This study assessed the potential cost-effectiveness of HICK, PICC, and PORT in routine clinical practice. METHODS: This is a cost-consequence analysis to determine the trade-offs between the following outcomes: complication, infection, noninfection, chemotherapy interruption, unplanned device removals, health utilities, device insertion cost, follow-up cost, and total cost, using data from the Cancer and Venous Access clinical trial. We conducted value of implementation analysis of a PORT service. RESULTS: PORT was superior in terms of overall complication rate compared with both HICK (incidence rate ratio 0.422; 95% CI 0.286-0.622) and PICC (incidence rate ratio 0.295; 95% CI 0.189-0.458) and less likely to lead to an unplanned device removal. There was no difference in chemotherapy interruption or health utilities. Total cost with device in situ was lower on PORT than HICK (-£98.86; 95% CI -189.20 to -8.53) and comparable with PICC -£48.57 (95% CI -164.99 to 67.86). Value of implementation analysis found that PORT was likely to be considered cost-effective within the National Health Service. CONCLUSION: Decision makers should consider including PORT within the suite of venous access devices available within in the National Health Service.

New horizons in evidence synthesis for older adults.

Evidence synthesis, embedded within a systematic review of the literature, is a well-established approach for collating and combining all the relevant information on a particular research question. A robust synthesis can establish the evidence base, which underpins best practice guidance. Such endeavours are frequently used by policymakers and practitioners to inform their decision making. Traditionally, an evidence synthesis of interventions consisted of a meta-analysis of quantitative data comparing two treatment alternatives addressing a specific and focussed clinical question. However, as the methods in the field have evolved, especially in response to the increasingly complex healthcare questions, more advanced evidence synthesis techniques have been developed. These can deal with extended data structures considering more than two treatment alternatives (network meta-analysis) and complex multicomponent interventions. The array of questions capable of being answered has also increased with specific approaches being developed for different evidence types including diagnostic, prognostic and qualitative data. Furthermore, driven by a desire for increasingly up-to-date evidence summaries, living systematic reviews have emerged. All of these methods can potentially have a role in informing older adult healthcare decisions. The aim of this review is to increase awareness and uptake of the increasingly comprehensive array of newer synthesis methods available and highlight their utility for answering clinically relevant questions in the context of older adult research, giving examples of where such techniques have already been effectively applied within the field. Their strengths and limitations are discussed, and we suggest user-friendly software options to implement the methods described.

How Least Developed to Lower-Middle Income Countries Use Health Technology Assessment: A Scoping Review.

Health Technology Assessment (HTA) is a multidisciplinary tool to inform healthcare decision-making. HTA has been implemented in high-income countries (HIC) for several decades but has only recently seen a growing investment in low- and middle-income countries. A scoping review was undertaken to define and compare the role of HTA in least developed and lower middle-income countries (LLMIC). MEDLINE and EMBASE databases were searched from January 2015 to August 2021. A matrix comprising categories on HTA objectives, methods, geographies, and partnerships was used for data extraction and synthesis to present our findings. The review identified 50 relevant articles. The matrix was populated and sub-divided into further categories as appropriate. We highlight topical aspects of HTA, including initiatives to overcome well-documented challenges around data and capacity development, and identify gaps in the research for consideration. Those areas we found to be under-studied or under-utilized included disinvestment, early HTA/implementation, system-level interventions, and cross-sectoral partnerships. We consider broad practical implications for decision-makers and researchers aiming to achieve greater interconnectedness between HTA and health systems and generate recommendations that LLMIC can use for HTA implementation. Whilst HIC may have led the way, LLMIC are increasingly beginning to develop HTA processes to assist in their healthcare decision-making. This review provides a forward-looking model that LLMIC can point to as a reference for their own implementation. We hope this can be seen as timely and useful contributions to optimize the impact of HTA in an era of investment and expansion and to encourage debate and implementation.

Clinicolaboratory Profile, Treatment, Intensive Care Needs, and Outcome of Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2: A Systematic Review and Meta-analysis.

This study was aimed to summarize the current data on clinicolaboratory features, treatment, intensive care needs, and outcome of pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2; PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C). Articles published in PubMed, Web of Science, Scopus, Google Scholar, and novel coronavirus disease 2019 (COVID-19) research database of World Health Organization (WHO), Centers for Disease Control and Prevention (CDC) database, and Cochrane COVID-19 study register between December 1, 2019 and July 10, 2020. Observational studies involving patients <21 years with PIMS-TS or MIS-C were reported the clinicolaboratory features, treatment, intensive care needs, and outcome. The search identified 422 citations and finally 18 studies with 833 participants that were included in this study, and pooled estimate was calculated for parameters of interest utilizing random effect model. The median age was 9 (range: 8-11) years. Fever, gastrointestinal symptoms, rash, conjunctival injection, and respiratory symptoms were common clinical features. Majority (84%) had positive SARS-CoV-2 antibody test and only one-third had positive reverse transcript polymerase chain reaction (RT-PCR). The most common laboratory abnormalities noted were elevated C-reactive protein (CRP), D-dimer, procalcitonin, brain natriuretic peptide (BNP), fibrinogen, ferritin, troponin, interleukin 6 (IL-6), lymphopenia, hypoalbuminemia, and thrombocytopenia. Cardiovascular complications included shock (65%), myocardial dysfunction (61%), myocarditis (65%), and coronary artery abnormalities (39%). Three-fourths of children required admission to pediatric intensive care unit (PICU) where they received vasoactive medications (61%) and mechanical ventilation (25%). Treatment strategies used included intravenous immunoglobulin (IVIg; 82%), steroids (54%), antiplatelet drugs (64%), and anticoagulation (51%). Mortality for patients with PIMS-TS or MIS-C was low ( n = 13). In this systematic review, we highlight key clinical features, laboratory findings, therapeutic strategies, intensive care needs, and observed outcomes for patients with PIMS-TS or MIS-C. Commonly observed clinical manifestations include fever, gastrointestinal symptoms, mucocutaneous findings, cardiac dysfunction, shock, and evidence of hyperinflammation. The majority of children required PICU admission, received immunomodulatory treatment, and had good outcome with low mortality.

Burden of Attention Deficit Hyperactivity Disorder (ADHD) in Indian Children: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the pooled prevalence of attention deficit hyperactivity disorder (ADHD) in Indian children. METHODS: The searching of published literature was conducted in different databases (PubMed, Ovid SP, and EMBASE). The authors also tried to acquire information from the unpublished literature about the prevalence of ADHD. A screening was done to include eligible original studies, community or school-based, cross-sectional or cohort, reporting the prevalence of ADHD in children aged ≤ 18 y in India. Retrieved data were analyzed using STATA MP12 (Texas College station). RESULTS: Of 729 studies retrieved by searching different databases, 183 studies were removed as duplicates, and 546 titles and abstracts were screened. After screening, 19 studies were included for quantitative analysis. Subgroup analysis was conducted with respect to their setting (school-based/community-based). Fifteen studies performed in a school-based setting showed 75.1 (95% CI 56.0-94.1) pooled prevalence of ADHD per 1000 children of 4-19 y of age. In community-based settings, the pooled prevalence per 1000 children surveyed was 18.6 (95% CI 8.8-28.4). The overall pooled prevalence of ADHD was observed as 63.2 (95% CI 49.2-77.1) in 1000 children surveyed. Significant heterogeneity was observed in the systemic review. CONCLUSIONS: ADHD accounts for a significant health burden, and understanding its burden is crucial for effective health policy-making for educational intervention and rehabilitation.

Global epidemiological burden of fungal infections in cirrhosis patients: A systematic review with meta-analysis.

BACKGROUND AND AIMS: Fungal infections (FIs) have serious implications, yet understated in cirrhosis. Therefore, we reviewed the epidemiology and trends of FIs among cirrhotics. METHODS: Four electronic databases were searched for full-text articles describing prevalence of FIs in cirrhosis. Studies from post-transplant, malignancy and classical-immuno-deficiency patients were excluded. A random-effects meta-analysis was done to pool estimates of FIs (overall, and by type and infection-site), and their variation(I2 ) was explored on moderator-analysis and meta-regression. Risk of bias and asymmetry in estimates was assessed by a checklist and Egger's regression, respectively.(CRD42019142782). RESULTS: Thirty-four low-risk and four moderate-risk studies (31 984 cirrhotics) were included. Pooled estimates of overall FIs (17 studies), invasive fungal infections (IFIs; 17 studies), invasive candidiasis (23 studies) and invasive aspergillosis (16 studies) in cirrhosis were 10.2%(6.0-16.9), 9.5%(5.4-16.2), 4.0%(2.0-8.0) and 2.8%(1.5-5.3), respectively (I2  > 90%;each). Site of FIs in decreasing order of pooled prevalence was pulmonary, urinary tract, bloodstream, peritoneal, oesophageal and cerebral. Geographic differences in these estimates were remarkable, with highest burden of overall FIs from Belgium, the United States and India. Non-albicans-Candida and Aspergillus infections have increased over the last decade in cirrhosis. Intensive-care-unit (ICU)-admitted and acute-on-chronic liver failure (ACLF) patients had the highest prevalence of IFIs. MELD score(cases), bias score and sample size across studies were the predictors of variance in overall FI estimates. Diabetes, steroid and broad-spectrum antibiotic-exposure, and multiple organ failures were the common predispositions reported in patients with FIs. CONCLUSIONS: FIs impose a substantial burden in cirrhosis. ACLF and ICU admission should be considered as a host factor for defining IFIs. Epidemiology of FIs can guide interpretation of biomarkers and antifungal treatment in cirrhosis.

Exploring the role of bacillus calmette-guerin vaccination in protection against COVID-19.

BACKGROUND: In recent studies, it has been established that countries having Bacillus Calmette-Guerin (BCG) vaccination programs reported less COVID-19 cases and deaths per population Preliminary studies suggest that BCG vaccination could upregulate the vaccine-induced immunity against SARS-CoV-2. Hence, the recent study was aimed to determine the association of BCG vaccine with the development of COVID-19 in health care workers. METHODS: The participants included in the study were healthcare workers (doctors, paramedics, and other supporting staff) working in the high and low-risk zones of COVID-19 in the hospital. The Graph Pad statistical analysis tool was used to determine the association of preliminary BCG vaccination with their COVID-19 status. RESULTS: A total of 200 health care workers working in different departments of the hospital were enrolled in the study. The relative risk of COVID-19 positivity in BCG vaccinated versus unvaccinated was 0.79 (0.50-1.25). There was also a significant negative correlation between two groups. The relative risk of COVID-19 positivity in those with a BCG scar was 0.63 (0.44-0.92). The relative risk of COVID-19 infection in those with a history of tuberculosis was 1.08 (0.56-2.09). CONCLUSION: The present study did not support the beneficial effect of BCG vaccine in protection against the development of COVID-19 disease.

Evaluation of Tele-rheumatology during the COVID-19 Pandemic in Asian Population: A Pilot Study.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic autoimmune condition associated with a potential for deformities. It is one of the common conditions to seek health care. Hence, the present study was conducted to assess the telemedicine services for patients suffering from rheumatoid arthritis during the COVID-19 pandemic in an Asian Indian population. METHODS: A prospective study was conducted (March 2020-June 2020) in the telemedicine department of a premier northern Indian tertiary care institution. Out of the total patients enrolled (N = 7577) in telemedicine services, 122 rheumatoid arthritis patients (1.6%) were followed for 1 month to assess change in functional status by modified Health Assessment Questionnaire (mHAQ). Telephonic interviews of the enrolled patients were conducted to determine the level of understanding of advice given by consultants, barriers during the consultation, and satisfaction with teleconsultations for rheumatology clinics. RESULTS: For the native people, language of the clinicians was the main barrier (20%) in telerheumatology. Saving of time and money was observed as beneficial factors for patients. More than three-quarters of all rheumatoid arthritis patients were ready to use teleconsultation in the near future. A similar proportion of patients were in support for the recommendation of these services to other persons. CONCLUSION: We report the successful use of telemedicine services in the evaluation and management of rheumatic diseases in the current COVID-19 pandemic situation.

Paracetamol exposure and asthma: What does the evidence say? An overview of systematic reviews.

OBJECTIVE: To conduct an umbrella review collating the existing evidence to determine whether there is an association between exposure of Paracetamol in-utero or in infancy and the development of childhood Asthma. METHODS: In this review, systematic reviews with or without meta-analysis that reported the association between paracetamol and asthma in children were included. To identify relevant reviews, a search was performed in the electronic databases PubMed, the Cochrane Library, and Ovid MEDLINE. The protocol was registered in PROSPERO CRD42020156023. A separate search was conducted for primary studies from the last 5 years not yet included in systematic reviews reporting the association from January 2016 to March 2021. RESULTS: The electronic searches identified 1966 review titles. After the removal of 493 duplicates, 1475 titles and abstracts were screened against the eligibility criteria. Full-text screening yielded six systematic reviews to be included in this review. The search for primary studies in the last 5 years yielded 1214 hits, out of which 5 studies were found suitable for inclusion. Three of them, that were not included in the systematic reviews, and have been summarised in this paper. The odds ratios (ORs) for the outcome of asthma in offspring of mothers with prenatal paracetamol consumption in any trimester were 1.28 (1.13-1.39) and 1.21 (1.02-1.44). For first trimester exposures, they were 1.12 (0.99-1.27), 1.39 (1.01-1.91), and 1.21 (1.14-1.28), for the second or third trimester, they were 1.49 (1.37-1.63) and 1.13 (1.04-1.23). For the third trimester only, the figure was 1.17 (1.04-1.31). Of the six reviews included, 1 had a low risk of bias, 2 had an unclear risk while 3 had a high risk of bias assessed using the ROBIS tool. There was no significant increased risk of asthma with early infancy exposure. The inter-study heterogeneity varied from I2 = 41% to I2 = 76% across reviews. In the primary studies, the OR for prenatal exposure ranged from 1.12 (0.25-4.98) to 4.66 (1.92-11.3) and for infancy exposure was 1.56 (1.06-2.30). All three included primary studies were adjudged to be of high quality using the Newcastle Ottawa scale. CONCLUSIONS: There is a modest association between paracetamol exposure in-utero and the future development of asthma. Exposure in infancy has a less consistant association. All the studies done thus far are observational in nature, with their inherent biases. Further research, preferably randomized controlled trials are recommended to answer this pertinent question.

Antiviral Therapy for Varicella Zoster Virus (VZV) and Herpes Simplex Virus (HSV)-Induced Anterior Uveitis: A Systematic Review and Meta-Analysis.

Topic: Herpes simplex virus (HSV) and varicella zoster virus (VZV) are the most common ocular pathogens associated with infectious anterior uveitis. Currently, there are a number of antiviral agents administered to treat viral anterior uveitis (VAU). However, there is no consensus or guidelines about the most appropriate approach leading for the best treatment outcomes with fewer ocular complications. Clinical Relevance: To perform a systematic review and meta-analysis of the efficacy of different antiviral therapies in the management of anterior uveitis secondary to HSV and VZV. Methods: We searched PubMed, Web of Science, CINAHL, OVID, and Embase up to January 2020. Randomized trials, non-randomized intervention studies, controlled before and after studies and observational studies assessing the effect of oral and or topical treatments for VAU were considered. Data extraction and analysis with evaluation of the risk of bias in the included trials were performed. Results: Oral acyclovir demonstrated a statistically significant good treatment outcome in the management of VZV anterior uveitis (vs. placebo) (OR 0.26, 95% CI 0.11-0.59), but did not have similar effect in HSV anterior uveitis (OR 0.47, 95% CI 0.15-1.50). In the treatment of VZV anterior uveitis, there was significant superiority of oral acyclovir-7 day course-over topical acyclovir (OR 4.17, 95% CI 1.28-13.52). Whereas, there was no significant superiority of one of the following treatment regimens over the others: topical acyclovir over topical corticosteroids (OR 1.86, 95% CI 0.67-5.17), and oral acyclovir-7 day course-over oral acyclovir-14 day course-(OR 0.21, 95% CI 0.01-4.50) or oral valaciclovir (OR 1.40, 95% CI 0.48-4.07). Conclusion: Treatment of HSV and VZV anterior uveitis is currently based on individual experiences and limited literature, largely due to weak clinical trial evidence in this regard. Our results highlight the existence of a substantial gap in our evidence base. This finding might contribute to future research studies to ascertain the role of different antiviral therapies in the treatment of VAU. Systematic Review Registration: PROSPERO registration number: CRD420202 00404.

Prevalence of Hypertension among Children and Adolescents in India: A Systematic Review and Meta-Analysis.

OBJECTIVE: To conduct a systematic review to provide pooled estimates of the prevalence of hypertension among children aged less than 18 y in India. METHODS: Three electronic databases (PubMed, EMBASE, and Web of Science) were searched from inception to August 2020 by using terms related to hypertension, children, prevalence, and India. Studies reporting the prevalence of hypertension, defined based on at least three measurements, were included. Two investigators independently performed the literature search, study selection, and data extraction for this review. Random effect meta-analysis was used to provide pooled estimates of hypertension. RESULTS: A total of 64 studies were included in this systematic review. The pooled prevalence was 7% (95% CI: 6%-8%) for hypertension, 4% (95% CI: 3%-4.1%) for sustained hypertension and 10% (95% CI: 8%-13%) for prehypertension. While there was no significant difference in hypertension across five different regions of the country, an upward rising trend was observed after the year 2005. Urban children had a higher prevalence of hypertension as compared to their rural counterparts. Children with obesity had a significantly high prevalence of hypertension (29%) than normal-weight children (7%). CONCLUSION: In this review, it was observed that considerable proportions (7%) of school going children are hypertensive in India. Prevalence was higher in urban and overweight children. This study highlights that hypertension is a public health problem in India; hence, there is a need to implement public health measures to prevent hypertension.

Comparative accuracy of 1,3 beta-D glucan and galactomannan for diagnosis of invasive fungal infections in pediatric patients: a systematic review with meta-analysis.

Invasive fungal infections (IFI) cause considerable morbidity and mortality in pediatric patients. Serum biomarkers such as 1,3-beta-D glucan (BDG) and galactomannan (GM) have been evaluated for the IFI diagnosis. However, most evidence regarding their utility is derived from studies in adult oncology patients. This systematic review aimed to compare the diagnostic accuracy of BDG and GM individually or in combination for diagnosing IFI in pediatric patients. PubMed, CINAHL, Embase, and Cochrane Library were searched until March 2019 for diagnostic studies evaluating both serum GM and BDG for diagnosing pediatric IFI. The pooled diagnostic odds ratio (DOR), specificity and sensitivity were computed. Receiver operating characteristics (ROC) curve and area under the curve (AUC) were used for summarizing overall assay performance. Six studies were included in the meta-analysis. The summary estimates of sensitivity, specificity, pooled DOR, AUC of the GM assay for proven or probable IFI were 0.74, 0.76, 13.25, and 0.845. The summary estimates of sensitivity, specificity, pooled DOR, AUC of the BDG assay were 0.70, 0.69, 4.3, and 0.722. The combined predictive ability of both tests was reported in two studies (sensitivity: 0.67, specificity: 0.877). Four studies were performed in hematology-oncology patients, while two were retrospective studies from pediatric intensive care units (ICUs). In the subgroup of hematology-oncology patients, DOR of BDG remained similar at 4.25 but increased to 40.28 for GM. We conclude that GM and BDG have a modest performance for identifying IFI in pediatric patients. GM has a better accuracy over BDG. Combining both improves the specificity at the cost of sensitivity.

Magnesium sulphate for treating acute bronchiolitis in children up to two years of age.

BACKGROUND: Acute bronchiolitis is a significant burden on children, their families and healthcare facilities. It mostly affects children younger than two years of age. Treatment involves adequate hydration, humidified oxygen supplementation, and nebulisation of medications, such as salbutamol, epinephrine, and hypertonic saline. The effectiveness of magnesium sulphate for acute bronchiolitis is unclear. OBJECTIVES: To assess the effects of magnesium sulphate in acute bronchiolitis in children up to two years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, CINAHL, and two trials registries to 30 April 2020. We contacted trial authors to identify additional studies. We searched conference proceedings and reference lists of retrieved articles. Unpublished and published studies were eligible for inclusion. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs, comparing magnesium sulphate, alone or with another treatment, with placebo or another treatment, in children up to two years old with acute bronchiolitis. Primary outcomes were time to recovery, mortality, and adverse events. Secondary outcomes were duration of hospital stay, clinical severity score at 0 to 24 hours and 25 to 48 hours after treatment, pulmonary function test, hospital readmission within 30 days, duration of mechanical ventilation, and duration of intensive care unit stay. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We used GRADE methods to assess the certainty of the evidence. MAIN RESULTS: We included four RCTs (564 children). One study received funding from a hospital and one from a university; two studies did not report funding sources. Comparator interventions differed among all four trials. Studies were conducted in Qatar, Turkey, Iran, and India. We assessed two studies to be at an overall low risk of bias, and two to be at unclear risk of bias, overall. The certainty of the evidence for all outcomes and comparisons was very low except for one: hospital re-admission rate within 30 days of discharge for magnesium sulphate versus placebo. None of the studies measured time to recovery, duration of mechanical ventilation, duration of intensive care unit stay, or pulmonary function. There were no events of mortality or adverse effects for magnesium sulphate compared with placebo (1 RCT, 160 children). The effects of magnesium sulphate on clinical severity are uncertain (at 0 to 24 hours: mean difference (MD) on the Wang score 0.13, 95% confidence interval (CI) -0.28 to 0.54; and at 25 to 48 hours: MD on the Wang score -0.42, 95% CI -0.84 to -0.00). Magnesium sulphate may increase hospital re-admission rate within 30 days of discharge (risk ratio (RR) 3.16, 95% CI 1.20 to 8.27; 158 children; low-certainty evidence). None of our primary outcomes were measured for magnesium sulphate compared with hypertonic saline (1 RCT, 220 children). Effects were uncertain on the duration of hospital stay in days (MD 0.00, 95% CI -0.28 to 0.28), and on clinical severity on the Respiratory Distress Assessment Instrument (RDAI) score at 25 to 48 hours (MD 0.10, 95% CI -0.39 to 0.59). There were no events of mortality or adverse effects for magnesium sulphate, with or without salbutamol, compared with salbutamol (1 RCT, 57 children). Effects on the duration of hospital stay were uncertain (magnesium sulphate: 24 hours (95% CI 25.8 to 47.4), magnesium sulphate + salbutamol: 20 hours (95% CI 15.3 to 39.0), and salbutamol: 24 hours (95% CI 23.4 to 76.9)). None of our primary outcomes were measured for magnesium sulphate + epinephrine compared with no treatment or normal saline + epinephrine (1 RCT,120 children). Effects were uncertain for the duration of hospital stay in hours (MD -0.40, 95% CI -3.94 to 3.14), and for RDAI scores (0 to 24 hours: MD -0.20, 95% CI -1.06 to 0.66; and 25 to 48 hours: MD -0.90, 95% CI -1.75 to -0.05). AUTHORS' CONCLUSIONS: There is insufficient evidence to establish the efficacy and safety of magnesium sulphate for treating children up to two years of age with acute bronchiolitis. No evidence was available for time to recovery, duration of mechanical ventilation and intensive care unit stay, or pulmonary function. There was no information about adverse events for some comparisons. Well-designed RCTs to assess the effects of magnesium sulphate for children with acute bronchiolitis are needed. Important outcomes, such as time to recovery and adverse events should be measured.

Ocular surface manifestations of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

PURPOSE: This study was performed to determine the occurrence of ocular surface manifestations in patients diagnosed with coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: A systematic search of electronic databases i.e. PubMed, Web of Science, CINAHL, OVID and Google scholar was performed using a comprehensive search strategy. The searches were current through 31st May 2020. Pooled data from cross-sectional studies was used for meta-analysis and a narrative synthesis was conducted for studies where a meta-analysis was not feasible. RESULTS: A total of 16 studies reporting 2347 confirmed COVID-19 cases were included. Pooled data showed that 11.64% of COVID-19 patients had ocular surface manifestations. Ocular pain (31.2%), discharge (19.2%), redness (10.8%), and follicular conjunctivitis (7.7%) were the main features. 6.9% patients with ocular manifestations had severe pneumonia. Viral RNA was detected from the ocular specimens in 3.5% patients. CONCLUSION: The most common reported ocular presentations of COVID-19 included ocular pain, redness, discharge, and follicular conjunctivitis. A small proportion of patients had viral RNA in their conjunctival/tear samples. The available studies show significant publication bias and heterogeneity. Prospective studies with methodical collection and data reporting are needed for evaluation of ocular involvement in COVID-19.

Efficacy and Safety of Anti-malarial Drugs (Chloroquine and Hydroxy-Chloroquine) in Treatment of COVID-19 Infection: A Systematic Review and Meta-Analysis.

Background: Anti-malarial drugs inhibit coronaviruses in-vitro. Few published studies have evaluated the safety and efficacy of these drugs in the treatment of COVID-19 infection. Materials and Methods: This is a systematic review and meta-analysis of clinical trials and observational studies. Major database searches were carried out up until June 5, 2020. Participants admitted with RT-PCR-confirmed SARS Cov-2 (COVID-19) infection were included. The "Intervention group" received anti-malarial drugs with or without other drugs (Azithromycin) administered as an adjunct to the standard treatment/care. The "Control group" received treatment except anti-malarial drugs. The primary outcome is "all-cause mortality." Secondary outcome measures were effects on clinical and laboratory parameters and adverse events. Results: Of 3,472 citations, 17 (six clinical trials and 11 observational studies) studies provided data of 8,071 participants. Compared to the control, Hydroxy-chloroquine (HCQ) has no significant effect on mortality [(OR 0.87; 95% CI 0.46-1.64); eight observational studies; N = 5,944]. Data from a single, small non-randomized trial (N = 42) also reached a similar conclusion (OR 1.94; 95% CI 0.07-50.57; p = 0.69). Compared to the control, HCQ plus Azithromycin (AZM) significantly increased mortality [(OR 2.84; 95% CI 2.19-3.69); four observational studies; N = 2,310]. Compared to the control, risk of any adverse event was significantly increased in HCQ group [(OR 3.35; 95% CI 1.58-7.13); four clinical trials; N = 263]. Compared to control, risk of adverse cardiac events (abnormal ECG, arrhythmia, or QT prolongation) were not significantly increased in HCQ group (but significantly increased in the HCQ plus AZM group). The GRADE evidence generated for all the outcomes was of "very low-quality." Conclusions: As very low quality evidence suggests an increased risk of mortality and adverse event with HCQ plus Azithromycin combination (not HCQ alone), caution should be exercised while prescribing this combination for treatment of hospitalized adults with COVID-19 infection. Good quality, multi-centric RCTs (including both hospitalized and non-hospitalized patients) are required for any firm recommendation to be made during the ongoing pandemic. OSF Protocol Registration Link: https://osf.io/6zxsu.

Palliative drug treatments for breathlessness in cystic fibrosis.

BACKGROUND: Cystic fibrosis is a life-limiting autosomal recessive genetic illness. A feeling of shortness of breath is common in cystic fibrosis, especially as the disease progresses. Reversing the underlying cause is the priority when treating breathlessness (dyspnoea), but when it is not feasible, palliation (easing) becomes the primary goal to improve an individual's quality of life. A range of drugs administered by various routes have been used, but no definite guidelines are available. A systematic review is needed to evaluate such treatments. OBJECTIVES: To assess the efficacy and safety of drugs used to ease breathlessness in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 18 November 2019. We searched databases (clinicaltrials.gov, the ISRCTN registry, the Clinical Trials Registry India and WHO ICTRP) for ongoing trials. These searches were last run on 06 March 2020. SELECTION CRITERIA: We planned to include randomised and quasi-randomised controlled trials in people with cystic fibrosis (diagnosed by a positive sweat chloride test or genetic testing) who have breathlessness. We considered studies comparing any drugs used for easing breathlessness to another drug administered by any route (inhaled (nebulised), intravenous, oral, subcutaneous, transmucosal (including buccal, sublingual and intra-nasal) and transdermal). DATA COLLECTION AND ANALYSIS: The authors assessed the search results according to the pre-defined inclusion criteria. MAIN RESULTS: The new searches in 2020 yielded two ongoing studies that were not relevant to the review question. Previous searches had found only one study (cross-over in design), which did not fulfil the inclusion criteria as no data were available from the first treatment period alone. AUTHORS' CONCLUSIONS: Due to the lack of available evidence, this review cannot provide any information for clinical practice. The authors call for specific research in this area after taking into account relevant ethical considerations. The research should focus on the efficacy and safety of the drugs with efficacy being measured in terms of improvement in quality of life, dyspnoea scores and hospital stay.