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Objectives To compare efficacy of aloe vera and probiotic mouthwashes vs fluoride mouthwash on Streptococcus mutans (S. mutans) in the plaque of orthodontic patients and to assess patient-reported outcomes and compliance. Materials and Methods This prospective randomized clinical trial included 90 patients aged 12–35 years and in permanent dentition, who were randomly allocated in a 1:1:1 ratio to three mouthwash groups: aloe vera, probiotic, or fluoride. Smartphone-based applications were used to improve patient compliance. The primary outcome was the change in S. mutans levels in plaque between two times: pre-intervention and after 30 days using real-time polymerase chain reaction (Q-PCR). Secondary outcomes were the evaluation of patient-reported outcomes and compliance. Results Mean differences between aloe vera vs probiotic: −0.53 (95% CI: −3.57 to 2.51), aloe vera vs fluoride: −1.99 (95% CI, −4.8 to 0.82), and probiotic vs fluoride: −1.46 (95% CI: −4.74 to 1.82) were not significant, P = .467. Intragroup comparison demonstrated a significant mean difference in all three groups of −0.67 (95% CI: −0.79 to −0.55), −1.27 (95% CI: −1.57 to −0.97), and −2.23 (95% CI: −2.44 to −2.00) respectively, P < .001. Adherence was above 95% in all groups. No significant differences in frequency of responses to patient-reported outcomes were found among groups. Conclusions No significant difference in efficacy among the three mouthwashes in reducing S. mutans level in plaque was found. Patient-reported assessments concerning burning sensation, taste, and tooth staining found no significant differences among mouthwashes. Smartphone-based applications can help improve patient compliance.

Background Studies have pointed to a complicated and mutual relationship between attention deficit hyperactivity disorder (ADHD) and attachment. In an observational follow-up study conducted in 2015 60 children from 7 years to 12 years recently diagnosed with ADHD were included and assessed according to attachment representation showing 85% of the children to be insecurely attached. Aim The aim of this study was to investigate the stability of this remarkably high frequency of insecure attachment in the same cohort of children. Methods Children previously assessed using the child attachment interview (CAI) when diagnosed with ADHD were contacted three years later for a follow-up CAI assessment. Results At follow-up, 31 children participated in the CAI-interviews. Since their diagnosis with ADHD, the children had received treatment as usual. The CAI-interviews showed a continued high rate of insecure attachment with 90% of the children classifying as insecurely attached compared to expected 38% in the normal population. Of these, the majority of children (77%) were classified as dismissing. Conclusion Our findings suggest that targeting ADHD-symptoms with our current treatment strategies does not in itself improve attachment security. Attachment security may in turn be a factor of importance when evaluating general functioning and prognosis.

Background: The role of endogenous Matrix Metallo Proteinases in resin dentin bond deterioration over time has been well documented. The present study aimed to systematically review the literature; in vitro and ex vivo studies that assessed the outcomes of natural cross-linkers for immediate and long-term tensile bond strength were included. Methods: The manuscript search was carried out in six electronic databases—PubMed/MEDLINE, LILACS, SciELO, Cochrane, Web of Science and DOAJ, without publication year limits. Only manuscripts in English (including the translated articles) were selected, and the last search was performed in December 2020. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed. Results: From the 128 potentially eligible studies, 48 full-text articles were assessed for eligibility. After eligibility assessment and exclusions, 14 studies were considered for systematic review and seven studies for meta-analysis. Amongst the selected studies for meta-analysis, three had a medium and four had a low risk of bias. Conclusions: It was evidenced by the available data that Proanthocyanidin is the most efficient natural cross-linker to date, in preserving the bond strength even after ageing.

To summarise latent tuberculosis infection (LTBI) management strategies among household contacts of bacteriologically confirmed pulmonary tuberculosis (TB) patients in high-TB burden countries.PubMed/MEDLINE (NCBI) and Scopus were searched (January 2006 to December 2021) for studies reporting primary data on LTBI management. Study selection, data management and data synthesis were protocol-driven (PROSPERO-CRD42021208715). Primary outcomes were the proportions of LTBI, initiating and completing tuberculosis preventive treatment (TPT). Reported factors influencing the LTBI care cascade were qualitatively synthesised.From 3694 unique records retrieved, 58 studies from 23 countries were included. Most identified contacts were screened (median 99%, interquartile range [IQR] 82%-100%; 46 studies). Random-effects meta-analysis yielded pooled proportions for: LTBI 41% (95% confidence interval [CI] 33%-49%; 21,566 tested contacts); TPT initiation 91% (95% CI 79%-97%; 129,573 eligible contacts, 34 studies); TPT completion 65% (95% CI 54%-74%; 108,679 TPT-initiated contacts, 28 studies). Heterogeneity was significant (IThe proportions of household contacts screened, detected with LTBI and initiated on TPT, though variable was high, but the proportions completing TPT were lower indicating current strategies used for LTBI management in high TB burden countries are not sufficient.

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the efficacy and harms or adverse events of immunomodulatory therapies in people with ALS compared with a placebo, no additional treatment, or a standard-of-care protocol (with or without riluzole, edaravone, or both).

To assess the systematic reviews and meta-analyses investigating the dental caries experience in children with cleft lip and/or palate (CL/P).A systematic search was carried out from MEDLINE Via PubMed, JBI Database of Systematic Reviews and Implementation Reports, EMBASE, OVID, Cochrane Database of Systematic Review, and Epistemonikos databases. Two independent reviewers carried out the collection and analysis of the study data. Methodological quality was assessed by ROBIS (Risk of bias assessment in systematic review) tool.An initial search of electronic databases yielded a total of 25 relevant reviews, of which only three systematic reviews were taken into consideration for qualitative synthesis. The total number of unique primary studies among the three included systematic reviews were 25, of which overlap of the studies was calculated using citation matrix. The corrected covered area (CCA) was estimated to be 0.26. Based on the ROBIS tool, only one systematic review reported with low risk of bias.Individuals with CL/P report more decayed, missing, or filled teeth/surfaces than those without CL/P in primary, mixed, and permanent dentition. Future studies should focus on the factors which could modify the caries risk of an individual with CL/P.This umbrella review offers a more reliable and balanced view regarding the dental caries experience among individuals with cleft lip and/or palate. This paper also highlights the important role of pediatric dentist in multidisciplinary health care team in implementing first dental visit and anticipatory guidance to consider early diagnosis and specific preventive interventions for Early Childhood Caries (ECC) in individuals with CL/P.Abirami S, Panchanadikar NT, Muthu MS

OBJECTIVE To assess the effect of different frequencies of ventilator circuit changes in neonates and children through a systematic review and meta-analysis. INTERVENTIONS (1) "No routine change of ventilator circuit (unless visibly soiled)" versus "routine change at any fixed interval"; (2) routine change of circuit at "less frequent" versus "more frequent" intervals. OUTCOMES Primary outcomes were VAP rate (number of VAP episodes per 1000 ventilator-days) and all-cause mortality before discharge. METHODS MEDLINE, CENTRAL, EMBASE, and CINAHL were systematically searched from inception till November 3, 2020. Two authors assessed trial eligibility and risk of bias, and independently extracted data. Data were synthesized using fixed effects model. GRADE was used to assess certainty of evidence (CoE). RESULTS We identified six studies enrolling 768 participants evaluating circuit changes at two fixed intervals. Meta-analysis of studies on circuit changes "once in less than 7 days" versus "once weekly" showed no difference in VAP rate (risk ratio: 0.83 [0.38-1.81]; one randomized controlled trial (RCT) and 0.94 [0.49-1.81]; two before-after studies) or mortality before discharge (0.67 [0.34-1.3]; one RCT and 1.01 [0.63-1.64]; two before-after studies). CoE was very low. Less frequent circuit changes reduced health-care costs. No study evaluating "circuit changes only when visibly soiled" versus "circuit changes at a fixed interval" was identified. CONCLUSION There is no evidence to suggest that ventilator circuits can be safely left unchanged until visibly soiled in neonates and children. Extending circuit changes interval to "once weekly" may not increase VAP rate (CoE-very low) and reduces healthcare costs.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To determine the efficacy and safety of favipiravir in patients with COVID‐19 as compared to standard of care without favipiravir.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: This review aims to look at the benefits and harms of antibiotics used in the treatment of acute pyelonephritis in adults. The aspects of treatment that will be evaluated are: 1. Different routes of administration; 2. Different durations of the same antibiotic; and 3. Comparison of different antibiotic agents in the same population.

Background: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurobiological disorders in childhood. Maternal resilience has been linked to treatment outcome in child ADHD. However, not much is known about factors that may facilitate maternal resilience. Aim: The aim of this study was to explore factors potentially facilitating resilience in mothers to children with ADHD. Method: The current study was part of a naturalistic observational study. 64 mothers to children diagnosed with ADHD completed a set of questionnaires and a short protocol including demographic and psychosocial items. Correlation matrix were estimated for each of the scores to establish the relationship between them. Results: We found significant negative correlations between maternal self-reported attachment style and self-reported resilience and between self-reported ADHD-symptoms and resilience-score. Conclusion: The findings indicate that selected factors in maternal functioning may contribute to development of resilience, which may in turn be a factor of importance in parenting.

(1) Background: The current evidence on management of infants under six months (u6m) with growth faltering is limited and of low quality. This review aimed at updating an existing review to inform the WHO guideline update on prevention and management of growth faltering in infants u6m. The objective is to synthesise evidence on interventions to manage breastfeeding difficulties in mothers or caregivers of infants u6m with growth faltering to improve breastfeeding practices and breastmilk intake. (2) Methods: We searched PubMed, CINAHL, and Cochrane Library from December 2018 to December 2021 for experimental studies. Using RoB 2.0 and ROBINS-I tools, we assessed study quality and results were synthesised narratively. Using the GRADE approach, we assessed the quality of evidence for four outcome domains—breastfeeding (critical), anthropometric (important), mortality (important), and morbidity (important). (3) Results: We identified seven studies, conducted among neonates (mainly preterm, n = 14 to 607), and assessed the following interventions: (a) non-nutritive sucking (NNS) on breast (n = 2) and (b) alternative supplemental feeding techniques (n = 5, cup feeding, spoon feeding, supplemental feeding tube device, and syringe feeding), and reported breastfeeding and anthropometric outcomes. None of the studies reported mortality and morbidity outcomes. The reported breastfeeding outcomes included LATCH (Latch, Audible swallowing, Type of nipple, Comfort, Hold) total score, PIBBS (Preterm Infants Breastfeeding Behaviour Scale) total score, EBF (exclusive breastfeeding) at various time points and time to transition to full breastfeeding, and reported anthropometric outcomes included weight gain and weight at different time points. Studies had ‘serious’ indirectness and ‘serious’ to ‘very serious’ risks of bias. From the limited studies we found, NNS on breast compared to NNS on finger may have some benefits on PIBBS total score; NNS on breast compared to NNS on pacifier may have some benefits on EBF at discharge; and cup feeding compared to bottle feeding may have some benefits on EBF at discharge, at three months and at six months. (4) Conclusions: Evidence on the effectiveness of interventions to manage breastfeeding difficulties in mothers or caregivers of infants u6m with growth faltering to improve breastfeeding practices and increase breastmilk intake is ‘limited’ and of ‘low’ to ‘very low’ quality. As the majority of the infants in the included studies were neonates, no new recommendations can be made for infants from one to six months due to lack of evidence in this population. We need more studies targeting infants from one to six months of age. The review was registered with PROSPERO (CRD42022309001).

The literature on the efficacy of erbium lasers for nonsurgical periodontal therapy is inconsistent. The objective of the umbrella review was to collate the information available in the systematic reviews to provide a comprehensive synthesis of clinical and patient reported outcomes following the use of erbium lasers for non-surgical periodontal therapy. An electronic database search was carried out, and systematic reviews/meta-analyses which assessed the efficacy of erbium lasers as monotherapy or as an adjunct to scaling and root planing were included. The methodological quality and reporting quality of the included studies were assessed. 15 Systematic reviews/meta-analyses were obtained after title, abstract, and full text search. The meta-analyses data revealed a clinical attachment level gain, reduction in probing pocket depth at 1 and 3-month follow-up, and no additional benefit at ≥ 6-month follow-up in the erbium laser group. The evidence gap map revealed lack of clinical outcome data at6-month follow-up and dearth in studies assessing patient reported outcome measures and adverse events. Erbium lasers may provide short-term clinical benefits, and further studies with standardized laser parameters evaluating long-term follow-up, patient-reported outcome measures, and adverse events are needed.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the efficacy and safety of plastic stents and metal stents in individuals undergoing endoscopic ultrasound‐guided transmural drainage of pancreatic fluid collections.

Technology-assisted parent-mediated interventions improve accessibility and are acceptable but not proven to be effective. We conducted a systematic search of 6 databases. We included and analysed results from studies on social and communication outcomes. Sixteen Randomised-Controlled-Trials (RCTs) with 748 participants were included. Most studies were rated as of good quality. Meta-analysis suggested that interventions were probably effective in improving emotion recognition. No significant differences were found in social communication, social functioning or language outcomes. At present, isolated tech interventions do not fulfil criteria for promising or established evidence-based interventions for ASD. Future research needs to focus on improving the effectiveness of technology-assisted parent-mediated interventions for ASD. Prospero Registration Number: CRD42020162825.

Background Scrub typhus, a vector-borne zoonotic infection caused by the bacteria Orientia tsutsugamushi, is one of the most common and clinically important rickettsial infections worldwide. An estimated one million cases occur annually with a high case fatality rate. Although scrub typhus is a major public health threat in India, the burden and distribution remains unclear. We aimed to estimate the burden of scrub typhus in India. Methodology We performed a systematic review of published literature on scrub typhus from India to extract information on epidemiology, morbidity, and mortality. Important databases were searched using keywords and appropriate combinations. We identified observational, interventional, and population-based studies and extracted the data to evaluate the number of cases diagnosed using serology or PCR and the number of deaths due to scrub typhus. We conducted a systematic narrative synthesis to summarize included studies. Principal findings In the last decade, there were 18,781 confirmed scrub typhus cases reported in 138 hospital-based studies and two community-based studies. IgM ELISA was used in 122 studies to confirm the cases in majority (89%). The proportion of scrub typhus among acute undifferentiated febrile illness (AUFI) studies was 25.3%, and community seroprevalence was 34.2%. Ninety studies had data published on multiple organ involvement out of which 17.4% of cases had multiple organ dysfunction syndromes, 20.4% patients required ICU admission, and 19.1% needed ventilation. The overall case-fatality rate was 6.3%, and the mortality among those with multi-organ dysfunction syndrome was as high as 38.9%. Conclusion/significance Scrub typhus, a common acute febrile illness in India causing severe morbidity, accounts for a large number of deaths. The burden of the disease has been underappreciated. Early diagnosis and prompt treatment can significantly reduce complications and mortality. Establishing good surveillance and instituting appropriate control measures are urgently needed., Author summary Scrub typhus is an infection that is caused by a rickettsial bacteria called Orientia tsutsugamushi and transmitted to humans through chigger mites. Scrub typhus has re-emerged as one of the most common life-threatening rickettsial infections accounting for a million cases annually. However, it is a largely overlooked public health problem in India. This systematic review aims to integrate data obtained from medical literature over the past 10 years to estimate the burden of scrub typhus in India. It also intends to summarize the diagnostic tests that are most commonly used to confirm scrub typhus cases and to map the distribution of cases across India. The insights provided from this review will further enable policymakers to establish a surveillance system to observe this disease and initiate strategies to effectively control, and prevent the spread of, this neglected disease. In this review, we found that scrub typhus is very common in India and affects multiple organs in the majority of positively tested patients. This increases complications and the risk of death. Improving awareness about this disease, increasing access to testing and initiating appropriate therapy early can help reduce this public health threat in the future.

IntroductionThe heterogeneity in people with borderline personality disorder (BPD) and the range of specialised psychotherapies means that people with certain BPD characteristics might benefit more or less from different types of psychotherapy. Identifying moderating characteristics of individuals is a key to refine and tailor standard treatments so they match the specificities of the individual participant. The objective of this is to improve the quality of care and the individual outcomes. We will do so by performing three systematic reviews with meta-analyses of individual participant data (IPD). The aim of these reviews is to investigate potential predictors and moderating patient characteristics on treatment outcomes for patients with BPD.Methods and analysisWe performed comprehensive searches in 22 databases and trial registries up to October 6th 2020. These will be updated with a top-up search up until June 2021. Our primary meta-analytic method will be the one-stage random-effects approach. To identify predictors, we will use the one-stage model that accounts for interaction between covariates and treatment allocation. Heterogeneity in case-mix will be assessed with a membership model based on a multinomial logistic regression where study membership is the outcome. A random-effects meta-analysis is chosen to account for expected levels of heterogeneity.Ethics and disseminationThe statistical analyses will be conducted on anonymised data that have already been approved by the respective ethical committees that originally assessed the included trials. The three IPD reviews will be published in high-impact factor journals and their results will be presented at international conferences and national seminars.PROSPERO registration numberCRD42021210688.

To estimate the incremental yield of single nucleotide polymorphism (SNP) array over karyotype and to assess the diagnostic accuracy of SNP array as a stand-alone test versus SNP array with karyotype in detecting chromosomal abnormalities for prenatal diagnosis in women with an abnormal fetal ultrasound.Studies in which SNP array and karyotype had been used for diagnosing chromosomal aberrations in fetuses with abnormal ultrasound findings were included. A systematic search of relevant studies published in the English language in EMBASE, PubMed, CENTRAL, CDSR (Cochrane database of systematic reviews), SCOPUS and Web of science between 1996 and May 2020 was performed. Primary outcome was incremental yield of SNP array over karyotype (number of patients with abnormalities detected by SNP array over number of patients with normal karyotype). Other outcomes included diagnostic accuracy of SNP array alone versus SNP array and karyotype for prenatal diagnosis. Pooled sensitivities, specificities, and their 95% confidence intervals (CI) were presented.Seven studies were included. The incremental yield of SNP array over karyotype was 8% (95% Confidence interval, CI 4-12%) while incremental yield of karyotype over SNP array in foetus with abnormal ultrasound was 0% (95% CI 0-1%). The agreement between SNP array and karyotype was 92%. The variant of unknown significance rates ranged between 4 and 8 %. The pooled sensitivity and specificity of SNP array versus SNP array and karyotype was 0.97 (95% CI 0.92-0.99) and 1.00 (95% CI1.00-1.00), respectively.SNP array provides additional information on chromosomal abnormalities over and above conventional karyotype. When used as a stand-alone test, SNP array performs favourably as a diagnostic modality when compared against SNP array and karyotype for prenatal diagnosis with an abnormal fetal ultrasound.

Bronchoscopic lung volume reduction (BLVR) methods have emerged as a new treatment option for patients with severe emphysema. Endobronchial valves and coils have been extensively studied. This review assesses efficacy, safety, and cost effectiveness of the BLVR procedures (stent, valves, vapor ablation, endobronchial coils, lung sealant) in patients with severe emphysema. Databases were searched until October 2016, and randomized controlled trials (RCTs) comparing available BLVR procedures to standard medical care or sham bronchoscopy were included. Random effect model and generic inverse variance approach were used for meta-analysis. Out of 381 identified records, 16 RCTs were included. As compared to recommended medical care or sham bronchoscopy, the BLVR procedures are more effective in improving quality of life [SGRQ score (WMD=−6.38; −9.12 to −3.65)] and 6MWT (WMD=24.21; 9.68–38.74) and percentage FEV1 (WMD=10.48; 7.07–13.89). Increased risk of serious adverse events (RR=2.18; 1.63–2.93), specifically for chronic pulmonary obstructive disease exacerbations and lower respiratory tract infection combined (RR=1.37; 1.07–1.75), were observed with bronchoscopic interventions, while there was no difference in number of deaths (RR=1.25; 0.79–1.99) and respiratory failure (RR=1.13; 0.57–2.21). The BLVR procedures, especially endobronchial coils, were found to be effective in the management of patients with severe emphysema irrespective of collateral ventilation. However, characterization of patients who would be most benefited from these procedures is required, and effectiveness of these procedures in long run needs to be established.

Atomoxetine is prescribed to children with autism spectrum disorder having symptoms of attention deficit hyperactivity disorder. We sought to examine the efficacy and safety of atomoxetine in this population. After screening for inclusion criteria, we identified three randomized placebo controlled trials involving 241 children. We assessed internal validity using standard Cochrane Risk of bias tool for randomized controlled trials (RCTs). We used Revman 5.3 for meta‐analysis and GRADE approach to create summary of findings with grading of the quality of evidence. Atomoxetine had a benefit on improving parent‐rated hyperactivity (standardized mean difference [SMD] = −0.73, 95% Confidence Interval, CI = −1.15 to −0.34) and parent‐rated inattention (SMD = −0.53, 95% CI = −0.93 to −0.12) but the magnitude of effects is uncertain. However, atomoxetine was also associated with increased risk of non‐serious adverse effects like nausea and vomiting, decreased sleep, and decreased appetite. Atomoxetine may be effective in improving hyperactivity and inattention in children with autism spectrum disorder and attention deficit hyperactivity disorder. However, we are uncertain about the true effect of this intervention and need more RCTs trials designed to evaluate this. Autism Research 2019, 12: 542–552. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.\ud \ud \ud \ud Lay Summary\ud \ud Atomoxetine is prescribed for Attention Deficit Hyperactivity Disorder (ADHD). About a third of children and adolescents with autism also suffer from ADHD. We carried out an analysis of data reported from a specific kind of medication trials which had examined the effectiveness and side effects of atomoxetine in this patient population. We could find only three such trials and analyzed the reported data. Our analysis revealed that atomoxetine is effective in improving symptoms of ADHD like hyperactivity and inattention and also causes side effects like nausea, vomiting, decreased sleep, and decreased appetite. However, the existing data are insufficient to provide a conclusive statement with certainty and more trials are needed for this.

Background Bacopa monnieri, a herb that has been used for many centuries in India, has shown neuroprotective effects in animal and in vitro studies; human studies on patients with Alzheimer disease have been inconclusive. Objective The primary objective of this review was to determine the clinical efficacy and safety of B. monnieri in persons with mild, moderate, or severe dementia, or mild cognitive impairment, due to Alzheimer disease. Methods We searched PubMed, Embase, Cochrane Library, clinical trial registries (World Health Organization, Australia-New Zealand, United States, and South Africa), the metaRegister of Controlled Trials, and CINAHL. We intended to include all randomized and quasi-randomized controlled trials that compared B. monnieri, its extract or active ingredients (at any dosage), with a placebo or a cholinesterase inhibitor among adults with dementia due to Alzheimer disease and in those with mild cognitive impairment due to Alzheimer disease. Results Our comprehensive search yielded 5 eligible studies. A total of 3 studies used B. monnieri in combination with herbal extracts while the remaining 2 used B. monnieri extracts only. Two studies compared B. monnieri with donepezil while the others used a placebo as the control. There was considerable variation in the B. monnieri dose used (ranging between 125 mg to 500 mg twice daily) and heterogeneity in treatment duration, follow-up, and outcomes. The major outcomes were Mini-Mental State Examination scores reported in 3 trials, Cognitive subscale scores of the Alzheimer’s Disease Assessment Scale in 1 study, and a battery of cognitive tests in 2 studies. Using the Cochrane risk-of-bias tool, overall, we judged all 5 studies to be at high risk of bias. While all studies reported a statistically significant difference between B. monnieri and the comparator in at least one outcome, we rated the overall quality of evidence for the Alzheimer’s Disease Assessment Scale-Cognitive Subscale, Postgraduate Institute Memory Scale, Mini-Mental State Examination, and Wechsler Memory Scale to be very low due to downgrading by 2 levels for high risk of bias and 1 more level for impreciseness due to small sample sizes and wide CIs. Conclusions There was no difference between B. monnieri and the placebo or donepezil in the treatment of Alzheimer disease based on very low certainty evidence. No major safety issues were reported in the included trials. Future randomized controlled trials should aim to recruit more participants and report clinically meaningful outcomes. Trial Registration PROSPERO CRD42020169421; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=169421

Background Health behaviour can change outcomes in both healthy and diseased populations and are particularly useful in promoting compliance to treatment and maintain fidelity to care seeking and follow-up options in chronic diseases. Interventions to change health behaviour based on psychological theory more often successful than those without any underlying theory. The theory of planned behaviour (TPB) is one such psychological theory which had been found to predict human behaviour with respect to disease prevention and when applied to interventions can change the outcomes of diseases. Most of the research evidence of TPB based interventions have been from developed world. Evidence is required whether TPB based interventions can be applied and works in low resource, low health literacy settings of low and middle income countries (LMICs).Methods The protocol has been developed as per PRISMA-P guidelines and incorporates PICO (population, intervention, comparison, outcomes) framework for describing the methodology. Population above 18 years of age and having any chronic disease will be selected while any health or educational intervention based on constructs of TPB will be included. Comparison will be with non TPB based interventions or treatment as usual without any intervention and the primary outcome will be the behaviour change effected by the TPB based intervention. Intervention studies will be considered and relevant databases like MEDLINE, EMBASE, Cochrane Library and ProQuest will be explored. Data extraction will done in a standardised form and quality assessment will be done using the Cochrane Collaboration’s Tool for Assessing the Risk of Bias. Narrative synthesis of the selected studies will be done to draw the conclusions and meta-analysis will be done if the heterogeneity is less than 50% by I-2 statistics.Discussion This systematic review will provide new evidence on fidelity and effectiveness of the TPB based interventions among chronic disease patients in low health literacy population of LMIC settings. This will provide us with new knowledge of how to plan and use such interventions to change health behaviour in chronic disease patients.Systematic review registration this protocol has been registered in PROSPERO with registration no. CRD42018104890.

Background Health behaviour can change outcomes in both healthy and unhealthy populations and are particularly useful in promoting compliance to treatment and maintaining fidelity to care seeking and follow-up options in chronic diseases. Interventions to change health behaviour based on psychological theory are more often successful than those without any underlying theory. The theory of planned behaviour (TPB) is one such psychological theory which had been found to predict human behaviour with respect to disease prevention and when applied to interventions can change the outcomes of diseases. Most of the research evidence of TPB-based interventions have been from developed world. Evidence is required whether TPB-based interventions can be applied and works in low-resource, low health-literacy settings of low- and middle-income countries (LMICs). Methods The protocol has been developed as per PRISMA-P guidelines and incorporates PICO (population, intervention, comparison, outcomes) framework for describing the methodology. Population above 18 years of age and having any chronic disease (as defined for this systematic review) will be selected, while any health or educational intervention based on constructs of TPB will be included. Comparison will be with non-TPB-based interventions or treatment as usual without any intervention, and the primary outcome will be the behaviour change effected by the TPB-based intervention. Intervention studies will be considered, and relevant databases like MEDLINE, Embase, Cochrane Library and ProQuest will be explored. Data extraction will done in a standardised form, and risk-of-bias assessment will be done using the Cochrane Collaboration’s tools for such assessment. Narrative synthesis of the selected studies will be done to draw the conclusions, and meta-analysis will be done to calculate the effect estimates with I-squared statistics to describe the heterogeneity. Discussion This systematic review will provide new evidence on fidelity and effectiveness of the TPB-based interventions among chronic disease patients from low health literacy, resource-poor background. It will inform of how to plan and use such interventions to change health behaviour in chronic disease patients, particularly in LMIC settings. Systematic review registration PROSPERO CRD42018104890.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: PRIMARY OBJECTIVE: To assess the efficacy and safety of antibiotics in adults with irritable bowel syndrome compared to placebo or standard medical therapy alone. SECONDARY OBJECTIVE: To determine the duration of response or time of recurrence following antibiotics in adults with irritable bowel syndrome.

Background The World Health Organization has recommended Vitamin A supplementation for children in low- and middle-income countries for many years to reduce child mortality. Nepal still practices routine Vitamin A supplementation. We examined the potential current impact of these programs using national data in Nepal combined with an update of the mortality effect estimate from a meta-analysis of randomized controlled trials. Methods We used the 2017 Cochrane review as a template for an updated meta-analysis. We conducted fresh searches, re-applied the inclusion criteria, re-extracted the data for mortality and constructed a summary of findings table using GRADE. We applied the best estimate of the effect obtained from the trials to the national statistics of the country to estimate the impact of supplementation on under-five mortality in Nepal. Results The effect estimates from well-concealed trials gave a 9% reduction in mortality (Risk Ratio: 0.91, 95% CI 0.85 to 0.97, 6 trials; 1,046,829 participants; low certainty evidence). The funnel plot suggested publication bias, and a meta-analysis of trials published since 2000 gave a smaller effect estimate (Risk Ratio: 0.96, 95% CI 0.89 to 1.03, 2 trials, 1,007,587 participants), with the DEVTA trial contributing 55.1 per cent to this estimate. Applying the estimate from well-concealed trials to Nepal’s under-five mortality rate, there may be a reduction in mortality, and this is small from 28 to 25 per 1000 live births; 3 fewer deaths (95% CI 1 to 4 fewer) for every 1000 children supplemented. Conclusions Vitamin A supplementation may only result in a quantitatively unimportant reduction in child mortality. Stopping blanket supplementation seems reasonable given these data.

IntroductionThe heterogeneity in people with BPD and the range of specialised psychotherapies means that people with certain BPD characteristics might benefit more or less from different types of psychotherapy. Identifying moderating characteristics of individuals is a key to refine and tailor standard treatments so they match the specificities of the individual patient. The objective of this is to improve the quality of care and the individual outcomes. Thus, the aim of the current reviews is to investigate potential predictors and moderating patient characteristics on treatment outcomes for patients with BPD.Methods and analysisOur primary meta-analytic method will be the one-stage random-effects approach. To identify predictors, we will be using the one-stage model that accounts for interaction between covariates and treatment allocation. Heterogeneity in case-mix will be assessed using a membership model based on a multinomial logistic regression where study membership is the outcome. A random-effects meta-analysis is chosen to account for expected levels of heterogeneity.Ethics and disseminationThe statistical analyses will be conducted on anonymised data that have already been approved by the respective ethical committees that originally assessed the included trials. The three IPD reviews will be published in high impact factor journals and their results will be presented at international conferences and national seminars.Protocol registrationThe IPD reviews, described in this study protocol, are registered with the PROSPERO International Prospective Register of Systematic Reviews (registration number: awaiting)Strengths and limitations of this protocolThese IPD-reviews are the first to systematically review and investigate psychotherapy for people with borderline personality disorder using individual participant data.The IPD-reviews will provide information on moderators and predictors in patients with borderline personality disorder that predict who may benefit most from which type of specialised psychotherapy.Individual participant data allows for a more precise risk of bias assessment and decreases the amount of unclear risk of bias in many of the included trials.A limitation to IPD-reviews in general is that data retrieval can be challenging.The IPD-reviews are limited to the outcomes and patient characteristics that have been assessed in the included trials.

Objectives: We sought to assess health literacy (HL) and its associated factors in the Bahraini community using a validated HL scale and address its deficient domains to inform policy. Methods: We carried out a conveniently sampled, cross-sectional survey using the All Aspects of Health Literacy Scale in the Bahraini community. The scale has three key aspects: basic or functional HL (FUN-4 items), which corresponds to basic reading and writing skills, and knowledge of health conditions and health systems; communicative or interactive HL (COM-3 items) on communicative and social skills to extract information from different forms of communication; and critical HL (CR-4 items), the advanced cognitive and social skills to critically analyze information and exert greater control over life events and situations relating to individual and community level wellbeing goals. We examined the association between sociodemographic and health information for the survey tool items using the chi-square test. The relationship between total scale score and subscale scores of the three domains of the survey tool to sociodemographic and health information was investigated using the t-test and ANOVA. Results: Of the 836 participants (mean age = 26.6 years), single (64.0%) and university students (76.6%) were predominant; 15.6% reported long-term sickness and visited the general physician often. The highest mean item scores were for empowerment (1.8) and lowest for functional HL (0.1). The significant domain-specific responses to the survey tool items were 12 for critical HL, 10 for functional HL, six for communicative HL, and five for empowerment. Participants aged < 30 years old, female, married, pursuing/completed Master’s program, employed, and whose self-rating of health was excellent had higher total HL scores. Conclusions: Older, less educated respondents with a poor self-rating of health had low HL scores. We recommend further studies to address the relative importance of functional, interactive, and critical HL in the community to promote health outcomes.

Background Virtual reality (VR) computer technology creates a simulated environment, perceived as comparable to the real world, with which users can actively interact. The effectiveness of VR distraction on acute pain intensity in children is uncertain. Objectives To assess the effectiveness and adverse effects of virtual reality (VR) distraction interventions for children (0 to 18 years) with acute pain in any healthcare setting. Search methods We searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO and four trial registries to October 2019. We also searched reference lists of eligible studies, handsearched relevant journals and contacted study authors. Selection criteria Randomised controlled trials (RCTs), including cross-over and cluster-RCTs, comparing VR distraction to no distraction, non-VR distraction or other VR distraction. Data collection and analysis We used standard Cochrane methodological processes. Two reviewers assessed risk of bias and extracted data independently. The primary outcome was acute pain intensity (during procedure, and up to one hour post-procedure). Secondary outcomes were adverse effects, child satisfaction with VR, pain-related distress, parent anxiety, rescue analgesia and cost. We used GRADE and created 'Summary of findings' tables. Main results We included 17 RCTs (1008 participants aged four to 18 years) undergoing various procedures in healthcare settings. We did not pool data because the heterogeneity in population (i.e. diverse ages and developmental stages of children and their different perceptions and reactions to pain) and variations in procedural conditions (e.g. phlebotomy, burn wound dressings, physical therapy sessions), and consequent level of pain experienced, made statistical pooling of data impossible. We narratively describe results. We judged most studies to be at unclear risk of selection bias, high risk of performance and detection bias, and high risk of bias for small sample sizes. Across all comparisons and outcomes, we downgraded the certainty of evidence to low or very low due to serious study limitations and serious or very serious indirectness. We also downgraded some of the evidence for very serious imprecision. 1: VR distraction versus no distraction Acute pain intensity: during procedure Self-report: one study (42 participants) found no beneficial effect of non-immersive VR (very low-certainty evidence). Observer-report: no data. Behavioural measurements (observer-report): two studies, 62 participants; low-certainty evidence. One study (n = 42) found no beneficial effect of non-immersive VR. One study (n = 20) found a beneficial effect favouring immersive VR. Acute pain intensity: post-procedure Self-report: 10 studies, 461 participants; very low-certainty evidence. Four studies (n = 95) found no beneficial effect of immersive and semi-immersive or non-immersive VR. Five studies (n = 357) found a beneficial effect favouring immersive VR. Another study (n = 9) reported less pain in the VR group. Observer-report: two studies (216 participants; low-certainty evidence) found a beneficial effect of immersive VR, as reported by primary caregiver/parents or nurses. One study (n = 80) found a beneficial effect of immersive VR, as reported by researchers. Behavioural measurements (observer-report): one study (42 participants) found no beneficial effect of non-immersive VR (very low-certainty evidence). Adverse effects: five studies, 154 participants; very low-certainty evidence. Three studies (n = 53) reported no adverse effects. Two studies (n = 101) reported mild adverse effects (e.g. nausea) in the VR group. 2: VR distraction versus other non-VR distraction Acute pain intensity: during procedure Self-report, observer-report and behavioural measurements (observer-report): two studies, 106 participants: Self-report: one study (n = 65) found a beneficial effect favouring immersive VR and one (n = 41) found no evidence of a difference in mean pain change scores (very low-certainty evidence). Observer-report: one study (n = 65) found a beneficial effect favouring immersive VR and one (n = 41) found no evidence of a difference in mean pain change scores (low-certainty evidence). Behavioural measurements (observer-report): one study (n = 65) found a beneficial effect favouring immersive VR and one (n = 41) reported a difference in mean pain change scores with fewer pain behaviours in VR group (low-certainty evidence). Acute pain intensity: post-procedure Self-report: eight studies, 575 participants; very low-certainty evidence. Two studies (n = 146) found a beneficial effect favouring immersive VR. Two studies (n = 252) reported a between-group difference favouring immersive VR. One study (n = 59) found no beneficial effect of immersive VR versus television and Child Life non-VR distraction. One study (n = 18) found no beneficial effect of semi-immersive VR. Two studies (n = 100) reported no between-group difference. Observer-report: three studies, 187 participants; low-certainty evidence. One study (n = 81) found a beneficial effect favouring immersive VR for parent, nurse and researcher reports. One study (n = 65) found a beneficial effect favouring immersive VR for caregiver reports. Another study (n = 41) reported no evidence of a difference in mean pain change scores. Behavioural measurements (observer-report): two studies, 106 participants; low-certainty evidence. One study (n = 65) found a beneficial effect favouring immersive VR. Another study (n = 41) reported no evidence of a difference in mean pain change scores. Adverse effects: six studies, 429 participants; very low-certainty evidence. Three studies (n = 229) found no evidence of a difference between groups. Two studies (n = 141) reported no adverse effects in VR group. One study (n = 59) reported no beneficial effect in reducing estimated cyber-sickness before and after VR immersion. 3: VR distraction versus other VR distraction We did not identify any studies for this comparison. Authors' conclusions We found low-certainty and very low-certainty evidence of the effectiveness of VR distraction compared to no distraction or other non-VR distraction in reducing acute pain intensity in children in any healthcare setting. This level of uncertainty makes it difficult to interpret the benefits or lack of benefits of VR distraction for acute pain in children. Most of the review primary outcomes were assessed by only two or three small studies. We found limited data for adverse effects and other secondary outcomes. Future well-designed, large, high-quality trials may have an important impact on our confidence in the results.

Introduction The association of Vitamin D and children with asthma is known and there are several individual studies on Vitamin D polymorphisms. However, systematic reviews on all vitamin D associated gene polymorphisms have not been done in children with asthma. Objective To investigate the association of Vitamin D associated gene polymorphisms and asthma in children (0–18 years) by systematic review and meta-analytic approach. Methods Our search included 20 full text articles of which 15 were case control studies and 5 used family based linkage disequilibrium method. Total of 2491cases and 3682 controls were included in case control studies, with mean age of 9.58 years and 10.16 years respectively. Quantitative and qualitative analysis were done. Results Quantitative analysis revealed significant association with protective effect of Apa1 polymorphism in allele (OR 0.81 (0.71,0.91) and homozygous major form (OR 0.83 (0.70,0.98) and Taq 1 minor allele in homozygous form (OR 0.73 (0.58,0.92) in children with asthma. However, the minor allele of Apa1(OR 1.21 (1.07,1.37), Bsm 1 in heterozygous (OR 1.35 (1.07,1.71) and homozygous minor form (OR 1.95 (1.59,2.39), major allele of Fok1(OR1.34 (1.17,1.52) and Taq1 (OR 1.22 (1.08,1.38) were found to be increasing the odds of asthma. Ethnic variations were noted in subgroup analysis. Qualitative analysis of the polymorphisms of the Vitamin D associated metabolic genes also showed significant associations. Conclusion Our review shows significant associations with VDR polymorphisms - Apa1, Bsm1, Fok 1, Taq 1, polymorphisms of Vitamin D metabolic genes – CYP27A1, CYP 2R1, CYP 24A1, GC and genes related to Vitamin D response element (VDRE) in children with asthma. Conducting large studies involving various ethnic regions will strengthen our knowledge on the association and aid in targeted interventions for control of asthma in children., Biotechnology; Genetics; Asthma in children; Vitamin D associated gene polymorphisms; Single nucleotide polymorphisms

Background Nutrition is an important aspect of management in severe acute pancreatitis. Enteral nutrition has advantages over parenteral nutrition and is the preferred method of feeding. Enteral feeding via nasojejunal tube is often recommended, but its benefits over nasogastric feeding are unclear. The placement of a nasogastric tube is technically simpler than the placement of a nasojejunal tube. Objectives To compare the mortality, morbidity, and nutritional status outcomes of people with severe acute pancreatitis fed via nasogastric tube versus nasojejunal tube. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS on 17 October 2019 without using any language restrictions. We also searched reference lists and conference proceedings for relevant studies and clinical trial registries for ongoing trials. We contacted authors for additional information. Selection criteria We included randomised controlled trials (RCTs) and quasi-RCTs comparing enteral feeding by nasogastric and nasojejunal tubes in participants with severe acute pancreatitis. Data collection and analysis Two review authors independently screened studies for inclusion, assessed risk of bias of the included studies, and extracted data. This information was independently verified by the other review authors. We used standard methods expected by Cochrane to assess the risk of bias and perform data synthesis. We rated the certainty of evidence according to GRADE. Main results We included five RCTs that randomised a total of 220 adult participants from India, Scotland, and the USA. Two of the trial reports were available only as abstracts. The trials differed in the criteria used to rate the severity of acute pancreatitis, and three trials excluded those who presented in severe shock. The duration of onset of symptoms before presentation in the trials ranged from within one week to four weeks. The trials also differed in the methods used to confirm the placement of the tubes and in what was considered to be nasojejunal placement. We assessed none of the trials as at high risk of bias, though reporting of methods in four trials was insufficient to judge the risk of bias for one or more of the domains assessed. There was no evdence of effect with nasogastric or nasojejunal placement on the primary outcome of mortality (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.36 to 1.17; I2 = 0%; 5 trials, 220 participants; very low-certainty evidence due to indirectness and imprecision). Similarly, there was no evidence of effect on the secondary outcomes for which data were available. These included organ failure (3 trials, 145 participants), rate of infection (2 trials, 108 participants), success rate (3 trials, 159 participants), complications associated with the procedure (2 trials, 80 participants), need for surgical intervention (3 trials, 145 participants), requirement of parenteral nutrition (2 trials, 80 participants), complications associated with feeds (4 trials, 195 participants), and exacerbation of pain (4 trials, 195 participants). However, the certainty of the evidence for these secondary outcomes was also very low due to indirectness and imprecision. Three trials (117 participants) reported on length of hospital stay, but the data were not suitable for meta-analysis. None of the trials reported data suitable for meta-analysis for the other secondary outcomes of this review, which included days taken to achieve full nutrition requirement, duration of tube feeding, and duration of analgesic requirement after feeding tube placement. Authors' conclusions There is insufficient evidence to conclude that there is superiority, inferiority, or equivalence between the nasogastric and nasojejunal mode of enteral tube feeding in people with severe acute pancreatitis.

Early Childhood Caries (ECC) is a serious public health problem in developed as well as developing nations, with high prevalence among children around the world. This systematic review of the national literature was undertaken to document the prevalence of Early Childhood Caries. Studies evaluating the prevalence of Early Childhood Caries (ECC) in the Indian population were investigated. The method under evaluation was the use of a caries experience index to calculate the prevalence of ECC. An extensive literature search was done in the following databases: PubMed, IndMED and Cochrane upto June 2016. A modified version of the Newcastle-Ottawa Scale for cross-sectional studies was used for assessment of the quality of the studies. A systematic literature search yielded 503 publications from the various databases searched. Based on the inclusion and exclusion criteria, the final number of included studies were 54. Among the included studies, 19 studies were carried out in the state of Karnataka. Analysis of all the included studies revealed the overall prevalence of ECC in India to be 49.6%. Andhra Pradesh was found to have the highest prevalence of ECC at 63%, and the lowest prevalence was reported in Sikkim (41.92%). This review has reported a high prevalence of ECC in India. None of the states reported prevalence below 40%. The government should identify ECC as a national priority which requires significant attention.

Background Tuberculosis causes more deaths than any other infectious disease worldwide, with pulmonary tuberculosis being the most common form. Standard first‐line treatment for drug‐sensitive pulmonary tuberculosis for six months comprises isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE) for two months, followed by HRE (in areas of high TB drug resistance) or HR, given over a four‐month continuation phase. Many people do not complete this full course. Shortened treatment regimens that are equally effective and safe could improve treatment success. Objectives To evaluate the efficacy and safety of shortened treatment regimens versus the standard six‐month treatment regimen for individuals with drug‐sensitive pulmonary tuberculosis. Search methods We searched the following databases up to 10 July 2019: the Cochrane Infectious Diseases Group Specialized Register; the Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE (PubMed); Embase; the Latin American Caribbean Health Sciences Literature (LILACS); Science Citation Index‐Expanded; Indian Medlars Center; and the South Asian Database of Controlled Clinical Trials. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform, ClinicalTrials.gov, the Clinical Trials Unit of the International Union Against Tuberculosis and Lung Disease, the UK Medical Research Council Clinical Trials Unit, and the Clinical Trials Registry India for ongoing trials. We checked the reference lists of identified articles to find additional relevant studies. Selection criteria We searched for randomized controlled trials (RCTs) or quasi‐RCTs that compared shorter‐duration regimens (less than six months) versus the standard six‐month regimen for people of all ages, irrespective of HIV status, who were newly diagnosed with pulmonary tuberculosis by positive sputum culture or GeneXpert, and with presumed or proven drug‐sensitive tuberculosis. The primary outcome of interest was relapse within two years of completion of anti‐tuberculosis treatment (ATT). Data collection and analysis Two review authors independently selected trials, extracted data, and assessed risk of bias for the included trials. For dichotomous outcomes, we used risk ratios (RRs) with 95% confidence intervals (CIs). When appropriate, we pooled data from the included trials in meta‐analyses. We assessed the certainty of evidence using the GRADE approach. Main results We included five randomized trials that compared fluoroquinolone‐containing four‐month ATT regimens versus standard six‐month ATT regimens and recruited 5825 adults with newly diagnosed drug‐sensitive pulmonary tuberculosis from 14 countries with high tuberculosis transmission in Asia, Africa, and Latin Ameria. Three were multi‐country trials that included a total of 572 HIV‐positive people. These trials excluded children, pregnant or lactating women, people with serious comorbid conditions, and those with diabetes mellitus. Four trials had multiple treatment arms. Moxifloxacin replaced ethambutol in standard four‐month, daily or thrice‐weekly ATT regimens in two trials; moxifloxacin replaced isoniazid in four‐month ATT regimens in two trials, was given daily in one trial, and was given with rifapentine instead of rifampicin daily for two months and twice weekly for two months in one trial. Moxifloxacin was added to standard ATT drugs for three to four months in one ongoing trial that reported interim results. Gatifloxacin replaced ethambutol in standard ATT regimens given daily or thrice weekly for four months in two trials. Follow‐up ranged from 12 months to 24 months after treatment completion for the majority of participants. Moxifloxacin‐containing four‐month ATT regimens Moxifloxacin‐containing four‐month ATT regimens that replaced ethambutol or isoniazid probably increased the proportions who experienced relapse after successful treatment compared to standard ATT regimens (RR 3.56, 95% CI 2.37 to 5.37; 2265 participants, 3 trials; moderate‐certainty evidence). For death from any cause, there was probably little or no difference between the two regimens (2760 participants, 3 trials; moderate‐certainty evidence). Treatment failure was rare, and there was probably little or no difference in proportions with treatment failure between ATT regimens (2282 participants, 3 trials; moderate‐certainty evidence). None of the participants given moxifloxacin‐containing regimens developed resistance to rifampicin, and these regimens may not increase the risk of acquired resistance (2282 participants, 3 trials; low‐certainty evidence). Severe adverse events were probably little or no different with moxifloxacin‐containing four‐month regimens that replaced ethambutol or isoniazid, and with three‐ to four‐month regimens that augmented standard ATT with moxifloxacin, when compared to standard six‐month ATT regimens (3548 participants, 4 trials; moderate‐certainty evidence). Gatifloxacin‐containing four‐month ATT regimens Gatifloxacin‐containing four‐month ATT regimens that replaced ethambutol probably increased relapse compared to standard six‐month ATT regimens in adults with drug‐sensitive pulmonary tuberculosis (RR 2.11, 95% CI 1.56 to 2.84; 1633 participants, 2 trials; moderate‐certainty evidence). The four‐month regimen probably made little or no difference in death compared to the six‐month regimen (1886 participants, 2 trials; moderate‐certainty evidence). Treatment failure was uncommon and was probably little or no different between the four‐month and six‐month regimens (1657 participants, 2 trials; moderate‐certainty evidence). Acquired resistance to isoniazid or rifampicin was not detected in those given the gatifloxacin‐containing shortened ATT regimen, but we are uncertain whether acquired drug resistance is any different in the four‐ and six‐month regimens (429 participants, 1 trial; very low‐certainty evidence). Serious adverse events were probably no different with either regimen (1993 participants, 2 trials; moderate‐certainty evidence). Authors' conclusions Evidence to date does not support the use of shortened ATT regimens in adults with newly diagnosed drug‐sensitive pulmonary tuberculosis. Four‐month ATT regimens that replace ethambutol with moxifloxacin or gatifloxacin, or isoniazid with moxifloxacin, increase relapse substantially compared to standard six‐month ATT regimens, although treatment success and serious adverse events are little or no different. The results of six large ongoing trials will help inform decisions on whether shortened ATT regimens can replace standard six‐month ATT regimens. 9 December 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (10 Jul, 2019) were included, Plain language summary Shorter treatment regimens for people with pulmonary tuberculosis What was the aim of this review? The aim of this Cochrane Review was to find out if the duration of anti‐tuberculosis treatment (ATT) for people with newly diagnosed drug‐sensitive pulmonary tuberculosis can be shortened to less than six months. Cochrane Review authors collected and analysed all relevant studies to answer this question and found five relevant studies. Key messages Shortened ATT regimens probably make little or no difference in death, treatment failure, or serious adverse events compared to six‐month ATT regimens, but they probably increase relapse of tuberculosis. Six large ongoing trials are studying this question. What was studied in the review? Tuberculosis is an infectious disease, and tuberculosis affecting the lungs (pulmonary tuberculosis) is the most common presentation of tuberculosis in adults. Tuberculosis is a major public health problem worldwide, and among infectious diseases, it is the leading cause of death. People with pulmonary tuberculosis are currently treated with a six‐month combination of drugs that include isoniazid, rifampicin, ethambutol, and pyrazinamide for two months, followed by isoniazid and rifampicin (with or without ethambutol) for four months. Many people do not finish the treatment or they take the drugs irregularly because of the long treatment duration, or because of drug side effects. Incomplete or irregular treatment can lead to treatment failure and can increase disease relapse. Such treatment can also lead to drug resistance. If newer drug combinations given for less than six months are found to be as effective and safe as the currently recommended six‐month ATT regimens, more people might be adherent and might complete treatment. This could help reduce drug resistance and could help to stop tuberculosis infection worldwide. What are the main results of the review? The five included trials studied 5825 adults with newly diagnosed drug‐sensitive pulmonary tuberculosis from 14 countries with high tuberculosis transmission in Asia, Africa, and Latin Ameria. Three trials included 572 HIV‐positive people, but all excluded people with other serious comorbid conditions and those with diabetes mellitus. This reduced the applicability of study results. All were funded by government or international agencies. Four studies replaced isoniazid or ethambutol with moxifloxacin or gatifloxacin in four‐month ATT regimens. Follow‐up was provided for 12 months to 24 months after treatment completion. In one ongoing study, moxifloxacin was added to four‐month ATT, but study authors provided only interim results. This review shows the following when four‐month ATT regimens are compared to standard six‐month ATT regimens. • Relapse after successful treatment is probably increased (moderate‐certainty evidence). • Death from any cause, treatment failure, and serious adverse events are probably little or no different (moderate‐certainty evidence). • Drug resistance may not be increased with moxifloxacin‐containing four‐month regimens (low‐certainty evidence), but we are uncertain whether this applies to gatifloxacin‐containing regimens (very low‐certainty evidence). How up‐to‐date is this review? The review authors searched for available studies up to 10 July 2019.

Pregnancies resulting from assisted reproductive techniques are at higher risk of adverse perinatal outcomes compared with spontaneous conceptions. Underlying infertility and IVF procedures have been linked to adverse perinatal outcomes. It is important to know if ovarian stimulation influences perinatal outcomes after IVF. A systematic search for relevant studies was conducted up to November 2016 on the following databases: PubMed, EMBASE, DARE and Cochrane Central Register of Controlled Trials. Perinatal outcomes included preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA), large for gestational age (LGA) and congenital anomalies. Data from four studies, which included a total of 96,996 and 704 singleton live births after stimulated IVF and natural or modified natural cycle IVF, were included in the meta-analysis. The risk of PTB (RR 1.27, 95% CI 1.03 to 1.58) and LBW (RR 1.95, 95% CI 1.03 to 3.67) were significantly higher after stimulated compared with natural or modified natural cycle IVF. Data from one study were available for SGA, LGA, congenital anomalies and no significant differences were reported between the groups. This study suggests a higher risk of PTB and LBW after stimulated IVF compared with natural or modified natural IVF, although the absolute increase in risk may be low.

Background: There is little evidence in the literature on the association between methylphenidate treatment and psychotic symptoms in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Objective: We examine the occurrence of psychotic symptoms during methylphenidate treatment of children and adolescents with ADHD. The data arise from our two Cochrane systematic reviews on methylphenidate, reported elsewhere. Methods: Electronic databases were searched up to January 2016 (for observational studies) and March 2017 (for randomized trials). We summarized data as risk ratios and pooled prevalences. Trial Sequential Analysis was used to control for random errors. We assessed the risk of bias and the quality of evidence according to Cochrane guidelines. Results: Ten randomized trials (1103 participants), 17 non-randomized studies (76,237 participants) and 12 patient reports or series (18 patients) were identified. In the randomized trials, there was no significant difference in the risk of developing psychotic symptoms [10 of 654 (pooled prevalence, 2.5%) methylphenidate versus 1 of 508 (pooled prevalence, 1.7%) placebo patients; risk ratio, 2.07; 95% confidence interval, 0.58 to 7.35]. Nine of 10 trials had a high risk of bias, and according to the Trial Sequential Analysis, the required information size was not achieved, that is, the meta-analysis was considerably underpowered. There were 873 instances of psychotic symptoms in the non-randomized studies among 55,603 participants (pooled prevalence, 1.2%; 95% confidence interval, 0.7 to 2.4). In the comparative cohort study, methylphenidate significantly increased the risk for any psychotic disorder by 36% (risk ratio, 1.36; 95% confidence interval, 1.17 to 1.57). The overall risk of bias was rated as critical for this study. Conclusions: Because of sparse data and low quality of evidence, we cannot confirm or refute whether methylphenidate increases the risk of psychotic symptoms in children and adolescents with ADHD. This possible adverse event may affect 1.1% to 2.5%, and physicians, patients and caregivers should be aware of this to ensure proper treatment in case of occurrence during methylphenidate treatment.

We planned a systematic review and meta-analysis of randomized clinical trials (RCTs) to examine the best available evidence regarding the intrauterine instillation of embryo culture supernatant prior to embryo transfer in ART. The outcomes were: (i) live birth; (ii) clinical pregnancy; (iii) multiple pregnancy; and (iv) miscarriage rates. Five RCTs were considered eligible and available for qualitative synthesis. Due to clinical heterogeneity, results from only two trials were combined for the meta-analysis. The live birth rate (risk ratio [RR], 0.47; 95% confidence interval [CI] 0.22–0.98; one study, 60 participants, low-quality evidence) was found to be significantly lower with intrauterine instillation of embryo culture supernatant compared to no intervention. The clinical pregnancy rate was similar between the embryo culture supernatant group and the control group (RR 1.02 RR, 95% CI 0.77–1.36; two trials, 156 participants, I2 = 0%). To conclude, this review did not find any improvement in clinical pregnancy rate with the intrauterine instillation of embryo culture supernatant prior to embryo transfer compared to no intervention in women undergoing ART and we remain uncertain regarding its effect on live birth rate.

In this systematic review, we aimed to assess role of plasma von-Willebrand factor (vWF), an endothelial activation marker, as prognostic marker in patients with chronc liver disease [cirrhosis and acute-on-chronic liver failure (ACLF)]. We searched published databases using predefined keywords to identify all studies up to June 2018, in which plasma vWF (antigen or activity assay) was used as prognostic marker predicting mortality in patients with chronic liver disease. Relevant extracted data from selected studies were narratively summarized. The individual study's area under ROC curve for plasma vWF as a predictor of mortality was pooled and meta-analyzed. Six studies (cirrhosis: 5; ACLF: 1) with an aggregate data of 765 patients (cirrhosis: 715 patients; ACLF: 50 patients) were included. Baseline plasma vWF-antigen was an independent predictor of medium-term mortality in patients with cirrhosis (summary area under the curve: 0.74; 95% confidence interval: 0.70-0.79) with an optimal cutoff of 318% (216-390%; median, range) over a period of 25.6 months (23.6-33 months). Plasma vWF also predicted short-term (over 7 days) mortality in patients with ACLF. Plasma vWF levels correlated with Child's score, model for end-stage liver disease (MELD) score and hepatic venous pressure gradient and performed as well as MELD score in predicting mortality in patients with cirrhosis and ACLF. Baseline plasma vWF level predicts mortality over a medium term (1-3 years) in cirrhosis and over a short term (1 week) in ACLF patients. The marked elevation of baseline plasma vWF levels in ACLF patients was associated with drastic truncation of survival when compared with cirrhosis patients.

Objective The aim of this systematic review and meta-analysis is to compare the outcomes of morphine vs. clonidine use as adjuvants in caudal anaesthesia. We are specifically focused on analgesic and side effect profiles. Methods We searched databases and trial registration sites and include here randomised controlled trials that compare the analgesic effects of caudal clonidine vs. morphine as adjuvants on postoperative pain. The risk ratio for evaluating pain scores, the need for rescue analgesia and all adverse effects were assessed. The i2 statistic was used to assess heterogeneity. We also assessed risk of bias with Cochrane's Collaboration tool. The quality of evidence was assessed with Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results Four randomised controlled trials (including 166 patients) that evaluated the use of clonidine vs. morphine as adjuvants in caudal block were included in this systematic review and meta-analysis. The pooled estimate for postoperative analgesia revealed no statistically significant differences between the clonidine group compared to morphine group (MD=2.90; 95% CI 4.05 to 9.85; i2 93%). Significantly less postoperative nausea and vomiting were reported among the patients that received clonidine vs. those that were treated with morphine (RR 0.57, 95% CI -0.36 to -0.90, i2 26%). There were no statistically significant differences between the two groups in assessments that included urinary retention, pain scores or need for rescue analgesia at 24 hours. Conclusion Clonidine is just as effective as morphine when used an adjuvant to local anaesthetic for caudal block, and has a more desirable side effect profile, particularly with respect to postoperative nausea and vomiting.

Background In routine clinical care of Rheumatoid arthritis (RA) Spondyloarthritis(SPA) and Psoriatic arthritis (PSA) there is a high rate of discontinuation of biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) due to loss of efficacy, side effects or lack of adherence. This can impact on the ability to achieve low disease activity. Objectives To evaluate the use of bDMARDs and tsDMARds and analyze the reasons for discontinuation of these drugs and to compare them to our standard DMARD Methotrexate. Methods In this retrospective cohort analysis we included consecutive patients aged ≥ 18 years with RA/SPA/PSA attending 2 Rheumatology clinics in the UAE from August- December 2019. Statistical analysis was performed using STATA version 13 and R-studio. Continuous data were summaries as mean and SD. Dichotomous data were presented as percentage. Chi square test, Proportion test and T-test were applied based on the data type and its distribution to calculated P-value at a 5% level of significance Results Of 745 patients who were included, 453 (60.8%) had RA,165(22.5%) SPA, and 127 (16.7%) PSA. Of these a total of 353(47.3%) received 565 treatment courses with bDMARDs and 106patients had (14.2%) had110 treatment courses with tsDMARD, and 480(64.4%) Methotrexate(MTX) 100/353(28.3%) of patients discontinued bDMARds; 35/106(33.0%) of patients discontinued tsDMARds; and 254/480(52.9%) MTX. 52% of treatment courses of bDMARD andd 36% courses of tsDMARD were discontinued. Reasons for discontinuation are in table 1. Factors such as age, gender,ethinicity were not significantly associated with the rate of discontinuation of medications (Chi-square test). 647/745(86.6%) of patients had medical insurance, however lack of insurance did not lead to discontinuation of bDMARDs (OR=0.54 95% CI (0.22 to 1.32)) and tsDMARDs (OR= 1.59 95% CI:(0.3 – 8.3)). A significant proportion of patients (15% -18%) in all the three groups have stopped the drugs of their own choice. We did not observe any statistical significant difference between the active and discontinued categories with respect to disease activity scores das 28 for RA; BASDAI for SPA and HAQ score for PSA. Conclusion A significantly higher proportion of patients discontinued MTX as compared to bDMARDs and tsDMARDs. Major reason for stopping MTX was side effects while bDMARDs and TsDMARDS were mainly stopped due to loss of efficacy or financial reasons. Safety and tolerability of bDMARDs and tsDMARDs was good in our cohort of patients. References [1] Ebina K,et al. Drug retention and discontinuation reasons between seven biologics in patients with rheumatoid arthritis -The ANSWER cohort study. PLoS One. 2018Mar15;13(3) [2] Favalli EG, et al. Real-life 10-year retention rate of first-line anti-TNF drugs for inflammatory arthritides in adult- andjuvenile-onset populations: similarities and differences. ClinRheumatol. 2017Aug;36(8):1747-1755. Disclosure of Interests None declared

Objective.A systematic literature review was performed to document published magnetic resonance imaging (MRI) lesion definitions and scoring systems for enthesitis in spondyloarthritis (SpA).Methods.PubMed, Embase, and Cochrane Library databases were searched for original publications involving adult patients with SpA undergoing MRI of axial/peripheral joints. Selected articles were assessed for quality using a standardized assessment tool and metric indices.Results.Considering the heterogeneous design, quality, and outcome measures of studies, statistical data pooling was considered inappropriate. A qualitative narrative of results was undertaken based on study designs.Conclusion.Lack of a comprehensive, validated score warrants additional research to develop an MRI enthesitis scoring system. PROSPERO registration number: CRD42018090537.

Background Granulocyte-colony stimulating factor (G-CSF) seems to play an important role in the process of embryo implantation and continuation of pregnancy. It has been used during in vitro fertilisation (IVF) treatment for subfertile women with chronically thin endometrium and those with previous multiple IVF failures. It is currently unknown whether G-CSF is effective in improving results following assisted reproductive technology (ART). Objectives To evaluate the effectiveness and safety of G-CSF in women undergoing ART. Search methods We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform in February 2019. We searched reference lists of relevant articles and handsearched relevant conference proceedings. Selection criteria Randomised controlled trials (RCTs) comparing G-CSF administration versus no treatment or placebo in subfertile women undergoing IVF treatment. Data collection and analysis Two review authors independently screened studies, extracted data, and assessed risk of bias. The primary outcomes were live-birth rate and miscarriage rate following G-CSF administration. We have reported ongoing pregnancy rate in cases where studies did not report live birth but reported ongoing pregnancy. Secondary outcomes were clinical pregnancy rate, multiple pregnancy rate, adverse events, ectopic pregnancy rate, small for gestational age at birth, abnormally adherent placenta, and congenital anomaly rate. We analysed data using risk ratio (RR), Peto odds ratio and a fixed-effect model. We assessed the quality of the evidence using the GRADE criteria. Main results We included 15 trials involving 622 women who received G-CSF and 631 women who received placebo or no additional treatment during IVF. The main limitations in the quality of the evidence were inadequate reporting of study methods and high risk of performance bias due to lack of blinding. We assessed only two of the 15 included trials as at a low risk of bias. None of the trials reported the primary effectiveness outcome of live-birth rate. We are uncertain whether G-CSF administration improves ongoing pregnancy rate compared to control in subfertile women undergoing ART (RR 1.42, 95% confidence interval (CI) 0.83 to 2.42; 2 RCTs; participants = 263; I² = 0%; very low-quality evidence). For a typical clinic with 14% ongoing pregnancy rate, G-CSF administration would be expected to result in ongoing pregnancy rates between 12% and 35%. We are uncertain whether G-CSF administration reduces miscarriage rate (Peto odds ratio 0.55, 95% CI 0.17 to 1.83; 3 RCTs; participants = 391; I² = 0%; very low-quality evidence) compared to the control group in subfertile women undergoing ART. We are uncertain whether G-CSF administration improves overall clinical pregnancy rate compared to control in subfertile women undergoing ART (RR 1.63, 95% CI 1.32 to 2.01; 14 RCTs; participants = 1253; I² = 13%; very low-quality evidence). For a typical clinic with 17% clinical pregnancy rate, G-CSF administration would be expected to result in clinical pregnancy rates between 23% and 35%. In the unselected IVF population, we are uncertain whether G-CSF administration improves clinical pregnancy rate compared to the control group (RR 1.11, 95% CI 0.77 to 1.60; 3 RCTs; participants = 404; I² = 0%; low-quality evidence). G-CSF administration may improve clinical pregnancy rate in women with two or more previous IVF failures compared to the control group (RR 2.11, 95% CI 1.56 to 2.85; 7 RCTs; participants = 643; I² = 0%; low-quality evidence). In subfertile women with thin endometrium undergoing ART, we are uncertain whether G-CSF administration improves clinical pregnancy rate compared to the control group (RR 1.58, 95% CI 0.95 to 2.63; 4 RCTs; participants = 206; I² = 30%; low-quality evidence). No study reported on multiple pregnancy rate. Only four trials reported adverse events as an outcome, and none of them reported any major adverse events following either G-CSF administration or placebo/no treatment. Authors' conclusions In subfertile women undergoing ART, we are uncertain whether the administration of G-CSF improves ongoing pregnancy or overall clinical pregnancy rates or reduces miscarriage rate compared to no treatment or placebo, whether in all women or those with thin endometrium, based on very low-quality evidence. Low-quality evidence suggests that G-CSF administration may improve clinical pregnancy rate in women with two or more IVF failures, but the included studies had unclear allocation concealment or were at high risk of performance bias.

PURPOSE: Although the use of steroids in the management of COVID-19 has been addressed by a few systematic review and meta-analysis, however, they also used data from “SARS-CoV” and “MERS-CoV.” Again, most of these studies addressed only one severity category of patients or addressed only one efficacy endpoint (mortality). In this context, we conducted this meta-analysis to evaluate the efficacy and safety of steroid therapy among all severity categories of patients with COVID-19 (mild to moderate and severe to critical category) in terms of “mortality,” “requirement of mechanical ventilation,” “requirement of ICU” and clinical cure parameters. METHODS: 11 databases were screened. Only randomized controlled trials (RCTs) or high quality (on the basis of risk of bias analysis) comparative-observational studies were included in the analysis. RevMan5.3 was used for the meta-analysis. RESULTS: A total of 15 studies (3 RCT and 12 comparative-observational studies) were included. In the mechanically-ventilated COVID-19 population, treatment with dexamethasone showed significant protection against mortality (single study). Among severe and critically ill combined population, steroid administration was significantly associated with lowered mortality (risk ratio [RR] 0.83 [0.76–0.910]), lowered requirement of mechanical ventilation (RR 0.59 [0.51–0.69]), decreased requirement of intensive care unit (ICU) (RR 0.62 [0.45–0.86]), lowered length of ICU stay (single-study) and decreased duration of mechanical ventilation (two-studies). In mild to moderate population, steroid treatment was associated with a higher “duration of hospital stay,” while no difference was seen in other domains. In patients at risk of progression to “acute respiratory distress syndrome,” steroid administration was associated with “reduced requirement of mechanical ventilation” (single-study). CONCLUSION: This study guides the use of steroid across patients with different severity categories of COVID-19. Among mechanically ventilated patients, steroid therapy may be beneficial in terms of reduced mortality. Among “severe and critical” patients; steroid therapy was associated with lowered mortality, decreased requirement of mechanical ventilation, and ICU. However, no benefit was observed in “mild to moderate” population. To conclude, among properly selected patient populations (based-upon clinical severity and biomarker status), steroid administration may prove beneficial in patients with COVID-19.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of extracorporeal shockwave therapy (ESWT) as a treatment option for men with erectile dysfunction (ED).