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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.

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: 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.

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.

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.

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.

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.

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.

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).

BACKGROUND: Upper gastrointestinal (GI) bleeding due to stress ulcers contributes to increased morbidity and mortality in people admitted to intensive care units (ICUs). Stress ulceration refers to GI mucosal injury related to the stress of being critically ill. ICU patients with major bleeding as a result of stress ulceration might have mortality rates approaching 48.5% to 65%. However, the incidence of stress‐induced GI bleeding in ICUs has decreased, and not all critically ill patients need prophylaxis. Stress ulcer prophylaxis can result in adverse events such as ventilator‐associated pneumonia; therefore, it is necessary to evaluate strategies that safely decrease the incidence of GI bleeding. OBJECTIVES: To assess the effect and risk‐benefit profile of interventions for preventing upper GI bleeding in people admitted to ICUs. SEARCH METHODS: We searched the following databases up to 23 August 2017, using relevant search terms: MEDLINE; Embase; the Cochrane Central Register of Controlled Trials; Latin American Caribbean Health Sciences Literature; and the Cochrane Upper Gastrointestinal and Pancreatic Disease Group Specialised Register, as published in the Cochrane Library (2017, Issue 8). We searched the reference lists of all included studies and those from relevant systematic reviews and meta‐analyses to identify additional studies. We also searched the World Health Organization International Clinical Trials Registry Platform search portal and contacted individual researchers working in this field, as well as organisations and pharmaceutical companies, to identify unpublished and ongoing studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi‐RCTs with participants of any age and gender admitted to ICUs for longer than 48 hours. We excluded studies in which participants were admitted to ICUs primarily for the management of GI bleeding and studies that compared different doses, routes, and regimens of one drug in the same class because we were not interested in intraclass effects of drugs. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as recommended by Cochrane. MAIN RESULTS: We identified 2292 unique records.We included 129 records reporting on 121 studies, including 12 ongoing studies and two studies awaiting classification. We judged the overall risk of bias of two studies as low. Selection bias was the most relevant risk of bias domain across the included studies, with 78 studies not clearly reporting the method used for random sequence generation. Reporting bias was the domain with least risk of bias, with 12 studies not reporting all outcomes that researchers intended to investigate. Any intervention versus placebo or no prophylaxis In comparison with placebo, any intervention seems to have a beneficial effect on the occurrence of upper GI bleeding (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.39 to 0.57; moderate certainty of evidence). The use of any intervention reduced the risk of upper GI bleeding by 10% (95% CI ‐12.0% to ‐7%). The effect estimate of any intervention versus placebo or no prophylaxis with respect to the occurrence of nosocomial pneumonia, all‐cause mortality in the ICU, duration of ICU stay, duration of intubation (all with low certainty of evidence), the number of participants requiring blood transfusions (moderate certainty of evidence), and the units of blood transfused was consistent with benefits and harms. None of the included studies explicitly reported on serious adverse events. Individual interventions versus placebo or no prophylaxis In comparison with placebo or no prophylaxis, antacids, H2 receptor antagonists, and sucralfate were effective in preventing upper GI bleeding in ICU patients. Researchers found that with H2 receptor antagonists compared with placebo or no prophylaxis, 11% less developed upper GI bleeding (95% CI ‐0.16 to ‐0.06; RR 0.50, 95% CI 0.36 to 0.70; 24 studies; 2149 participants; moderate certainty of evidence). Of ICU patients taking antacids versus placebo or no prophylaxis, 9% less developed upper GI bleeding (95% CI ‐0.17 to ‐0.00; RR 0.49, 95% CI 0.25 to 0.99; eight studies; 774 participants; low certainty of evidence). Among ICU patients taking sucralfate versus placebo or no prophylaxis, 5% less had upper GI bleeding (95% CI ‐0.10 to ‐0.01; RR 0.53, 95% CI 0.32 to 0.88; seven studies; 598 participants; moderate certainty of evidence). The remaining interventions including proton pump inhibitors did not show a significant effect in preventing upper GI bleeding in ICU patients when compared with placebo or no prophylaxis. Regarding the occurrence of nosocomial pneumonia, the effects of H2 receptor antagonists (RR 1.12, 95% CI 0.85 to 1.48; eight studies; 945 participants; low certainty of evidence) and of sucralfate (RR 1.33, 95% CI 0.86 to 2.04; four studies; 450 participants; low certainty of evidence) were consistent with benefits and harms when compared with placebo or no prophylaxis. None of the studies comparing antacids versus placebo or no prophylaxis provided data regarding nosocomial pneumonia. H2 receptor antagonists versus proton pump inhibitors H2 receptor antagonists and proton pump inhibitors are most commonly used in practice to prevent upper GI bleeding in ICU patients. Proton pump inhibitors significantly more often prevented upper GI bleeding in ICU patients compared with H2 receptor antagonists (RR 2.90, 95% CI 1.83 to 4.58; 18 studies; 1636 participants; low certainty of evidence). When taking H2 receptor antagonists, 4.8% more patients might experience upper GI bleeding (95% CI 2.1% to 9%). Nosocomial pneumonia occurred in similar proportions of participants taking H2 receptor antagonists and participants taking proton pump inhibitors (RR 1.02, 95% CI 0.77 to 1.35; 10 studies; 1256 participants; low certainty of evidence). AUTHORS' CONCLUSIONS: This review shows that antacids, sucralfate, and H2 receptor antagonists might be more effective in preventing upper GI bleeding in ICU patients compared with placebo or no prophylaxis. The effect estimates of any treatment versus no prophylaxis on nosocomial pneumonia were consistent with benefits and harms. Evidence of low certainty suggests that proton pump inhibitors might be more effective than H2 receptor antagonists. Therefore, patient‐relevant benefits and especially harms of H2 receptor antagonists compared with proton pump inhibitors need to be assessed by larger, high‐quality RCTs to confirm the results of previously conducted, smaller, and older studies.

Background Edentulism is relatively common and is often treated with the provision of complete or partial removable dentures. Clinicians make final impressions of complete dentures (CD) and removable partial dentures (RPD) using different techniques and materials. Applying the correct impression technique and material, based on an individual's oral condition, improves the quality of the prosthesis, which may improve quality of life. Objectives To assess the effects of different final-impression techniques and materials used to make complete dentures, for retention, stability, comfort, and quality of life in completely edentulous people.To assess the effects of different final-impression techniques and materials used to make removable partial dentures, for stability, comfort, overextension, and quality of life in partially edentulous people. Search methods Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 22 November 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Register of Studies, to 22 November 2017), MEDLINE Ovid (1946 to 22 November 2017), and Embase Ovid (21 December 2015 to 22 November 2017). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on language or publication status when searching the electronic databases, however the search of Embase was restricted by date due to the Cochrane Centralised Search Project to identify all clinical trials and add them to CENTRAL. Selection criteria We included randomised controlled trials (RCTs) comparing different final-impression techniques and materials for treating people with complete dentures (CD) and removable partial dentures (RPD). For CD, we included trials that compared different materials or different techniques or both. In RPD for tooth-supported conditions, we included trials comparing the same material and different techniques, or different materials and the same technique. In tooth- and tissue-supported RPD, we included trials comparing the same material and different dual-impression techniques, and different materials with different dual-impression techniques. Data collection and analysis Two review authors independently, and in duplicate, screened studies for eligibility, extracted data, and assessed the risk of bias for each included trial. We expressed results as risk ratios (RR) for dichotomous outcomes, and as mean differences (MD) or standardised mean differences (SMD) for continuous outcomes, with 95% confidence intervals (CI), using the random-effects model. We constructed 'Summary of findings' tables for the main comparisons and outcomes (participant-reported oral health-related quality of life, quality of the denture, and denture border adjustments). Main results We included nine studies in this review. Eight studies involved 485 participants with CD. We assessed six of the studies to be at high risk of bias, and two to be at low risk of bias. We judged one study on RPD with 72 randomised participants to be at high risk of bias.Overall, the quality of the evidence for each comparison and outcome was either low or very low, therefore, results should be interpreted with caution, as future research is likely to change the findings.Complete denturesTwo studies compared the same material and different techniques (one study contributed data to a secondary outcome only); two studies compared the same technique and different materials; and four studies compared different materials and techniques.One study (10 participants) evaluated two stage-two step, Biofunctional Prosthetic system (BPS) using additional silicone elastomer compared to conventional methods, and found no evidence of a clear difference for oral health-related quality of life, or quality of the dentures (denture satisfaction). The study reported that BPS required fewer adjustments. We assessed the quality of the evidence as very low.One study (27 participants) compared selective pressure final-impression technique using wax versus polysulfide elastomeric (rubber) material. The study did not measure quality of life or dentures, and found no evidence of a clear difference between interventions in the need for adjustments (RR 0.81, 95% CI 0.38 to 1.70). We assessed the quality of the evidence as very low.One study compared two stage-two step final impression with alginate versus silicone elastomer. Oral health-related quality of life measured by the OHIP-EDENT seemed to be better with silicone (MD 7.20, 95% CI 2.71 to 11.69; 144 participants). The study found no clear differences in participant-reported quality of the denture (comfort) after a two-week 'confirmation' period, but reported that silicone was better for stability and chewing efficiency. We assessed the quality of the evidence as low.Three studies compared single-stage impressions with alginate versus two stage-two step with elastomer (silicone, polysulfide, or polyether) impressions. There was no evidence of a clear difference in the OHIP-EDENT at one month (MD 0.05, 95% CI -2.37 to 2.47; two studies, 98 participants). There was no evidence of a clear difference in participant-rated general satisfaction with dentures at six months (MD 0.00, 95% CI -8.23 to 8.23; one study, 105 participants). We assessed the quality of the evidence as very low.One study compared single-stage alginate versus two stage-two step using zinc-oxide eugenol, and found no evidence of a clear difference in OHIP-EDENT (MD 0.50, 95% CI -2.67 to 3.67; 39 participants), or general satisfaction (RR 3.15, 95% CI 0.14 to 72.88; 39 participants) at six months. We assessed the quality of the evidence as very low.Removable partial denturesOne study randomised 72 participants and compared altered-cast technique versus one-piece cast technique. The study did not measure quality of life, but reported that most participants were satisfied with the dentures and there was no evidence of any clear difference between groups for general satisfaction at one-year follow-up (low-quality evidence). There was no evidence of a clear difference in number of intaglio adjustments at one year (RR 1.43, 95% CI 0.61 to 3.34) (very low-quality evidence). Authors' conclusions We conclude that there is no clear evidence that one technique or material has a substantial advantage over another for making complete dentures and removable partial dentures. Available evidence for the relative benefits of different denture fabrication techniques and final-impression materials is limited and is of low or very low quality. More high-quality RCTs are required.

Background Early and accurate diagnosis of tuberculosis is a priority for TB programs globally to initiate treatment early and improve treatment outcomes. Currently, Ziehl–Neelsen (ZN) stain-based microscopy, GeneXpert and Light Emitting Diode-Fluorescence Microscopy (LED-FM) are used for diagnosing pulmonary drug sensitive tuberculosis. Published evidence synthesising the cost-effectiveness of these diagnostic tools is scarce. Methodology PubMed, EMBASE and Cost-effectiveness analysis registry were searched for studies that reported on the cost-effectiveness of GeneXpert and LED-FM, compared to ZN microscopy for diagnosing pulmonary TB. Risk of bias was assessed independently by four authors using the Consensus Health Economic Criteria (CHEC) extended checklist. The data variables included the study settings, population, type of intervention, type of comparator, year of study, duration of study, type of study design, costs for the test and the comparator and effectiveness indicators. Incremental cost-effectiveness ratio (ICER) was used for assessing the relative cost-effectiveness in this review. Results Of the 496 studies identified by the search, thirteen studies were included after removing duplicates and studies that did not fulfil inclusion criteria. Four studies compared LED-FM with ZN and nine studies compared GeneXpert with ZN. Three studies used patient cohorts and eight were modelling studies with hypothetical cohorts used to evaluate cost-effectiveness. All these studies were conducted from a health system perspective, with four studies utilising cost utility analysis. There were considerable variations in costing parameters and effectiveness indicators that precluded meta-analysis. The key findings from the included studies suggest that LED-FM and GeneXpert may be cost effective for pulmonary TB diagnosis from a health system perspective. Conclusion Our review identifies a consistent trend of the cost effectiveness of LED-FM and GeneXpert for pulmonary TB diagnosis in different countries with diverse context of socio-economic condition, HIV burden and geographical distribution. However, all the studies used different parameters to estimate the impact of these tools and this underscores the need for improving the methodological issues related to the conduct and reporting of cost-effectiveness studies.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of occlusal interventions in people diagnosed with TMD, compared to other interventions or no treatment, for reduction in joint pain, muscle pain at rest and during mastication, quality of life, and discomfort.

To summarise the evidence for the efficacy of oral health educational programmes provided to expectant mothers for preventing Early Childhood Caries (ECC) and to determine the most effective intervention programme.The search strategy included clinical trials in the Cochrane Oral Health Group's Trials Register, PubMed, Science Direct, Google Scholar, LILACS and ClinicalKey (up to 26 August 2013) in English. Reference lists of identified randomised controlled trials (RCTs) and review articles were also hand searched. Studies were selected according to predefined inclusion and exclusion criteria.The search identified 392 studies, only four of which were included. Risk ratios (RR) were calculated. The quality of the evidence was assessed by the GRADE approach. Results showed statistically significant decreases in caries incidence (RR = 0.18, 95% CI [from 0.06 to 0.52]) in one study. Meta-analysis could not be performed.Oral health educational programmes for expectant mothers may have a positive impact in preventing ECC, although the evidence is weak.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the efficacy and safety of prophylactic paracetamol to prevent fever in children receiving vaccination as part of a childhood immunization schedule.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the efficacy of thalidomide in the treatment of gastrointestinal angiodysplasia and the side effects associated with its use.

Granulocyte-colony stimulating factor (G-CSF), a glycoprotein, has been used in women undergoing Assisted Reproductive Technology (ART). We decided to undertake a systematic review to evaluate the effectiveness of G-CSF in women with thin endometrium and recurrent implantation failure (RIF) undergoing ART. The outcomes included an increase in endometrial thickness, live birth, clinical pregnancy rates and adverse effects. We included two trials evaluating women with thin endometrium and another two trials evaluating women with RIF. The pooled data did not reveal statistically significant increase in endometrial thickness following G-CSF in women with thin endometrium (mean difference 0.47, 95% CI -1.36-2.31; I2 82%). However significantly higher clinical pregnancy rate was noted (RR 2.43, 95% CI 1.09-5.40; I2 0%) following G-CSF compared to no intervention and quality of evidence for both these outcomes was very low. In RIF population, the administration of G-CSF was associated with a significantly higher clinical pregnancy rate compared to no intervention with pooled risk ratio of 2.51 (95% CI 1.36-4.63; I2 0%) and quality of evidence being low. Findings of current review suggest a possible benefit of G-CSF in women with thin endometrium undergoing ART and RIF. However these findings need to be further validated in larger trials before G-CSF can be used in routine clinical practice.