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Aim The aim of this systematic review was to evaluate the efficacy of anti-plaque chemical formulations for managing gingivitis, in 6-month, home-use, randomised clinical trials ( RCTs). Material and Methods A protocol was designed, including inclusion and exclusion criteria to identify RCTs assessing gingival and/or bleeding indices. Electronic and hand-searches identified relevant papers, which were screened and evaluated for inclusion. Full-papers were retrieved and relevant information was extracted (also plaque indices), including quality and risk of bias. Mean treatment effects were calculated to obtain weighted mean differences ( WMD) and 95% confidence intervals. Results After the process of screening and selection, 87 articles with 133 comparisons, were included in the review. The additional effects of the tested products were statistically significant in terms of Löe & Silness gingival index (46 comparisons, WMD −0.217), modified gingival index ( n = 23, −0.415), gingivitis severity index ( n = 26, −14.939%) or bleeding index ( n = 23, −7.626%), with significant heterogeneity. For plaque, additional effects were found for Turesky (66 studies, WMD −0.475), Silness & Löe ( n = 26, −0.109), and plaque severity ( n = 12, −23.4%) indices, with significant heterogeneity. Conclusion Within the limitations of the present study, formulations with specific agents for chemical plaque control provide statistically significant improvements in terms of gingival, bleeding and plaque indices. [ABSTRACT FROM AUTHOR]

Aim To report the evidence on the effect of mechanical and/or chemical plaque control in the simultaneous management of gingivitis and caries. Material and Methods A protocol was designed to identify randomized ( RCTs) and controlled ( CCTs) clinical trials, cohort studies and prospective case series ( PCS), with at least 6 months of follow-up, reporting on plaque, gingivitis and caries. Relevant information was extracted from full papers, including quality and risk of bias. Meta-analyses were performed whenever possible. Results After the screening of 1,373 titles, 15 RCTs, 10 CCTs and 2 PCS were included. Low to moderate evidence support that combined professional and self-performed mechanical plaque control significantly reduces standardized plaque index [ n = 4; weighted mean difference ( WMD) = 1.294; 95% CI (0.445; 2.144); p = 0.003] and gingivitis scores [ n = 4; WMD = 1.728; 95% CI (0.631; 2.825); p = 0.002]. The addition of fluoride to mechanical plaque control is relevant for caries management [ n = 5; WMD = 1.159; 95% CI (0.145; 2.172); p = 0.025] while chlorhexidine rinses are relevant for gingivitis. Conclusion Mechanical plaque control procedures are effective in reducing plaque and gingivitis. The addition of fluoride to mechanical plaque control is significant for caries management. Chlorhexidine rinse has a positive effect on gingivitis and inconclusive role in caries. [ABSTRACT FROM AUTHOR]

Objective We aimed to explore whether the prevalence of manic switch was underestimated in randomized controlled trials ( RCTs) compared to observational studies ( OSs). Method Meta-analyses and simple and systematic reviews were identified by two reviewers in a blinded, standardized manner. All relevant references were extracted to include RCTs and OSs that provided data about manic switch prevalence after antidepressant treatment for a major depressive episode. The primary outcome was manic switch prevalence in the different arms of each study. A meta-regression was conducted to quantify the impact of certain variables on manic switch prevalence. Results A total of 57 papers (35 RCTs and 22 OSs) were included in the main analysis. RCTs underestimated the rate of manic switch [0.53 (0.32-0.87)]. Overestimated prevalence was related to imipraminics [1.85 (1.22-2.79)]; to serotonin-norepinephrine reuptake inhibitors [1.74 (1.06-2.86)]; and to other classes of drugs [1.58 (1.08-2.31)], compared to placebo treatment. The prevalence of manic switch was lower among adults than among children [0.2 (0.07-0.59)]; and higher [20.58 (8.41-50.31)] in case of bipolar disorder. Conclusion Our results highlight an underestimation of the rates of manic switch under antidepressants in RCTs compared to the rates observed in observational studies. [ABSTRACT FROM AUTHOR]

Background Both misoprostol and prostaglandin E2 (PGE2) gel are used for labor induction in women with premature rupture of membranes (PROM). Objectives To evaluate studies comparing the effects of misoprostol and PGE2 gel in labor induction. Search strategy Databases including Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched for relevant papers. Selection criteria Randomized controlled trials comparing the use of misoprostol and PGE2 gel for labor induction in women with PROM were included. Data collection and analysis For meta-analyses, the Mantel–Haenszel method was used for dichotomous data, and the inverse variance method was used for continuous data. Main results Four randomized controlled studies (n = 615) were included. There were no significant differences between the two groups in the induction-to-delivery interval (mean difference – 4.44 hours; 95% confidence interval [CI] –9.35 to 0.48), rate of cesarean delivery (odds ratio [OR] 0.90; 95% CI 0.44–1.85), and rate of neonatal intensive care unit admission (OR 0.89; 95% CI 0.57–1.38). Women receiving misoprostol had a significantly higher rate of tachysystole than did those receiving PGE2 gel (OR 4.84; 95% CI 2.46–9.54). Conclusions Misoprostol is as efficacious and safe as PGE2 gel for labor induction in women with PROM. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of sirolimus (SIR)-based graft-versus-host disease (GVHD) prophylaxis in patients who were subjected to allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain to be clarified; this meta-analysis was conducted to evaluate these factors.Study Design and Methods: Data from original research were obtained from PubMed, Embase, and Cochrane central register of controlled trials databases. Randomized controlled trials (RCTs) evaluating the efficacy of SIR-based prophylaxis in allo-HSCT were included. The risk ratio (RR), with a 95% confidence interval (CI), was used to pool data. The random effects model was used, irrespective of the presence or absence of heterogeneity.Results: Five RCTs were included in the meta-analysis. SIR was observed to significantly decrease the incidence of Grade II to IV acute GVHD (aGVHD; RR, 0.65; 95% CI, 0.47-0.89). However, the incidence of Grade III to IV aGVHD and chronic GVHD was not decreased (RR, 0.91; 95% CI, 0.59-1.40; RR, 1.04; 95% CI, 0.88-1.23, respectively). An analysis of the toxic effects of SIR revealed that SIR effected a significant increase in the incidence of sinusoidal obstructive syndrome (RR, 2.24; 95% CI, 1.26-4.01), while that of thrombotic microangiopathy was not significantly increased (RR, 2.48; 95% CI, 0.87-7.06). Moreover, SIR did not improve event-free survival and overall survival (RR, 0.97; 95% CI, 0.85-1.10; and RR, 0.92; 95% CI, 0.82-1.02, respectively).Conclusion: This meta-analysis indicated that the SIR-based regimen is an effective and safe alternative prophylaxis strategy for GVHD. [ABSTRACT FROM AUTHOR]

Aim: We performed a systematic review and meta‐analysis to compare the efficacy and safety of ticagrelor and prasugrel with those of clopidogrel in CYP2C19 reduced‐metabolizers. Methods: PubMed, Cochrane and Web of Science were systematically searched for randomized controlled trials or cohort studies up to January 2020. The primary endpoint was major adverse cardiovascular events (MACE), including cardiovascular (CV) death, all‐cause death, myocardial infarction (MI), stent thrombosis and stroke. The secondary endpoint was bleeding. Pooled effects were measured by relative risk (RR) with 95% confidence intervals (CIs). Publication bias was evaluated with Egger's regression test and adjusted by trim and fill method. Results: Twelve studies comprising 5829 CV patients with CYP2C19 loss‐of‐function alleles were included. Patients who received ticagrelor or prasugrel showed a lower risk of MACE than those who received clopidogrel (RR 0.524; 95% CI: 0.375, 0.731). The former also had lower risks of CV death (RR 0.409; 95% CI: 0.177, 0.946), all‐cause death (RR 0.441; 95% CI: 0.263, 0.739), MI (RR 0.554; 95% CI: 0.414, 0.741) and stent thrombosis (RR 0.587; 95% CI: 0.348, 0.988) than the latter patient group. The risk of stroke was not significantly different between patients receiving the alternatives and those receiving clopidogrel (RR 0.605; 95% CI: 0.257, 1.425). Major and minor bleeding risk was not significantly different between patients treated with alternatives and clopidogrel (RR 1.019; 95% CI: 0.827, 1.260 and RR 1.235; 95% CI: 0.581, 2.628, respectively). Conclusion: CYP2C19 reduced‐metabolizers can expect better clinical outcome on using prasugrel or ticagrelor rather than clopidogrel. [ABSTRACT FROM AUTHOR]

Objectives: Cariprazine is a partial agonist at D2/D3 receptors that has been approved for the treatment of mania associated with bipolar disorder (BD). This meta‐analysis aimed to assess the efficacy and tolerability of cariprazine in the treatment of BD. Methods: Randomized controlled trials investigating the efficacy of cariprazine in BD were included. Of the 391 studies yielded by search, 7 were included. The PRISMA protocol was followed and a set of analyses involving random‐effects model with restricted maximum‐likelihood estimator were used to synthesize effect sizes. Results: Cariprazine was associated with a moderate and significant reduction of manic symptoms based on YMRS change scores (SMD: −0.52; 95%CI: −0.82 to −0.21; P =.018). Cariprazine resulted in significantly higher remission (OR: 2.05; 95%CI: 1.61‐2.61; P =.006) and response rates (OR: 2.31; 95%CI: 1.35‐3.95; P =.021) for manic and mixed episodes compared with placebo. Both cariprazine 1.5 mg and 3 mg doses were associated with small but significant reduction in depressive symptoms assessed with MADRS scores (SMD: −0.26, 95%CI: −0.49 to −0.02; P =.040) (SMD: −0.21, 95%CI: −0.41 to −0.01; P =.045), respectively. Cariprazine was significantly associated with the development of adverse effects but not with dropouts due to these adverse effects, when compared to placebo. Conclusion: Cariprazine appears to be safe and efficacious in the treatment of acute mania and mixed episodes associated with BD. Cariprazine at doses of 1.5‐3 mg/day is efficacious in acute bipolar depression but the effect sizes were smaller. Controlled studies evaluating its efficacy for prophylaxis are needed. [ABSTRACT FROM AUTHOR]

Aim: We aimed to systematically assess the evidence on the efficacy and safety of alpha‐blockers in patients with multiple sclerosis (MS) suffering from neurogenic lower urinary tract dysfunction (NLUTD). Methods: The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement was used to perform this systematic review. An electronic search of Cochrane register, Embase, Medline, Scopus (last search 3 March 2018) and screening of reference lists as well as reviews were used to identify the studies. Articles were included if they reported on efficacy/safety of alpha‐blockers for the treatment of NLUTD in patients with MS. Results: After screening of 7′015 abstracts, three studies enrolling a total of 50 patients were included: one randomized, placebo‐controlled, single‐blind trial and two prospective cohort studies. Alpha‐blocker treatment was successful in 50% to 96% of the patients. Pooling data from the three included studies, the relative risk for successful alpha‐blocker treatment was 3.89 (95% confidence interval 2.7‐7.0). The general safety profile of alpha‐blockers was favorable with 8% of the patients reporting adverse events. Conclusions: Alpha‐blockers may be effective and safe for treating NLUTD in female and male patients with MS but the studies were small and the overall quality of evidence was low. To make definitive conclusions, well designed randomized controlled trials are highly warranted. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine (TCM) has recorded knowledge of diabetes for over 2000 years. Because a considerable number of TCM studies exhibit design defects, such as limited intervention duration, small sample sizes and inconsistent efficacy evaluations, the role of TCM in the treatment of diabetes cannot be fully elucidated. In this review, we evaluate randomized controlled trials of prediabetes, diabetes and diabetic complications published in the past decade. We found that TCM could significantly improve glucose control and clinical indices in patients with diabetes and effectively delay the progression of diabetes. We also summarize potential pharmacological mechanisms underlying the efficacy of TCM medication/herbs and their active ingredients for treating diabetes. More rigorously designed experiments and long‐term evaluation of TCM for diabetes will allow for more effective diabetes management. [ABSTRACT FROM AUTHOR]

Aim: The aim of this meta‐analysis of randomized trials was to assess the effects of SGLT‐2i on the overall incidence of malignancies and on different types of cancer, summerizing the results of trials with a duration of at least 1 year. This was done in light of the effect of SGLT‐2 inhibitors (SGLT‐2is) that has been highlighted by some studies, showing an increased incidence of bladder cancer, particularly with use of empagliflozin. Materials and methods: A Medline and Embase search for "Canaglifozin", "Dapaglifozin", "Empaglifozin", "Ertuglifozin", "Ipraglifozin", Tofoglifozin" or "Luseoglifozin" was performed, identifying randomized trials with a duration of more than 52 weeks up to 1 December 2018 that compared SGLT‐2is with placebo or active comparators. The outcomes considered were all types of cancer and several site‐specific cancers (ie, breast, pulmonary, gastrointestinal, hepatic, pancreatic, skin, prostate and bladder). Mantel–Haenszel odds ratios with 95% Confidence Intervals (MH‐OR, 95% CI) were calculated for all outcomes. Results: A total of 27 trials fulfilled the inclusion criteria. Retrieved trials had enrolled 27 744 and 20 441 patients in SGLT‐2 inhibitor and comparator groups, respectively. No difference was observed in the incidence of all malignancies between patients allocated to SGLT‐2i and comparators (MH‐OR 0.98[0.77–1.24]). The incidence of bladder cancer, and of any other type of cancer, was not significantly increased by treatment with any SGLT‐2i. Conclusions: Available data from randomized trials do not suggest a detrimental effect of SGLT‐2is on the incidence of malignancies in general, or in bladder cancer in particular. [ABSTRACT FROM AUTHOR]

Objective: To assess the effects of non‐pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Patients and Methods: We performed a comprehensive search using multiple databases, trial registries, grey literature and conference proceedings with no restrictions on the language of publication or publication status. The date of the latest search of all databases was August 2017. We included randomized controlled trials in men with a diagnosis of CP/CPPS. We included all available non‐pharmacological interventions. Two review authors independently classified studies and abstracted data from the included studies, performed statistical analyses and rated quality of evidence (QoE) according to the Grading of Recommendations Assessment, Development and Evaluation methods. The primary outcomes were prostatitis symptoms and adverse events. The secondary outcomes were sexual dysfunction, urinary symptoms, quality of life, anxiety and depression. Results: We included 38 unique studies in 3290 men with CP/CPPS across 23 comparisons, reporting outcomes mostly at short‐term follow‐up. Our analysis showed that acupuncture probably leads to clinically meaningful reduction in prostatitis symptoms compared with a sham procedure (mean difference [MD] in total National Institutes of Health – Chronic Prostatitis Symptom Index [NIH‐CPSI] score −5.79, 95% confidence interval [CI] −7.32 to −4.26, moderate QoE). Acupuncture may result in little or no difference in adverse events (low QoE). Acupuncture may also lead to a clinically meaningful reduction in prostatitis symptoms compared with standard medical therapy (MD −6.05, 95% CI −7.87 to −4.24, two studies, 78 participants, low QoE). Lifestyle modifications may be associated with a reduction in prostatitis symptoms compared with control (risk ratio for improvement in NIH‐CPSI scores 3.90, 95% CI 2.20 to 6.92, very low QoE), but we found no information regarding adverse events. A physical activity programme may cause a small reduction in prostatitis symptoms compared with control (NIH‐CPSI score MD −2.50, 95% CI −4.69 to −0.31, low QoE), but we found no information regarding adverse events. It was uncertain whether prostatic massage reduces or increases prostatitis symptoms compared with control (very low QoE) and we found no information regarding adverse events. Extracorporeal shockwave therapy reduces prostatitis symptoms compared with control (NIH‐CPSI score MD −6.18, 95% CI −7.46 to −4.89, high QoE), but these results may not be sustained at medium‐term follow‐up (low QoE). This treatment may not be associated with a greater incidence of adverse events (low QoE). Transrectal thermotherapy, alone or in combination with medical therapy, may decrease prostatitis symptoms slightly when compared with medical therapy alone (NIH‐CPSI score MD −2.50, 95% CI −3.82 to −1.18, low QoE). One included study reported that participants may experience transient adverse events. Conclusions: Based on the findings with moderate to high QoE, this review found that some non‐pharmacological interventions, such as acupuncture and extracorporeal shockwave therapy, are likely to result in a decrease in prostatitis symptoms and may not be associated with a greater incidence of adverse events. The QoE for most other comparisons was predominantly low. Future clinical trials should include a full report of their methods, including adequate masking, consistent assessment of all patient‐important outcomes including potential treatment‐related adverse events and appropriate sample sizes. [ABSTRACT FROM AUTHOR]

Network meta-analysis (NMA) technique extends the standard meta-analysis methods, allowing pairwise comparison of all treatments in a network in the absence of head-to-head comparisons. Traditional NMA models consider a single endpoint for each trial. However, in many cases, trials in the network have different durations and/or report data at multiple time points. Moreover, these time points are often not the same for all trials. In this work, we review the most relevant methods that incorporate multiple time points and allow indirect comparisons of treatment effects across different longitudinal studies. In particular, we focus on the mixed treatment comparison developed by Dakin et al,[10] on the Bayesian evidence synthesis techniques-integrated two-component prediction developed by Ding et al,[11] and on the more recent method based on fractional polynomials by Jansen et al.[12] We highlight the main features of each model and illustrate them in simulations and in a real data application. Our study shows that methods based on fractional polynomials offer a flexible modeling strategy in most applications. [ABSTRACT FROM AUTHOR]

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) results in a progressively worsening course associated with substantial morbidity and mortality. The purpose of this comprehensive study was to determine the clinical efficacy of targeted therapeutic interventions for this disease. Methods: We searched Medline, Embase, Cochrane databases and Pubmed for relevant clinical studies. Randomized controlled trials comparing the effects of targeted treatments to control in CTEPH population were included. Pooled estimates were calculated using a random effect model. Heterogeneity was determined using the I2 statistic. Results: This analysis included 6 studies with a total of 565 patients. We found that targeted treatments approved for pulmonary arterial hypertension (PAH) were associated with a larger improvement in exercise capacity, haemodynamic parameters, functional status and clinical symptom. There were no statistically significant differences associated with targeted treatments compared with control in all‐cause mortality and safety outcomes. Conclusions: This is the first systematic review and meta‐analysis of randomized controlled trials revealing a positive role of PAH‐targeted therapies in CTEPH. Future larger randomized trials with a focus on long‐term clinical outcomes are urgently needed. [ABSTRACT FROM AUTHOR]

Background: Tranexamic acid (TXA) is an inexpensive therapy effective at minimizing perioperative blood loss and transfusion. However, it remains underutilized due to safety concerns. To date, no evidence-based guidelines exist identifying which patients should not receive TXA therapy. This study determined patient groups for whom safety information regarding TXA is lacking due to common exclusion from perioperative TXA trials.Study Design and Methods: A systematic review searching the databases Medline, EMBASE, CENTRAL, and Clinicaltrials.gov was performed. Randomized controlled trials (RCTs) administering systemic TXA perioperatively to elective or emergent surgery patients were eligible. Our primary outcome was to describe exclusion criteria of RCTs, and the secondary outcome was TXA safety. A descriptive synthesis of exclusion criteria was performed, and TXA safety was assessed by meta-analysis.Results: A total of 268 eligible RCTs were included. Meta-analysis showed that systemic TXA did not increase risk of adverse events compared to placebo or no intervention (relative risk, 1.05; 95% confidence interval, 0.99-1.12). Patient groups commonly excluded from perioperative TXA trials, and thus potentially lacking TXA safety data, were those with major comorbidities, a history of thromboembolism, medication use affecting coagulation, TXA allergy, and coagulopathy. Exclusion of patients with major comorbidities may not be necessary; we showed that the risk of adverse events was similar in studies that excluded patients with major comorbidities and those that did not.Conclusion: Sufficient evidence exists to develop perioperative guidelines for TXA use in many populations. Further studies evaluating perioperative TXA use in patients with a history of thromboembolism are warranted. [ABSTRACT FROM AUTHOR]

Objectives: The effectiveness of psychological therapies for those receiving acute adult mental health inpatient care remains unclear, partly because of the difficulty in conducting randomized controlled trials (RCTs) in this setting. The aim of this meta‐analysis was to synthesize evidence from all controlled trials of psychological therapy carried out with this group, to estimate its effects on a number of important outcomes and examine whether the presence of randomization and rater blinding moderated these estimates. Method: A systematic review and meta‐analysis of all controlled trials of psychological therapy delivered in acute inpatient settings was conducted, with a focus on psychotic symptoms, readmissions or emotional distress (anxiety and depression). Studies were identified through ASSIA, EMBASE, CINAHL, Cochrane, MEDLINE, and PsycINFO using a combination of the key terms ‘inpatient’, ‘psychological therapy’, and ‘acute’. No restriction was placed on diagnosis. The moderating effect of the use of assessor‐blind RCT methodology was examined via subgroup and sensitivity analyses. Results: Overall, psychological therapy was associated with small‐to‐moderate improvements in psychotic symptoms at end of therapy but the effect was smaller and not significant at follow‐up. Psychological therapy was also associated with reduced readmissions, depression, and anxiety. The use of single‐blind randomized controlled trial methodology was associated with significantly reduced benefits on psychotic symptoms and was also associated with reduced benefits on readmission and depression; however, these reductions were not statistically significant. Conclusions: The provision of psychological therapy to acute psychiatric inpatients is associated with improvements; however, the use of single‐blind RCT methodology was associated with reduced therapy‐attributable improvements. Whether this is a consequence of increased internal validity or reduced external validity is unclear. Trials with both high internal and external validity are now required to establish what type, format, and intensity of brief psychological therapy is required to achieve sustained benefits. Practitioner points: Clinical implications: This review provides the first meta‐analytical synthesis of brief psychological therapy delivered in acute psychiatric inpatient settings. This review suggests that brief psychological therapy may be associated with reduced emotional distress and readmissions. Limitations: The evidence in this review is of limited quality. The type, format, and intensity of brief psychological therapy required to achieve sustained benefits are yet to be established. [ABSTRACT FROM AUTHOR]

Aims: A network meta-analysis (NMA) of all recommended drug groups for the treatment of heart failure with reduced ejection fraction (HFrEF), including their combinations, was performed to assess the relative efficacy and incremental benefit.Methods and Results: A search was made in biomedical databases for randomized controlled trials published between 1987 and 2017 on angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers (BBs), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs), ivabradine (IVA), or angiotensin receptor-neprilysin inhibitors (ARNI). A total of 58 relevant trials were identified. The relative efficacy of each treatment group (or combination) in terms of all-cause mortality, cardiovascular mortality, all-cause hospitalizations and hospitalizations for heart failure, per patient-year of follow-up, were combined in a random-effects Bayesian NMA. The pairwise comparison between each regimen and for each outcome was estimated. The NMA was dominated by 15 large-scale trials with between 1984 and 18 898 patient-years of follow-up. Combinations of drug groups showed incremental benefits on outcomes over single groups. The most effective combinations were ARNI+BB + MRA and ACEI+BB + MRA + IVA, showing reductions in all-cause mortality (vs. placebo) of 62% and 59%, respectively; hazard ratios were 0.38 [credible interval (CrI) 0.20-0.65] and 0.41 (CrI 0.21-0.70); and in all-cause hospitalizations with reductions of 42% for both. These two combinations were also the most effective for the other outcomes studied.Conclusion: Our analysis shows that the incremental use of combinations of disease-modifying therapies has resulted in the progressive improvement in mortality and hospitalization outcomes in HFrEF. Our findings support the current guideline recommendations. [ABSTRACT FROM AUTHOR]

Aim: Although human chorionic gonadotropin (hCG) has long been employed in the management of cryptorchidism, its safety and efficacy is still controversial. Hence, in the present study, we conducted a meta-analysis of the treatment of cryptorchidism using hCG.Methods: We searched the Medline, Embase, CINAHL, EBSCO, The Cochrane Library, China National Knowledge Infrastructure and WanFang databases. Data were extracted by two reviewers using the designed extraction form. Data up to July 2015 were obtained using the terms 'cryptorchidism', 'chorionic gonadotropin' and 'randomised controlled trials'. All the publications were downloaded, and the respective authors were contacted for any further details and clarifications, if deemed necessary. The data analysis included randomised controlled trials that compared hCG with other hormone treatments offered to prepubescent males presenting with cryptorchidism. Testicular descent rate was used as the final positive outcome of the treatments offered. The software Review Manager (RevMan 5.3, The Cochrane Collaboration, London, UK) was used to review the management and data analysis. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled with a fixed effect model if no heterogeneity was present.Results: A total of seven trials satisfied the selection criteria. The overall quality of the studies downloaded from various databases was low. Data from these seven studies were divided into three subgroups depending on the design of the trials: Two studies compared hCG with a placebo, and three studies compared hCG with gonadotropin-releasing hormone (GnRH) in unilateral cryptorchidism, whereas two other studies compared hCG with GnRH in bilateral cryptorchidism. Analysis of these trials revealed no significant differences between the effectiveness of hCG treatment and GnRH treatment in bilateral (RR 0.05, 95% CI (-0.29-0.40), two trials, n = 104, P = 0.76) as well as unilateral cryptorchidism (RR 0.04, 95% CI (-0.12, 0.21), three trials, n = 81, P = 0.61). A meta-analysis of these studies showed that hCG treatment is not superior to placebo (RR 7.74, 95% CI (0.14-425.72), two trials, n = 31, P = 0.32).Conclusion: A meta-analysis of the seven studies led us to conclude that hCG treatment is no more effective than placebo, and there were no significant differences in the effectiveness of hCG versus GnRH treatment. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is an increasingly prevalent disorder, associated with low blood vitamin D level.Objectives: To evaluate the relationship between vitamin D and GDM.Search Strategy: EMBASE, MEDLINE, Cochrane Library and China Biology Medicine disc were searched up to May 2017. The references of previous studies were screened.Selection Criteria: Observational studies on the relationship between vitamin D and GDM free from Hawthorne effect and randomised controlled trials of vitamin D supplementation during pregnancy for preventing or treating GDM were included.Data Collection and Analysis: Data and information of included articles were extracted by duplicate using piloted tables. Newcastle-Ottawa Scale and Cochrane Handbook were used for quality assessment. Random-effects models were used for meta-analyses. Heterogeneity tests, sensitivity analysis and analysis of publication bias were conducted.Main Results: Eighty-seven observational studies and 25 randomised controlled trials involving 55 859 and 2445 women, respectively, were included. Low blood vitamin D level during pregnancy was associated with a higher risk of GDM (OR 1.850, 95% CI 1.471-2.328). Blood vitamin D level for women with GDM were lower than in the control women. Blood vitamin D level was associated with fasting plasma glucose (FPG) and homeostasis model of assessment for insulin resistance index (HOMA-IR) (r = -0.100 and r = -0.351), whereas the correlation between blood vitamin D level and fasting insulin (FINS) might be concealed by publication bias. Vitamin D intervention during pregnancy could change the blood levels of vitamin D, FINS, FPG, HOMA-IR, glutathione, C-reactive protein and lipid.Conclusions: Low blood vitamin D level could increase the risk of GDM, and vitamin D supplementation during pregnancy could ameliorate the condition of GDM.Tweetable Abstract: Low blood vitamin D increases gestational diabetes mellitus (GDM) risk. Vitamin D supplementation ameliorates GDM condition. [ABSTRACT FROM AUTHOR]

Burning mouth syndrome (BMS) is a chronic oral pain syndrome that primarily affects peri‐ and postmenopausal women. It is characterized by oral mucosal burning and may be associated with dysgeusia, paresthesia, dysesthesia, and xerostomia. The etiology of the disease process is unknown, but is thought to be neuropathic in origin. The goal of this systematic review was to assess the efficacy of the various treatments for BMS. Literature searches were conducted through PubMed, Web of Science, and Cochrane Library databases, which identified 22 randomized controlled trials. Eight studies examined alpha‐lipoic acid (ALA), three clonazepam, three psychotherapy, and two capsaicin, which all showed modest evidence of potentially decreasing pain/burning. Gabapentin was seen in one study to work alone and synergistically with ALA. Other treatments included vitamins, benzydamine hydrochloride, bupivacaine, Catuama, olive oil, trazodone, urea, and Hypericum perforatum. Of these other treatments, Catuama and bupivacaine were the only ones with significant positive results in symptom improvement. ALA, topical clonazepam, gabapentin, and psychotherapy may provide modest relief of pain in BMS. Gabapentin may also boost the effect of ALA. Capsaicin is limited by its side effects. Catuama showed potential for benefit. Future studies with standardized methodology and outcomes containing more patients are needed. [ABSTRACT FROM AUTHOR]

Loop diuretics remain a fundamental pharmacological therapy to remove excess fluid and improve symptom control in acute decompensated heart failure. Several recent randomised controlled trials have examined the clinical benefit of continuous vs. bolus furosemide in acute decompensated heart failure, but have reported conflicting findings. The aim of this review was to compare the effects of continuous and bolus furosemide with regard to mortality, length of hospital stay and its efficacy profile in acute decompensated heart failure. All parallel-arm randomised controlled trials from MEDLINE, EMBASE, PubMed and the Cochrane Database of Systematic Reviews from inception until May 2017 were included. Cross-over randomised controlled trials, observational studies, case reports, case series and non-systematic reviews that involved children were excluded. Eight trials (n = 669) were eligible for inclusion. There was no difference between furosemide continuous infusion and bolus administration for all-cause mortality (four studies; n = 491; I2 = 0%; OR 1.65; 95%CI 0.93-2.91; p = 0.08) or duration of hospitalisation (six studies; n = 576; I2 = 71%; mean difference 0.27; 95%CI -1.35 to 1.89 days; p = 0.74). Continuous infusion of intravenous furosemide was associated with increased weight reduction (five studies; n = 516; I2 = 0%; mean difference 0.70; 95%CI 0.12-1.28 kg; p = 0.02); increased total urine output in 24 h (four studies; n = 390; I2 = 33%; mean difference 461.5; 95%CI 133.7-789.4 ml; p < 0.01); and reduced brain natriuretic peptide (two studies; n = 390; I2 = 0%; mean difference 399.5; 95%CI 152.7-646.3 ng.l-1 ; p < 0.01), compared with the bolus group. There was no difference in the incidence of raised creatinine and hypokalaemia between the two groups. In summary, there was no difference between continuous infusion and bolus of furosemide for all-cause mortality, length of hospital stay and electrolyte disturbance, but continuous infusion was superior to bolus administration with regard to diuretic effect and reduction in brain natriuretic peptide. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aims: Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders (AUDs) is an emerging concept. Our objective was to explore the comparative effectiveness of drugs used in this indication. Design: Systematic review with direct and network meta‐analysis of double‐blind randomized controlled trials (RCTs) assessing the efficacy of nalmefene, naltrexone, acamprosate, baclofen or topiramate in non‐abstinent adults diagnosed with alcohol dependence or AUDs. Two independent reviewers selected published and unpublished studies on Medline, the Cochrane Library, Embase, ClinicalTrials.gov, contacted pharmaceutical companies, the European Medicines Agency and the Food and Drug Administration, and extracted data. Setting: Thirty‐two RCTs. Participants: A total of 6036 patients. Measurements: The primary outcome was total alcohol consumption (TAC). Other consumption outcomes and health outcomes were considered as secondary outcomes. Findings: No study provided direct comparisons between drugs. A risk of incomplete outcome data was identified in 26 studies (81%) and risk of selective outcome reporting in 17 (53%). Nalmefene [standardized mean difference (SMD) = −0.19, 95% confidence interval (CI) = −0.29, –0.10; I2 = 0%], baclofen (SMD = −1.00, 95% CI = −1.80, −0.19; one study) and topiramate (SMD = −0.77, 95% CI = −1.12, –0.42; I2 = 0%) showed superiority over placebo on TAC. No efficacy was observed for naltrexone or acamprosate. Similar results were observed for other consumption outcomes, except for baclofen (the favourable outcome on TAC was not reproduced). The number of withdrawals for safety reasons increased under nalmefene and naltrexone. No treatment demonstrated any harm reduction (no study was powered to explore health outcomes). Indirect comparisons suggested that topiramate was superior to nalmefene, naltrexone and acamprosate on consumption outcomes, but its safety profile is known to be poor. Conclusions: There is currently no high‐grade evidence for pharmacological treatment to control drinking using nalmefene, naltrexone, acamprosate, baclofen or topiramate in patients with alcohol dependence or alcohol use disorder. Some treatments show low to medium efficacy in reducing drinking across a range of studies with a high risk of bias. None demonstrates any benefit on health outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Ezetimibe is widely used in combination with statins to reduce low‐density lipoprotein. We sought to examine the impact of ezetimibe when added to statins on patient‐important outcomes. Medline, EMBASE, CINAHL, and CENTRAL were searched through July, 2016. Randomized controlled trials (RCTs) of ezetimibe combined with statins versus statins alone that followed patients for at least 6 months and reported on at least one of all‐cause mortality, cardiovascular deaths, non‐fatal myocardial infarctions (MI), and non‐fatal strokes were included. Pairs of reviewers extracted study data and assessed risk of bias independently and in duplicate. Quality of evidence was assessed using the GRADE approach. We conducted a narrative review with complementary subgroup and sensitivity analyses. IMPROVE‐IT study enrolled 93% of all patients enrolled in the 8 included trials. Our analysis of the IMPROVE‐IT study results showed that in patients at high risk of cardiovascular events, ezetimibe added to statins was associated with i) a likely reduction in non‐fatal MI (17 fewer/1000 treated over 6 years, moderate certainty in evidence); ii) a possible reduction in non‐fatal stroke (6 fewer/1000 treated over 6 years, low certainty); iii) no impact on myopathy (moderate certainty); iv) potentially no impact on all‐cause mortality and cardiovascular death (both moderate certainty); and v) possibly no impact on cancer (low certainty). Addition of ezetimibe to moderate‐dose statins is likely to result in 17 fewer MIs and possibly 6 fewer strokes/1000 treated over 6 years but is unlikely to reduce all‐cause mortality or cardiovascular death. Patients who place a high value on a small absolute reduction in MI and are not adverse to use of an additional medication over a long duration may opt for ezetimibe in addition to statin therapy. Our analysis revealed no increased specific harms associated with addition of ezetimibe to statins. [ABSTRACT FROM AUTHOR]

There is variable international practice regarding the technique used for image-guided enema reduction in paediatric intussusception. A recent meta-analysis found pneumatic reduction to be more effective than hydrostatic techniques. Clinical practice variation may impact on perforation rates, ionizing radiation exposure and requirement for surgery. The aim of this study was to review the literature regarding the efficacy and safety of fluoroscopically guided pneumatic reduction (FGPR) compared to ultrasound (US) guided intussusception reduction (USGIR) techniques for paediatric intussusception treatment. Articles were identified by searching OVID Medline on 21/02/14 and by scanning retrieved articles reference lists. The search was repeated on 30/09/15. Systematic reviews (SR) were appraised with the PRISMA critical appraisal tool. Primary studies underwent a separate critical appraisal process. Successful reductions and perforations per attempt were calculated for each study. Pooled estimates of proportions were calculated for each of these dichotomous outcomes. A SR and 42 primary studies were included in the review. No randomised control trial (RCT) study was included. Non-randomised comparative studies and non-comparative studies suggest that hydrostatic reduction under US control has a similar efficacy and safety profile to pneumatic reduction under fluoroscopic control, but USGIR data are dominated by a single large, non-comparative study performed in China. US-guided intussusception reduction should be considered an alternative to FGPR as it has similar efficacy and safety, and affords no ionised radiation exposure. However, RCT data are required to inform practice. [ABSTRACT FROM AUTHOR]

Copyright of International Journal of Eating Disorders is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This health technology assessment evaluated the efficacy of pharmacological treatment in patients with oro-facial pain. Randomised controlled trials were included if they reported pharmacological treatment in patients ≥18 years with chronic (≥3 months) oro-facial pain. Patients were divided into subgroups: TMD-muscle [temporomandibular disorders ( TMD) mainly associated with myalgia]; TMD-joint ( TMD mainly associated with temporomandibular joint pain); and burning mouth syndrome ( BMS). The primary outcome was pain intensity reduction after pharmacological treatment. The scientific quality of the evidence was rated according to GRADE. An electronic search in PubMed, Cochrane Library, and EMBASE from database inception to 1 March 2017 combined with a handsearch identified 1552 articles. After screening of abstracts, 178 articles were reviewed in full text and 57 studies met the inclusion criteria. After risk of bias assessment, 41 articles remained: 15 studies on 790 patients classified as TMD-joint, nine on 375 patients classified as TMD-muscle and 17 on 868 patients with BMS. Of these, eight studies on TMD-muscle, and five on BMS were included in separate network meta-analysis. The narrative synthesis suggests that NSAIDs as well as corticosteroid and hyaluronate injections are effective treatments for TMD-joint pain. The network meta-analysis showed that clonazepam and capsaicin reduced pain intensity in BMS, and the muscle relaxant cyclobenzaprine, for the TMD-muscle group. In conclusion, based on a limited number of studies, evidence provided with network meta-analysis showed that clonazepam and capsaicin are effective in treatment of BMS and that the muscle relaxant cyclobenzaprine has a positive treatment effect for TMD-muscle pain. [ABSTRACT FROM AUTHOR]

We performed a systematic review and meta-analysis to assess whether selective serotonin reuptake inhibitors ( SSRIs) and phosphodiesterase type 5 inhibitors ( PDE5-Is ) may have an additive therapeutic effect. A literature review was performed to identify all published randomised controlled trials ( RCT) that used SSRIs combined with PDE5-Is therapy for the treatment of primary PE. The search included the following databases: EMBASE, MEDLINE and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. Five publications involving a total of 419 patients were used in the analysis, including 5 RCTs that compared PDE5-Is plus SSRIs with SSRIs treating primary PE. Primary efficacy endpoints: IELT (the standardised mean difference ( SMD) = 1.07, 95% confidence interval ( CI) = 1.00 to 1.14, P < 0.00001) indicated that utilisation of PDE5-Is and SSRIs was more effective than the SSRIs alone for a long time in patients with primary PE. Safety assessments included headache (odds ratio ( OR) = 3.16, 95% CI = 1.63 to 6.11, P = 0.0006), and flushing indicated that PDE5-Is plus SSRIs were well tolerated. This meta-analysis indicates that PDE5-Is combined with SSRIs seem to provide significantly better ejaculatory latency time as compared with SSRIs alone in patients with primary PE. [ABSTRACT FROM AUTHOR]

Objective To systematically examine the randomized controlled trial ( RCT) evidence regarding efficacy and tolerability of topiramate cotreatment with antipsychotics in schizophrenia-spectrum disorders. Methods Random-effects meta-analysis of RCTs of topiramate cotreatment with antipsychotics vs. placebo/ongoing antipsychotic treatment in schizophrenia-spectrum disorders. Standardized or weighted mean difference ( SMD/ WMD), risk ratio ( RR) ±95% confidence intervals ( CIs), and number needed to harm ( NNH) were calculated. Results Across 16 RCTs ( n = 934, duration = 11.8 ± 5.6 weeks), topiramate outperformed the comparator regarding change/endpoint of total ( SMD: −0.58, 95% CI: −0.82, −0.35, P < 0.00001), positive ( SMD: −0.37, 95% CI: −0.61, −0.14, P = 0.002), negative ( SMD: −0.58, 95% CI: −0.87, −0.29, P < 0.0001), and general symptoms ( SMD: −0.68, 95% CI: −0.95, −0.40, P < 0.00001). Furthermore, topiramate was superior regarding body weight ( WMD: -2.75 kg, 95% CI: −4.03, −1.47, P < 0.0001), body mass index ( BMI) ( WMD: -1.77, 95% CI: −2.38, −1.15, P < 0.00001), triglycerides ( P = 0.006), and insulin levels ( P < 0.00001). Superiority regarding psychopathology and body weight/ BMI was consistent across Chinese/Asian and Western RCTs, double-blind and open designs, clozapine and non-clozapine cotreatment, augmentation and co-initiation RCTs, and higher and lower quality RCTs. In meta-regression analyses, topiramate's efficacy for total symptoms was moderated by shorter illness duration ( P = 0.047), while weight loss was greater in prevention/co-initiation vs. intervention/augmentation RCTs (−4.11 kg, 95% CI: −6.70, −1.52 vs. −1.41 kg, 95% CI: −2.23, −0.59, P < 0.001). All-cause discontinuation was similar between topiramate and comparators (RR: 1.28, 95% CI: 0.91, 1.81, P = 0.16). While topiramate led to more concentration/attention difficulties ( P = 0.03, NNH = 8, 95% CI=4-25), psychomotor slowing ( P = 0.02, NNH = 7, 95% CI = 4-25), and paresthesia ( P = 0.05, NNH = 2, 95% CI = 4-33), it led to less ≥7% weight gain ( P = 0.0001, NNH = 2, 95% CI = 2-3) and constipation ( P = 0.04, NNH = 9, 95% CI = 5-100) than the comparator. Conclusions These results indicate that adjunctive topiramate to antipsychotics is an effective and safe treatment choice for symptomatic improvement and weight reduction in patients with schizophrenia-spectrum disorders. [ABSTRACT FROM AUTHOR]

Aims To determine the effectiveness and safety of varenicline in treating tobacco dependence in patients with severe mental illness. Design A systematic reviewand meta-analysis of randomised controlled trials that compared varenicline with a placebo or an alternative intervention for smoking cessation or reduction. Setting Both in- and out-patient settings in any country. Participants Adult patients aged 18 years and over with any type of severe mental illness. The systematic review included eight studies comprising 398 participants. Measures Primary outcome measures were (1) smoking cessation, (2) smoking reduction measured by changes in the number of cigarettes smoked per day and (3) number of psychiatric adverse events, which were collected at the end of treatment. Findings The random-effect pooled estimates from the five studies that reported smoking-related outcomes found that varenicline is statistically superior to placebo in smoking cessation [risk ratios 4.33; 95% confidence interval (CI)=1.96-9.56], and smoking reduction was higher in varenicline groups (mean reduced daily cigarettes was 6.39; 95% CI=2.22-10.56). There is no significant difference regarding neuropsychiatric and other adverse events. Conclusions Varenicline appears to be significantly more effective than placebo in assisting with smoking cessation and reduction in people with severe mental illness. There appears to be no clear evidence that varenicline was associated with an increased risk of neuropsychiatric or other adverse events compared with placebo. [ABSTRACT FROM AUTHOR]

Several clinical trials describe the effectiveness of xenogeneic collagen matrix ( XCM) as an alternative option to surgical mucogingival procedures for the treatment of marginal tissue recession and augmentation of insufficient zones of keratinized tissue ( KT). The aim of this systematic review and meta-analysis was to evaluate the clinical and patient-centred outcomes of XCM compared to other mucogingival procedures. Applying guidelines of the Preferred Reporting Items for Systematic Reviews and Meta analyses statement, randomized controlled trials were searched for in electronic databases and complemented by hand searching. The risk of bias was assessed using the Cochrane Collaboration's Risk of Bias tool and data were analysed using statistical software. A total of 645 studies were identified, of which, six trials were included with 487 mucogingival defects in 170 participants. Overall meta-analysis showed that connective tissue graft ( CTG) in conjunction with the coronally advanced flap ( CAF) had a significantly higher percentage of complete/mean root coverage and mean recession reduction than XCM. Insufficient evidence was found to determine any significant differences in width of KT between XCM and CTG. The XCM had a significantly higher mean root coverage, recession reduction and gain in KT compared to CAF alone. No significant differences in patient's aesthetic satisfaction were found between XCM and CTG, except for postoperative morbidity in favour of XCM. Operating time was significantly reduced with the use of XCM compared with CTG but not with CAF alone. There is no evidence to demonstrate the effectiveness of XCM in achieving greater root coverage, recession reduction and gain in KT compared to CTG plus CAF. Superior short-term results in treating root coverage compared with CAF alone are possible. There is limited evidence that XCM may improve aesthetic satisfaction, reduce postoperative morbidity and shorten the operating time. Further long-term randomized controlled trials are required to endorse the supposed advantages of XCM. [ABSTRACT FROM AUTHOR]

Scaling and root planing are widely considered as effective methods for treating chronic periodontitis. A meta-analysis published in 2008 showed no statistically significant differences between full-mouth disinfection ( FMD) or full-mouth scaling and root planing ( FMS) and quadrant scaling and root planing (Q- SRP). The FMD approach only resulted in modest additional improvements in several indices. Whether differences exist between these two approaches requires further validation. Accordingly, a study was conducted to further validate whether FMD with antiseptics or FMS without the use of antiseptics within 24 h provides greater clinical improvement than Q- SRP in patients with chronic periodontitis. Medline (via OVID), EMBASE (via OVID), PubMed and CENTRAL databases were searched up to 27 January 2015. Randomized controlled trials comparing FMD or FMS with Q- SRP after at least 3 mo were included. Meta-analysis was performed to obtain the weighted mean difference ( WMD), together with the corresponding 95% confidence intervals. Thirteen articles were included in the meta-analysis. The WMD of probing pocket depth reduction was 0.25 mm ( p < 0.05) for FMD vs. Q- SRP in single-rooted teeth with moderate pockets, and clinical attachment level gain in single- and multirooted teeth with moderate pockets was 0.33 mm ( p < 0.05) for FMD vs. Q- SRP. Except for those, no statistically significant differences were found in the other subanalyses of FMD vs. Q- SRP, FMS vs. Q- SRP and FMD vs. FMS. Therefore, the meta-analysis results showed that FMD was better than Q- SRP for achieving probing pocket depth reduction and clinical attachment level gain in moderate pockets. Additionally, regardless of the treatment, no serious complications were observed. FMD, FMS and Q- SRP are all effective for the treatment of adult chronic periodontitis, and they do not lead to any obvious discomfort among patients. Moreover, FMD had modest additional clinical benefits over Q- SRP, so we prefer to recommend FMD as the first choice for the treatment of adult chronic periodontitis. [ABSTRACT FROM AUTHOR]

Copyright of Ultrasound in Obstetrics & Gynecology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims To assess the efficacy of topiramate in treating cocaine use disorder (i.e. retention, efficacy, safety and craving reduction) through a systematic review and meta-analysis. Methods We searched six scientific databases from inception to 23 December 2014 with no date limits. Data were reviewed, extracted and analysed systematically. Studies were included if they were peer-reviewed randomized control trials with participants meeting diagnostic criteria for cocaine dependence or cocaine use disorder, with the treatment arm involving topiramate with or without psychosocial intervention, and the control arm involving no intervention or psychosocial intervention with or without placebo. A random-effects meta-analytical model was computed. Results Five studies met inclusion criteria ( n = 518). Topiramate was compared with placebo (four studies) and no medication (one study). In a meta-analysis, we observed no significant differences between topiramate and placebo in improving treatment retention risk ratio (RR) = 0.85; 95% confidence interval (CI) = 0.60-1.22, P = 0.38. However, compared with a placebo, use of topiramate was associated with increased continuous abstinence in two of five studies (RR = 2.43; 95% CI = 1.31-4.53, P = 0.005). No differences were observed in frequency of adverse effects reported between topiramate and placebo (RR = 1.06; 95% CI = 0.91-1.23, P = 0.48). Topiramate was associated significantly ( P < 0.05) with a reduction in craving in only one of five studies. Conclusions Evidence does not currently support the use of topiramate to improve treatment retention for cocaine use disorder, although it may extend cocaine abstinence with a similar risk of adverse events compared with placebo. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to assess the net clinical and prognostic effects of intravenous (i.v.) iron therapy in patients with systolic heart failure (HF) and iron deficiency (ID).Methods and Results: We performed an aggregate data meta-analysis (random effects model) of randomized controlled trials that evaluated the effects of i.v. iron therapy in iron-deficient patients with systolic HF. We searched electronic databases up to September 2014. We identified five trials which fulfilled the inclusion criteria (509 patients received i.v. iron therapy in comparison with 342 controls). Intravenous iron therapy has been shown to reduce the risk of the combined endpoint of all-cause death or cardiovascular hospitalization [odds ratio (OR) 0.44, 95% confidence interval (CI) 0.30-0.64, P < 0.0001], and the combined endpoint of cardiovascular death or hospitalization for worsening HF (OR 0.39, 95% CI 0.24-0.63, P = 0.0001). Intravenous iron therapy resulted in a reduction in NYHA class (data are reported as a mean net effect with 95% CIs for all continuous variables) (-0.54 class, 95% CI -0.87 to -0.21, P = 0.001); an increase in 6-min walking test distance (+31 m, 95% CI 18-43, P < 0.0001); and an improvement in quality of life [Kansas City Cardiomyopathy Questionnaire (KCCQ) score +5.5 points, 95% CI 2.8-8.3, P < 0.0001; European Quality of Life-5 Dimensions (EQ-5D) score +4.1 points, 95% CI 0.8-7.3, P = 0.01; Minnesota Living With Heart Failure Questionnaire (MLHFQ) score -19 points, 95% CI:-23 to -16, P < 0.0001; and Patient Global Assessment (PGA) +0.70 points, 95% CI 0.31-1.09, P = 0004].Conclusion: The evidence indicates that i.v. iron therapy in iron-deficient patients with systolic HF improves outcomes, exercise capacity, and quality of life, and alleviates HF symptoms. [ABSTRACT FROM AUTHOR]

Background and Aim: The aim of this study was to compare the feasibility and safety of both balloon-occluded retrograde transvenous obliteration (BRTO) versus transjugular intrahepatic portosystemic shunt (TIPS) for treatment of gastric varices due to portal hypertension through the method of meta-analysis. Methods: PubMed, Embase, and Cochrane Library were searched for both randomized controlled trials and cohort studies concerning BRTO compared with TIPS in the treatment of gastric varices from their inception to April 26, 2015. The Cochrane network RevMan 5.3 software was used for statistic analysis. The primary markers that need to be evaluated contained technical success rate, hemostasis rate, incidence rate of postoperative rebleeding, incidence rate of hepatic encephalopathy, and postoperative procedure-related complication. Study-specific odds ratios (ORs) were combined to calculate pooled value by using random effects model. Results: Five original studies were included in total. Meta-analysis showed that BRTO and TIPS had no difference in aspects of technical success rate (OR, 0.19; 95% confidence interval [CI], 0.03-1.08; P = 0.06), hemostasis rate (OR, 3.41; 95% CI, 0.33-35.40; P = 0.30), and incidence rate of postoperative procedure-related complication (OR, 1.98; 95% CI, 0.44-8.84; P = 0.37). However, BRTO had a lower incidence rate of post-operative rebleeding (OR, 0.27; 95% CI, 0.09-0.81; P = 0.02) and a lower incidence rate of postoperative encephalopathy (OR, 0.05; 95% CI, 0.02-0.13; P < 0.00001). Conclusions: Balloon-occluded retrograde transvenous obliteration was a technically feasible as well as a secure method for the treatment of gastric varices originated from portal hypertension. It may have the potential to be an alterative shunt approach of TIPS, when suitable patients selected. [ABSTRACT FROM AUTHOR]

Aim Prolonged postoperative ileus (PPOI) after colorectal surgery remains a leading cause of delayed postoperative recovery and prolonged hospital stay. Its exact incidence is unknown. The aim of this systematic review is to investigate the definitions and incidence of PPOI previously described. Method MEDLINE, Embase and the Cochrane Database of Systematic Reviews (up to July 2014) were searched. Two authors independently reviewed citations using predefined inclusion and exclusion criteria. Results The search strategy yielded 3233 citations; 54 were eligible, comprising 18 983 patients. Twenty-six studies were prospective [17 of these being randomized controlled trials (RCTs)] and 28 were retrospective. Meta-analysis revealed an incidence of PPOI of 10.3% (95% CI 8.4-12.5) and 10.2% (95% CI 5.6-17.8) for non-RCTs and RCTs, respectively. Significant heterogeneity was observed for both non-RCTs and for RCTs. The used definition of PPOI, the type of surgery and access (laparoscopic, open) and the duration of surgery lead to significant variability of reported PPOI incidence between studies. The incidence of PPOI is lower after laparoscopic colonic resection. Conclusion There is a large variation in the reported incidence of PPOI. A uniform definition of PPOI is needed to allow meaningful inter-study comparisons and to evaluate strategies to prevent PPOI. [ABSTRACT FROM AUTHOR]

Unlabelled: A systematic review and meta-analysis were performed to determine the effect of therapeutic hypothermia using low-technology methods, in settings with facilities for intensive care, in term or near-term infants with hypoxic-ischaemic encephalopathy on mortality, neurological morbidity at discharge and neurological morbidity at 6-24 months.Conclusion: Meta-analysis of three randomised controlled studies showed that low-technology therapeutic hypothermia in an intensive care setting significantly reduced the mortality and the neurological morbidity in survivors at discharge. [ABSTRACT FROM AUTHOR]

Focused Question: In patients suffering from peri-implant diseases, what is the efficacy of air polishing on changing signs of inflammation compared with control treatments (i.e. alternative measures for plaque removal with or without adjunctive antiseptic and/ or antibiotic therapy)? Material & Methods: After electronic database and hand search, 10 full-text articles were independently screened by two reviewers. Finally, a total of five studies (six publications) fulfilled the inclusion criteria. The weighted mean difference (WMD) [p; 95% CI] in bleeding on probing-(BOP) (primary outcome) and probing pocket depth-(PD) reductions was estimated using a random effect model. Results: All studies reported on residual BOP scores after therapy. A narrative data synthesis did not reveal any major improvement of bleeding index/ BOP or disease resolution following air polishing over mechanical debridement at mucositis sites. At peri-implantitis sites, WMD in BOP reduction between test and control (mechanical debridement with or without local antiseptic therapy, Er:YAG laser) groups was -23.83% [p = 0.048; 95% CI (-47.47, -0.20)] favouring air polishing over control measures. Conclusions: While glycine powder air polishing is as effective as the control treatments at mucositis sites, it may improve the efficacy of non-surgical treatment of peri-implantitis over the control measures investigated. A complete disease resolution was commonly not obtained. [ABSTRACT FROM AUTHOR]

Background and aims Varenicline increases the likelihood of long-term abstinence following a quit attempt. It has been suggested that (1) part of its benefit arises from 'recruiting into abstinence' smokers who are not able to stop on the target quit date and (2) there may be a higher rate of relapse after treatment. This study addressed these issues. Methods Meta-analyses of data from randomized controlled trials (RCTs) of varenicline identified from the 2012 Cochrane review of nicotine receptor partial agonists for smoking cessation were used to compare the abstinence and relapse patterns on active drug and placebo. Studies of varenicline compared with placebo in adult daily smokers with longest follow-up at either 6 or 12 months and with at least three follow-ups in the first month were included. Biochemically verified abstinence rates at each of six follow-up time-points (2, 3, 4, 12, 24 and 52 weeks) were pooled for studies reporting point prevalence abstinence. Biochemically verified abstinence rates at three follow-up time-periods (9-12 weeks, 9-24 weeks and 9-52 weeks) were pooled for studies reporting continuous abstinence. Random effects meta-analysis was used to estimate pooled proportions with 95% confidence intervals. Results Nineteen RCTs were included. In varenicline-treated participants, point-prevalence abstinence increased by 22 percentage points from week 2 [32%: 95% confidence interval (CI) = 25-40%] to week 12 (54%: 95% CI = 48-61%). The increase was 8 percentage points in the placebo group: 16% (95% CI = 11-21%) to 24% (95% CI = 17-33%). In varenicline-treated participants the relapse from weeks 9-12 to week 52 was 55%: 49% abstinent in weeks 9-12 (95% CI = 45-53%) versus 22% at week 52 (95% CI = 19-25%). In placebo-treated participants it was 53%: 17% (95% CI = 13-25%) in weeks 9-12 versus 8% (95% CI = 6-12%) at week 52. Conclusions Varenicline recruits smokers into abstinence following the target quit date to a greater extent than placebo. Relapse rates from end of treatment to 52 weeks are similar in varenicline- and placebo-treated smokers. [ABSTRACT FROM AUTHOR]

Background and Purpose Low-level laser therapy (LLLT) is proposed as a treatment for tendinopathies. This is the first systematic review focusing solely on LLLT treatment effects in shoulder tendinopathy. Methods A systematic review with meta-analysis and primary outcome measures pain relief on 100-mm visual analogue scale (VAS) and relative risk for global improvement. Two independent assessors rated the included studies according to the PEDro scale. Intervention quality assessments were performed of LLLT dosage and treatment procedures according to World Association for Laser Therapy guidelines. The included trials were sub-grouped by intervention quality and use of other physiotherapy interventions. Results Seventeen randomized controlled trials (RCTs) met the inclusion criteria, and 13 RCTs were of high and 4 RCTs of moderate methodological quality. Significant and clinically important pain relief was found with weighted mean differences (WMD) over placebo, for LLLT as monotherapy at 20.41 mm (95% CI: 12.38 to 28.44) and as adjunct to exercise therapy at 16.00 mm (95% CI: 11.88 to 20.12). The WMD when LLLT was used in a multimodal physiotherapy treatment regime reached statistical significance over placebo at 12.80 (95% CI: 1.67-23.94) mm pain reduction on VAS. Relative risks for global improvement were statistically significant at 1.96 (95% CI: 1.25-3.08) and 1.51 (95% CI: 1.12-2.03), for laser as monotherapy or adjunctive in a physiotherapy regime, respectively. Secondary outcome measures of shoulder function were only significantly in favour of LLLT when used as monotherapy. Trials performed with inadequate laser doses were ineffective across all outcome measures. Conclusion This review shows that optimal LLLT can offer clinically relevant pain relief and initiate a more rapid course of improvement, both alone and in combination with physiotherapy interventions. Our findings challenge the conclusions in previous multimodal shoulder reviews of physiotherapy and their lack of intervention quality assessments. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims To determine the efficacy of acamprosate and naltrexone in the treatment of those who are alcohol-dependent in reducing lapse/relapse to alcohol consumption and treatment discontinuation, and to examine whether a proportion of the variance in study outcome can be explained by the country in which the trials have taken place. Method A systematic review and meta-analysis of randomized controlled trials published before September 2013 was conducted. The primary outcome measures were the efficacy of acamprosate or naltrexone in reducing lapse/relapse compared to placebo in the treatment of alcohol dependence and treatment discontinuation. Twenty-two randomized controlled trials (RCTs) of the efficacy of acamprosate met inclusion criteria for the meta-analysis, with a total of 2649 participants in the acamprosate group and 2587 in the placebo group. Twenty-seven RCTs of the efficacy of naltrexone met inclusion criteria for the meta-analysis, with a total of 2253 participants in the naltrexone group and 1946 in the placebo group. A random-effects model using a Mantel-Haenszel method was applied to conduct the meta-analysis. Variance in study outcomes was explored using subgroup analysis of Europe versus the rest of the world (ROW). Results The risk of returning to any drinking at 6 months was significantly lower for acamprosate [risk ratio (RR) = 0.83, 95% confidence interval (CI) = 0.78-0.89]. There was little difference in the risk of participants discontinuing treatment for any reason (RR = 0.91, 95% CI = 0.83-1.00) or due to adverse events (RR = 1.30, 95% CI = 0.96-1.75) for the acamprosate compared to placebo groups. The risk of individuals returning to any drinking at approximately 3 months was reduced significantly for the naltrexone group (RR = 0.92, 95% CI = 0.86-1.00), as was the risk of individuals relapsing to heavy drinking at 3 months (RR = 0.85, 95% CI = 0.78-0.93). There was no significant difference between naltrexone and placebo for the risk of individuals discontinuing treatment for any reason (RR = 0.94, 95% CI = 0.84-1.05). There was a significantly greater risk of participants in the naltrexone group discontinuing treatment due to adverse events compared to placebo (RR = 1.72, 95% CI = 1.10-2.70). Subgroup analysis by country (Europe versus ROW) revealed no difference in risk between acamprosate and placebo for the outcomes returning to any drinking at 6 months and discontinuing treatment due to adverse events. For the outcome discontinuation of treatment for any reason, there was a significant difference in RR between Europe and the ROW (χ2 = 11.65, P <0.001) for acamprosate. Acamprosate was associated with a reduction in risk of discontinuing treatment for Europe (RR = 0.86, 95% CI = 0.79-0.95), but an increase in risk of discontinuing treatment for ROW (RR = 1.23, 95% CI = 1.03-1.48). Conclusions Both acamprosate and naltrexone appear to reduce the risk of individuals returning to drinking alcohol in those who are alcohol-dependent. The country in which a randomized control trial (RCT) for the efficacy of acamprosate and naltrexone is completed does not appear to explain the variance in trial outcomes for returning to drinking alcohol or discontinuing drinking due to adverse effects. However, the country in which the RCT of acamprosate are completed may be important for explaining the variance between studies for the outcome 'discontinuing treatment for any reason'. [ABSTRACT FROM AUTHOR]

Background Eosinophilic oesophagitis (EoE) is a growing cause of dysphagia. Current therapies include dietary manipulation, steroids and biological drugs. Aim To perform a systematic review and summarise the effect of different medical interventions on EoE. Methods Two reviewers searched Pubmed and Embase for studies on treatment for EoE. We included randomised controlled trials ( RCT) limited to pharmacological interventions. Two reviewers selected studies. Meta-analysis was done using random effects model to estimate odds ratio ( OR). Heterogeneity was determined by Cochran's Q statistic and I2. Results Seventeen references met our inclusion criteria. Eleven RCTs involving 455 participants were included in the meta-analysis. 325 participants were evaluated for symptomatic improvement and 330 were evaluated for histological remission. Symptomatic improvement with topical steroids (7 studies, 250 participants) compared to the control group (placebo or PPI) was noted ( OR: 3.03, 95% confidence interval, CI: 1.57-5.87). Histological remission was also noted in nine studies involving 330 participants ( OR: 13.66, 95% CI: 2.65-70.34) comparing topical steroids to a control (placebo or PPI). There was no difference between anti- IL-5 drugs and placebo in terms of symptomatic improvement ( OR: 0.69, 95% CI: 0.34-1.42). Conclusions Topical steroids induce significant symptomatic and histological remission, and should be considered as a first line treatment. Anti- IL-5 therapy has a minor effect on eosinophilic oesophagitis. Future research in eosinophilic oesophagitis should standardise methodology according to published guidelines to improve quality and allow direct comparison between therapies. [ABSTRACT FROM AUTHOR]

Objectives Acupuncture is commonly used as a complimentary treatment for pain management. However, there has been no systematic review summarizing the current evidence concerning the effectiveness of acupuncture for acute postoperative pain after back surgery. This systematic review aimed at evaluating the effectiveness of acupuncture treatment for acute postoperative pain (≤1 week) after back surgery. Methods We searched 15 electronic databases without language restrictions. Two reviewers independently assessed studies for eligibility and extracted data, outcomes, and risk of bias. Random effect meta-analyses and subgroup analyses were performed. Results Five trials, including 3 of high quality, met our inclusion criteria. The meta-analysis showed positive results for acupuncture treatment of pain after surgery in terms of the visual analogue scale ( VAS) for pain intensity 24 hours after surgery, when compared to sham acupuncture (standard mean difference −0.67 (−1.04 to −0.31), P = 0.0003), whereas the other meta-analysis did not show a positive effect of acupuncture on 24-hour opiate demands when compared to sham acupuncture (standard mean difference −0.23 (−0.58 to 0.13), P = 0.21). Conclusion Our systematic review finds encouraging but limited evidence for the effectiveness of acupuncture treatment for acute postoperative pain after back surgery. Further rigorously designed clinical trials are required. [ABSTRACT FROM AUTHOR]

Aim The aim is to assess the effect of desensitizing toothpaste on dentin hypersensitivity. Methods We searched PubMed, CENTRAL, and Embase on December 20, 2013. Results Out of the 626 articles searched, a total of 31 randomized controlled clinical trials were included. The Standardized mean differences ( SMD) for potassium-containing toothpaste ( n = 8) was −1.28 (95% Confidence interval ( CI) −2.05 to −0.51; I2 = 93%); Stannous fluoride- ( n = 6) was −1.37 (95% CI, −2.30 to −0.44; I2 = 95%); Potassium and stannous fluoride- ( n = 3) was −2.50 (95% CI, −4.10 to −0.91; I2 = 95%); Calcium sodium phosphosilicate - ( n = 4) was −2.36 (95% CI, −3.72 to −1.00; I2 = 92%); Arginine- ( n = 8) was −3.25 (95% CI, −3.87 to −2.63; I2 = 86%). The desensitizing effect was favoured in the intervention group treated with potassium-, stannous fluoride-, potassium and stannous fluoride-, calcium sodium phosphosilicate-, and arginine-containing toothpaste compared to placebo. Whereas, strontium-containing toothpaste ( SMD, 0.05; 95% CI, −0.34 to 0.44; I2 = 64%) was found to have no statistically significant desensitizing effect in the meta-analysis of four studies. Conclusions The study reports that there is sufficient evidence to support the use of potassium-, stannous fluoride-, potassium and stannous fluoride-, calcium sodium phosphosilicate-, and arginine-containing desensitizing toothpastes for dentin hypersensitivity, but not the use of strontium-containing desensitizing toothpaste. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the efficiency and safety of combination therapy of ursodeoxycholic acid ( UDCA) and bezafibrate for primary biliary cirrhosis. A meta-analysis of all long-term randomized controlled trials comparing the combination of UDCA and bezafibrate with UDCA monotherapy was performed via electronic searches. Seven trials, which included 177 patients, were assessed. Combination therapy with UDCA and bezafibrate was more effective than UDCA monotherapy in improving liver biochemistry, alkaline phosphatase (mean difference [ MD], −146.15 IU/L; 95% confidence interval [ CI], −193.58 to −98.72; P < 0.00001), γ-glutamyltransferase ( MD, −20.64 IU/L; 95% CI, −30.86 to −10.43; P < 0.0001), immunoglobulin M ( MD, −90.96 mg/dL; 95% CI, −137.36 to −44.56; P = 0.0001) and triglycerides ( MD, −15.49 mg/dL; 95% CI, −30.25 to −0.74; P = 0.04). However, their effects on pruritus (odds ratio [ OR], 0.82; 95% CI, 0.30-2.24; P = 0.70) and alanine aminotransferase ( MD, −8.41 IU/L; 95% CI, −22.57 to 5.75; P = 0.24) did not differ significantly. This meta-analysis revealed no significant differences in the incidence of all-cause mortality ( OR, 0.72; 95% CI, 0.10-5.49; P = 0.75) and adverse events ( OR, 0.35; 95% CI, 0.07-1.84; P = 0.22) between patients treated with combination therapy and those treated with monotherapy. In this meta-analysis, combination therapy with UDCA and bezafibrate was more effective than UDCA monotherapy. Combination therapy improved liver biochemistry, but did not improve clinical symptoms, incidence of death or adverse events more effectively than monotherapy. [ABSTRACT FROM AUTHOR]

This study seeks to evaluate the potential benefits of high doses of ambroxol treatment for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) by conducting a meta-analysis based on randomized controlled trials (RCTs). We searched the Pubmed, Embase, China National Knowledge Infrastructure, and Wanfang databases through December 2013. Only RCTs evaluating high doses of ambroxol (=15 mg/kg or 1000 mg/day) treatment for patients with ALI/ARDS were selected. We included 10 RCTs involving 508 patients. Adjuvant treatment with high doses of ambroxol increased PaO2/FiO2 (weight mean differences [WMD] = 69.18, 95% confidence intervals [CI]: 41.71-96.65), PO2 (WMD = 11.74, 95% CI: 8.50-14.99), and SaO2 (WMD = 2.15, 95% CI: 1.60-2.71) compared with usual treatment. Treatment with high doses of ambroxol appeared to reduce serum tumor necrosis factor-a level (WMD -7.92 μg/L; 95% CI, -10.94 to -4.9) and interleukin-6 level (WMD = -20.65 μg/L, 95% CI: -24.74 to -16.55) and to increase serum superoxide dismutase level (WMD = 19.07 NU/mL, 95% CI: 6.16-31.97). The findings suggest that treatment with high doses of ambroxol appears to improve PaO2/FiO2, PO2, and SaO2, and the benefits might be related to ambroxol's anti-oxidant and anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

The article discusses research studies on the psychological impact of antidepressants on children and adolescents with depression. Topics discussed include the meta-analyses of randomized controlled trials of antidepressants, suicidal risk of children and adolescents taking antidepressants, risk difference between placebo and antidepressants, pharmacoepidemiological studies on rare outcomes of antidepressants, and clinical implications.

A letter to the editor is presented in response to the article "Safety of coadministration of ezetimbe and statins in patients with hypercholesterolemia: a meta-analysis," by L. Luo and colleagues in issue 45.

An introduction is presented in which the author discusses an article in in the journal which deals with a systemic review and a network meta-analysis of the pharmacological treatment of orofacial pain, and it mentions a method for reviewing randomized controlled trials.