Overall Low Quality Of Evidence Research Articles

The effect of preoperative mechanical bowel preparation in paediatric bowel surgery on postoperative wound related complications: A meta-analysis.

Mechanical bowel preparation (MBP), a routine nursing procedure before paediatric bowel surgery, is widely should in clinical practice, but its necessity remains controversial. In a systematic review and meta-analysis, we evaluated the effect of preoperative MBP in paediatric bowel surgery on postoperative wound-related complications in order to analyse the clinical application value of MBP in paediatric bowel surgery. As of November 2023, we searched four online databases: the Cochrane Library, Embase, PubMed, and Web of Science. Two investigators screened the collected studies against inclusion and exclusion criteria, and ROBINS-I was used to evaluate the quality of studies. Using RevMan5.3, a meta-analysis of the collected data was performed, and a fixed-effect model or a random-effect model was used to analyse OR, 95% CI, SMD, and MD. A total of 11 studies with 2556 patients were included. Most of studies had moderate-to-severe quality bias. The results of meta-analysis showed no statistically significant difference in the incidence of complications related to postoperative infections in children with MBP before bowel surgery versus those with No MBP, wound infection (OR 1.11, 95% CI:0.76 ~ 1.61, p = 0.59, I2 = 5%), intra-abdominal infection (OR 1.26, 95% CI:0.58 ~ 2.77, p = 0.56, I2 = 9%). There was no significant difference in the risk of postoperative bowel anastomotic leak (OR 1.07, 95% CI:0.68 ~ 1.68, p = 0.78, I2 = 12%), and anastomotic dehiscence (OR 1.67, 95% CI:0.13 ~ 22.20, p = 0.70, I2 = 73%). Patients' intestinal obstruction did not show an advantage of undergoing MBP preoperatively, with an incidence of intestinal obstruction (OR 1.95, 95% CI:0.55 ~ 6.93, p = 0.30, I2 = 0%). Based on existing evidence that preoperative MBP in paediatric bowel surgery did not reduce the risk of postoperative wound complications, we cautiously assume that MBP before surgery is unnecessary for children undergoing elective bowel surgery. However, due to the limited number of study participants selected for this study and the overall low quality of evidence, the results need to be interpreted with caution. It is suggested that more high quality, large-sample, multicenter clinical trials are required to validate our findings.

Buccal Fat Pad in Primary and Secondary Cleft Palate Repair: A Systematic Review of the Literature.

To review the evidence supporting the use of buccal fat pad (BFP) in primary and secondary cleft palate repair and its short- and long- term clinical outcomes. Systematic review conducted by 2 independent reviewers following PRISMA guidelines. Articles were identified from three databases (Pubmed/Medline, Embase and Web of Science). Search terms included "cleft palate", "palatoplasty", "palate repair", "buccal fat pad". Use of BFP in primary and secondary cleft palatoplasty. Primary outcomes were immediate postoperative complications, postoperative fistula, and maxillary growth. Secondary outcomes were palatal length, speech, and donor site morbidity. Ninety-one reports were retrieved after excluding duplicates. Twenty-three studies were included (13 case series and 10 comparative studies). Overall level of evidence was low. Randomized and non-randomized studies had a high risk of bias. In primary palatoplasty, BFP was more frequently used filling lateral relaxing incisions(57.4%), or in the hard-soft palate junction and covering mucosal defects(30.1%). In these patients, post operative fistula incidence was 2.8%. Two studies found wider transverse maxillary dimensions after BFP use. No higher incidence of bleeding, infection, dehiscence, or flap necrosis was reported. In secondary palatoplasty, no recurrent fistulas were reported for patients undergoing BFP for fistula repair. BFP appears to be associated with a favorable impact in fistula prevention and management, as well as in transverse maxillary growth. However, there is a high heterogeneity among studies, high risk of bias and overall low quality of evidence. More high-quality research with long-term follow-up is warranted.

Antimicrobial Pharmacokinetics and Dosing in Critically Ill Adults Receiving Prolonged Intermittent Renal Replacement Therapy: A Systematic Review.

Prolonged intermittent renal replacement therapy (PIRRT) is gaining popularity as a renal replacement modality in intensive care units, but there is a relative lack of guidance regarding antimicrobial clearance and dosing when compared with other modalities. The objectives of this systematic review were to: 1) identify and describe the pharmacokinetics (PK) of relevant antimicrobials used in critically ill adults receiving PIRRT, 2) evaluate the quality of evidence supporting this data, and 3) propose dosing recommendations based on the synthesis of this data. A search strategy for multiple databases was designed and executed to identify relevant published evidence describing the PK of antimicrobials used in critically ill adults receiving PIRRT. Quality assessment, evaluation of reporting, and relevant data extraction was conducted in duplicate. Synthesis of PK/pharmacodynamic (PD) outcomes, dosing recommendations from study authors, and physicochemical properties of included antibiotics were assessed by investigators in addition to the quality of evidence to develop dosing recommendations. Thirty-nine studies enrolling 452 patients met criteria for inclusion and provided PK and/or PD data for 20 antimicrobials in critically ill adults receiving PIRRT. Nineteen studies describe both PK and PD outcomes. Vancomycin (12 studies, 171 patients), meropenem (7 studies, 84 patients), and piperacillin/tazobactam (5 studies, 56 patients) were the most frequent antimicrobials encountered. The quality of evidence was deemed strong for 7/20 antimicrobials, and strong dosing recomendations were determined for 9/20 antimicrobials. This systematic review updates and addresses issues of quality in previous systematic reviews on this topic. Despite an overall low quality of evidence, strong recommendations were able to be made for almost half of the identified antimicrobials. Knowledge gaps persist for many antimicrobials and higher quality studies (i.e., population PK studies with assessment of PD target attainment) are needed to address these gaps.

Use of Virtual Reality-Based Games to Improve Balance and Gait of Children and Adolescents with Sensorineural Hearing Loss: A Systematic Review and Meta-Analysis.

Children and adolescents with sensorineural hearing loss (SNHL) often experience motor skill disturbances, particularly in balance and gait, due to potential vestibular dysfunctions resulting from inner ear damage. Consequently, several studies have proposed the use of virtual reality-based games as a technological resource for therapeutic purposes, aiming to improve the balance and gait of this population. The objective of this systematic review is to evaluate the quality of evidence derived from randomized or quasi-randomized controlled trials that employed virtual reality-based games to enhance the balance and/or gait of children and adolescents with SNHL. A comprehensive search was conducted across nine databases, encompassing articles published in any language until 1 July 2023. The following inclusion criteria were applied: randomized or quasi-randomized controlled trials involving volunteers from both groups with a clinical diagnosis of bilateral SNHL, aged 6-19 years, devoid of physical, cognitive, or neurological deficits other than vestibular dysfunction, and utilizing virtual reality-based games as an intervention to improve balance and/or gait outcomes. Initially, a total of 5984 articles were identified through the searches. Following the removal of duplicates and screening of titles and abstracts, eight studies remained for full reading, out of which three trials met the eligibility criteria for this systematic review. The included trials exhibited a very low quality of evidence concerning the balance outcome, and none of the trials evaluated gait. The meta-analysis did not reveal significant differences in balance improvement between the use of traditional balance exercises and virtual reality-based games for adolescents with SNHL (effect size: -0.48; [CI: -1.54 to 0.57]; p = 0.37; I2 = 0%). Virtual reality-based games show promise as a potential technology to be included among the therapeutic options for rehabilitating the balance of children and adolescents with SNHL. However, given the methodological limitations of the trials and the overall low quality of evidence currently available on this topic, caution should be exercised when interpreting the results of the trials analyzed in this systematic review.

Anthropometric Parameters in Patients with Fatty Acid Oxidation Disorders: A Case-Control Study, Systematic Review and Meta-Analysis.

This study compared the anthropometric parameters of patients with fatty acid oxidation disorders (FAOD) and healthy controls, showing an increased prevalence of abnormal body weight (overweight and obesity) in the FAOD group. First, differences in BMI, BMI percentiles and z-scores, and weight and weight percentiles were compared in a cohort of 39 patients with FAOD and 156 healthy controls, as well as between patients born before and after the introduction of a populational newborn screening programme (NBS) in 2014 in Poland. We also performed a systematic literature review yielding 12 studies mentioning anthropometric parameters in 80 FAOD patients and 121 control subjects, followed by a meta-analysis of data from 8 studies and our cohort. There were significant differences in body weight percentiles (p = 0.001), BMI (p = 0.022), BMI percentiles (p = 0.003) and BMI z-scores (p = 0.001) between FAOD patients and controls in our cohort but not between pre- and post-newborn-screening patients. The meta-analysis did not show any differences in weight and BMI in all tested subgroups, i.e., all FAOD patients vs. controls, medium-chain acyl-CoA dehydrogenase (MCADD) patients vs. controls and patients with FAOD types other than MCAD vs. controls. These results, however, should be interpreted with caution due to the overall low quality of evidence as assessed by GRADE, the small sample sizes and the significant heterogeneity of the included data.

Review article: E-learning in emergency medicine: A systematic review.

E‐learning (EL) has been developing as a medical education resource since the arrival of the internet. The COVID‐19 pandemic has minimised clinical exposure for medical trainees and forced educators to use EL to replace traditional learning (TL) resources. The aim of this review was to determine the impact of EL versus TL on emergency medicine (EM) learning outcomes of medical trainees. A systematic review was conducted according to the Preferred Reporting Items for Systematic Review and Meta‐analysis statement using articles sourced from CINAHL, Embase, OVID Medline and PubMed. Articles were independently reviewed by two reviewers following strict inclusion and exclusion criteria. Bias was assessed using the Cochrane Risk of Bias tool. The search yielded a total of 1586 non‐duplicate studies. A total of 19 studies were included for data extraction. Fifteen of the included studies assessed knowledge gain of participants using multiple‐choice questions as an outcome measure. Eleven of the 15 demonstrated no statistically significant difference while two studies favoured EL with statistical significance and two favoured TL with statistical significance. Six of the included studies assessed practical skill gain of participants. Five of the six demonstrated no statistical significance while one study favoured EL with statistical significance. This systematic review suggests that EL may be comparable to TL for the teaching of EM. The authors encourage the integration of EL as an adjunct to face‐to‐face teaching where possible in EM curricula; however, the overall low quality of evidence precludes definitive conclusions from being drawn.

Effectiveness of rehabilitation interventions on the secondary consequences of surviving a cardiac arrest: a systematic review and meta-analysis

AimThe aim of this systematic review was to assess the effectiveness of rehabilitation interventions on the secondary physical, neurological and psychological consequences of cardiac arrest (CA) for adult survivors.MethodsA literature...

Association of specialized enteral nutrition with glycemic control and clinical outcomes in critically ill patients: A meta-analysis of randomized controlled trials

To evaluate the association of glycemic-control formulae (GCF) with measurements of glycemic control and clinical outcomes compared to standard enteral formulae (SF) in critically ill patients. MEDLINE, EMBASE, Scopus and the Cochrane Central Register of Controlled Trials were searched from inception up to January, 2021. RCTs that assessed the effects of GCF relative to SF in adult critically ill patients. Measurements of glycemic control were the primary outcomes. Secondary outcomes included insulin requirements, mechanical ventilation (MV), length of intensive care unit (ICU) stay and mortality. Two authors independently extracted data and assessed risk of bias using the Cochrane's RoB 2 tool and the GRADE approach was used to assess the quality of evidence. Ten studies (12 reports, 685 patients) were included. The use of GCFs was associated with lower blood glucose (WMD,-16.06mg/dL; 95% CI -23.48 to-8.63; I2=47%) and lower daily administered insulin (WMD,-7.20 IU; 95% CI -13.92 to-0.48; I2=53%). Glycemic variability, measured by the coefficient of variation, was also associated with the use of GCFs (WMD,-6.84%; 95% CI,-13.57 to-0.11; I2=95%). In contrast, analyses for length of ICU stay (WMD,-0.12, 95% CI -1.77 to 1.52; I2=0%), duration of MV (WMD,-0.34 days; 95% CI,-1.72 to 1.04; I2=0%) and mortality (RR, 1.13; 95% CI 0.82 to 1.56; I2=0%) were not statistically significant. Quality of evidence ranged from low to very low, and only one study was judged as at low risk of bias. In this meta-analysis, GCFs were significantly associated with lower insulin requirements and improved glycemic control. Although results for clinical outcomes were not statistically significant, there is insufficient evidence to confirm or exclude important differences due to serious imprecision in the effect estimates and overall low quality of evidence. The effects of GCFs on clinical outcomes require confirmation in larger randomized trials.

The Effect of Antibiotic Restriction Programs on Prevalence of Antimicrobial Resistance: A Systematic Review and Meta-Analysis.

BackgroundIn hospital settings, restriction of selected classes of antibiotics is usually believed to contribute to containment of resistance development. We performed a systematic review and meta-analysis to assess the effect of restricting the use of specific antibiotic classes on the prevalence of resistant bacterial pathogens.MethodsWe conducted a systematic literature search in Embase and PubMed/OVID MEDLINE. We included studies until June 4, 2020 in which a restrictive antibiotic policy was applied and prevalence of resistance and use of antibiotics were reported. We calculated the overall effect of antimicrobial resistance between postintervention versus preintervention periods using pooled odds ratios (ORs) from a mixed-effects model. We stratified meta-analysis by antibiotic-pathogen combinations. We assessed heterogeneity between studies using the I2 statistic and sources of heterogeneity using meta-regression.ResultsWe included 15 individual studies with an overall low quality of evidence. In meta-analysis, significant reductions in resistance were only observed with nonfermenters after restricting fluoroquinolones (OR = 0.77, 95% confidence interval [CI] = 0.62–0.97) and piperacillin-tazobactam (OR = 0.81, 95% CI = 0.72–0.92). High degrees of heterogeneity were observed with studies restricting carbapenem (Enterobacterales, I2 = 70.8%; nonfermenters, I2 = 81.9%), third-generation cephalosporins (nonfermenters, I2 = 63.3%), and fluoroquiolones (nonfermenters, I2 = 64.0%). Results were comparable when excluding studies with fewer than 50 bacteria. There was no evidence of publication bias for any of the antibiotic-pathogen combinations.ConclusionsWe could not confirm that restricting carbapenems or third-generation cephalosporins leads to decrease in prevalence of antibiotic resistance among Enterobacterales, nonfermenters, or Gram-positive bacteria in hospitalized patients. Nevertheless, reducing fluoroquinolone and piperacilline-tazobactam use may decrease resistance in nonfermenters.

Association of periodontitis and cognitive impairment: A systematic review and meta‐analysis

AbstractBackgroundEmerging evidence suggests link between poor periodontal status and cognitive impairment. This review systematically assessed longitudinal evidence on the association of periodontitis and tooth loss with cognition.MethodsComprehensive literature search for studies examining effect of periodontitis on cognition was conducted on two electronic databases, Medline and Scopus. Longitudinal studies having periodontitis or its surrogate measure (tooth loss) as exposure and cognition as outcome were included. Meta‐analysis was conducted on RevMAN‐5 software. Primary random effects model analyzing the effect of periodontitis (all measures) on cognition was generated. Secondary analyses included models based on periodontal specific measures 1 and tooth loss. Quality assessment of included studies was conducted.ResultsOut of 97 studies, 16 were included in the systematic review. Meta‐analysis included 9 studies. In preliminary results, primary model showed significant association between periodontitis and cognitive impairment (OR=1.22, 95%CI:1.01–1.49, p=0.04). In secondary analyses, neither periodontitis (based on specific measures) nor tooth loss was associated with cognitive impairment. However, further stratification of tooth loss found significant association between partial tooth loss and cognitive impairment (OR=1.53, 95%CI:1.03–2.29, p=0.04). The overall quality of evidence was low.ConclusionPeriodontitis appears to contribute to overall risk of cognitive impairment. This association may be driven by specific aspects of periodontitis such as severity, chronicity and corresponding tooth count. However, firm conclusions cannot be drawn due to overall low quality of evidence and lack of coherent methodology among studies (e.g. variability across periodontal and cognitive assessments). Well‐designed longitudinal studies with larger sample size and including comprehensive and standardized assessment of both periodontal and cognitive status are warranted.

Particle therapy toxicity outcomes: A systematic review.

Owing to its physical properties, particle therapy (PT), including proton beam therapy (PBT) and carbon ion therapy (CIT), can enhance the therapeutic ratio in radiation therapy. The major factor driving PT implementation is the reduction in exit and integral dose compared to photon plans, which is expected to translate to reduced toxicity and improved quality of life. This study extends the findings from a recent systematic review by the current authors which concentrated on tumour outcomes for PT, to now examine toxicity as a separate focus. Together, these reviews provide a comprehensive collation of the evidence relating to PT outcomes in clinical practice. Three major databases were searched by two independent researchers, and evidence quality was classified according to the National Health and Medical Research Council evidence hierarchy. One hundred and seventy-nine studies were included. Most demonstrated acceptable and favourable toxicity results. Comparative evidence reported reduced morbidities and improvement in quality of life in head and neck, paediatrics, sarcomas, adult central nervous system, gastrointestinal, ocular and prostate cancers compared to photon radiotherapy. This suggestion for reduced morbidity must be counterbalanced by the overall low quality of evidence. A concerted effort in the design of appropriate comparative clinical trials is needed which takes into account integration of PT's pace of technological advancements, including evolving delivery techniques, image guidance availability and sophistication of planning algorithms.

Needling after trabeculectomy - does augmentation by anti-metabolites provide better outcomes and is Mitomycin C better than 5-Fluoruracil? A systematic review with network meta-analyses.

Favourable outcome after glaucoma surgery depends on proper control of the inflammatory response. Failing filtration bleb and consequently increased intraocular pressure is an important cause of continuous visual field deterioration after uncomplicated glaucoma surgery. The present systematic review and meta-analysis aimed to compare the effects of employing either Mitomycin C (MMC), 5-Fluoruracil (5-FU) or no anti-metabolite in needling revision of trabeculectomies. We performed a systematic literature search in PubMed, Cochrane and EMBASE to identify randomized and non-randomized trials published between year 2000 and March 2019 comparing the efficacy of needling filtering blebs when using no anti-fibrotic agent, MMC or 5-FU in patients with glaucoma. Efficacy was defined as intraocular pressure at 12months or latest follow-up, rate of complications, rates of success and the number of re-needling cases. Comparisons were made using network meta-analyses. We identified one randomized trial and five retrospective trials. Twelve months after needling revision of trabeculectomy, no significant difference was observed when comparing the effect of the use of MMC with 5-FU or without any use of anti-metabolite on intraocular pressure, complication rates, qualified success, complete success or number of re-needling cases. We found no significant difference in the efficacy of using either MMC, 5-FU or no anti-metabolite in needling revision of trabeculectomies. The number of studies meeting our inclusion criteria was limited. Considering the design of studies, only one was randomized leading to an overall low quality of evidence on the subject matter. Further research is warranted.

Particle therapy tumour outcomes: An updated systematic review.

Particle therapy (PT) offers the potential for reduced normal tissue damage as well as escalation of target dose, thereby enhancing the therapeutic ratio in radiation therapy. Reflecting the building momentum of PT use worldwide, construction has recently commenced for The Australian Bragg Centre for Proton Therapy and Research in Adelaide - the first PT centre in Australia. This systematic review aims to update the clinical evidence base for PT, both proton beam and carbon ion therapy. The purpose is to inform clinical decision-making for referral of patients to PT centres in Australia as they become operational and overseas in the interim. Three major databases were searched by two independent researchers, and evidence quality was classified according to the National Health and Medical Research Council evidence hierarchy. One hundred and thirty-six studies were included, two-thirds related to proton beam therapy alone. PT at the very least provides equivalent tumour outcomes compared to photon controls with the possibility of improved control in the case of carbon ion therapy. There is suggestion of reduced morbidities in a range of tumour sites, supporting the predictions from dosimetric modelling and the wide international acceptance of PT for specific indications based on this. Though promising, this needs to be counterbalanced by the overall low quality of evidence found, with 90% of studies of level IV (case series) evidence. Prospective comparative clinical trials, supplemented by database-derived outcome information, preferably conducted within international and national networks, are strongly recommended as PT is introduced into Australasia.

Neoadjuvant treatments for resectable rectal cancer: A network meta-analysis.

Different neoadjuvant therapy regimens are available for rectal cancer, but the relative effects are controversial. The aim of the present network meta-analysis (NMA) was to estimate the relative efficacy and safety of neoadjuvant therapies for resectable rectal cancer. MEDLINE, EMBASE and Cochrane Central Registry of Controlled Trials were searched for publications dated from 1946 up to June 2018. The present study included randomized clinical trials that compared treatments for resected rectal cancer: Surgery alone, surgery preceded by neoadjuvant radiotherapy (RT), neoadjuvant chemotherapy (CT) or neoadjuvant chemoradiotherapy (CRT). Direct pairwise comparisons and NMA were conducted. A total of 23 randomized controlled trials were included in the present study. RT had an overall survival (OS) benefit when compared with surgery alone [HR (hazard ratio), 0.89; 95% confidence interval (CI), 0.82-0.97; quality of evidence, high]. All three neoadjuvant regimens were associated with lower local recurrence (LR) when compared with surgery alone [RT: odds ratio (OR), 0.44; 95% CI, 0.35-0.65; quality of evidence, high; CRT: OR, 0.34; 95% CI, 0.23-0.56; quality of evidence, low and CT: OR, 0.32; 95% CI, 0.11-1.00; quality of evidence, low]. There were no significant differences in OS and LR between CRT and RT (OS: OR, 1.10); 95% CI, 0.93-1.20; LR: OR, 0.81; 95% CI, 0.61-1.10). Ranking probabilities indicated that CRT was the best strategy for local control, with a surface under the cumulative ranking curve (SUCRA) of 78.78%. Patients treated with RT had improved disease-free survival compared with those treated with surgery alone (HR, 0.82; 95% CI, 0.64-1.00; quality of evidence, low). Neoadjuvant RT or CRT did not significantly improve distant metastases compared with surgery alone (RT: OR, 0.87; 95% CI, 0.69-1.10 and CRT: OR, 0.75; 95% CI, 0.47-1.10). CRT had an improved pathological complete response rate compared with RT (OR, 4.90; 95% CI, 21.80-17.00; quality of evidence, low). No significant difference for the risk of anastomotic leak between each treatment was observed in the NMA. In conclusion, RT decreased the LR and improved OS compared with surgery alone for resected rectal cancer. CRT was the best neoadjuvant therapy analyzed and CT was likely the second best for all outcomes based on SUCRA. However, these findings were limited by overall low quality of evidence.

The Effects of Green Exercise on Physical and Mental Wellbeing: A Systematic Review.

We aimed to examine the evidence for the proposed additive effect of exercise in the presence of nature (green exercise) by systematically reviewing studies that investigated the effects of outdoor or virtual green exercise compared with indoor exercise. Our review updates an earlier review, whose searches were conducted in April 2010. Trials were eligible if: (a) participants in an outdoor or virtual exercise condition were exposed to views of nature (green exercise); (b) green exercise was compared with indoor exercise with no exposure to nature; (c) included an outcome related to physical or mental health; (d) used comparative or crossover trial design. We searched the following databases from 1st January 2010 to 28th June 2018: PubMed, CENTRAL, EMBASE, PsycINFO, GreenFile, and Sports DISCUS. We assessed risk of bias using the Cochrane “risk of bias” tool. Where possible we conducted a meta-analysis using the inverse variance random-effects method, and where this approach was not possible we presented the results qualitatively and in harvest plots. We identified 28 eligible trials. In a meta-analysis of just three longitudinal trials, the only statistical finding was slightly lower post-intervention perceived exertion with green versus indoor exercise (mean difference: −1.02; 95% confidence intervals: −1.88, −0.16). Compared with indoor exercise, acute bouts of outdoor green exercise may favorably influence affective valence and enjoyment, but not emotion, perceived exertion, exercise intensity, and biological markers. No other consistent statistical differences were observed, apart from a higher enjoyment of outdoor green versus virtual green exercise. We found a high risk of bias across trials and an overall low quality of evidence. In conclusion, there was limited evidence to support the view that green exercise offers superior benefits to exercise without exposure to nature. The low quality of evidence prohibits clear interpretation of trial findings. Future robust and rigorously designed trials are needed to evaluate the effects of long-term and multiple-bout exposure to nature during exercise compared with exercise indoors.

Effect of prolonged treatment with phosphodiesterase-5-inhibitors on endothelial dysfunction in vascular diseases and vascular risk conditions: A systematic review analysis and meta-analysis of randomized double-blind placebo-controlled trials.

To challenge the argument that continuous use of phosphodiesterase-5-selective inhibitors may reduce endothelial cell dysfunction in patients with vascular diseases or vascular risk conditions. This study included systematic reviews and meta-analysis of randomized double-blind placebo-controlled trials dealing with the prolonged use of phosphodiesterase-5-selective inhibitors. The risk of bias and quality of trials were assessed by the Cochrane algorithm. Fixed or random effect models, standardised mean differences and heterogeneity were estimated in the study. Systematic search for randomized double-blind placebo-controlled trials was done in PubMed, Scopus, CINAHL, Science direct and the Cochrane Library. Randomized double-blind placebo-controlled trials reporting measures of endothelial cell dysfunction and/or endothelial cell activation were included. On the whole, 469 subjects were allocated to the phosphodiesterase-5-selective inhibitor group, while 463 were assigned to the placebo group in 13 randomized double-blind placebo-controlled trials. Flow-mediated dilation of the brachial artery was found to improve after the administration of phosphodiesterase-5-selective inhibitors (P<0.0001). The results were questioned by the elevated and uncorrectable heterogeneity (I2 =92%) and the asymmetry of the funnel plot suggested a publication bias. Phosphodiesterase-5-selective inhibitors have no effect on endothelial cell dysfunction, as assessed in the resistance vessels by digital arterial tonometry. The blood level of endothelin-1 was observed to be decreased in phosphodiesterase-5-selective inhibitors arm (P=0.03), although the effect disappeared once the publication bias and heterogeneity were corrected. The effect of phosphodiesterase-5-selective inhibitors on biomarkers of endothelial cell activation was found to be inconsistent. The results on the benefits of a prolonged use of phosphodiesterase-5-selective inhibitors, with the objective of lowering endothelial cell dysfunction in patients with vascular diseases or vascular risk conditions are not convincing. This is because of the overall low quality of evidence, giving an unclear scientific support to this treatment. Systematic review registration: PROSPERO registration: CRD42017055399.

Effectiveness of needle and syringe Programmes in people who inject drugs \u2013 An overview of systematic reviews

BackgroundNeedle and syringe programmes (NSP) are a critical component of harm reduction interventions among people who inject drugs (PWID). Our primary objective was to summarize the evidence on the effectiveness of NSP for PWID in reducing blood-borne infection transmission and injecting risk behaviours (IRB).MethodsWe conducted an overview of systematic reviews that included PWID (excluding prisons and consumption rooms), addressed community-based NSP, and provided estimates of the effect regarding incidence/prevalence of Human Immunodeficiency Virus (HIV), Hepatitis C virus (HCV), Hepatitis B virus (HBV) and bacteremia/sepsis, and/or measures of IRB. Systematic literature searches were undertaken on relevant databases, including EMBASE, MEDLINE, and PsychINFO (up to May 2015). For each review we identified relevant studies and extracted data on methods, and findings, including risk of bias and quality of evidence assessed by review authors. We evaluated the risk of bias of each systematic review using the ROBIS tool. We categorized reviews by reported outcomes and use of meta-analysis; no additional statistical analysis was performed.ResultsWe included thirteen systematic reviews with 133 relevant unique studies published between 1989 and 2012. Reported outcomes related to HIV (n = 9), HCV (n = 8) and IRB (n = 6). Methods used varied at all levels of design and conduct, with four reviews performing meta-analysis. Only two reviews were considered to have low risk of bias using the ROBIS tool, and most included studies were evaluated as having low methodological quality by review authors. We found that NSP was effective in reducing HIV transmission and IRB among PWID, while there were mixed results regarding a reduction of HCV infection. Full harm reduction interventions provided at structural level and in multi-component programmes, as well as high level of coverage, were more beneficial.ConclusionsThe heterogeneity and the overall low quality of evidence highlights the need for future community-level studies of adequate design to support these results.Trial registrationThe protocol of this systematic review was registered in Prospective Register of Systematic Reviews (PROSPERO 2015:CRD42015026145).

Preoperative predictors for outcomes after total hip replacement in patients with osteoarthritis: a systematic review

BackgroundThis systematic review examines which patient related factors influence functional and clinical outcomes after total hip arthroplasty (THA) in patients with hip osteoarthritis (OA).MethodsWe performed a systematic review according to the PRISMA guidelines. We searched databases and trial registries for prospective studies including OA patients who underwent primary THA. Studies with preoperative measurements on predictors, with at least 1 year follow-up were included. Risk of bias and confounding was assessed for two domains: follow-up rate and looking at independent effects.ResultsThirty-five studies were included (138,039 patients). Only nine studies (29 %) had low risk of bias for all domains thus suggesting an overall low quality of evidence. Studies were heterogeneous in the predictors tested and in the observed directions of the associations. Overall, preoperative function (13 studies (37 %), 2 with low risk of bias) and radiological OA (6 studies (17 %), 1 with low risk of bias) were predictors with the most consistent findings. Worse preoperative function and more severe radiological OA were associated with larger postoperative improvement. However, these patients never reached the level of postoperative functioning as patients with better preoperative function or less severe radiological OA. For age, gender, comorbidity, pain and quality of life the results of studies were conflicting. For BMI, some studies (n = 5, 2 with low risk of bias) found worse outcomes for patients with higher BMI. However, substantial improvement was still achieved regardless of their BMI.ConclusionThere is not enough evidence to draw succinct conclusions on preoperative predictors for postoperative outcome in THA, as results of studies are conflicting and the methodological quality is low. Results suggest to focus on preoperative function and radiological osteoarthritis to decide when THA will be most effective. The present mapping of current evidence on the relationship between patient related factors and outcomes provides better information compared to individual studies and may help to set patient expectations before surgery. In addition, these findings may contribute to discussions on how to achieve the best possible postoperative outcome for specific patient groups.Trial registrationThis systematic review was registered in Prospero, registration number RD42014009977.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-016-1070-3) contains supplementary material, which is available to authorized users.

Effect of Surgical Intervention for Removal of Mandibular Third Molar on Periodontal Healing of Adjacent Mandibular Second Molar: A Systematic Review and Bayesian Network Meta-Analysis.

The aim of this systematic review is to evaluate and synthesize scientific evidence on the effect of surgical interventions for removal of mandibular third molar (M3M) on periodontal healing of adjacent mandibular second molar (M2M). The protocol was registered at PROSPERO (International Prospective Register of Systematic Reviews) as CRD42012003059. Medline, Cochrane, and EMBASE databases were interrogated to identify randomized controlled trials (RCTs) up to December 22, 2014. Patients with M3Ms fully developed, unilaterally or bilaterally impacted, were considered. Outcomes were clinical attachment level gain (CALg) and probing depth reduction (PDr) with a follow-up ≥ 6 months. Patient-subjective outcomes, such as pain, discomfort, and complications, and financial aspects and chair time, were also explored. A Bayesian network meta-analysis model was used to estimate direct and indirect effects and to establish a ranking of treatments. Sixteen RCTs were included and categorized into four groups investigating the following: 1) regenerative/grafting procedures (10 RCTs); 2) flap design (three RCTs); 3) type of suturing (one RCT); and 4) periodontal care of M2M (two RCTs). Guided tissue regeneration (GTR) with resorbable (GTRr) and non-resorbable (GTRnr) membrane and GTRr with anorganic xenograft (GTRr + AX) showed the highest mean ranking for CALg (2.99, 90% credible interval [CrI] = 1 to 5; 2.80, 90% CrI = 1 to 6; and 2.29, 90% CrI = 1 to 6, respectively) and PDr (2.83, 90% CrI = 1 to 5; 2.52, 90% CrI = 1 to 5; and 2.77, 90% CrI = 1 to 6, respectively). GTRr + AX showed the highest probability (Pr) of being the best treatment for CALg (Pr = 45%) and PDr (Pr = 32%). Direct and network quality of evidence were rated from very low to moderate. To the best of the authors' knowledge, the present review is the first one to evaluate quantitatively and qualitatively the effect of different interventions on periodontal healing distal to the second molar after extraction of the third molar. GTR-based procedures with or without combined grafting therapies provide some adjunctive clinical benefit compared to standard non-regenerative/non-grafting procedures. However, the overall low quality of evidence suggests a low degree of confidence and certainty in treatment effects. Evidence on variations of surgical M3M removal techniques based on flap design, type of suturing, and periodontal care of M2M is limited both qualitatively and quantitatively.

Prehospital management and identification of sepsis by emergency medical services: a systematic review

ObjectiveTo identify studies describing the accuracy of prehospital sepsis identification and to summarise results of studies of prehospital management of patients with sepsis, severe sepsis or septic shock.MethodsWe conducted a...