Mechanical endovascular thrombectomy for acute ischemic stroke: a retrospective multicenter study in Belgium.

Clinical trials have shown a beneficial effect of mechanical thrombectomy in acute ischemic stroke patients treated within six up to even 12 h after symptom onset. This treatment was already performed in selected hospitals in Belgium before completion of the randomized controlled trials. Outcome data on these procedures in Belgium have not been published. We performed a retrospective multicenter study of all patients with acute ischemic stroke treated with mechanical endovascular therapy in four hospitals in Belgium. Clinical outcomes, as measured by the modified Rankin Scale (mRS), site of arterial occlusion, reperfusion and the association between these variables were studied. The study included 80 patients: 65 patients with an occlusion in the anterior circulation and 15 with an occlusion in the posterior circulation. Good functional outcome (GFO) rates, defined as mRS 0-2 at 90 days, were 42 % in all patients, 44 % in anterior circulation stroke and 34 % in posterior circulation stroke. Reperfusion was achieved in 78 % of patients; more (100 %) in patients with posterior compared to patients with anterior circulation stroke (72 %; p = 0.02). The rate of GFO was greater in patients with reperfusion versus patients in whom reperfusion was not achieved (adjusted OR 8.2, 95 % CI 2.0-34.2). Symptomatic intracerebral hemorrhage was documented in 5 % of all patients. Endovascular treatment with mechanical devices for acute ischemic stroke in Belgium results in GFO and reperfusion rates similar to recently published results in the endovascular-treated arms of randomized clinical trials. Rates of symptomatic intracranial hemorrhage are low and comparable to other cohort studies and clinical trials.

Developments in mechanical thrombectomy devices for the treatment of acute ischemic stroke

Several recent prospective randomized controlled trials of endovascular stroke therapy using latest generation thrombectomy devices, so called stent-retrievers, have shown significantly improved clinical outcome compared to the standard treatment with intra-venous thrombolysis using r-tPA alone. Despite some differences in inclusion criteria between these studies, all required non-invasive vessel imaging to proof occlusion of a major brain supplying vessel. Furthermore, in most studies additional imaging techniques were used to exclude patients with already established large cerebral infarction or unfavorable collateral or penumbral status. Patients with small infarct volume, severe neurological deficits and in whom thrombectomy can be initiated within the first 6 hours after symptom onset seem to benefit the most. Therefore, mechanical thrombectomy using stent-retrievers in addition to intra-venous thrombolysis is recommended for the treatment of acute ischemic stroke with proven major vessel occlusion in the anterior circulation.

Endoscopic and Open Release Similarly Safe for the Treatment of Carpal Tunnel Syndrome. A Systematic Review and Meta-Analysis.

BACKGROUND The Endoscopic Release of Carpal Tunnel Syndrome (ECTR) is a minimal invasive approach for the treatment of Carpal Tunnel Syndrome. There is scepticism regarding the safety of this technique, based on the assumption that this is a rather "blind" procedure and on the high number of severe complications that have been reported in the literature. PURPOSE To evaluate whether there is evidence supporting a higher risk after ECTR in comparison to the conventional open release. METHODS We searched MEDLINE (January 1966 to November 2013), EMBASE (January 1980 to November 2013), the Cochrane Neuromuscular Disease Group Specialized Register (November 2013) and CENTRAL (2013, issue 11 in The Cochrane Library). We hand-searched reference lists of included studies. We included all randomized or quasi-randomized controlled trials (e.g. study using alternation, date of birth, or case record number) that compare any ECTR with any OCTR technique. Safety was assessed by the incidence of major, minor and total number of complications, recurrences, and re-operations.The total time needed before return to work or to return to daily activities was also assessed. We synthesized data using a random-effects meta-analysis in STATA. We conducted a sensitivity analysis for rare events using binomial likelihood. We judged the conclusiveness of meta-analysis calculating the conditional power of meta-analysis. CONCLUSIONS ECTR is associated with less time off work or with daily activities. The assessment of major complications, reoperations and recurrence of symptoms does not favor either of the interventions. There is an uncertain advantage of ECTR with respect to total minor complications (more transient paresthesia but fewer skin-related complications). Future studies are unlikely to alter these findings because of the rarity of the outcome. The effect of a learning curve might be responsible for reduced recurrences and reoperations with ECTR in studies that are more recent, although formal statistical analysis failed to provide evidence for such an association. LEVEL OF EVIDENCE I.

Effect of endovascular reperfusion in relation to site of arterial occlusion

OBJECTIVE To assess whether the association between reperfusion and improved clinical outcomes after stroke differs depending on the site of the arterial occlusive lesion (AOL). METHODS We pooled data from Solitaire With the Intention for Thrombectomy (SWIFT), Solitaire FR Thrombectomy for Acute Revascularisation (STAR), Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), and Interventional Management of Stroke Trial (IMS III) to compare the strength of the associations between reperfusion and clinical outcomes in patients with internal carotid artery (ICA), proximal middle cerebral artery (MCA) (M1), and distal MCA (M2/3/4) occlusions. RESULTS Among 710 included patients, the site of the AOL was the ICA in 161, the proximal MCA in 389, and the distal MCA in 160 patients (M2 = 131, M3 = 23, and M4 = 6). Reperfusion was associated with an increase in the rate of good functional outcome (modified Rankin Scale [mRS] score 0-2) in patients with ICA (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.7-7.2) and proximal MCA occlusions (OR 6.2, 95% CI 3.8-10.2), but not in patients with distal MCA occlusions (OR 1.4, 95% CI 0.8-2.6). Among patients with M2 occlusions, a subset of the distal MCA cohort, reperfusion was associated with excellent functional outcome (mRS 0-1; OR 2.2, 95% CI 1.0-4.7). CONCLUSIONS The association between endovascular reperfusion and better clinical outcomes is more profound in patients with ICA and proximal MCA occlusions compared to patients with distal MCA occlusions. Because there are limited data from randomized controlled trials on the effect of endovascular therapy in patients with distal MCA occlusions, these results underscore the need for inclusion of this subgroup in future endovascular therapy trials.

Failure of fixed orthodontic retainers: A systematic review

OBJECTIVE To evaluate the risk of failure of fixed orthodontic retention protocols. DATA Screening for inclusion eligibility, quality assessment of studies and data extraction was performed independently by two authors. SOURCES The electronic databases MEDLINE, EMBASE and CENTRAL were searched with no restrictions on publication date or language using detailed strategies. The main outcome assessed was bond failure. STUDY SELECTION Twenty-seven studies satisfied the inclusion criteria. Randomised controlled trials and prospective studies were evaluated according to the Cochrane risk of bias tool. Retrospective studies were graded employing the predetermined criteria of Bondemark. RESULTS Nine randomised controlled trials, four of which were of low quality, were identified. Six studies had a prospective design and all were of low quality. Twelve studies were retrospective. The quality of trial reporting was poor in general. Four studies assessing glass-fibre retainers, three RCTs and one prospective, reported bond failures from 11 to 71%, whereas twenty studies evaluating multistranded retainers – nine RCTs, two prospective and nine retrospective – reported failures ranging from 12 to 50%. One comparison was performed, multistranded wires vs. polyehtylene woven ribbon (RR: 1.74; 95% CI: 0.45, 6.73; p=0.42). CONCLUSION The quality of the available evidence is low. No conclusive evidence was found in order to guide orthodontists in the selection of the best protocol. CLINICAL SIGNIFICANCE Although fixed orthodontic retainers have been used for years in clinical practice, the selection of the best treatment protocol still remains a subjective issue. The available studies, and their synthesis, cannot provide reliable evidence in this field.

Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia: A Network Meta-analysis.

Importance In treatment-resistant schizophrenia, clozapine is considered the standard treatment. However, clozapine use has restrictions owing to its many adverse effects. Moreover, an increasing number of randomized clinical trials (RCTs) of other antipsychotics have been published. Objective To integrate all the randomized evidence from the available antipsychotics used for treatment-resistant schizophrenia by performing a network meta-analysis. Data Sources MEDLINE, EMBASE, Biosis, PsycINFO, PubMed, Cochrane Central Register of Controlled Trials, World Health Organization International Trial Registry, and clinicaltrials.gov were searched up to June 30, 2014. Study Selection At least 2 independent reviewers selected published and unpublished single- and double-blind RCTs in treatment-resistant schizophrenia (any study-defined criterion) that compared any antipsychotic (at any dose and in any form of administration) with another antipsychotic or placebo. Data Extraction and Synthesis At least 2 independent reviewers extracted all data into standard forms and assessed the quality of all included trials with the Cochrane Collaboration's risk-of-bias tool. Data were pooled using a random-effects model in a Bayesian setting. Main Outcomes and Measures The primary outcome was efficacy as measured by overall change in symptoms of schizophrenia. Secondary outcomes included change in positive and negative symptoms of schizophrenia, categorical response to treatment, dropouts for any reason and for inefficacy of treatment, and important adverse events. Results Forty blinded RCTs with 5172 unique participants (71.5% men; mean [SD] age, 38.8 [3.7] years) were included in the analysis. Few significant differences were found in all outcomes. In the primary outcome (reported as standardized mean difference; 95% credible interval), olanzapine was more effective than quetiapine (-0.29; -0.56 to -0.02), haloperidol (-0. 29; -0.44 to -0.13), and sertindole (-0.46; -0.80 to -0.06); clozapine was more effective than haloperidol (-0.22; -0.38 to -0.07) and sertindole (-0.40; -0.74 to -0.04); and risperidone was more effective than sertindole (-0.32; -0.63 to -0.01). A pattern of superiority for olanzapine, clozapine, and risperidone was seen in other efficacy outcomes, but results were not consistent and effect sizes were usually small. In addition, relatively few RCTs were available for antipsychotics other than clozapine, haloperidol, olanzapine, and risperidone. The most surprising finding was that clozapine was not significantly better than most other drugs. Conclusions and Relevance Insufficient evidence exists on which antipsychotic is more efficacious for patients with treatment-resistant schizophrenia, and blinded RCTs-in contrast to unblinded, randomized effectiveness studies-provide little evidence of the superiority of clozapine compared with other second-generation antipsychotics. Future clozapine studies with high doses and patients with extremely treatment-refractory schizophrenia might be most promising to change the current evidence.

Publication of statistically significant research findings in prosthodontics & implant dentistry in the context of other dental specialties

OBJECTIVES To assess the hypothesis that there is excessive reporting of statistically significant studies published in prosthodontic and implantology journals, which could indicate selective publication. METHODS The last 30 issues of 9 journals in prosthodontics and implant dentistry were hand-searched for articles with statistical analyses. The percentages of significant and non-significant results were tabulated by parameter of interest. Univariable/multivariable logistic regression analyses were applied to identify possible predictors of reporting statistically significance findings. The results of this study were compared with similar studies in dentistry with random-effects meta-analyses. RESULTS From the 2323 included studies 71% of them reported statistically significant results, with the significant results ranging from 47% to 86%. Multivariable modeling identified that geographical area and involvement of statistician were predictors of statistically significant results. Compared to interventional studies, the odds that in vitro and observational studies would report statistically significant results was increased by 1.20 times (OR: 2.20, 95% CI: 1.66-2.92) and 0.35 times (OR: 1.35, 95% CI: 1.05-1.73), respectively. The probability of statistically significant results from randomized controlled trials was significantly lower compared to various study designs (difference: 30%, 95% CI: 11-49%). Likewise the probability of statistically significant results in prosthodontics and implant dentistry was lower compared to other dental specialties, but this result did not reach statistical significant (P>0.05). CONCLUSIONS The majority of studies identified in the fields of prosthodontics and implant dentistry presented statistically significant results. The same trend existed in publications of other specialties in dentistry.

Single crowns versus conventional fillings for the restoration of root-filled teeth.

BACKGROUND Endodontic treatment involves removal of the dental pulp and its replacement by a root canal filling. Restoration of root filled teeth can be challenging due to structural differences between vital and non-vital root-filled teeth. Direct restoration involves placement of a restorative material e.g. amalgam or composite, directly into the tooth. Indirect restorations consist of cast metal or ceramic (porcelain) crowns. The choice of restoration depends on the amount of remaining tooth, and may influence durability and cost. The decision to use a post and core in addition to the crown is clinician driven. The comparative clinical performance of crowns or conventional fillings used to restore root-filled teeth is unknown. This review updates the original, which was published in 2012. OBJECTIVES To assess the effects of restoration of endodontically treated teeth (with or without post and core) by crowns versus conventional filling materials. SEARCH METHODS We searched the following databases: the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE via OVID, EMBASE via OVID, CINAHL via EBSCO, LILACS via BIREME. We also searched the reference lists of articles and ongoing trials registries.There were no restrictions regarding language or date of publication. The search is up-to-date as of 26 March 2015. SELECTION CRITERIA Randomised controlled trials (RCTs) or quasi-randomised controlled trials in participants with permanent teeth that have undergone endodontic treatment. Single full coverage crowns compared with any type of filling materials for direct restoration or indirect partial restorations (e.g. inlays and onlays). Comparisons considered the type of post and core used (cast or prefabricated post), if any. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data from the included trial and assessed its risk of bias. We carried out data analysis using the 'treatment as allocated' patient population, expressing estimates of intervention effect for dichotomous data as risk ratios, with 95% confidence intervals (CI). MAIN RESULTS We included one trial, which was judged to be at high risk of performance, detection and attrition bias. The 117 participants with a root-filled, premolar tooth restored with a carbon fibre post, were randomised to either a full coverage metal-ceramic crown or direct adhesive composite restoration. None experienced a catastrophic failure (i.e. when the restoration cannot be repaired), although only 104 teeth were included in the final, three-year assessment. There was no clear difference between the crown and composite group and the composite only group for non-catastrophic failures of the restoration (1/54 versus 3/53; RR 0.33; 95% CI 0.04 to 3.05) or failures of the post (2/54 versus 1/53; RR 1.96; 95% CI 0.18 to 21.01) at three years. The quality of the evidence for these outcomes is very low. There was no evidence available for any of our secondary outcomes: patient satisfaction and quality of life, incidence or recurrence of caries, periodontal health status, and costs. AUTHORS' CONCLUSIONS There is insufficient evidence to assess the effects of crowns compared to conventional fillings for the restoration of root-filled teeth. Until more evidence becomes available, clinicians should continue to base decisions about how to restore root-filled teeth on their own clinical experience, whilst taking into consideration the individual circumstances and preferences of their patients.

Primary prophylaxis for venous thromboembolism in patients undergoing cardiac or thoracic surgery.

BACKGROUND Cardiac and thoracic surgery are associated with an increased risk of venous thromboembolism (VTE). The safety and efficacy of primary thromboprophylaxis in patients undergoing these types of surgery is uncertain. OBJECTIVES To assess the effects of primary thromboprophylaxis on the incidence of symptomatic VTE and major bleeding in patients undergoing cardiac or thoracic surgery. SEARCH METHODS The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched May 2014) and CENTRAL (2014, Issue 4). The authors searched the reference lists of relevant studies, conference proceedings, and clinical trial registries. SELECTION CRITERIA Randomised controlled trials (RCTs) and quasi-RCTs comparing any oral or parenteral anticoagulant or mechanical intervention to no intervention or placebo, or comparing two different anticoagulants. DATA COLLECTION AND ANALYSIS We extracted data on methodological quality, participant characteristics, interventions, and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively. MAIN RESULTS We identified 12 RCTs and one quasi-RCT (6923 participants), six for cardiac surgery (3359 participants) and seven for thoracic surgery (3564 participants). No study evaluated fondaparinux, the new oral direct thrombin, direct factor Xa inhibitors, or caval filters. All studies had major study design flaws and most lacked a placebo or no treatment control group. We typically graded the quality of the overall body of evidence for the various outcomes and comparisons as low, due to imprecise estimates of effect and risk of bias. We could not pool data because of the different comparisons and the lack of data. In cardiac surgery, 71 symptomatic VTEs occurred in 3040 participants from four studies. In a study of 2551 participants, representing 85% of the review population in cardiac surgery, the combination of unfractionated heparin with pneumatic compression stockings was associated with a 61% reduction of symptomatic VTE compared to unfractionated heparin alone (1.5% versus 4.0%; risk ratio (RR) 0.39; 95% confidence interval (CI) 0.23 to 0.64). Major bleeding was only reported in one study, which found a higher incidence with vitamin K antagonists compared to platelet inhibitors (11.3% versus 1.6%, RR 7.06; 95% CI 1.64 to 30.40). In thoracic surgery, 15 symptomatic VTEs occurred in 2890 participants from six studies. In the largest study evaluating unfractionated heparin versus an inactive control the rates of symptomatic VTE were 0.7% versus 0%, respectively, giving a RR of 6.71 (95% CI 0.40 to 112.65). There was insufficient evidence to determine if there was a difference in the risk of major bleeding from two studies evaluating fixed-dose versus weight-adjusted low molecular weight heparin (2.7% versus 8.1%, RR 0.33; 95% CI 0.07 to 1.60) and unfractionated heparin versus low molecular weight heparin (6% and 4%, RR 1.50; 95% CI 0.26 to 8.60). AUTHORS' CONCLUSIONS The evidence regarding the efficacy and safety of thromboprophylaxis in cardiac and thoracic surgery is limited. Data for important outcomes such as pulmonary embolism or major bleeding were often lacking. Given the uncertainties around the benefit-to-risk balance, no conclusions can be drawn and a case-by-case risk evaluation of VTE and bleeding remains preferable.

A systematic review on the innervation of peri-implant tissues with special emphasis on the influence of implant placement and loading protocols

OBJECTIVES To systematically review the available literature on the influence of dental implant placement and loading protocols on peri-implant innervation. MATERIAL AND METHODS The database MEDLINE, Cochrane, EMBASE, Web of Science, LILACS, OpenGrey and hand searching were used to identify the studies published up to July 2013, with a populations, exposures and outcomes (PEO) search strategy using MeSH keywords, focusing on the question: Is there, and if so, what is the effect of time between tooth extraction and implant placement or implant loading on neural fibre content in the peri-implant hard and soft tissues? RESULTS Of 683 titles retrieved based on the standardized search strategy, only 10 articles fulfilled the inclusion criteria, five evaluating the innervation of peri-implant epithelium, five elucidating the sensory function in peri-implant bone. Three included studies were considered having a methodology of medium quality and the rest were at low quality. All those papers reported a sensory innervation around osseointegrated implants, either in the bone-implant interface or peri-implant epithelium, which expressed a particular innervation pattern. Compared to unloaded implants or extraction sites without implantation, a significant higher density of nerve fibres around loaded dental implants was confirmed. CONCLUSIONS To date, the published literature describes peri-implant innervation with a distinct pattern in hard and soft tissues. Implant loading seems to increase the density of nerve fibres in peri-implant tissues, with insufficient evidence to distinguish between the innervation patterns following immediate and delayed implant placement and loading protocols. Variability in study design and loading protocols across the literature and a high risk of bias in the studies included may contribute to this inconsistency, revealing the need for more uniformity in reporting, randomized controlled trials, longer observation periods and standardization of protocols.

Effect of Chronic Kidney Disease in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents: A Patient-Level Pooled Analysis of Randomized Controlled Trials.

OBJECTIVES This study sought to evaluate: 1) the effect of impaired renal function on long-term clinical outcomes in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES); and 2) the safety and efficacy of new-generation compared with early-generation DES in women with chronic kidney disease (CKD). BACKGROUND The prevalence and effect of CKD in women undergoing PCI with DES is unclear. METHODS We pooled patient-level data for women enrolled in 26 randomized trials. The study population was categorized by creatinine clearance (CrCl) <45 ml/min, 45 to 59 ml/min, and ≥60 ml/min. The primary endpoint was the 3-year rate of major adverse cardiovascular events (MACE). Participants for whom baseline creatinine was missing were excluded from the analysis. RESULTS Of 4,217 women included in the pooled cohort treated with DES and for whom serum creatinine was available, 603 (14%) had a CrCl <45 ml/min, 811 (19%) had a CrCl 45 to 59 ml/min, and 2,803 (66%) had a CrCl ≥60 ml/min. A significant stepwise gradient in risk for MACE was observed with worsening renal function (26.6% vs. 15.8% vs. 12.9%; p < 0.01). Following multivariable adjustment, CrCl <45 ml/min was independently associated with a higher risk of MACE (adjusted hazard ratio: 1.56; 95% confidence interval: 1.23 to 1.98) and all-cause mortality (adjusted hazard ratio: 2.67; 95% confidence interval: 1.85 to 3.85). Compared with older-generation DES, the use of newer-generation DES was associated with a reduction in the risk of cardiac death, myocardial infarction, or stent thrombosis in women with CKD. The effect of new-generation DES on outcomes was uniform, between women with or without CKD, without evidence of interaction. CONCLUSIONS Among women undergoing PCI with DES, CKD is a common comorbidity associated with a strong and independent risk for MACE that is durable over 3 years. The benefits of newer-generation DES are uniform in women with or without CKD.

Surgical adjunctive procedures for accelerating orthodontic treatment

BACKGROUND A range of surgical and non-surgical techniques have received increasing attention in recent years in an effort to reduce the duration of a course of orthodontic treatment. Various surgical techniques have been used; however, uncertainty exists in relation to the effectiveness of these procedures and the possible adverse effects related to them. OBJECTIVES To assess the effects of surgically assisted orthodontics on the duration and outcome of orthodontic treatment. SEARCH METHODS We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 10 September 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 8), MEDLINE via OVID (1946 to 10 September 2014), EMBASE via OVID (1980 to 10 September 2014), LILACS via BIREME (1980 to 10 September 2014), metaRegister of Controlled Trials (to 10 September 2014), ClinicalTrials.gov (to 10 September 2014), and the World Health Organization (WHO) International Clinical Trials Registry Platform (to 10 September 2014). We checked the reference lists of all trials identified for further studies. There were no restrictions regarding language or date of publication in the electronic searches. SELECTION CRITERIA Randomised controlled trials (RCTs) evaluating the effect of surgical adjunctive procedures for accelerating tooth movement compared with conventional treatment (no surgical adjunctive procedure). DATA COLLECTION AND ANALYSIS At least two review authors independently assessed the risk of bias in the trials and extracted data. We used the fixed-effect model and expressed results as mean differences (MD) with 95% confidence intervals (CI). We investigated heterogeneity with reference to both clinical and methodological factors. MAIN RESULTS We included four RCTs involving a total of 57 participants ranging in age from 11 to 33 years. The interventions evaluated were corticotomies to facilitate orthodontic space closure or alignment of an ectopic maxillary canine, with the effect of repeated surgical procedures assessed in one of these studies. The studies did not report directly on the primary outcome as prespecified in our protocol: duration of orthodontic treatment, number of visits during active treatment (scheduled and unscheduled) and duration of visits. The main outcome assessed within the trials was the rate of tooth movement, with periodontal effects assessed in one trial and pain assessed in one trial. A maximum of just three trials with small sample sizes were available for each comparison and outcome. We assessed all of the studies as being at unclear risk of bias.Tooth movement was found to be slightly quicker with surgically assisted orthodontics in comparison with conventional treatment over periods of one month (MD 0.61 mm; 95% CI 0.49 to 0.72; P value < 0.001) and three months (MD 2.03 mm, 95% CI 1.52 to 2.54; P value < 0.001). Our results and conclusions should be interpreted with caution given the small number of included studies. Information on adverse events was sought; however, no data were reported in the included studies. AUTHORS' CONCLUSIONS This review found that there is limited research concerning the effectiveness of surgical interventions to accelerate orthodontic treatment, with no studies directly assessing our prespecified primary outcome. The available evidence is of low quality, which indicates that further research is likely to change the estimate of the effect. Based on measured outcomes in the short-term, these procedures do appear to show promise as a means of accelerating tooth movement. It is therefore possible that these procedures may prove useful; however, further prospective research comprising assessment of the entirety of treatment with longer follow-up is required to confirm any possible benefit.

Outcome discrepancies and selective reporting: impacting the leading journals?

BACKGROUND Selective outcome reporting of either interesting or positive research findings is problematic, running the risk of poorly-informed treatment decisions. We aimed to assess the extent of outcome and other discrepancies and possible selective reporting between registry entries and published reports among leading medical journals. METHODS Randomized controlled trials published over a 6-month period from July to December 31st, 2013, were identified in five high impact medical journals: The Lancet, British Medical Journal, New England Journal of Medicine, Annals of Internal Medicine and Journal of American Medical Association were obtained. Discrepancies between published studies and registry entries were identified and related to factors including registration timing, source of funding and presence of statistically significant results. RESULTS Over the 6-month period, 137 RCTs were found. Of these, 18% (n = 25) had discrepancies related to primary outcomes with the primary outcome changed in 15% (n = 20). Moreover, differences relating to non-primary outcomes were found in 64% (n = 87) with both omission of pre-specified non-primary outcomes (39%) and introduction of new non-primary outcomes (44%) common. No relationship between primary or non-primary outcome change and registration timing (prospective or retrospective; P = 0.11), source of funding (P = 0.92) and presence of statistically significant results (P = 0.92) was found. CONCLUSIONS Discrepancies between registry entries and published articles for primary and non-primary outcomes were common among trials published in leading medical journals. Novel approaches are required to address this problem.

Interventions for hirsutism (excluding laser and photoepilation therapy alone)

BACKGROUND Hirsutism occurs in 5% to 10% of women of reproductive age when there is excessive terminal hair growth in androgen-sensitive areas (male pattern). It is a distressing disorder with a major impact on quality of life. The most common cause is polycystic ovary syndrome. There are many treatment options, but it is not clear which are most effective. OBJECTIVES To assess the effects of interventions (except laser and light-based therapies alone) for hirsutism. SEARCH METHODS We searched the Cochrane Skin Group Specialised Register, CENTRAL (2014, Issue 6), MEDLINE (from 1946), EMBASE (from 1974), and five trials registers, and checked reference lists of included studies for additional trials. The last search was in June 2014. SELECTION CRITERIA Randomised controlled trials (RCTs) in hirsute women with polycystic ovary syndrome, idiopathic hirsutism, or idiopathic hyperandrogenism. DATA COLLECTION AND ANALYSIS Two independent authors carried out study selection, data extraction, 'Risk of bias' assessment, and analyses. MAIN RESULTS We included 157 studies (sample size 30 to 80) comprising 10,550 women (mean age 25 years). The majority of studies (123/157) were 'high', 30 'unclear', and four 'low' risk of bias. Lack of blinding was the most frequent source of bias. Treatment duration was six to 12 months. Forty-eight studies provided no usable or retrievable data, i.e. lack of separate data for hirsute women, conference proceedings, and losses to follow-up above 40%.Primary outcomes, 'participant-reported improvement of hirsutism' and 'change in health-related quality of life', were addressed in few studies, and adverse events in only half. In most comparisons there was insufficient evidence to determine if the number of reported adverse events differed. These included known adverse events: gastrointestinal discomfort, breast tenderness, reduced libido, dry skin (flutamide and finasteride); irregular bleeding (spironolactone); nausea, diarrhoea, bloating (metformin); hot flushes, decreased libido, vaginal dryness, headaches (gonadotropin-releasing hormone (GnRH) analogues)).Clinician's evaluation of hirsutism and change in androgen levels were addressed in most comparisons, change in body mass index (BMI) and improvement of other clinical signs of hyperandrogenism in one-third of studies.The quality of evidence was moderate to very low for most outcomes.There was low quality evidence for the effect of two oral contraceptive pills (OCPs) (ethinyl estradiol + cyproterone acetate versus ethinyl estradiol + desogestrel) on change from baseline of Ferriman-Gallwey scores. The mean difference (MD) was -1.84 (95% confidence interval (CI) -3.86 to 0.18).There was very low quality evidence that flutamide 250 mg, twice daily, reduced Ferriman-Gallwey scores more effectively than placebo (MD -7.60, 95% CI -10.53 to -4.67 and MD -7.20, 95% CI -10.15 to -4.25). Participants' evaluations in one study with 20 participants confirmed these results (risk ratio (RR) 17.00, 95% CI 1.11 to 259.87).Spironolactone 100 mg daily was more effective than placebo in reducing Ferriman-Gallwey scores (MD -7.69, 95% CI -10.12 to -5.26) (low quality evidence). It showed similar effectiveness to flutamide in two studies (MD -1.90, 95% CI -5.01 to 1.21 and MD 0.49, 95% CI -1.99 to 2.97) (very low quality evidence), as well as to finasteride in two studies (MD 1.49, 95% CI -0.58 to 3.56 and MD 0.40, 95% CI -1.18 to 1.98) (low quality evidence).Although there was very low quality evidence of a difference in reduction of Ferriman-Gallwey scores for finasteride 5 mg to 7.5 mg daily versus placebo (MD -5.73, 95% CI -6.87 to -4.58), it was unlikely it was clinically meaningful. These results were reinforced by participants' assessments (RR 2.06, 95% CI 0.99 to 4.29 and RR 11.00, 95% CI 0.69 to 175.86). However, finasteride showed inconsistent results in comparisons with other treatments, and no firm conclusions could be reached.Metformin demonstrated no benefit over placebo in reduction of Ferriman-Gallwey scores (MD 0.05, 95% CI -1.02 to 1.12), but the quality of evidence was low. Results regarding the effectiveness of GnRH analogues were inconsistent, varying from minimal to important improvements.We were unable to pool data for OCPs with cyproterone acetate 20 mg to 100 mg due to clinical and methodological heterogeneity between studies. However, addition of cyproterone acetate to OCPs provided greater reductions in Ferriman-Gallwey scores.Two studies, comparing finasteride 5 mg and spironolactone 100 mg, did not show differences in participant assessments and reduction of Ferriman-Gallwey scores (low quality evidence). Ferriman-Gallwey scores from three studies comparing flutamide versus metformin could not be pooled (I² = 62%). One study comparing flutamide 250 mg twice daily with metformin 850 mg twice daily for 12 months, which reached a higher cumulative dosage than two other studies evaluating this comparison, showed flutamide to be more effective (MD -6.30, 95% CI -9.83 to -2.77) (very low quality evidence). Data showing reductions in Ferriman-Gallwey scores could not be pooled for four studies comparing finasteride with flutamide as the results were inconsistent (I² = 67%).Studies examining effects of hypocaloric diets reported reductions in BMI, but which did not result in reductions in Ferriman-Gallwey scores. Although certain cosmetic measures are commonly used, we did not identify any relevant RCTs. AUTHORS' CONCLUSIONS Treatments may need to incorporate pharmacological therapies, cosmetic procedures, and psychological support. For mild hirsutism there is evidence of limited quality that OCPs are effective. Flutamide 250 mg twice daily and spironolactone 100 mg daily appeared to be effective and safe, albeit the evidence was low to very low quality. Finasteride 5 mg daily showed inconsistent results in different comparisons, therefore no firm conclusions can be made. As the side effects of antiandrogens and finasteride are well known, these should be accounted for in any clinical decision-making. There was low quality evidence that metformin was ineffective for hirsutism and although GnRH analogues showed inconsistent results in reducing hirsutism they do have significant side effects.Further research should consist of well-designed, rigorously reported, head-to-head trials examining OCPs combined with antiandrogens or 5α-reductase inhibitor against OCP monotherapy, as well as the different antiandrogens and 5α-reductase inhibitors against each other. Outcomes should be based on standardised scales of participants' assessment of treatment efficacy, with a greater emphasis on change in quality of life as a result of treatment.

Tibial Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review

CONTEXT Tibial nerve stimulation (TNS) is a promising therapy for non-neurogenic lower urinary tract dysfunction and might also be a valuable option for patients with an underlying neurological disorder. OBJECTIVE We systematically reviewed all available evidence on the efficacy and safety of TNS for treating neurogenic lower urinary tract dysfunction (NLUTD). EVIDENCE ACQUISITION The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. EVIDENCE SYNTHESIS After screening 1943 articles, 16 studies (4 randomized controlled trials [RCTs], 9 prospective cohort studies, 2 retrospective case series, and 1 case report) enrolling 469 patients (283 women and 186 men) were included. Five studies reported on acute TNS and 11 on chronic TNS. In acute and chronic TNS, the mean increase of maximum cystometric capacity ranged from 56 to 132mL and from 49 to 150mL, and the mean increase of bladder volume at first detrusor overactivity ranged from 44 to 92mL and from 93 to 121mL, respectively. In acute and chronic TNS, the mean decrease of maximum detrusor pressure during the storage phase ranged from 5 to 15cm H2O and from 4 to 21cm H2O, respectively. In chronic TNS, the mean decrease in number of voids per 24h, in number of leakages per 24h, and in postvoid residual ranged from 3 to 7, from 1 to 4, and from 15 to 55mL, respectively. No TNS-related adverse events have been reported. Risk of bias and confounding was high in most studies. CONCLUSIONS Although preliminary data of RCTs and non-RCTs suggest TNS might be effective and safe for treating NLUTD, the evidence base is poor, derived from small, mostly noncomparative studies with a high risk of bias and confounding. More reliable data from well-designed RCTs are needed to reach definitive conclusions. PATIENT SUMMARY Early data suggest tibial nerve stimulation might be effective and safe for treating neurogenic lower urinary tract dysfunction, but more reliable evidence is required.