Interventions for pityriasis rosea.

How effective are interventions to reduce Staphylococcus aureus in eczema?

Interventions to reduce Staphylococcus aureus in the management of eczema.

This is a copy of an article published in the Cochrane Database of Systematic Reviews © 2016 Cochrane Collaboration Publications. © The Author(s). http://www.cochranelibrary.com/

A variety of alpha-blockers are used for treating lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). Silodosin is a novel, more selective alpha-blocker, which is specific to the lower urinary tract and may have fewer side effects than other alpha-blockers. To assess the effects of silodosin for the treatment of LUTS in men with BPH. We performed a comprehensive search using multiple databases (Cochrane Library, MEDLINE, EMBASE, Scopus, Google Scholar, and Web of Science), trials registries, other sources of grey literature, and conference proceedings with no restrictions on the language of publication or publication status up until 13 June 2017. We included all parallel, randomized controlled trials. We also included cross-over designs. Two review authors independently classified studies and abstracted data from the included studies. We performed statistical analyses using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of evidence according to the GRADE approach. We included 19 unique studies with 4295 randomized participants across four comparisons for short-term follow-up. The mean age, prostate volume, and International Prostate Symptom Score were 66.5 years, 38.2 mL, and 19.1, respectively. Silodosin versus placeboBased on four studies with a total of 1968 randomized participants, silodosin may reduce urologic symptom scores in an appreciable number of men (mean difference (MD) -2.65, 95% confidence interval (CI) -3.23 to -2.08; low-quality evidence). Silodosin likely does not result in a clinically important reduction in quality of life (MD -0.42, 95% CI -0.71 to -0.13; moderate-quality evidence). It may not increase rates of treatment withdrawal for any reason (relative risk (RR) 1.08, 95% CI 0.70 to 1.66; low-quality evidence). We are uncertain about the effect of silodosin on cardiovascular adverse events (RR 1.28, 95% CI 0.67 to 2.45; very low-quality evidence). Silodosin likely increases sexual adverse events (RR 26.07, 95% CI 12.36 to 54.97; moderate-quality evidence); this would result in 180 more sexual adverse events per 1000 men (95% CI 82 more to 388 more). Silodosin versus tamsulosinBased on 13 studies with a total of 2129 randomized participants, silodosin may result in little to no difference in urologic symptom scores (MD -0.04, 95% CI -1.31 to 1.24; low-quality evidence) and quality of life (MD -0.15, 95% CI -0.53 to 0.22; low-quality evidence). We are uncertain about treatment withdrawals for any reason (RR 1.02, 95% CI 0.62 to 1.69; very low-quality evidence). Silodosin may result in little to no difference in cardiovascular adverse events (RR 0.77, 95% CI 0.53 to 1.12; low-quality evidence). Silodosin likely increases sexual adverse events (RR 6.05, 95% CI 3.55 to 10.31; moderate-quality evidence); this would result in 141 more sexual adverse events per 1000 men (95% CI 71 more to 261 more). Silodosin versus naftopidilBased on five studies with a total of 763 randomized participants, silodosin may result in little to no differences in urologic symptom scores (MD -0.85, 95% CI -2.57 to 0.87; low-quality evidence), quality of life (MD -0.17, 95% CI -0.60 to 0.27; low-quality evidence), treatment withdrawal for any reason (RR 1.25, 95% CI 0.81 to 1.93; low-quality evidence), and cardiovascular adverse events (RR 1.02, 95% CI 0.41 to 2.56; low-quality evidence). Silodosin likely increases sexual adverse events (RR 5.93, 95% CI 2.16 to 16.29; moderate-quality evidence); this would result in 74 more sexual adverse events per 1000 men (95% CI 17 more to 231 more). Silodosin versus alfuzosinBased on two studies with a total of 155 randomized participants, silodosin may or may not result in a clinically important increase in urologic symptom scores (MD 3.83, 95% CI 0.12 to 7.54; low-quality evidence). Silodosin likely results in little to no difference in quality of life (MD 0.14, 95% CI -0.46 to 0.74; moderate-quality evidence). We found no event of treatment withdrawal for any reason. Silodosin may not reduce cardiovascular adverse events (RR 0.67, 95% CI 0.36 to 1.24; low-quality evidence) but likely increases sexual adverse events (RR 37.21, 95% CI 5.32 to 260.07; moderate-quality evidence); this would result in 217 more sexual adverse events per 1000 men (95% CI 26 more to 1000 more). Silodosin may reduce urologic symptom scores in an appreciable number of men compared to placebo. Quality of life and treatment withdrawals for any reason appears similar. Its efficacy appears similar to that of other alpha blockers (tamsulosin, naftopidil and alfuzosin) but the rate of sexual side effects is likely higher. Our certainty in the estimates of effect was lowered due to study limitations, inconsistency and imprecision.

Stable angina pectoris is a chronic medical condition with significant impact on mortality and quality of life; it can be macrovascular or microvascular in origin. Ranolazine is a second-line anti-anginal drug approved for use in people with stable angina. However, the effects of ranolazine for people with angina are considered to be modest, with uncertain clinical relevance. To assess the effects of ranolazine on cardiovascular and non-cardiovascular mortality, all-cause mortality, quality of life, acute myocardial infarction incidence, angina episodes frequency and adverse events incidence in stable angina patients, used either as monotherapy or as add-on therapy, and compared to placebo or any other anti-anginal agent. We searched CENTRAL, MEDLINE, Embase and the Conference Proceedings Citation Index - Science in February 2016, as well as regional databases and trials registers. We also screened reference lists. Randomised controlled trials (RCTs) which directly compared the effects of ranolazine versus placebo or other anti-anginals in people with stable angina pectoris were eligible for inclusion. Two authors independently selected studies, extracted data and assessed risk of bias. Estimates of treatment effects were calculated using risk ratios (RR), mean differences (MD) and standardised mean differences (SMD) with 95% confidence intervals (CI) using a fixed-effect model. Where we found statistically significant heterogeneity (Chi² P < 0.10), we used a random-effects model for pooling estimates. Meta-analysis was not performed where we found considerable heterogeneity (I² ≥ 75%). We used GRADE criteria to assess evidence quality and the GRADE profiler (GRADEpro GDT) to import data from Review Manager 5.3 to create 'Summary of findings' tables. We included 17 RCTs (9975 participants, mean age 63.3 years). We found very limited (or no) data to inform most planned comparisons. Summary data were used to inform comparison of ranolazine versus placebo. Overall, risk of bias was assessed as unclear.For add-on ranolazine compared to placebo, no data were available to estimate cardiovascular and non-cardiovascular mortality. We found uncertainty about the effect of ranolazine on: all-cause mortality (1000 mg twice daily, RR 0.83, 95% CI 0.26 to 2.71; 3 studies, 2053 participants; low quality evidence); quality of life (any dose, SMD 0.25, 95% CI -0.01 to 0.52; 4 studies, 1563 participants; I² = 73%; moderate quality evidence); and incidence of non-fatal acute myocardial infarction (AMI) (1000mg twice daily, RR 0.40, 95% CI 0.08 to 2.07; 2 studies, 1509 participants; low quality evidence). Add-on ranolazine 1000 mg twice daily reduced the fervour of angina episodes (MD -0.66, 95% CI -0.97 to -0.35; 3 studies, 2004 participants; I² = 39%; moderate quality evidence) but increased the risk of non-serious adverse events (RR 1.22, 95% CI 1.06 to 1.40; 3 studies, 2053 participants; moderate quality evidence).For ranolazine as monotherapy compared to placebo, we found uncertain effect on cardiovascular mortality (1000 mg twice daily, RR 1.03, 95% CI 0.56 to 1.88; 1 study, 2604 participants; low quality evidence). No data were available to estimate non-cardiovascular mortality. We also found an uncertain effect on all-cause mortality for ranolazine (1000 mg twice daily, RR 1.00, 95% CI 0.81 to 1.25; 3 studies, 6249 participants; low quality evidence), quality of life (1000 mg twice daily, MD 0.28, 95% CI -1.57 to 2.13; 3 studies, 2254 participants; moderate quality evidence), non-fatal AMI incidence (any dose, RR 0.88, 95% CI 0.69 to 1.12; 3 studies, 2983 participants; I² = 50%; low quality evidence), and frequency of angina episodes (any dose, MD 0.08, 95% CI -0.85 to 1.01; 2 studies, 402 participants; low quality evidence). We found an increased risk for non-serious adverse events associated with ranolazine (any dose, RR 1.50, 95% CI 1.12 to 2.00; 3 studies, 947 participants; very low quality evidence). We found very low quality evidence showing that people with stable angina who received ranolazine as monotherapy had increased risk of presenting non-serious adverse events compared to those given placebo. We found low quality evidence indicating that people with stable angina who received ranolazine showed uncertain effect on the risk of cardiovascular death (for ranolazine given as monotherapy), all-cause death and non-fatal AMI, and the frequency of angina episodes (for ranolazine given as monotherapy) compared to those given placebo. Moderate quality evidence indicated that people with stable angina who received ranolazine showed uncertain effect on quality of life compared with people who received placebo. Moderate quality evidence also indicated that people with stable angina who received ranolazine as add-on therapy had fewer angina episodes but increased risk of presenting non-serious adverse events compared to those given placebo.

RV1 and RV5 prevent episodes of rotavirus diarrhoea. The vaccine efficacy is lower in high-mortality countries; however, due to the higher burden of disease, the absolute benefit is higher in these settings. No increased risk of serious adverse events including intussusception was detected, but post-introduction surveillance studies are required to detect rare events associated with vaccination.

Analysis 1.1. Comparison 1 LABA versus placebo: both groups receiving similar dose of ICS, Outcome 1 # participants with exacerbations requiring systemic steroids. . . . . . . . . . . . . . . . . . . . . . . Analysis 1.2. Comparison 1 LABA versus placebo: both groups receiving similar dose of ICS, Outcome 2 # participants with exacerbations requiring hospitalisation. . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.3. Comparison 1 LABA versus placebo: both groups receiving similar dose of ICS, Outcome 3 # participants with exacerbations requiring urgent care visit. . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.4. Comparison 1 LABA versus placebo: both groups receiving similar dose of ICS, Outcome 4 Serious adverse events. . . . . . . . . . . . . . . . . . . . . . . . . . . . .

There was high quality evidence to support the effectiveness of topical azelaic acid, topical ivermectin, brimonidine, doxycycline and isotretinoin for rosacea. Moderate quality evidence was available for topical metronidazole and oral tetracycline. There was low quality evidence for low dose minocycline, laser and intense pulsed light therapy and ciclosporin ophthalmic emulsion for ocular rosacea. Time needed to response and response duration should be addressed more completely, with more rigorous reporting of adverse events. Further studies on treatment of ocular rosacea are warranted.

We are grateful to the editors and peer referees who have provided valuable comments on draBs of this update and to Sheila Wallace for her help with the searches. We are also grateful to Dr Karen Boyd for providing information about her trial. We would like to acknowledge the work of all contributors to previous versions of the review, particularly Don Wilson who was responsible for the review from its inception. An earlier version of this review was part of a project to add brief economic commentaries to Cochrane Incontinence's reviews on surgery for urinary incontinence in women (Dean 2017). This project was supported by the National Institute for Health Research (NIHR), via the Cochrane Review Incentive Scheme 2016.

Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for people at high risk and people with established cardiovascular disease. This is an update to a previously published review from 2011. To review the benefit and harm of adding clopidogrel to aspirin therapy for preventing cardiovascular events in people who have coronary disease, ischaemic cerebrovascular disease, peripheral arterial disease, or were at high risk of atherothrombotic disease, but did not have a coronary stent. We updated the searches of CENTRAL (2017, Issue 6), MEDLINE (Ovid, 1946 to 4 July 2017) and Embase (Ovid, 1947 to 3 July 2017) on 4 July 2017. We also searched ClinicalTrials.gov and the WHO ICTRP portal, and handsearched reference lists. We applied no language restrictions. We included all randomised controlled trials comparing over 30 days use of aspirin plus clopidogrel with aspirin plus placebo or aspirin alone in people with coronary disease, ischaemic cerebrovascular disease, peripheral arterial disease, or at high risk of atherothrombotic disease. We excluded studies including only people with coronary drug-eluting stent (DES) or non-DES, or both. We collected data on mortality from cardiovascular causes, all-cause mortality, fatal and non-fatal myocardial infarction, fatal and non-fatal ischaemic stroke, major and minor bleeding. The overall treatment effect was estimated by the pooled risk ratio (RR) with 95% confidence interval (CI), using a fixed-effect model (Mantel-Haenszel); we used a random-effects model in cases of moderate or severe heterogeneity (I2 ≥ 30%). We assessed the quality of the evidence using the GRADE approach. We used GRADE profiler (GRADE Pro) to import data from Review Manager to create a 'Summary of findings' table. The search identified 13 studies in addition to the two studies in the previous version of our systematic review. Overall, we included data from 15 trials with 33,970 people. We completed a 'Risk of bias' assessment for all studies. The risk of bias was low in four trials because they were at low risk of bias for all key domains (random sequence generation, allocation concealment, blinding, selective outcome reporting and incomplete outcome data), even if some of them were funded by the pharmaceutical industry.Analysis showed no difference in the effectiveness of aspirin plus clopidogrel in preventing cardiovascular mortality (RR 0.98, 95% CI 0.88 to 1.10; participants = 31,903; studies = 7; moderate quality evidence), and no evidence of a difference in all-cause mortality (RR 1.05, 95% CI 0.87 to 1.25; participants = 32,908; studies = 9; low quality evidence).There was a lower risk of fatal and non-fatal myocardial infarction with clopidogrel plus aspirin compared with aspirin plus placebo or aspirin alone (RR 0.78, 95% CI 0.69 to 0.90; participants = 16,175; studies = 6; moderate quality evidence). There was a reduction in the risk of fatal and non-fatal ischaemic stroke (RR 0.73, 95% CI 0.59 to 0.91; participants = 4006; studies = 5; moderate quality evidence).However, there was a higher risk of major bleeding with clopidogrel plus aspirin compared with aspirin plus placebo or aspirin alone (RR 1.44, 95% CI 1.25 to 1.64; participants = 33,300; studies = 10; moderate quality evidence) and of minor bleeding (RR 2.03, 95% CI 1.75 to 2.36; participants = 14,731; studies = 8; moderate quality evidence).Overall, we would expect 13 myocardial infarctions and 23 ischaemic strokes be prevented for every 1000 patients treated with the combination in a median follow-up period of 12 months, but 9 major bleeds and 33 minor bleeds would be caused during a median follow-up period of 10.5 and 6 months, respectively. The available evidence demonstrates that the use of clopidogrel plus aspirin in people at high risk of cardiovascular disease and people with established cardiovascular disease without a coronary stent is associated with a reduction in the risk of myocardial infarction and ischaemic stroke, and an increased risk of major and minor bleeding compared with aspirin alone. According to GRADE criteria, the quality of evidence was moderate for all outcomes except all-cause mortality (low quality evidence) and adverse events (very low quality evidence).

While transvaginal permanent mesh is associated with lower rates of awareness of prolapse, reoperation for prolapse, and prolapse on examination than native tissue repair, it is also associated with higher rates of reoperation for prolapse, stress urinary incontinence, or mesh exposure and higher rates of bladder injury at surgery and de novo stress urinary incontinence. The risk-benefit profile means that transvaginal mesh has limited utility in primary surgery. While it is possible that in women with higher risk of recurrence the benefits may outweigh the risks, there is currently no evidence to support this position.Limited evidence suggests that absorbable mesh may reduce rates of recurrent prolapse on examination compared to native tissue repair, but there was insufficient evidence on absorbable mesh for us to draw any conclusions for other outcomes. There was also insufficient evidence for us to draw any conclusions regarding biological grafts compared to native tissue repair.In 2011, many transvaginal permanent meshes were voluntarily withdrawn from the market, and the newer, lightweight transvaginal permanent meshes still available have not been evaluated within a RCT. In the meantime, these newer transvaginal meshes should be utilised under the discretion of the ethics committee.

The optimal treatment of superficial thrombophlebitis (ST) of the legs remains poorly defined. While improving or relieving the local painful symptoms, treatment should aim at preventing venous thromboembolism (VTE), which might complicate the natural history of ST. This is the third update of a review first published in 2007. To assess the efficacy and safety of topical, medical, and surgical treatments for ST of the leg in improving local symptoms and decreasing thromboembolic complications. For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register (March 2017), CENTRAL (2017, Issue 2), and trials registries (March 2017). We handsearched the reference lists of relevant papers and conference proceedings. Randomised controlled trials (RCTs) evaluating topical, medical, and surgical treatments for ST of the legs that included people with a clinical diagnosis of ST of the legs or objective diagnosis of a thrombus in a superficial vein. Two authors assessed the trials for inclusion in the review, extracted the data, and assessed the quality of the studies. Data were independently extracted from the included studies and any disagreements resolved by consensus. We assessed the quality of the evidence using the GRADE approach. We identified three additional trials (613 participants), therefore this update considered 33 studies involving 7296 people with ST of the legs. Treatment included fondaparinux; rivaroxaban; low molecular weight heparin (LMWH); unfractionated heparin (UFH); non-steroidal anti-inflammatory drugs (NSAIDs); compression stockings; and topical, intramuscular, or intravenous treatment to surgical interventions such as thrombectomy or ligation. Only a minority of trials compared treatment with placebo rather than an alternative treatment and many studies were small and of poor quality. Pooling of the data was possible for few outcomes, and none were part of a placebo-controlled trial. In one large, placebo-controlled RCT of 3002 participants, subcutaneous fondaparinux was associated with a significant reduction in symptomatic VTE (risk ratio (RR) 0.15, 95% confidence interval (CI) 0.04 to 0.50; moderate-quality evidence), ST extension (RR 0.08, 95% CI 0.03 to 0.22; moderate-quality evidence), and ST recurrence (RR 0.21, 95% CI 0.08 to 0.54; moderate-quality evidence) relative to placebo. Major bleeding was infrequent in both groups with very wide CIs around risk estimate (RR 0.99, 95% CI 0.06 to 15.86; moderate-quality evidence). In one RCT on 472 high-risk participants with ST, fondaparinux was associated with a non-significant reduction of symptomatic VTE compared to rivaroxaban 10 mg (RR 0.33, 95% CI 0.03 to 3.18; low-quality evidence). There were no major bleeding events in either group (low-quality evidence). In another placebo-controlled trial, both prophylactic and therapeutic doses of LMWH (prophylactic: RR 0.44, 95% CI 0.26 to 0.74; therapeutic: RR 0.46, 95% CI 0.27 to 0.77) and NSAIDs (RR 0.46, 95% CI 0.27 to 0.78) reduced the extension (low-quality evidence) and recurrence of ST (low-quality evidence) in comparison to placebo, with no significant effects on symptomatic VTE (low-quality evidence) or major bleeding (low-quality evidence). Overall, topical treatments improved local symptoms compared with placebo, but no data were provided on the effects on VTE and ST extension. Surgical treatment combined with elastic stockings was associated with a lower VTE rate and ST progression compared with elastic stockings alone. However, the majority of studies that compared different oral treatments, topical treatments, or surgery did not report VTE, ST progression, adverse events, or treatment adverse effects. Prophylactic dose fondaparinux given for 45 days appears to be a valid therapeutic option for ST of the legs for most people. The evidence on topical treatment or surgery is too limited and does not inform clinical practice about the effects of these treatments in terms of VTE. Further research is needed to assess the role of rivaroxaban and other direct oral factor-X or thrombin inhibitors, LMWH, and NSAIDs; the optimal doses and duration of treatment in people at various risk of recurrence; and whether a combination therapy may be more effective than single treatment. Adequately designed and conducted studies are required to clarify the role of topical and surgical treatments.

Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The etiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularization to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain. To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease. The Cochrane Vascular Trials Search Co-ordinator searched their Specialised Register (last searched in April 2015) and the Cochrane Register of Studies (Issue 3, 2015). The review authors searched trial registers and the European grey literature; screened reference lists of relevant studies, and contacted study authors and major pharmaceutical companies. Randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease. Two review authors, independently assessed the studies, extracted data and performed data analysis. Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid.Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; one study; moderate quality evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; one study; moderate quality evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; one study; moderate quality evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; two studies; I² = 0%; very low quality evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; one study; low quality evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; one study; moderate quality evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; one study; moderate quality evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; one study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; one study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low quality evidence).Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study.Overall, the quality of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information regarding for example baseline tobacco exposure. Moderate quality evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Verylow and low quality evidence suggests there is no difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very-low quality evidence suggests there is no difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. High quality trials assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.

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.

Systematic with meta-analysis OBJECTIVES.: The aim of this study was to investigate the efficacy and safety of epidural corticosteroid injections compared with placebo injection in reducing leg pain and disability in patients with sciatica. Conservative treatments, including pharmacological and nonpharmacological treatments, are typically the first treatment options for sciatica but the evidence to support their use is limited. The overall quality of evidence found by previous systematic reviews varies between moderate and high, which suggests that future trials may change the conclusions. New placebo-controlled randomized trials have been published recently which highlights the importance of an updated systematic review. The searches were performed without language restrictions in the following databases from 2012 to 25 September 2019: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, PubMed, Embase, CINAHL, PsycINFO, International Pharmaceutical Abstracts, and trial registers. We included placebo-controlled randomized trials investigating epidural corticosteroid injections in patients with sciatica. The primary outcomes were leg pain intensity and disability. The secondary outcomes were adverse events, overall pain, and back pain intensity. We grouped similar trials according to outcome measures and their respective follow-up time points. Short-term follow-up (>2 weeks but ≤3 months) was considered the primary follow-up time point due to the expected mechanism of action of epidural corticosteroid injection. Weighted mean differences (MDs) and risk ratios (RRs) with their respective 95% confidence intervals (CIs) were estimated. We assessed the overall quality of evidence using the GRADE approach and conducted the analyses using random effects. We included 25 clinical trials (from 29 publications) providing data for a total of 2470 participants with sciatica, an increase of six trials when compared to the previous review. Epidural corticosteroid injections were probably more effective than placebo in reducing short-term leg pain (MD -4.93, 95% CI -8.77 to -1.09 on a 0-100 scale), short-term disability (MD -4.18, 95% CI: -6.04 to -2.17 on a 0-100 scale) and may be slightly more effective in reducing short-term overall pain (MD -9.35, 95% CI -14.05 to -4.65 on a 0-100 scale). There were mostly minor adverse events (i.e., without hospitalization) after epidural corticosteroid injections and placebo injections without difference between groups (RR 1.14, 95% CI: 0.91-1.42). The quality of evidence was at best moderate mostly due to problems with trial design and inconsistency. A review of 25 placebo-controlled trials provides moderate-quality evidence that epidural corticosteroid injections are effective, although the effects are small and short-term. There is uncertainty on safety due to very low-quality evidence. 1.