Strategies for partner notification for sexually transmitted infections, including HIV

BACKGROUND Partner notification (PN) is the process whereby sexual partners of an index patient are informed of their exposure to a sexually transmitted infection (STI) and the need to obtain treatment. For the person (index patient) with a curable STI, PN aims to eradicate infection and prevent re-infection. For sexual partners, PN aims to identify and treat undiagnosed STIs. At the level of sexual networks and populations, the aim of PN is to interrupt chains of STI transmission. For people with viral STI, PN aims to identify undiagnosed infections, which can facilitate access for their sexual partners to treatment and help prevent transmission. OBJECTIVES To assess the effects of different PN strategies in people with STI, including human immunodeficiency virus (HIV) infection. SEARCH METHODS We searched electronic databases (the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE) without language restrictions. We scanned reference lists of potential studies and previous reviews and contacted experts in the field. We searched three trial registries. We conducted the most recent search on 31 August 2012. SELECTION CRITERIA Published or unpublished randomised controlled trials (RCTs) or quasi-RCTs comparing two or more PN strategies. Four main PN strategies were included: patient referral, expedited partner therapy, provider referral and contract referral. Patient referral means that the patient notifies their sexual partners, either with (enhanced patient referral) or without (simple patient referral) additional verbal or written support. In expedited partner therapy, the patient delivers medication or a prescription for medication to their partner(s) without the need for a medical examination of the partner. In provider referral, health service personnel notify the partners. In contract referral, the index patient is encouraged to notify partner, with the understanding that the partners will be contacted if they do not visit the health service by a certain date. DATA COLLECTION AND ANALYSIS We analysed data according to paired partner referral strategies. We organised the comparisons first according to four main PN strategies (1. enhanced patient referral, 2. expedited partner therapy, 3. contract referral, 4. provider referral). We compared each main strategy with simple patient referral and then with each other, if trials were available. For continuous outcome measures, we calculated the mean difference (MD) with 95% confidence intervals (CI). For dichotomous variables, we calculated the risk ratio (RR) with 95% CI. We performed meta-analyses where appropriate. We performed a sensitivity analysis for the primary outcome re-infection rate of the index patient by excluding studies with attrition of greater than 20%. Two review authors independently assessed the risk of bias and extracted data. We contacted study authors for additional information. MAIN RESULTS We included 26 trials (17,578 participants, 9015 women and 8563 men). Five trials were conducted in developing countries. Only two trials were conducted among HIV-positive patients. There was potential for selection bias, owing to the methods of allocation used and of performance bias, owing to the lack of blinding in most included studies. Seven trials had attrition of greater than 20%, increasing the risk of bias.The review found moderate-quality evidence that expedited partner therapy is better than simple patient referral for preventing re-infection of index patients when combining trials of STIs that caused urethritis or cervicitis (6 trials; RR 0.71, 95% CI 0.56 to 0.89, I(2) = 39%). When studies with attrition greater than 20% were excluded, the effect of expedited partner therapy was attenuated (2 trials; RR 0.8, 95% CI 0.62 to 1.04, I(2) = 0%). In trials restricted to index patients with chlamydia, the effect was attenuated (2 trials; RR 0.90, 95% CI 0.60 to 1.35, I(2) = 22%). Expedited partner therapy also increased the number of partners treated per index patient (three trials) when compared with simple patient referral in people with chlamydia or gonorrhoea (MD 0.43, 95% CI 0.28 to 0.58) or trichomonas (MD 0.51, 95% CI 0.35 to 0.67), and people with any STI syndrome (MD 0.5, 95% CI 0.34 to 0.67). Expedited partner therapy was not superior to enhanced patient referral in preventing re-infection (3 trials; RR 0.96, 95% CI 0.60 to 1.53, I(2) = 33%, low-quality evidence). Home sampling kits for partners (four trials) did not result in lower rates of re-infection in the index case (measured in one trial), or higher numbers of partners elicited (three trials), notified (two trials) or treated (one trial) when compared with simple patient referral. There was no consistent evidence for the relative effects of provider, contract or other patient referral methods. In one trial among men with non-gonococcal urethritis, more partners were treated with provider referral than with simple patient referral (MD 0.5, 95% CI 0.37 to 0.63). In one study among people with syphilis, contract referral elicited treatment of more partners than provider referral (MD 2.2, 95% CI 1.95 to 2.45), but the number of partners receiving treatment was the same in both groups. Where measured, there was no statistical evidence of differences in the incidence of adverse effects between PN strategies. AUTHORS' CONCLUSIONS The evidence assessed in this review does not identify a single optimal strategy for PN for any particular STI. When combining trials of STI causing urethritis or cervicitis, expedited partner therapy was more successful than simple patient referral for preventing re-infection of the index patient but was not superior to enhanced patient referral. Expedited partner therapy interventions should include all components that were part of the trial intervention package. There was insufficient evidence to determine the most effective components of an enhanced patient referral strategy. There are too few trials to allow consistent conclusions about the relative effects of provider, contract or other patient referral methods for different STIs. More high-quality RCTs of PN strategies for HIV and syphilis, using biological outcomes, are needed.

Adjudication-related processes are underreported and lack standardization in clinical trials of venous thromboembolism: a systematic review

OBJECTIVES Although the use of an adjudication committee (AC) for outcomes is recommended in randomized controlled trials, there are limited data on the process of adjudication. We therefore aimed to assess whether the reporting of the adjudication process in venous thromboembolism (VTE) trials meets existing quality standards and which characteristics of trials influence the use of an AC. STUDY DESIGN AND SETTING We systematically searched MEDLINE and the Cochrane Library from January 1, 2003, to June 1, 2012, for randomized controlled trials on VTE. We abstracted information about characteristics and quality of trials and reporting of adjudication processes. We used stepwise backward logistic regression model to identify trial characteristics independently associated with the use of an AC. RESULTS We included 161 trials. Of these, 68.9% (111 of 161) reported the use of an AC. Overall, 99.1% (110 of 111) of trials with an AC used independent or blinded ACs, 14.4% (16 of 111) reported how the adjudication decision was reached within the AC, and 4.5% (5 of 111) reported on whether the reliability of adjudication was assessed. In multivariate analyses, multicenter trials [odds ratio (OR), 8.6; 95% confidence interval (CI): 2.7, 27.8], use of a data safety-monitoring board (OR, 3.7; 95% CI: 1.2, 11.6), and VTE as the primary outcome (OR, 5.7; 95% CI: 1.7, 19.4) were associated with the use of an AC. Trials without random allocation concealment (OR, 0.3; 95% CI: 0.1, 0.8) and open-label trials (OR, 0.3; 95% CI: 0.1, 1.0) were less likely to report an AC. CONCLUSION Recommended processes of adjudication are underreported and lack standardization in VTE-related clinical trials. The use of an AC varies substantially by trial characteristics.

Antibiotic prophylaxis for urinary tract infections after removal of urinary catheter: meta-analysis

Abstract Objective To determine whether antibiotic prophylaxis at the time of removal of a urinary catheter reduces the risk of subsequent symptomatic urinary tract infection. Design Systematic review and meta-analysis of studies published before November 2012 identified through PubMed, Embase, Scopus, and the Cochrane Library; conference abstracts for 2006-12 were also reviewed. Inclusion criteria Studies were included if they examined antibiotic prophylaxis administered to prevent symptomatic urinary tract infection after removal of a short term (≤14 days) urinary catheter. Results Seven controlled studies had symptomatic urinary tract infection after catheter removal as an endpoint; six were randomized controlled trials (five published; one in abstract form) and one was a non-randomized controlled intervention study. Five of these seven studies were in surgical patients. Studies were heterogeneous in the type and duration of antimicrobial prophylaxis and the period of observation. Overall, antibiotic prophylaxis was associated with benefit to the patient, with an absolute reduction in risk of urinary tract infection of 5.8% between intervention and control groups. The risk ratio was 0.45 (95% confidence interval 0.28 to 0.72). The number needed to treat to prevent one urinary tract infection was 17 (12 to 30). Conclusions Patients admitted to hospital who undergo short term urinary catheterization might benefit from antimicrobial prophylaxis when the catheter is removed as they experience fewer subsequent urinary tract infections. Potential disadvantages of more widespread antimicrobial prophylaxis (side effects and cost of antibiotics, development of antimicrobial resistance) might be mitigated by the identification of which patients are most likely to benefit from this approach.

Critical Analysis of Bladder Sparing with Trimodal Therapy in Muscle-invasive Bladder Cancer: A Systematic Review.

CONTEXT Aims of bladder preservation in muscle-invasive bladder cancer (MIBC) are to offer a quality-of-life advantage and avoid potential morbidity or mortality of radical cystectomy (RC) without compromising oncologic outcomes. Because of the lack of a completed randomised controlled trial, oncologic equivalence of bladder preservation modality treatments compared with RC remains unknown. OBJECTIVE This systematic review sought to assess the modern bladder-preservation treatment modalities, focusing on trimodal therapy (TMT) in MIBC. EVIDENCE ACQUISITION A systematic literature search in the PubMed and Cochrane databases was performed from 1980 to July 2013. EVIDENCE SYNTHESIS Optimal bladder-preservation treatment includes a safe transurethral resection of the bladder tumour as complete as possible followed by radiation therapy (RT) with concurrent radiosensitising chemotherapy. A standard radiation schedule includes external-beam RT to the bladder and limited pelvic lymph nodes to an initial dose of 40Gy, with a boost to the whole bladder to 54Gy and a further tumour boost to a total dose of 64-65Gy. Radiosensitising chemotherapy with phase 3 trial evidence in support exists for cisplatin and mitomycin C plus 5-fluorouracil. A cystoscopic assessment with systematic rebiopsy should be performed at TMT completion or early after TMT induction. Thus, nonresponders are identified early to promptly offer salvage RC. The 5-yr cancer-specific survival and overall survival rates range from 50% to 82% and from 36% to 74%, respectively, with salvage cystectomy rates of 25-30%. There are no definitive data to support the benefit of using of neoadjuvant or adjuvant chemotherapy. Critical to good outcomes is proper patient selection. The best cancers eligible for bladder preservation are those with low-volume T2 disease without hydronephrosis or extensive carcinoma in situ. CONCLUSIONS A growing body of accumulated data suggests that bladder preservation with TMT leads to acceptable outcomes and therefore may be considered a reasonable treatment option in well-selected patients. PATIENT SUMMARY Treatment based on a combination of resection, chemotherapy, and radiotherapy as bladder-sparing strategies may be considered as a reasonable treatment option in properly selected patients.

Psychological interventions for acute pain after open heart surgery (Protocol)

The objectives are as follows: To assess the efficacy of psychological interventions as an adjunct to standard surgical care compared to standard surgical care or attention control in adults undergoing open heart surgery.

Selection criteria for selective dorsal rhizotomy in children with spastic cerebral palsy: a systematic review of the literature

AIM Information regarding the selection procedure for selective dorsal rhizotomy (SDR) in children with spastic cerebral palsy (CP) is scarce. Therefore, the aim of this study was to summarize the selection criteria for SDR in children with spastic CP. METHOD A systematic review was carried out using the following databases: MEDLINE, CINAHL, EMBASE, PEDro, and the Cochrane Library. Additional studies were identified in the reference lists. Search terms included 'selective dorsal rhizotomy', 'functional posterior rhizotomy', 'selective posterior rhizotomy', and 'cerebral palsy'. Studies were selected if they studied mainly children (<18y of age) with spastic CP, if they had an intervention of SDR, if they had a detailed description of the selection criteria, and if they were in English. The levels of evidence, conduct of studies, and selection criteria for SDR were scored. RESULTS Fifty-two studies were included. Selection criteria were reported in 16 International Classification of Functioning, Disability and Health model domains including 'body structure and function' (details concerning spasticity [94%], other movement abnormalities [62%], and strength [54%]), 'activity' (gross motor function [27%]), and 'personal and environmental factors' (age [44%], diagnosis [50%], motivation [31%], previous surgery [21%], and follow-up therapy [31%]). Most selection criteria were not based on standardized measurements. INTERPRETATION Selection criteria for SDR vary considerably. Future studies should describe clearly the selection procedure. International meetings of experts should develop more uniform consensus guidelines, which could form the basis for selecting candidates for SDR.

Selenium for preventing cancer

BACKGROUND This review is an update of the first Cochrane publication on selenium for preventing cancer (Dennert 2011).Selenium is a metalloid with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers. OBJECTIVES Two research questions were addressed in this review: What is the evidence for:1. an aetiological relation between selenium exposure and cancer risk in humans? and2. the efficacy of selenium supplementation for cancer prevention in humans? SEARCH METHODS We conducted electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 1), MEDLINE (Ovid, 1966 to February 2013 week 1), EMBASE (1980 to 2013 week 6), CancerLit (February 2004) and CCMed (February 2011). As MEDLINE now includes the journals indexed in CancerLit, no further searches were conducted in this database after 2004. SELECTION CRITERIA We included prospective observational studies (cohort studies including sub-cohort controlled studies and nested case-control studies) and randomised controlled trials (RCTs) with healthy adult participants (18 years of age and older). DATA COLLECTION AND ANALYSIS For observational studies, we conducted random effects meta-analyses when five or more studies were retrieved for a specific outcome. For RCTs, we performed random effects meta-analyses when two or more studies were available. The risk of bias in observational studies was assessed using forms adapted from the Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies; the criteria specified in the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate the risk of bias in RCTs. MAIN RESULTS We included 55 prospective observational studies (including more than 1,100,000 participants) and eight RCTs (with a total of 44,743 participants). For the observational studies, we found lower cancer incidence (summary odds ratio (OR) 0.69, 95% confidence interval (CI) 0.53 to 0.91, N = 8) and cancer mortality (OR 0.60, 95% CI 0.39 to 0.93, N = 6) associated with higher selenium exposure. Gender-specific subgroup analysis provided no clear evidence of different effects in men and women (P value 0.47), although cancer incidence was lower in men (OR 0.66, 95% CI 0.42 to 1.05, N = 6) than in women (OR 0.90, 95% CI 0.45 to 1.77, N = 2). The most pronounced decreases in risk of site-specific cancers were seen for stomach, bladder and prostate cancers. However, these findings have limitations due to study design, quality and heterogeneity that complicate interpretation of the summary statistics. Some studies suggested that genetic factors may modify the relation between selenium and cancer risk-a hypothesis that deserves further investigation.In RCTs, we found no clear evidence that selenium supplementation reduced the risk of any cancer (risk ratio (RR) 0.90, 95% CI 0.70 to 1.17, two studies, N = 4765) or cancer-related mortality (RR 0.81, 95% CI 0.49 to 1.32, two studies, N = 18,698), and this finding was confirmed when the analysis was restricted to studies with low risk of bias. The effect on prostate cancer was imprecise (RR 0.90, 95% CI 0.71 to 1.14, four studies, N = 19,110), and when the analysis was limited to trials with low risk of bias, the interventions showed no effect (RR 1.02, 95% CI 0.90 to 1.14, three studies, N = 18,183). The risk of non-melanoma skin cancer was increased (RR 1.44, 95% CI 0.95 to 1.17, three studies, N = 1900). Results of two trials-the Nutritional Prevention of Cancer Trial (NPCT) and the Selenium and Vitamin E Cancer Trial (SELECT)-also raised concerns about possible increased risk of type 2 diabetes, alopecia and dermatitis due to selenium supplements. An early hypothesis generated by NPCT that individuals with the lowest blood selenium levels at baseline could reduce their risk of cancer, particularly of prostate cancer, by increasing selenium intake has not been confirmed by subsequent trials. As the RCT participants were overwhelmingly male (94%), gender differences could not be systematically assessed. AUTHORS' CONCLUSIONS Although an inverse association between selenium exposure and the risk of some types of cancer was found in some observational studies, this cannot be taken as evidence of a causal relation, and these results should be interpreted with caution. These studies have many limitations, including issues with assessment of exposure to selenium and to its various chemical forms, heterogeneity, confounding and other biases. Conflicting results including inverse, null and direct associations have been reported for some cancer types.RCTs assessing the effects of selenium supplementation on cancer risk have yielded inconsistent results, although the most recent studies, characterised by a low risk of bias, found no beneficial effect on cancer risk, more specifically on risk of prostate cancer, as well as little evidence of any influence of baseline selenium status. Rather, some trials suggest harmful effects of selenium exposure. To date, no convincing evidence suggests that selenium supplements can prevent cancer in humans.

Exercise for osteoarthritis of the hip.

BACKGROUND Current international treatment guidelines recommending therapeutic exercise for people with symptomatic hip osteoarthritis (OA) report are based on limited evidence. OBJECTIVES To determine whether land-based therapeutic exercise is beneficial for people with hip OA in terms of reduced joint pain and improved physical function and quality of life. SEARCH METHODS We searched five databases from inception up to February 2013. SELECTION CRITERIA All randomised controlled trials (RCTs) recruiting people with hip OA and comparing some form of land-based therapeutic exercise (as opposed to exercises conducted in water) with a non-exercise group. DATA COLLECTION AND ANALYSIS Four review authors independently selected studies for inclusion. We resolved disagreements through consensus. Two review authors independently extracted data, assessed risk of bias and the quality of the body of evidence for each outcome using the GRADE approach. We conducted analyses on continuous outcomes (pain, physical function and quality of life) and dichotomous outcomes (proportion of study withdrawals). MAIN RESULTS We considered that seven of the 10 included RCTs had a low risk of bias. However, the results may be vulnerable to performance and detection bias as none of the RCTs were able to blind participants to treatment allocation and, while most RCTs reported blinded outcome assessment, pain, physical function and quality of life were participant self reported. One of the 10 RCTs was only reported as a conference abstract and did not provide sufficient data for the evaluation of bias risk.High-quality evidence from nine trials (549 participants) indicated that exercise reduced pain (standardised mean difference (SMD) -0.38, 95% confidence interval (CI) -0.55 to -0.20) and improved physical function (SMD -0.38, 95% CI -0.54 to -0.05) immediately after treatment. Pain and physical function were estimated to be 29 points on a 0- to 100-point scale (0 was no pain or loss of physical function) in the control group; exercise reduced pain by an equivalent of 8 points (95% CI 4 to 11 points; number needed to treat for an additional beneficial outcome (NNTB) 6) and improved physical function by an equivalent of 7 points (95% CI 1 to 12 points; NNTB 6). Only three small studies (183 participants) evaluated quality of life, with overall low quality evidence, with no benefit of exercise demonstrated (SMD -0.07, 95% CI -0.23 to 0.36). Quality of life was estimated to be 50 points on a norm-based mean (standard deviation (SD)) score of 50 (10) in the general population in the control group; exercise improved quality of life by 0 points. Moderate-quality evidence from seven trials (715 participants) indicated an increased likelihood of withdrawal from the exercise allocation (event rate 6%) compared with the control group (event rate 3%), but this difference was not significant (risk difference 1%; 95% CI -1% to 4%). Of the five studies reporting adverse events, each study reported only one or two events and all were related to increased pain attributed to the exercise programme.The reduction in pain was sustained at least three to six months after ceasing monitored treatment (five RCTs, 391 participants): pain (SMD -0.38, 95% CI -0.58 to -0.18). Pain was estimated to be 29 points on a 0- to 100-point scale (0 was no pain) in the control group, the improvement in pain translated to a sustained reduction in pain intensity of 8 points (95% CI 4 to 12 points) compared with the control group (0 to 100 scale). The improvement in physical function was also sustained (five RCTs, 367 participants): physical function (SMD -0.37, 95% CI -0.57 to -0.16). Physical function was estimated to be 24 points on a 0- to 100-point scale (0 was no loss of physical function) in the control group, the improvement translated to a mean of 7 points (95% CI 4 to 13) compared with the control group.Only five of the 10 RCTs exclusively recruited people with symptomatic hip OA (419 participants). There was no significant difference in pain or physical function outcomes compared with five studies recruiting participants with hip or knee OA (130 participants). AUTHORS' CONCLUSIONS Pooling the results of these 10 RCTs demonstrated that land-based therapeutic exercise programmes can reduce pain and improve physical function among people with symptomatic hip OA.

Self-monitoring of blood glucose in type 2 diabetes: recent studies

The increasing role for structured and personalized self-monitoring of blood glucose (SMBG) in management of type 2 diabetes has been underlined by randomized and prospective clinical trials. These include Structured Testing Program (or STeP), St. Carlos, Role of Self-Monitoring of Blood Glucose and Intensive Education in Patients with Type 2 Diabetes Not Receiving Insulin, and Retrolective Study Self-Monitoring of Blood Glucose and Outcome in Patients with Type 2 Diabetes (or ROSSO)-in-praxi follow-up. The evidence for the benefit of SMBG both in insulin-treated and non-insulin-treated patients with diabetes is also supported by published reviews, meta-analyses, and guidelines. A Cochrane review reported an overall effect of SMBG on glycemic control up to 6 months after initiation, which was considered to subside after 12 months. Particularly, the 12-month analysis has been criticized for the inclusion of a small number of studies and the conclusions drawn. The aim of this article is to review key publications on SMBG and also to put them into perspective with regard to results of the Cochrane review and current aspects of diabetes management.

Comparative effectiveness of long term drug treatment strategies to prevent asthma exacerbations: network meta-analysis

Objective To determine the comparative effectiveness and safety of current maintenance strategies in preventing exacerbations of asthma. Design Systematic review and network meta-analysis using Bayesian statistics. Data sources Cochrane systematic reviews on chronic asthma, complemented by an updated search when appropriate. Eligibility criteria Trials of adults with asthma randomised to maintenance treatments of at least 24 weeks duration and that reported on asthma exacerbations in full text. Low dose inhaled corticosteroid treatment was the comparator strategy. The primary effectiveness outcome was the rate of severe exacerbations. The secondary outcome was the composite of moderate or severe exacerbations. The rate of withdrawal was analysed as a safety outcome. Results 64 trials with 59 622 patient years of follow-up comparing 15 strategies and placebo were included. For prevention of severe exacerbations, combined inhaled corticosteroids and long acting β agonists as maintenance and reliever treatment and combined inhaled corticosteroids and long acting β agonists in a fixed daily dose performed equally well and were ranked first for effectiveness. The rate ratios compared with low dose inhaled corticosteroids were 0.44 (95% credible interval 0.29 to 0.66) and 0.51 (0.35 to 0.77), respectively. Other combined strategies were not superior to inhaled corticosteroids and all single drug treatments were inferior to single low dose inhaled corticosteroids. Safety was best for conventional best (guideline based) practice and combined maintenance and reliever therapy. Conclusions Strategies with combined inhaled corticosteroids and long acting β agonists are most effective and safe in preventing severe exacerbations of asthma, although some heterogeneity was observed in this network meta-analysis of full text reports.

Integrated care programmes for adults with chronic conditions: a meta-review.

OBJECTIVE To review systematic reviews and meta-analyses of integrated care programmes in chronically ill patients, with a focus on methodological quality, elements of integration assessed and effects reported. DESIGN Meta-review of systematic reviews and meta-analyses identified in Medline (1946-March 2012), Embase (1980-March 2012), CINHAL (1981-March 2012) and the Cochrane Library of Systematic Reviews (issue 1, 2012). MAIN OUTCOME MEASURES Methodological quality assessed by the 11-item Assessment of Multiple Systematic Reviews (AMSTAR) checklist; elements of integration assessed using a published list of 10 key principles of integration; effects on patient-centred outcomes, process quality, use of healthcare and costs. RESULTS Twenty-seven systematic reviews were identified; conditions included chronic heart failure (CHF; 12 reviews), diabetes mellitus (DM; seven reviews), chronic obstructive pulmonary disease (COPD; seven reviews) and asthma (five reviews). The median number of AMSTAR checklist items met was five: few reviewers searched for unpublished literature or described the primary studies and interventions in detail. Most reviews covered comprehensive services across the care continuum or standardization of care through inter-professional teams, but organizational culture, governance structure or financial management were rarely assessed. A majority of reviews found beneficial effects of integration, including reduced hospital admissions and re-admissions (in CHF and DM), improved adherence to treatment guidelines (DM, COPD and asthma) or quality of life (DM). Few reviews showed reductions in costs. CONCLUSIONS Systematic reviews of integrated care programmes were of mixed quality, assessed only some components of integration of care, and showed consistent benefits for some outcomes but not others.

Oral or transdermal opioids for osteoarthritis of the knee or hip.

BACKGROUND Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in older people. Opioids may be a viable treatment option if people have severe pain or if other analgesics are contraindicated. However, the evidence about their effectiveness and safety is contradictory. This is an update of a Cochrane review first published in 2009. OBJECTIVES To determine the effects on pain, function, safety, and addiction of oral or transdermal opioids compared with placebo or no intervention in people with knee or hip osteoarthritis. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL (up to 28 July 2008, with an update performed on 15 August 2012), checked conference proceedings, reference lists, and contacted authors. SELECTION CRITERIA We included randomised or quasi-randomised controlled trials that compared oral or transdermal opioids with placebo or no treatment in people with knee or hip osteoarthritis. We excluded studies of tramadol. We applied no language restrictions. DATA COLLECTION AND ANALYSIS We extracted data in duplicate. We calculated standardised mean differences (SMDs) and 95% confidence intervals (CI) for pain and function, and risk ratios for safety outcomes. We combined trials using an inverse-variance random-effects meta-analysis. MAIN RESULTS We identified 12 additional trials and included 22 trials with 8275 participants in this update. Oral oxycodone was studied in 10 trials, transdermal buprenorphine and oral tapentadol in four, oral codeine in three, oral morphine and oral oxymorphone in two, and transdermal fentanyl and oral hydromorphone in one trial each. All trials were described as double-blind, but the risk of bias for other domains was unclear in several trials due to incomplete reporting. Opioids were more beneficial in pain reduction than control interventions (SMD -0.28, 95% CI -0.35 to -0.20), which corresponds to a difference in pain scores of 0.7 cm on a 10-cm visual analogue scale (VAS) between opioids and placebo. This corresponds to a difference in improvement of 12% (95% CI 9% to 15%) between opioids (41% mean improvement from baseline) and placebo (29% mean improvement from baseline), which translates into a number needed to treat (NNTB) to cause one additional treatment response on pain of 10 (95% CI 8 to 14). Improvement of function was larger in opioid-treated participants compared with control groups (SMD -0.26, 95% CI -0.35 to -0.17), which corresponds to a difference in function scores of 0.6 units between opioids and placebo on a standardised Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability scale ranging from 0 to 10. This corresponds to a difference in improvement of 11% (95% CI 7% to 14%) between opioids (32% mean improvement from baseline) and placebo (21% mean improvement from baseline), which translates into an NNTB to cause one additional treatment response on function of 11 (95% CI 7 to 14). We did not find substantial differences in effects according to type of opioid, analgesic potency, route of administration, daily dose, methodological quality of trials, and type of funding. Trials with treatment durations of four weeks or less showed larger pain relief than trials with longer treatment duration (P value for interaction = 0.001) and there was evidence for funnel plot asymmetry (P value = 0.054 for pain and P value = 0.011 for function). Adverse events were more frequent in participants receiving opioids compared with control. The pooled risk ratio was 1.49 (95% CI 1.35 to 1.63) for any adverse event (9 trials; 22% of participants in opioid and 15% of participants in control treatment experienced side effects), 3.76 (95% CI 2.93 to 4.82) for drop-outs due to adverse events (19 trials; 6.4% of participants in opioid and 1.7% of participants in control treatment dropped out due to adverse events), and 3.35 (95% CI 0.83 to 13.56) for serious adverse events (2 trials; 1.3% of participants in opioid and 0.4% of participants in control treatment experienced serious adverse events). Withdrawal symptoms occurred more often in opioid compared with control treatment (odds ratio (OR) 2.76, 95% CI 2.02 to 3.77; 3 trials; 2.4% of participants in opioid and 0.9% of participants control treatment experienced withdrawal symptoms). AUTHORS' CONCLUSIONS The small mean benefit of non-tramadol opioids are contrasted by significant increases in the risk of adverse events. For the pain outcome in particular, observed effects were of questionable clinical relevance since the 95% CI did not include the minimal clinically important difference of 0.37 SMDs, which corresponds to 0.9 cm on a 10-cm VAS.

Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy.

BACKGROUND Venous thromboembolism (VTE) often complicates the clinical course of cancer. The risk is further increased by chemotherapy, but the safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain. This is an update of a review first published in February 2012. OBJECTIVES To assess the efficacy and safety of primary thromboprophylaxis for VTE in ambulatory cancer patients receiving chemotherapy compared with placebo or no thromboprophylaxis. SEARCH METHODS For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched May 2013), CENTRAL (2013, Issue 5), and clinical trials registries (up to June 2013). SELECTION CRITERIA Randomised controlled trials (RCTs) comparing any oral or parenteral anticoagulant or mechanical intervention to no intervention or placebo, or comparing two different anticoagulants. DATA COLLECTION AND ANALYSIS Data were extracted on methodological quality, patients, interventions, and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively. MAIN RESULTS We identified 12 additional RCTs (6323 patients) in the updated search so that this update considered 21 trials with a total of 9861 patients, all evaluating pharmacological interventions and performed mainly in patients with advanced cancer. Overall, the risk of bias varied from low to high. One large trial of 3212 patients found a 64% (risk ratio (RR) 0.36, 95% confidence interval (CI) 0.22 to 0.60) reduction of symptomatic VTE with the ultra-low molecular weight heparin (uLMWH) semuloparin relative to placebo, with no apparent difference in major bleeding (RR 1.05, 95% CI 0.55 to 2.00). LMWH, when compared with inactive control, significantly reduced the incidence of symptomatic VTE (RR 0.53, 95% CI 0.38 to 0.75; no heterogeneity, Tau(2) = 0%) with similar rates of major bleeding events (RR 1.30, 95% CI 0.75 to 2.23). In patients with multiple myeloma, LMWH was associated with a significant reduction in symptomatic VTE when compared with the vitamin K antagonist warfarin (RR 0.33, 95% CI 0.14 to 0.83), while the difference between LMWH and aspirin was not statistically significant (RR 0.51, 95% CI 0.22 to 1.17). No major bleeding was observed in the patients treated with LMWH or warfarin and in less than 1% of those treated with aspirin. Only one study evaluated unfractionated heparin against inactive control and found an incidence of major bleeding of 1% in both study groups while not reporting on VTE. When compared with placebo, warfarin was associated with a statistically insignificant reduction of symptomatic VTE (RR 0.15, 95% CI 0.02 to 1.20). Antithrombin, evaluated in one study involving paediatric patients, had no significant effect on VTE nor major bleeding when compared with inactive control. The new oral factor Xa inhibitor apixaban was evaluated in a phase-II dose finding study that suggested a promising low rate of major bleeding (2.1% versus 3.3%) and symptomatic VTE (1.1% versus 10%) in comparison with placebo. AUTHORS' CONCLUSIONS In this update, we confirmed that primary thromboprophylaxis with LMWH significantly reduced the incidence of symptomatic VTE in ambulatory cancer patients treated with chemotherapy. In addition, the uLMWH semuloparin significantly reduced the incidence of symptomatic VTE. However, the broad confidence intervals around the estimates for major bleeding suggest caution in the use of anticoagulation and mandate additional studies to determine the risk to benefit ratio of anticoagulants in this setting. Despite the encouraging results of this review, routine prophylaxis in ambulatory cancer patients cannot be recommended before safety issues are adequately addressed.

Three-dimensional imaging methods for quantitative analysis of facial soft tissues and skeletal morphology in patients with orofacial clefts: a systematic review.

BACKGROUND Current guidelines for evaluating cleft palate treatments are mostly based on two-dimensional (2D) evaluation, but three-dimensional (3D) imaging methods to assess treatment outcome are steadily rising. OBJECTIVE To identify 3D imaging methods for quantitative assessment of soft tissue and skeletal morphology in patients with cleft lip and palate. DATA SOURCES Literature was searched using PubMed (1948-2012), EMBASE (1980-2012), Scopus (2004-2012), Web of Science (1945-2012), and the Cochrane Library. The last search was performed September 30, 2012. Reference lists were hand searched for potentially eligible studies. There was no language restriction. STUDY SELECTION We included publications using 3D imaging techniques to assess facial soft tissue or skeletal morphology in patients older than 5 years with a cleft lip with/or without cleft palate. We reviewed studies involving the facial region when at least 10 subjects in the sample size had at least one cleft type. Only primary publications were included. DATA EXTRACTION Independent extraction of data and quality assessments were performed by two observers. RESULTS Five hundred full text publications were retrieved, 144 met the inclusion criteria, with 63 high quality studies. There were differences in study designs, topics studied, patient characteristics, and success measurements; therefore, only a systematic review could be conducted. Main 3D-techniques that are used in cleft lip and palate patients are CT, CBCT, MRI, stereophotogrammetry, and laser surface scanning. These techniques are mainly used for soft tissue analysis, evaluation of bone grafting, and changes in the craniofacial skeleton. Digital dental casts are used to evaluate treatment and changes over time. CONCLUSION Available evidence implies that 3D imaging methods can be used for documentation of CLP patients. No data are available yet showing that 3D methods are more informative than conventional 2D methods. Further research is warranted to elucidate it.