Pharmacological interventions for primary sclerosing cholangitis: an attempted network meta-analysis.

BACKGROUND: Primary sclerosing cholangitis is a chronic cholestatic liver disease that is associated with both hepatobiliary and colorectal malignancies, which can result in liver cirrhosis and its complications. The optimal pharmacological treatment for patients with primary sclerosing cholangitis remains controversial. OBJECTIVES: To assess the comparative benefits and harms of different pharmacological interventions in people with primary sclerosing cholangitis by performing a network meta-analysis, and to generate rankings of available pharmacological interventions according to their safety and efficacy. Given that it was not possible to assess whether potential effect modifiers were similar across comparisons, we did not perform the network meta-analysis but instead used standard Cochrane methods.When trials begin to provide an adequate description of potential effect modifiers, we will attempt to conduct network meta-analysis. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Science Citation Index - Expanded, the WHO International Clinical Trials Registry Platform, and randomised controlled trials registers until February 2017 to identify randomised clinical trials (RCT) on pharmacological interventions for primary sclerosing cholangitis. SELECTION CRITERIA: We included only RCTs, irrespective of language, blinding, or publication status, in which participants were given a diagnosis of primary sclerosing cholangitis. We excluded trials that included previously liver-transplanted participants. We considered any of various pharmacological interventions compared with one other or with placebo. We excluded trials that compared different doses of various pharmacological interventions or that reported different treatment durations, except for ursodeoxycholic acid (UDCA). As UDCA is the drug most commonly investigated for primary sclerosing cholangitis, we performed a second analysis in which we stratified the dose of UDCA. DATA COLLECTION AND ANALYSIS: We calculated the odds ratio and the rate ratio with 95% confidence intervals (CIs) using both fixed-effect and random-effects models based on available-participant analysis with Review Manager. We assessed risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE. MAIN RESULTS: We identified 22 RCTs in which 1211 participants were randomised to 13 different interventions. Most were placebo-controlled trials. Trials had few restrictions apart from an established diagnosis of primary sclerosing cholangitis, evidence of cholestasis, absence of decompensated liver disease, and absence of malignancy. However, some trials included symptomatic participants only, and others included both symptomatic and asymptomatic participants. A total of 11 RCTs (706 participants) provided data for one or more outcomes. The period of follow-up ranged from three months to three years in most trials. Only three trials reported follow-up longer than three years. Investigators found no evidence of differences in important clinical benefits such as reduction in mortality at maximal follow-up and improvement in health-related quality of life. Primary outcomes Mortality: Effect estimates: colchicine versus placebo: odds ratio 0.44, 95% CI 0.04 to 5.07, participants = 84, one trial; penicillamine versus placebo: odds ratio 1.18, 95% CI 0.39 to 3.58, participants = 70, one trial; steroids versus placebo: odds ratio 3.00, 95% CI 0.10 to 90.96, participants = 11, one trial; ursodeoxycholic acid versus placebo: odds ratio 1.51, 95% CI 0.63 to 3.63, participants = 348, two trials, I2 = 0%; vancomycin versus placebo: not estimable because no events in either group, participants = 29, one trial. Serious adverse events (proportion): Effect estimates: infliximab versus placebo: odds ratio not estimable (because of zero events in both arms), participants = 7, one trial; steroids versus placebo: odds ratio 20.00, 95% CI 0.93 to 429.90, participants = 11, one trial; vancomycin versus placebo: not estimable because no events in either group, participants = 29, one trial. Serious adverse events (number): Effect estimates: infliximab versus placebo: rate ratio 0.80, 95% CI 0.02 to 40.44, participants = 7, one trial; penicillamine versus placebo: rate ratio 13.60, 95% CI 0.78 to 237.83, participants = 70, one trial; steroids versus placebo: rate ratio 3.32, 95% CI 0.71 to 15.62, participants = 11, one trial. Adverse events (proportion): Effect estimates: steroids versus placebo: odds ratio 20.00, 95% CI 0.93 to 429.90, participants = 11, one trial; ursodeoxycholic acid versus placebo: odds ratio 1.22, 95% CI 0.68 to 2.17, participants = 198, one trial; vancomycin versus placebo: not estimable because no events in either group, participants = 29, one trial. Adverse events (number): Effect estimates: cyclosporin versus placebo: rate ratio 2.64, 95% CI 0.99 to 7.03, participants = 26, one trial; steroids versus placebo: rate ratio 3.32, 95% CI 0.71 to 15.62, participants = 11, one trial; ursodeoxycholic acid plus metronidazole versus ursodeoxycholic acid: rate ratio 2.36, 95% CI 0.98 to 5.71, participants = 71, one trial. Health-related quality of life: ursodeoxycholic acid versus placebo: mean difference 1.30, 95% CI -5.61 to 8.21, participants = 198, one trial (Short Form (SF)-36 General Health Scale). Secondary outcomes Studies provided no evidence of differences in clinical benefits such as a reduction in the requirement for liver transplantation or a reduction in the incidence proportion of cholangiocarcinoma. One small trial (29 participants) comparing vancomycin versus placebo reported no malignancies, no liver decompensation, and no liver transplantation in either group after a very short follow-up period of 12 weeks after treatment. None of the remaining trials clearly reported other clinical benefits such as decreased development of all malignancies, colorectal cancer, liver decompensation, time to liver decompensation, time to liver transplantation, or requirement for cholecystectomy to allow comparisons between different interventions. SOURCE OF FUNDING: Fifteen trials reported the source of funding; three were funded by parties without vested interest in results of the trial, and 12 were funded in part or in full by drug companies. AUTHORS' CONCLUSIONS: Evidence is currently insufficient to show differences in effectiveness measures such as mortality, health-related quality of life, cirrhosis, or liver transplantation between any active pharmacological intervention and no intervention. However, trials were at high risk of bias and included small numbers of participants, had short follow-up periods, and reported few clinical outcomes. An urgent need exists to identify an effective medical treatment for primary sclerosing cholangitis through well-designed RCTs with adequate follow-up that aim to identify differences in outcomes important to people with primary sclerosing cholangitis.

Early versus delayed dressing removal after primary closure of clean and clean-contaminated surgical wounds.

BACKGROUND: Most surgical procedures involve a cut in the skin that allows the surgeon to gain access to the deeper tissues or organs. Most surgical wounds are closed fully at the end of the procedure (primary closure). The surgeon covers the closed surgical wound with either a dressing or adhesive tape. The dressing can act as a physical barrier to protect the wound until the continuity of the skin is restored (within about 48 hours) and to absorb exudate from the wound, keeping it dry and clean, and preventing bacterial contamination from the external environment. Some studies have found that the moist environment created by some dressings accelerates wound healing, although others believe that the moist environment can be a disadvantage, as excessive exudate can cause maceration (softening and deterioration) of the wound and the surrounding healthy tissue. The utility of dressing surgical wounds beyond 48 hours of surgery is, therefore, controversial. OBJECTIVES: To evaluate the benefits and risks of removing a dressing covering a closed surgical incision site within 48 hours permanently (early dressing removal) or beyond 48 hours of surgery permanently with interim dressing changes allowed (delayed dressing removal), on surgical site infection. SEARCH METHODS: In March 2015 we searched the following electronic databases: The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We also searched the references of included trials to identify further potentially-relevant trials. SELECTION CRITERIA: Two review authors independently identified studies for inclusion. We included all randomised clinical trials (RCTs) conducted with people of any age and sex, undergoing a surgical procedure, who had their wound closed and a dressing applied. We included only trials that compared early versus delayed dressing removal. We excluded trials that included people with contaminated or dirty wounds. We also excluded quasi-randomised studies, and other study designs. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data on the characteristics of the trial participants, risk of bias in the trials and outcomes for each trial. We calculated risk ratios (RR) with 95% confidence intervals (CI) for binary outcomes and mean difference (MD) with 95% CI for continuous outcomes. We used RevMan 5 software to perform these calculations. MAIN RESULTS: Four trials were identified for inclusion in this review. All the trials were at high risk of bias. Three trials provided information for this review. Overall, this review included 280 people undergoing planned surgery. Participants were randomised to early dressing removal (removal of the wound dressing within the 48 hours following surgery) (n = 140) or delayed dressing removal (continued dressing of the wound beyond 48 hours) (n = 140) in the three trials. There were no statistically significant differences between the early dressing removal group and delayed dressing removal group in the proportion of people who developed superficial surgical site infection within 30 days (RR 0.64; 95% CI 0.32 to 1.28), superficial wound dehiscence within 30 days (RR 2.00; 95% CI 0.19 to 21.16) or serious adverse events within 30 days (RR 0.83; 95% CI 0.28 to 2.51). No deep wound infection or deep wound dehiscence occurred in any of the participants in the trials that reported this outcome. None of the trials reported quality of life. The hospital stay was significantly shorter (MD -2.00 days; 95% CI -2.82 to -1.18) and the total cost of treatment significantly less (MD EUR -36.00; 95% CI -59.81 to -12.19) in the early dressing removal group than in the delayed dressing removal group in the only trial that reported these outcomes. AUTHORS' CONCLUSIONS: The early removal of dressings from clean or clean contaminated surgical wounds appears to have no detrimental effect on outcomes. However, it should be noted that the point estimate supporting this statement is based on very low quality evidence from three small randomised controlled trials, and the confidence intervals around this estimate were wide. Early dressing removal may result in a significantly shorter hospital stay, and significantly reduced costs, than covering the surgical wound with wound dressings beyond the first 48 hours after surgery, according to very low quality evidence from one small randomised controlled trial. Further randomised controlled trials of low risk of bias are necessary to investigate whether dressings are necessary after 48 hours in different types of surgery and levels of contamination and investigate whether antibiotic therapy influences the outcome.

Early versus delayed post-operative bathing or showering to prevent wound complications.

BACKGROUND: Many people undergo surgical operations during their life-time, which result in surgical wounds. After an operation the incision is closed using stiches, staples, steri-strips or an adhesive glue. Usually, towards the end of the surgical procedure and before the patient leaves the operating theatre, the surgeon covers the closed surgical wound using gauze and adhesive tape or an adhesive tape containing a pad (a wound dressing) that covers the surgical wound. There is currently no guidance about when the wound can be made wet by post-operative bathing or showering. Early bathing may encourage early mobilisation of the patient, which is good after most types of operation. Avoiding post-operative bathing or showering for two to three days may result in accumulation of sweat and dirt on the body. Conversely, early washing of the surgical wound may have an adverse effect on healing, for example by irritating or macerating the wound, and disturbing the healing environment. OBJECTIVES: To compare the benefits (such as potential improvements to quality of life) and harms (potentially increased wound-related morbidity) of early post-operative bathing or showering (i.e. within 48 hours after surgery, the period during which epithelialisation of the wound occurs) compared with delayed post-operative bathing or showering (i.e. no bathing or showering for over 48 hours after surgery) in patients with closed surgical wounds. SEARCH METHODS: We searched The Cochrane Wounds Group Specialised Register (30th June 2015); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); The Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL; the metaRegister of Controlled Trials (mRCT) and the International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: We considered all randomised trials conducted in patients who had undergone any surgical procedure and had surgical closure of their wounds, irrespective of the location of the wound and whether or not the wound was dressed. We excluded trials if they included patients with contaminated, dirty or infected wounds and those that included open wounds. We also excluded quasi-randomised trials, cohort studies and case-control studies. DATA COLLECTION AND ANALYSIS: We extracted data on the characteristics of the patients included in the trials, risk of bias in the trials and outcomes from each trial. For binary outcomes, we calculated the risk ratio (RR) with 95% confidence interval (CI). For continuous variables we planned to calculate the mean difference (MD), or standardised mean difference (SMD) with 95% CI. For count data outcomes, we planned to calculate the rate ratio (RaR) with 95% CI. We used RevMan 5 software for performing these calculations. MAIN RESULTS: Only one trial was identified for inclusion in this review. This trial was at a high risk of bias. This trial included 857 patients undergoing minor skin excision surgery in the primary care setting. The wounds were sutured after the excision. Patients were randomised to early post-operative bathing (dressing to be removed after 12 hours and normal bathing resumed) (n = 415) or delayed post-operative bathing (dressing to be retained for at least 48 hours before removal and resumption of normal bathing) (n = 442). The only outcome of interest reported in this trial was surgical site infection (SSI). There was no statistically significant difference in the proportion of patients who developed SSIs between the two groups (857 patients; RR 0.96; 95% CI 0.62 to 1.48). The proportions of patients who developed SSIs were 8.5% in the early bathing group and 8.8% in the delayed bathing group. AUTHORS' CONCLUSIONS: There is currently no conclusive evidence available from randomised trials regarding the benefits or harms of early versus delayed post-operative showering or bathing for the prevention of wound complications, as the confidence intervals around the point estimate are wide, and, therefore, a clinically significant increase or decrease in SSI by early post-operative bathing cannot be ruled out. We recommend running further randomised controlled trials to compare early versus delayed post-operative showering or bathing.

Pharmacological interventions for prevention or treatment of postoperative pain in people undergoing laparoscopic cholecystectomy.

BACKGROUND: While laparoscopic cholecystectomy is generally considered less painful than open surgery, pain is one of the important reasons for delayed discharge after day-surgery and overnight stay following laparoscopic cholecystectomy. The safety and effectiveness of different pharmacological interventions such as non-steroidal anti-inflammatory drugs, opioids, and anticonvulsant analgesics in people undergoing laparoscopic cholecystectomy is unknown. OBJECTIVES: To assess the benefits and harms of different analgesics in people undergoing laparoscopic cholecystectomy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, and the World Health Organization International Clinical Trials Registry Platform portal (WHO ICTRP) to March 2013 to identify randomised clinical trials of relevance to this review. SELECTION CRITERIA: We considered only randomised clinical trials (irrespective of language, blinding, or publication status) comparing different pharmacological interventions with no intervention or inactive controls for outcomes related to benefit in this review. We considered comparative non-randomised studies with regards to treatment-related harms. We also considered trials that compared one class of drug with another class of drug for this review. DATA COLLECTION AND ANALYSIS: Two review authors collected the data independently. We analysed the data with both fixed-effect and random-effects models using Review Manager 5 analysis. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: We included 25 trials with 2505 participants randomised to the different pharmacological agents and inactive controls. All the trials were at unclear risk of bias. Most trials included only low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. Participants were allowed to take additional analgesics as required in 24 of the trials. The pharmacological interventions in all the included trials were aimed at preventing pain after laparoscopic cholecystectomy. There were considerable differences in the pharmacological agents used and the methods of administration. The estimated effects of the intervention on the proportion of participants who were discharged as day-surgery, the length of hospital stay, or the time taken to return to work were imprecise in all the comparisons in which these outcomes were reported (very low quality evidence). There was no mortality in any of the groups in the two trials that reported mortality (183 participants, very low quality evidence). Differences in serious morbidity outcomes between the groups were imprecise across all the comparisons (very low quality evidence). None of the trials reported patient quality of life or time taken to return to normal activity. The pain at 4 to 8 hours was generally reduced by about 1 to 2 cm on the visual analogue scale of 1 to 10 cm in the comparisons involving the different pharmacological agents and inactive controls (low or very low quality evidence). The pain at 9 to 24 hours was generally reduced by about 0.5 cm (a modest reduction) on the visual analogue scale of 1 to 10 cm in the comparisons involving the different pharmacological agents and inactive controls (low or very low quality evidence). AUTHORS' CONCLUSIONS: There is evidence of very low quality that different pharmacological agents including non-steroidal anti-inflammatory drugs, opioid analgesics, and anticonvulsant analgesics reduce pain scores in people at low anaesthetic risk undergoing elective laparoscopic cholecystectomy. However, the decision to use these drugs has to weigh the clinically small reduction in pain against uncertain evidence of serious adverse events associated with many of these agents. Further randomised clinical trials of low risk of systematic and random errors are necessary. Such trials should include important clinical outcomes such as quality of life and time to return to work in their assessment.

Methods of intraperitoneal local anaesthetic instillation for laparoscopic cholecystectomy.

BACKGROUND: Intraperitoneal local anaesthetic instillation may decrease pain in people undergoing laparoscopic cholecystectomy. However, the optimal method to administer the local anaesthetic is unknown. OBJECTIVES: To determine the optimal local anaesthetic agent, the optimal timing, and the optimal delivery method of the local anaesthetic agent used for intraperitoneal instillation in people undergoing laparoscopic cholecystectomy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, and the World Health Organization International Clinical Trials Registry Platform portal (WHO ICTRP) to March 2013 to identify randomised clinical trials for assessment of benefit and comparative non-randomised studies for the assessment of treatment-related harms. SELECTION CRITERIA: We considered only randomised clinical trials (irrespective of language, blinding, or publication status) comparing different methods of local anaesthetic intraperitoneal instillation during laparoscopic cholecystectomy for the review. DATA COLLECTION AND ANALYSIS: Two review authors collected the data independently. We analysed the data with both fixed-effect and random-effects models using Review Manager 5 analysis. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: We included 12 trials with 798 participants undergoing elective laparoscopic cholecystectomy randomised to different methods of intraperitoneal local anaesthetic instillation. All the trials were at high risk of bias. Most trials included only people with low anaesthetic risk. The comparisons included in the trials that met the eligibility criteria were the following; comparison of one local anaesthetic agent with another local anaesthetic agent (three trials); comparison of timing of delivery (six trials); comparison of different methods of delivery of the anaesthetic agent (two trials); comparison of location of the instillation of the anaesthetic agent (one trial); three trials reported mortality and morbidity.There were no mortalities or serious adverse events in either group in the following comparisons: bupivacaine (0/100 (0%)) versus lignocaine (0/106 (0%)) (one trial; 206 participants); just after creation of pneumoperitoneum (0/55 (0%)) versus end of surgery (0/55 (0%)) (two trials; 110 participants); just after creation of pneumoperitoneum (0/15 (0%)) versus after the end of surgery (0/15 (0%)) (one trial; 30 participants); end of surgery (0/15 (0%)) versus after the end of surgery (0/15 (0%)) (one trial; 30 participants).None of the trials reported quality of life, the time taken to return to normal activity, or the time taken to return to work. The differences in the proportion of people who were discharged as day-surgery and the length of hospital stay were imprecise in all the comparisons included that reported these outcomes (very low quality evidence). There were some differences in the pain scores on the visual analogue scale (1 to 10 cm) but these were neither consistent nor robust to fixed-effect versus random-effects meta-analysis or sensitivity analysis. AUTHORS' CONCLUSIONS: The currently available evidence is inadequate to determine the effects of one method of local anaesthetic intraperitoneal instillation compared with any other method of local anaesthetic intraperitoneal instillation in low anaesthetic risk individuals undergoing elective laparoscopic cholecystectomy. Further randomised clinical trials of low risk of systematic and random errors are necessary. Such trials should include important clinical outcomes such as quality of life and time to return to work in their assessment.

Laparoscopic surgical box model training for surgical trainees with limited prior laparoscopic experience.

BACKGROUND: Surgical training has traditionally been one of apprenticeship, where the surgical trainee learns to perform surgery under the supervision of a trained surgeon. This is time consuming, costly, and of variable effectiveness. Training using a box model physical simulator is an option to supplement standard training. However, the value of this modality on trainees with limited prior laparoscopic experience is unknown. OBJECTIVES: To compare the benefits and harms of box model training for surgical trainees with limited prior laparoscopic experience versus standard surgical training or supplementary animal model training. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded to May 2013. SELECTION CRITERIA: We planned to include all randomised clinical trials comparing box model trainers versus other forms of training including standard laparoscopic training and supplementary animal model training in surgical trainees with limited prior laparoscopic experience. We also planned to include trials comparing different methods of box model training. DATA COLLECTION AND ANALYSIS: Two authors independently identified trials and collected data. We analysed the data with both the fixed-effect and the random-effects models using Review Manager 5. For each outcome, we calculated the risk ratio (RR), mean difference (MD), or standardised mean difference (SMD) with 95% confidence intervals (CI) based on intention-to-treat analysis whenever possible. MAIN RESULTS: We identified eight trials that met the inclusion criteria. One trial including 17 surgical trainees did not contribute to the meta-analysis. We included seven trials (249 surgical trainees belonging to various postgraduate years ranging from year one to four) in which the participants were randomised to supplementary box model training (122 trainees) versus standard training (127 trainees). Only one trial (50 trainees) was at low risk of bias. The box trainers used in all the seven trials were video trainers. Six trials were conducted in USA and one trial in Canada. The surgeries in which the final assessments were made included laparoscopic total extraperitoneal hernia repairs, laparoscopic cholecystectomy, laparoscopic tubal ligation, laparoscopic partial salpingectomy, and laparoscopic bilateral mid-segment salpingectomy. The final assessments were made on a single operative procedure.There were no deaths in three trials (0/82 (0%) supplementary box model training versus 0/86 (0%) standard training; RR not estimable; very low quality evidence). The other trials did not report mortality. The estimated effect on serious adverse events was compatible with benefit and harm (three trials; 168 patients; 0/82 (0%) supplementary box model training versus 1/86 (1.1%) standard training; RR 0.36; 95% CI 0.02 to 8.43; very low quality evidence). None of the trials reported patient quality of life. The operating time was significantly shorter in the supplementary box model training group versus the standard training group (1 trial; 50 patients; MD -6.50 minutes; 95% CI -10.85 to -2.15). The proportion of patients who were discharged as day-surgery was significantly higher in the supplementary box model training group versus the standard training group (1 trial; 50 patients; 24/24 (100%) supplementary box model training versus 15/26 (57.7%) standard training; RR 1.71; 95% CI 1.23 to 2.37). None of the trials reported trainee satisfaction. The operating performance was significantly better in the supplementary box model training group versus the standard training group (seven trials; 249 trainees; SMD 0.84; 95% CI 0.57 to 1.10).None of the trials compared box model training versus animal model training or versus different methods of box model training. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine whether laparoscopic box model training reduces mortality or morbidity. There is very low quality evidence that it improves technical skills compared with standard surgical training in trainees with limited previous laparoscopic experience. It may also decrease operating time and increase the proportion of patients who were discharged as day-surgery in the first total extraperitoneal hernia repair after box model training. However, the duration of the benefit of box model training is unknown. Further well-designed trials of low risk of bias and random errors are necessary. Such trials should assess the long-term impact of box model training on clinical outcomes and compare box training with other forms of training.

Intraperitoneal local anaesthetic instillation versus no intraperitoneal local anaesthetic instillation for laparoscopic cholecystectomy.

BACKGROUND: While laparoscopic cholecystectomy is generally considered less painful than open surgery, pain is one of the important reasons for delayed discharge after day surgery and overnight stay laparoscopic cholecystectomy. The safety and effectiveness of intraperitoneal local anaesthetic instillation in people undergoing laparoscopic cholecystectomy is unknown. OBJECTIVES: To assess the benefits and harms of intraperitoneal instillation of local anaesthetic agents in people undergoing laparoscopic cholecystectomy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded to March 2013 to identify randomised clinical trials of relevance to this review. SELECTION CRITERIA: We considered only randomised clinical trials (irrespective of language, blinding, or publication status) comparing local anaesthetic intraperitoneal instillation versus placebo, no intervention, or inactive control during laparoscopic cholecystectomy for the review with regards to benefits while we considered quasi-randomised studies and non-randomised studies for treatment-related harms. DATA COLLECTION AND ANALYSIS: Two review authors collected the data independently. We analysed the data with both fixed-effect and random-effects models using Review Manager 5 analysis. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: We included 58 trials, of which 48 trials with 2849 participants randomised to intraperitoneal local anaesthetic instillation (1558 participants) versus control (1291 participants) contributed data to one or more of the outcomes. All the trials except one trial with 30 participants were at high risk of bias. Most trials included only low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. Various intraperitoneal local anaesthetic agents were used but bupivacaine in the liquid form was the most common local anaesthetic used. There were considerable differences in the methods of local anaesthetic instillation including the location (subdiaphragmatic, gallbladder bed, or both locations) and timing (before or after the removal of gallbladder) between the trials. There was no mortality in either group in the eight trials that reported mortality (0/236 (0%) in local anaesthetic instillation versus 0/210 (0%) in control group; very low quality evidence). One participant experienced the outcome of serious morbidity (eight trials; 446 participants; 1/236 (0.4%) in local anaesthetic instillation group versus 0/210 (0%) in the control group; RR 3.00; 95% CI 0.13 to 67.06; very low quality evidence). Although the remaining trials did not report the overall morbidity, three trials (190 participants) reported that there were no intra-operative complications. Twenty trials reported that there were no serious adverse events in any of the 715 participants who received local anaesthetic instillation. None of the trials reported participant quality of life, return to normal activity, or return to work.The effect of local anaesthetic instillation on the proportion of participants discharged as day surgery between the two groups was imprecise and compatible with benefit and no difference of intervention (three trials; 242 participants; 89/160 (adjusted proportion 61.0%) in local anaesthetic instillation group versus 40/82 (48.8%) in control group; RR 1.25; 95% CI 0.99 to 1.58; very low quality evidence). The MD in length of hospital stay was 0.04 days (95% CI -0.23 to 0.32; five trials; 335 participants; low quality evidence). The pain scores as measured by the visual analogue scale (VAS) were significantly lower in the local anaesthetic instillation group than the control group at four to eight hours (32 trials; 2020 participants; MD -0.99 cm; 95% CI -1.10 to -0.88 on a VAS scale of 0 to 10 cm; very low quality evidence) and at nine to 24 hours (29 trials; 1787 participants; MD -0.53 cm; 95% CI -0.62 to -0.44; very low quality evidence). Various subgroup analyses and meta-regressions to investigate the influence of the different local anaesthetic agents, different methods of local anaesthetic instillation, and different controls on the effectiveness of local anaesthetic intraperitoneal instillation were inconsistent. AUTHORS' CONCLUSIONS: Serious adverse events were rare in studies evaluating local anaesthetic intraperitoneal instillation (very low quality evidence). There is very low quality evidence that it reduces pain in low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. However, the clinical importance of this reduction in pain is unknown and likely to be small. Further randomised clinical trials of low risk of systematic and random errors are necessary. Such trials should include important clinical outcomes such as quality of life and time to return to work in their assessment.

Continuous versus interrupted skin sutures for non-obstetric surgery.

BACKGROUND: Most surgical procedures involve a cut in the skin, allowing the surgeon to gain access to the surgical site. Most surgical wounds are closed fully at the end of the procedure; this review focuses on these closed wounds. There are many ways to close the surgical incision, for example, using sutures (stitches), staples, tissue adhesives or tapes. Skin sutures can be continuous or interrupted. In general, continuous sutures are usually subcuticular and can be absorbable or non-absorbable, while interrupted sutures are usually non-absorbable and involve the full thickness of the skin - although some surgeons do use absorbable interrupted sutures. OBJECTIVES: To compare the benefits and harms of continuous compared with interrupted skin closure techniques in participants undergoing non-obstetric surgery. SEARCH METHODS: In August 2013 we searched the following databases: Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid Embase; and EBSCO CINAHL. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) that compared skin closure using continuous sutures with skin closure using interrupted sutures, irrespective of whether there were differences in the nature of the suture materials used in the two groups. We included all relevant RCTs in the analysis, irrespective of language of publication, publication status, publication year or sample size. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the trials and extracted data. We calculated the risk ratio (RR) with 95% confidence intervals (CI) for comparing binary outcomes between the groups, and calculated the mean difference (MD) with 95% CI for comparing continuous outcomes. We performed meta-analysis using a fixed-effect model and a random-effects model. We performed intention-to-treat analysis whenever possible. MAIN RESULTS: We included five RCTs with a total of 827 participants. Outcomes were available for 730 participants (384 participants randomised to continuous sutures and 346 participants to interrupted sutures). All the trials were of unclear or high risk of bias. The participants underwent abdominal or groin operations. The only outcomes reported in the trials were superficial surgical site infection, superficial wound dehiscence (breakdown) and length of hospital stay. Other important outcomes such as quality of life, long-term patient outcomes and use of healthcare resources were not reported in these trials.Overall, 6.5% (39/602 participants, four trials) developed superficial surgical site infections. There was no significant difference between the groups in the proportion of participants who developed superficial surgical site infections (RR 0.73; 95% CI 0.40 to 1.33). A total of 23 participants (23/625 (3.7%), four trials) developed superficial wound dehiscence. Twenty-two of the 23 participants belonged to the interrupted suture group.The proportion of participants who developed superficial wound dehiscence was statistically significantly lower in the continuous suture group compared to the interrupted suture group (RR 0.08; 95% CI 0.02 to 0.35). Most of these wound dehiscences were reported in two recent trials in which the continuous skin suture groups received absorbable subcuticular sutures while the interrupted skin suture groups received non-absorbable transcutaneous sutures. The non-absorbable sutures were removed seven to nine days after surgery in the interrupted sutures groups whilst sutures in the comparator groups were not removed, being absorbable. The continuous suture technique with absorbable suture does not require suture removal and provides support for the wound for a longer period of time. This may have contributed to the difference between the two groups in the proportion of participants who developed superficial wound dehiscence. There was no significant difference in the length of the hospital stay between the two groups (MD -1.40 days; 95% CI -7.14 to 4.34). AUTHORS' CONCLUSIONS: Superficial wound dehiscence may be reduced by using continuous subcuticular sutures. However, there is uncertainty about this because of the quality of the evidence. Besides, the nature of the suture material used may have led to this observation, as the continuous suturing technique used suture material that did not need to be removed, whereas the comparator used interrupted (non-absorbable) sutures that did need to be removed. Differences in the methods of skin closure have the potential to affect patient outcomes and use of healthcare resources. Further well-designed trials at low risk of bias are necessary to determine which type of suturing is better.

Subcutaneous closure versus no subcutaneous closure after non-caesarean surgical procedures.

BACKGROUND: Most surgical procedures involve a cut in the skin that allows the surgeon to gain access to the surgical site. Most surgical wounds are closed fully at the end of the procedure, and this review focuses on these. The human body has multiple layers of tissues, and the skin is the outermost of these layers. The loose connective tissue just beneath the skin is called subcutaneous tissue, and this generally contains fat. There is uncertainty about closure of subcutaneous tissue after surgery: some surgeons advocate closure of subcutaneous tissue, as they consider this closes dead space and leads to a decrease in wound complications; others consider closure of subcutaneous tissue to be an unnecessary step that increases operating time and involves the use of additional suture material without offering any benefit. OBJECTIVES: To compare the benefits (such as decreased wound-related complications) and consequences (such as increased operating time) of subcutaneous closure compared with no subcutaneous closure in participants undergoing non-caesarean surgical procedures. SEARCH METHODS: In August 2013 we searched the following databases: Cochrane Wounds Group Specialised Register (searched 29 August, 2013); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 7); Ovid MEDLINE (1946 to August Week 3 2013); Ovid MEDLINE (In-Process & Other Non-Indexed Citations August 28, 2013); Ovid EMBASE (1974 to 2013 Week 34); and EBSCO CINAHL (1982 to 23 August 2013). We did not restrict studies with respect to language, date of publication or study setting. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) comparing subcutaneous closure with no subcutaneous closure irrespective of the nature of the suture material(s) or whether continuous or interrupted sutures were used. We included all RCTs in the analysis, regardless of language, publication status, publication year, or sample size. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the trials and extracted data. We calculated the risk ratio (RR) with 95% confidence intervals (CI) for comparing binary (dichotomous) outcomes between the groups and calculated the mean difference (MD) with 95% CI for continuous outcomes. We performed meta-analysis using the fixed-effect model and random-effects model. We performed intention-to-treat analysis whenever possible. MAIN RESULTS: Eight RCTs met the inclusion criteria. Six of the trials provided data for this review and all of these were at high risk of bias. Six trials randomised a total of 815 participants to subcutaneous closure (410 participants) or no subcutaneous closure (405 participants). Overall, 7.7% of participants (63/815 of participants) developed superficial surgical site infections and there was no clear evidence of a difference between the two intervention groups (RR 0.84; 95% CI 0.53 to 1.33; very low quality evidence). Only two trials reported superficial wound dehiscence, with 7.9% (17/215) of participants developing the problem. It is not clear whether the lack of reporting of this outcome in other trials was because it did not occur, or was not measured. There was no clear evidence of a between-group difference in the proportion of participants who developed superficial wound dehiscence in the trials that reported this outcome (RR 0.56; 95% CI 0.22 to 1.41; very low quality evidence). Only one trial reported deep wound dehiscence, which occurred in 8.3% (5/60) of participants. There was no clear evidence of a difference in the proportion of participants who developed deep wound dehiscence between the two groups (RR 0.25; 95% CI 0.03 to 2.11; very low quality evidence). Three trials reported the length of hospital stay and found no significant difference between groups (MD 0.10 days; 95% CI -0.45 to 0.64; very low quality evidence). We do not know whether this review reveals a lack of effect or lack of evidence of effect. The confidence intervals for these outcomes were wide, and significant benefits or harms from subcutaneous closure cannot be ruled out. In addition, none of the trials assessed the impact of subcutaneous closure on quality of life, long-term patient outcomes (the follow-up period in the trials varied between one week and two months after surgery) or financial implications to the healthcare provider. AUTHORS' CONCLUSIONS: There is currently evidence of very low quality which is insufficient to support or refute subcutaneous closure after non-caesarean operations. The use of subcutaneous closure has the potential to affect patient outcomes and utilisation of healthcare resources. Further well-designed trials at low risk of bias are necessary.

Laparoscopic surgical box model training for surgical trainees with no prior laparoscopic experience.

BACKGROUND: Surgical training has traditionally been one of apprenticeship, where the surgical trainee learns to perform surgery under the supervision of a trained surgeon. This is time consuming, costly, and of variable effectiveness. Training using a box model physical simulator - either a video box or a mirrored box - is an option to supplement standard training. However, the impact of this modality on trainees with no prior laparoscopic experience is unknown. OBJECTIVES: To compare the benefits and harms of box model training versus no training, another box model, animal model, or cadaveric model training for surgical trainees with no prior laparoscopic experience. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded to May 2013. SELECTION CRITERIA: We included all randomised clinical trials comparing box model trainers versus no training in surgical trainees with no prior laparoscopic experience. We also included trials comparing different methods of box model training. DATA COLLECTION AND ANALYSIS: Two authors independently identified trials and collected data. We analysed the data with both the fixed-effect and the random-effects models using Review Manager for analysis. For each outcome, we calculated the standardised mean difference (SMD) with 95% confidence intervals (CI) based on intention-to-treat analysis whenever possible. MAIN RESULTS: Twenty-five trials contributed data to the quantitative synthesis in this review. All but one trial were at high risk of bias. Overall, 16 trials (464 participants) provided data for meta-analysis of box training (248 participants) versus no supplementary training (216 participants). All the 16 trials in this comparison used video trainers. Overall, 14 trials (382 participants) provided data for quantitative comparison of different methods of box training. There were no trials comparing box model training versus animal model or cadaveric model training. Box model training versus no training: The meta-analysis showed that the time taken for task completion was significantly shorter in the box trainer group than the control group (8 trials; 249 participants; SMD -0.48 seconds; 95% CI -0.74 to -0.22). Compared with the control group, the box trainer group also had lower error score (3 trials; 69 participants; SMD -0.69; 95% CI -1.21 to -0.17), better accuracy score (3 trials; 73 participants; SMD 0.67; 95% CI 0.18 to 1.17), and better composite performance scores (SMD 0.65; 95% CI 0.42 to 0.88). Three trials reported movement distance but could not be meta-analysed as they were not in a format for meta-analysis. There was significantly lower movement distance in the box model training compared with no training in one trial, and there were no significant differences in the movement distance between the two groups in the other two trials. None of the remaining secondary outcomes such as mortality and morbidity were reported in the trials when animal models were used for assessment of training, error in movements, and trainee satisfaction. Different methods of box training: One trial (36 participants) found significantly shorter time taken to complete the task when box training was performed using a simple cardboard box trainer compared with the standard pelvic trainer (SMD -3.79 seconds; 95% CI -4.92 to -2.65). There was no significant difference in the time taken to complete the task in the remaining three comparisons (reverse alignment versus forward alignment box training; box trainer suturing versus box trainer drills; and single incision versus multiport box model training). There were no significant differences in the error score between the two groups in any of the comparisons (box trainer suturing versus box trainer drills; single incision versus multiport box model training; Z-maze box training versus U-maze box training). The only trial that reported accuracy score found significantly higher accuracy score with Z-maze box training than U-maze box training (1 trial; 16 participants; SMD 1.55; 95% CI 0.39 to 2.71). One trial (36 participants) found significantly higher composite score with simple cardboard box trainer compared with conventional pelvic trainer (SMD 0.87; 95% CI 0.19 to 1.56). Another trial (22 participants) found significantly higher composite score with reverse alignment compared with forward alignment box training (SMD 1.82; 95% CI 0.79 to 2.84). There were no significant differences in the composite score between the intervention and control groups in any of the remaining comparisons. None of the secondary outcomes were adequately reported in the trials. AUTHORS' CONCLUSIONS: The results of this review are threatened by both risks of systematic errors (bias) and risks of random errors (play of chance). Laparoscopic box model training appears to improve technical skills compared with no training in trainees with no previous laparoscopic experience. The impacts of this decreased time on patients and healthcare funders in terms of improved outcomes or decreased costs are unknown. There appears to be no significant differences in the improvement of technical skills between different methods of box model training. Further well-designed trials of low risk of bias and random errors are necessary. Such trials should assess the impacts of box model training on surgical skills in both the short and long term, as well as clinical outcomes when the trainee becomes competent to operate on patients.

Antiviral prophylaxis for the prevention of chronic hepatitis C virus in patients undergoing liver transplantation.

BACKGROUND: It is not clear whether prophylactic antiviral therapy is indicated to improve patient and graft survival in patients undergoing liver transplantation for chronic decompensated hepatitis C virus (HCV) infection. OBJECTIVES: To compare the benefits and harms of different prophylactic antiviral therapies for patients undergoing liver transplantation for chronic HCV infection. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 1, 2013), MEDLINE, EMBASE, and Science Citation Index Expanded to February 2013. SELECTION CRITERIA: Only randomised clinical trials irrespective of language, blinding, or publication status and comparing various prophylactic antiviral therapies (alone or in combination) in the prophylactic treatment of patients undergoing liver transplantation for chronic HCV infection. DATA COLLECTION AND ANALYSIS: Two authors collected the data independently. We calculated the risk ratio (RR) or mean difference (MD) or hazard ratio (HR) with 95% confidence intervals (CI) using the fixed-effect and the random-effects models based on available case analysis. MAIN RESULTS: A total of 501 liver transplant recipients undergoing liver transplantation for chronic HCV infection were randomised in 12 trials to various experimental interventions and control interventions. The proportion of genotype I varied between 49% and 100% in the seven trials that reported the genotype. Only one or two trials were included under each comparison. All the trials were of high risk of bias. Ten trials including 441 liver transplant recipients provided data for this review.There were no significant differences in the 90-day mortality (1 trial; 81 participants; 5/35 (adjusted proportion: 14.2%) in interferon group versus 5/46 (10.9%) in control group; RR 1.31; 95% CI 0.41 to 4.19); mortality at maximal follow-up (2 trials; 105 participants; 7/47 (adjusted proportion: 14.8%) in interferon group versus 10/58 (17.2%) in control group; RR 0.86; 95% CI 0.36 to 2.08); long-term mortality (1 trial; 81 participants; HR 0.45; 95% CI 0.13 to 1.56); mortality at maximal follow-up (1 trial; 54 participants; 1/26 (3.9%) in pegylated interferon group versus 2/28 (7.1%) in control group; RR 0.54; 95% CI 0.05 to 5.59); 90-day mortality (1 trial; 115 participants; 5/55 (9.1%) in pegylated interferon plus ribavirin group versus 3/60 (5.0%) in control group; RR 1.82; 95% 0.46 to 7.25); 90-day mortality (3 trials; 53 participants; 3/37 (adjusted proportion: 4.3%) in HCV antibody group versus 1/16 (6.3%) in placebo group; RR 0.69; 95% CI 0.15 to 3.11); or 90-day mortality (2 trials; 31 participants; 2/14 (adjusted proportion: 16.2%) in HCV antibody high-dose group versus 1/17 (5.9%) in HCV antibody low-dose group; RR 2.75; 95% CI; 0.30 to 25.35). There were no significant differences in the retransplantation at maximal follow-up (2 trials; 105 participants; 2/47 (adjusted proportion: 4.0%) in interferon group versus 2/58 (3.4%) in control group; RR 1.17; 95% CI 0.22 to 6.2); 90-day retransplantation (1 trial; 18 participants; 1/12 (8.3%) in HCV antibody group versus 0/6 (0%) in control group; RR 1.71; 95% CI 0.09 to 32.93); or 90-day retransplantation (1 trial; 12 participants; 1/6 (17.7%) in HCV antibody high-dose group versus 0/6 (0%) in HCV antibody low-dose group; RR 3.00; 95% CI 0.15 to 61.74). There were no significant differences in serious adverse events, graft rejection, worsening of fibrosis, or HCV recurrence between intervention and control groups in any of the comparisons that reported these outcomes. None of the trials reported quality of life, liver decompensation, intensive therapy unit stay, or hospital stay. Life-threatening adverse events were not reported in either group in any of the comparisons. AUTHORS' CONCLUSIONS: There is currently no evidence to recommend prophylactic antiviral treatment to prevent recurrence of HCV infection either in primary liver transplantation or retransplantation. Further randomised clinical trials with adequate trial methodology and adequate duration of follow-up are necessary.

Antiviral interventions for liver transplant patients with recurrent graft infection due to hepatitis C virus.

BACKGROUND: Antiviral therapy for recurrent hepatitis C infection after liver transplantation is controversial due to unresolved balance between benefits and harms. OBJECTIVES: To compare the therapeutic benefits and harms of different antiviral regimens in patients with hepatitis C re-infected grafts after liver transplantation. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 1, 2013), MEDLINE, EMBASE, and Science Citation Index Expanded to February 2013. SELECTION CRITERIA: We considered only randomised clinical trials (irrespective of language, blinding, or publication status) comparing various antiviral therapies (alone or in combination) in the treatment of hepatitis C virus recurrence in liver transplantation for the review. DATA COLLECTION AND ANALYSIS: Two authors collected the data independently. We calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) using the fixed-effect and the random-effects models based on available case-analysis. In the presence of only trials for a dichotomous outcome, we performed the Fisher's exact test. MAIN RESULTS: Overall, 17 trials with 736 patients met the inclusion criteria for this review. All trials had high risk of bias. Five hundred and one patients randomised in 11 trials provided information for various comparisons in this systematic review after excluding post-randomisation drop-outs and patients from trials that did not report any of the outcomes of interest for this review. The comparisons for which outcomes were available included pegylated (peg) interferon versus control; peg interferon plus ribavirin versus control; ribavirin plus peg interferon versus peg interferon; peg interferon (1.5 µg/kg/week) plus ribavirin versus peg interferon (0.5 µg/kg/week) plus ribavirin; amantadine plus peg interferon plus ribavirin versus peg interferon plus ribavirin; interferon versus control; interferon plus ribavirin versus control; ribavirin versus interferon; and ribavirin versus placebo. Long-term follow-up was not available in these trials. There were no significant differences in mortality, retransplantation, graft rejections requiring retransplantation or medical treatment, or fibrosis worsening between the groups in any of the comparisons in which these outcomes were reported. Quality of life and liver decompensation were not reported in any of the trials. There was a significantly higher proportion of participants who developed serious adverse events in the ribavirin plus peg interferon combination therapy group than in the peg interferon monotherapy group (1 trial; 56 participants; 17/28 (60.7%) in the intervention group versus 5/28 (17.9%) in the control group; RR 3.40; 95% CI 1.46 to 7.94). There was no significant difference in proportion of participants who developed serious adverse events or in the number of serious adverse events between the intervention and control groups in the other comparisons that reported serious adverse events. AUTHORS' CONCLUSIONS: Considering the lack of clinical benefit, there is currently no evidence to recommend or refute antiviral treatment for recurrent liver graft infection with hepatitis C virus. Further randomised clinical trials with low risk of bias and low risk of random errors with adequate duration of follow-up are necessary.

Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) in non surgical wounds.

BACKGROUND: Non surgical wounds include chronic ulcers (pressure or decubitus ulcers, venous ulcers, diabetic ulcers, ischaemic ulcers), burns and traumatic wounds. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonisation (i.e. presence of MRSA in the absence of clinical features of infection such as redness or pus discharge) or infection in chronic ulcers varies between 7% and 30%. MRSA colonisation or infection of non surgical wounds can result in MRSA bacteraemia (infection of the blood) which is associated with a 30-day mortality of about 28% to 38% and a one-year mortality of about 55%. People with non surgical wounds colonised or infected with MRSA may be reservoirs of MRSA, so it is important to treat them, however, we do not know the optimal antibiotic regimen to use in these cases. OBJECTIVES: To compare the benefits (such as decreased mortality and improved quality of life) and harms (such as adverse events related to antibiotic use) of all antibiotic treatments in people with non surgical wounds with established colonisation or infection caused by MRSA. SEARCH METHODS: We searched the following databases: The Cochrane Wounds Group Specialised Register (searched 13 March 2013); The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2); Database of Abstracts of Reviews of Effects (2013, Issue 2); NHS Economic Evaluation Database (2013, Issue 2); Ovid MEDLINE (1946 to February Week 4 2013); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, March 12, 2013); Ovid EMBASE (1974 to 2013 Week 10); EBSCO CINAHL (1982 to 8 March 2013). SELECTION CRITERIA: We included only randomised controlled trials (RCTs) comparing antibiotic treatment with no antibiotic treatment or with another antibiotic regimen for the treatment of MRSA-infected non surgical wounds. We included all relevant RCTs in the analysis, irrespective of language, publication status, publication year, or sample size. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the trials, and extracted data from the trial reports. We calculated the risk ratio (RR) with 95% confidence intervals (CI) for comparing the binary outcomes between the groups and planned to calculate the mean difference (MD) with 95% CI for comparing the continuous outcomes. We planned to perform the meta-analysis using both fixed-effect and random-effects models. We performed intention-to-treat analysis whenever possible. MAIN RESULTS: We identified three trials that met the inclusion criteria for this review. In these, a total of 47 people with MRSA-positive diabetic foot infections were randomised to six different antibiotic regimens. While these trials included 925 people with multiple pathogens, they reported the information on outcomes for people with MRSA infections separately (MRSA prevalence: 5.1%). The only outcome reported for people with MRSA infection in these trials was the eradication of MRSA. The three trials did not report the review's primary outcomes (death and quality of life) and secondary outcomes (length of hospital stay, use of healthcare resources and time to complete wound healing). Two trials reported serious adverse events in people with infection due to any type of bacteria (i.e. not just MRSA infections), so the proportion of patients with serious adverse events was not available for MRSA-infected wounds. Overall, MRSA was eradicated in 31/47 (66%) of the people included in the three trials, but there were no significant differences in the proportion of people in whom MRSA was eradicated in any of the comparisons, as shown below.1. Daptomycin compared with vancomycin or semisynthetic penicillin: RR of MRSA eradication 1.13; 95% CI 0.56 to 2.25 (14 people).2. Ertapenem compared with piperacillin/tazobactam: RR of MRSA eradication 0.71; 95% CI 0.06 to 9.10 (10 people).3. Moxifloxacin compared with piperacillin/tazobactam followed by amoxycillin/clavulanate: RR of MRSA eradication 0.87; 95% CI 0.56 to 1.36 (23 people). AUTHORS' CONCLUSIONS: We found no trials comparing the use of antibiotics with no antibiotic for treating MRSA-colonised non-surgical wounds and therefore can draw no conclusions for this population. In the trials that compared different antibiotics for treating MRSA-infected non surgical wounds, there was no evidence that any one antibiotic was better than the others. Further well-designed RCTs are necessary.

Early versus delayed post-operative bathing or showering to prevent wound complications.

BACKGROUND: Many people undergo surgical operations during their life-time, which result in surgical wounds. After an operation the incision is closed using stiches, staples, steri-strips or an adhesive glue. Usually, towards the end of the surgical procedure and before the patient leaves the operating theatre, the surgeon covers the closed surgical wound using gauze and adhesive tape or an adhesive tape containing a pad (a wound dressing) that covers the surgical wound. There is currently no guidance about when the wound can be made wet by post-operative bathing or showering. Early bathing may encourage early mobilisation of the patient, which is good after most types of operation. Avoiding post-operative bathing or showering for two to three days may result in accumulation of sweat and dirt on the body. Conversely, early washing of the surgical wound may have an adverse effect on healing, for example by irritating or macerating the wound, and disturbing the healing environment. OBJECTIVES: To compare the benefits (such as potential improvements to quality of life) and harms (potentially increased wound-related morbidity) of early post-operative bathing or showering (i.e. within 48 hours after surgery, the period during which epithelialisation of the wound occurs) compared with delayed post-operative bathing or showering (i.e. no bathing or showering for over 48 hours after surgery) in patients with closed surgical wounds. SEARCH METHODS: We searched The Cochrane Wounds Group Specialised Register;The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); The Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL; the metaRegister of Controlled Trials (mRCT) and the International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: We considered all randomised trials conducted in patients who had undergone any surgical procedure and had surgical closure of their wounds, irrespective of the location of the wound and whether or not the wound was dressed. We excluded trials if they included patients with contaminated, dirty or infected wounds and those that included open wounds. We also excluded quasi-randomised trials, cohort studies and case-control studies. DATA COLLECTION AND ANALYSIS: We extracted data on the characteristics of the patients included in the trials, risk of bias in the trials and outcomes from each trial. For binary outcomes, we calculated the risk ratio (RR) with 95% confidence interval (CI). For continuous variables we planned to calculate the mean difference (MD), or standardised mean difference (SMD) with 95% CI. For count data outcomes, we planned to calculate the rate ratio (RaR) with 95% CI. We used RevMan 5 software for performing these calculations. MAIN RESULTS: Only one trial was identified for inclusion in this review. This trial was at a high risk of bias. This trial included 857 patients undergoing minor skin excision surgery in the primary care setting. The wounds were sutured after the excision. Patients were randomised to early post-operative bathing (dressing to be removed after 12 hours and normal bathing resumed) (n = 415) or delayed post-operative bathing (dressing to be retained for at least 48 hours before removal and resumption of normal bathing) (n = 442). The only outcome of interest reported in this trial was surgical site infection (SSI). There was no statistically significant difference in the proportion of patients who developed SSIs between the two groups (857 patients; RR 0.96; 95% CI 0.62 to 1.48). The proportions of patients who developed SSIs were 8.5% in the early bathing group and 8.8% in the delayed bathing group. AUTHORS' CONCLUSIONS: There is currently no conclusive evidence available from randomised trials regarding the benefits or harms of early versus delayed post-operative showering or bathing for the prevention of wound complications, as the confidence intervals around the point estimate are wide, and, therefore, a clinically significant increase or decrease in SSI by early post-operative bathing cannot be ruled out. We recommend running further randomised controlled trials to compare early versus delayed post-operative showering or bathing.

Early versus delayed dressing removal after primary closure of clean and clean-contaminated surgical wounds.

BACKGROUND: Most surgical procedures involve a cut in the skin that allows the surgeon to gain access to the deeper tissues or organs. Most surgical wounds are closed fully at the end of the procedure (primary closure). The surgeon covers the closed surgical wound with either a dressing or adhesive tape. The dressing can act as a physical barrier to protect the wound until the continuity of the skin is restored (within about 48 hours) and to absorb exudate from the wound, keeping it dry and clean, and preventing bacterial contamination from the external environment. Some studies have found that the moist environment created by some dressings accelerates wound healing, although others believe that the moist environment can be a disadvantage, as excessive exudate can cause maceration (softening and deterioration) of the wound and the surrounding healthy tissue. The utility of dressing surgical wounds beyond 48 hours of surgery is, therefore, controversial. OBJECTIVES: To evaluate the benefits and risks of removing a dressing covering a closed surgical incision site within 48 hours permanently (early dressing removal) or beyond 48 hours of surgery permanently with interim dressing changes allowed (delayed dressing removal), on surgical site infection. SEARCH METHODS: In July 2013 we searched the following electronic databases: The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We also searched the references of included trials to identify further potentially-relevant trials. SELECTION CRITERIA: Two review authors independently identified studies for inclusion. We included all randomised clinical trials (RCTs) conducted with people of any age and sex, undergoing a surgical procedure, who had their wound closed and a dressing applied. We included only trials that compared early versus delayed dressing removal. We excluded trials that included people with contaminated or dirty wounds. We also excluded quasi-randomised studies, and other study designs. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data on the characteristics of the trial participants, risk of bias in the trials and outcomes for each trial. We calculated risk ratios (RR) with 95% confidence intervals (CI) for binary outcomes and mean difference (MD) with 95% CI for continuous outcomes. We used RevMan 5 software to perform these calculations. MAIN RESULTS: Four trials were identified for inclusion in this review. All the trials were at high risk of bias. Three trials provided information for this review. Overall, this review included 280 people undergoing planned surgery. Participants were randomised to early dressing removal (removal of the wound dressing within the 48 hours following surgery) (n = 140) or delayed dressing removal (continued dressing of the wound beyond 48 hours) (n = 140) in the three trials. There were no statistically significant differences between the early dressing removal group and delayed dressing removal group in the proportion of people who developed superficial surgical site infection within 30 days (RR 0.64; 95% CI 0.32 to 1.28), superficial wound dehiscence within 30 days (RR 2.00; 95% CI 0.19 to 21.16) or serious adverse events within 30 days (RR 0.83; 95% CI 0.28 to 2.51). No deep wound infection or deep wound dehiscence occurred in any of the participants in the trials that reported this outcome. None of the trials reported quality of life. The hospital stay was significantly shorter (MD -2.00 days; 95% CI -2.82 to -1.18) and the total cost of treatment significantly less (MD EUR -36.00; 95% CI -59.81 to -12.19) in the early dressing removal group than in the delayed dressing removal group in the only trial that reported these outcomes. AUTHORS' CONCLUSIONS: The early removal of dressings from clean or clean contaminated surgical wounds appears to have no detrimental effect on outcomes. However, it should be noted that the point estimate supporting this statement is based on very low quality evidence from three small randomised controlled trials, and the confidence intervals around this estimate were wide. Early dressing removal may result in a significantly shorter hospital stay, and significantly reduced costs, than covering the surgical wound with wound dressings beyond the first 48 hours after surgery, according to very low quality evidence from one small randomised controlled trial. Further randomised controlled trials of low risk of bias are necessary to investigate whether dressings are necessary after 48 hours in different types of surgery and levels of contamination and investigate whether antibiotic therapy influences the outcome.

Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in surgical wounds.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection after surgery is usually rare, but incidence can be up to 33% in certain types of surgery. Postoperative MRSA infection can occur as surgical site infections (SSI), chest infections, or bloodstream infections (bacteraemia). The incidence of MRSA SSIs varies from 1% to 33% depending upon the type of surgery performed and the carrier status of the individuals concerned. The optimal antibiotic regimen for the treatment of MRSA in surgical wounds is not known. OBJECTIVES: To compare the benefits and harms of various antibiotic treatments in people with established surgical site infections (SSIs) caused by MRSA . SEARCH METHODS: In February 2013 we searched the following databases: The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL); Database of Abstracts of Reviews of Effects (DARE); NHS Economic Evaluation Database; Health Technology Assessment (HTA) Database; Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) comparing one antibiotic regimen with another antibiotic regimen for the treatment of SSIs due to MRSA. All RCTs irrespective of language, publication status, publication year, or sample size were included in the analysis. DATA COLLECTION AND ANALYSIS: Two review authors independently decided on inclusion and exclusion of trials, and extracted data. We planned to calculate the risk ratio (RR) with 95% confidence intervals (CI) for comparing the binary outcomes between the groups and mean difference (MD) with 95% CI for comparing the continuous outcomes. We planned to perform the meta-analysis using both a fixed-effect and a random-effects model. We performed intention-to-treat analysis whenever possible. MAIN RESULTS: We included one trial involving 59 people hospitalised because of MRSA SSIs. Thirty participants were randomised to linezolid (600 mg either intravenously or orally every 12 hours for seven to 14 days) and 29 to vancomycin (1 g intravenously every 12 hours for seven to 14 days). The type of surgical procedures that were performed were not reported. The trial reported one outcome, which was the eradication of MRSA. The proportion of people in whom MRSA was eradicated was statistically significantly higher in the linezolid group than in the vancomycin group (RR 1.80; 95% CI 1.20 to 2.68). AUTHORS' CONCLUSIONS: There is currently no evidence to recommend any specific antibiotic in the treatment of MRSA SSIs. Linezolid is superior to vancomycin in the eradication of MRSA SSIs on the basis of evidence from one small trial that was at high risk of bias, but the overall clinical implications of using linezolid instead of vancomycin are not known. Further well-designed randomised clinical trials are necessary in this area.