Prospective analysis of hydrogel spacer for patients with prostate cancer undergoing radiotherapy.

OBJECTIVE: To report on the dosimetric benefits and late toxicity outcomes after injection of hydrogel spacer (HS) between the prostate and rectum for patients treated with prostate radiotherapy (RT). PATIENTS AND METHODS: In all, 76 patients with a clinical stage of T1-T3a prostate cancer underwent general anaesthesia for fiducial marker insertion plus injection of the HS into the perirectal space before intensity-modulated RT (IMRT) or volumetric-modulated arc RT (VMAT). HS safety, dosimetric benefits, and the immediate- to long-term effects of gastrointestinal (GI) toxicity were assessed. RESULTS: There were no postoperative complications reported. The mean (range) prostate size was 66.0 (25.0-187.0) mm. Rectal dose volume parameters were observed and the volume of rectum receiving 70 Gy (rV70 ), 75 Gy (rV75 ) and 78 Gy (rV78 ) was 7.8%, 3.6% and 0.4%, respectively. In all, 21% of patients (16/76) developed acute Grade 1 GI toxicities, but all were resolved completely by 3 months after treatment; whilst, 3% of patients (2/76) developed late Grade 1 GI toxicities. No patients had acute or late Grade ≥2 GI toxicities. CONCLUSION: Injection of HS resulted in a reduction of irradiated rectal dose volumes along with minimal GI toxicities, irrespective of prostate size.

Appraisal of systematic reviews on the management of peri-implant diseases with two methodological tools.

AIM: This study aimed to evaluate and compare the performance of two methodological instruments to appraise systematic reviews and to identify potential disagreements of systematic review authors regarding risk of bias (RoB) evaluation of randomized controlled trials (RCTs) included in systematic reviews on peri-implant diseases. MATERIAL/METHODS: We searched Medline, Web of Science, Cochrane Library, PubMed Central, and Google Scholar for systematic reviews on peri-implant diseases published before July 11, 2017. Two authors independently evaluated the RoB and methodological quality of the systematic reviews by applying the Risk of Bias in Systematic Reviews (ROBIS) tool and Assessing the Methodological Quality of Systematic Reviews (AMSTAR) checklist, respectively. We assessed the RoB scores of the same RCTs published in different systematic reviews. RESULTS: Of the 32 systematic reviews identified, 23 reviews addressed the clinical topic of peri-implantitis. A high RoB was detected for most systematic reviews (n=25) using ROBIS, whilst five systematic reviews displayed low methodological quality by AMSTAR. Almost 30% of the RoB comparisons (for the same RCTs) had different RoB ratings across systematic reviews. CONCLUSIONS: The ROBIS tool appears to provide more conservative results than AMSTAR checklist. Considerable disagreement was found among systematic review authors rating the same RCT included in different systematic reviews.

Non-clinical interventions for reducing unnecessary caesarean section.

BACKGROUND: Caesarean section rates are increasing globally. The factors contributing to this increase are complex, and identifying interventions to address them is challenging. Non-clinical interventions are applied independently of a clinical encounter between a health provider and a patient. Such interventions may target women, health professionals or organisations. They address the determinants of caesarean births and could have a role in reducing unnecessary caesarean sections. This review was first published in 2011. This review update will inform a new WHO guideline, and the scope of the update was informed by WHO's Guideline Development Group for this guideline. OBJECTIVES: To evaluate the effectiveness and safety of non-clinical interventions intended to reduce unnecessary caesarean section. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL and two trials registers in March 2018. We also searched websites of relevant organisations and reference lists of related reviews. SELECTION CRITERIA: Randomised trials, non-randomised trials, controlled before-after studies, interrupted time series studies and repeated measures studies were eligible for inclusion. The primary outcome measures were: caesarean section, spontaneous vaginal birth and instrumental birth. DATA COLLECTION AND ANALYSIS: We followed standard methodological procedures recommended by Cochrane. We narratively described results of individual studies (drawing summarised evidence from single studies assessing distinct interventions). MAIN RESULTS: We included 29 studies in this review (19 randomised trials, 1 controlled before-after study and 9 interrupted time series studies). Most of the studies (20 studies) were conducted in high-income countries and none took place in low-income countries. The studies enrolled a mixed population of pregnant women, including nulliparous women, multiparous women, women with a fear of childbirth, women with high levels of anxiety and women having undergone a previous caesarean section.Overall, we found low-, moderate- or high-certainty evidence that the following interventions have a beneficial effect on at least one primary outcome measure and no moderate- or high-certainty evidence of adverse effects.Interventions targeted at women or familiesChildbirth training workshops for mothers alone may reduce caesarean section (risk ratio (RR) 0.55, 95% confidence interval (CI) 0.33 to 0.89) and may increase spontaneous vaginal birth (RR 2.25, 95% CI 1.16 to 4.36). Childbirth training workshops for couples may reduce caesarean section (RR 0.59, 95% CI 0.37 to 0.94) and may increase spontaneous vaginal birth (RR 2.13, 95% CI 1.09 to 4.16). We judged this one study with 60 participants to have low-certainty evidence for the outcomes above.Nurse-led applied relaxation training programmes (RR 0.22, 95% CI 0.11 to 0.43; 104 participants, low-certainty evidence) and psychosocial couple-based prevention programmes (RR 0.53, 95% CI 0.32 to 0.90; 147 participants, low-certainty evidence) may reduce caesarean section. Psychoeducation may increase spontaneous vaginal birth (RR 1.33, 95% CI 1.11 to 1.61; 371 participants, low-certainty evidence). The control group received routine maternity care in all studies.There were insufficient data on the effect of the four interventions on maternal and neonatal mortality or morbidity.Interventions targeted at healthcare professionalsImplementation of clinical practice guidelines combined with mandatory second opinion for caesarean section indication slightly reduces the risk of overall caesarean section (mean difference in rate change -1.9%, 95% CI -3.8 to -0.1; 149,223 participants). Implementation of clinical practice guidelines combined with audit and feedback also slightly reduces the risk of caesarean section (risk difference (RD) -1.8%, 95% CI -3.8 to -0.2; 105,351 participants). Physician education by local opinion leader (obstetrician-gynaecologist) reduced the risk of elective caesarean section to 53.7% from 66.8% (opinion leader education: 53.7%, 95% CI 46.5 to 61.0%; control: 66.8%, 95% CI 61.7 to 72.0%; 2496 participants). Healthcare professionals in the control groups received routine care in the studies. There was little or no difference in maternal and neonatal mortality or morbidity between study groups. We judged the certainty of evidence to be high.Interventions targeted at healthcare organisations or facilitiesCollaborative midwifery-labourist care (in which the obstetrician provides in-house labour and delivery coverage, 24 hours a day, without competing clinical duties), versus a private practice model of care, may reduce the primary caesarean section rate. In one interrupted time series study, the caesarean section rate decreased by 7% in the year after the intervention, and by 1.7% per year thereafter (1722 participants); the vaginal birth rate after caesarean section increased from 13.3% before to 22.4% after the intervention (684 participants). Maternal and neonatal mortality were not reported. We judged the certainty of evidence to be low.We studied the following interventions, and they either made little or no difference to caesarean section rates or had uncertain effects.Moderate-certainty evidence suggests little or no difference in caesarean section rates between usual care and: antenatal education programmes for physiologic childbirth; antenatal education on natural childbirth preparation with training in breathing and relaxation techniques; computer-based decision aids; individualised prenatal education and support programmes (versus written information in pamphlet).Low-certainty evidence suggests little or no difference in caesarean section rates between usual care and: psychoeducation; pelvic floor muscle training exercises with telephone follow-up (versus pelvic floor muscle training without telephone follow-up); intensive group therapy (cognitive behavioural therapy and childbirth psychotherapy); education of public health nurses on childbirth classes; role play (versus standard education using lectures); interactive decision aids (versus educational brochures); labourist model of obstetric care (versus traditional model of obstetric care).We are very uncertain as to the effect of other interventions identified on caesarean section rates as the certainty of the evidence is very low. AUTHORS' CONCLUSIONS: We evaluated a wide range of non-clinical interventions to reduce unnecessary caesarean section, mostly in high-income settings. Few interventions with moderate- or high-certainty evidence, mainly targeting healthcare professionals (implementation of guidelines combined with mandatory second opinion, implementation of guidelines combined with audit and feedback, physician education by local opinion leader) have been shown to safely reduce caesarean section rates. There are uncertainties in existing evidence related to very-low or low-certainty evidence, applicability of interventions and lack of studies, particularly around interventions targeted at women or families and healthcare organisations or facilities.

A survey of prevalence of narrative and systematic reviews in five major medical journals.

BACKGROUND: Systematic reviews may provide less biased evidence than narrative reviews because they observe a strict methodology, similarly to primary studies. Hence, for clinical research questions, systematic reviews should be the study design of choice. It would be important to evaluate the prevalence and characteristics of narrative and systematic reviews published in prominent medical journals. Researchers and clinicians give great value to articles published in such scientific journals. This study sought to evaluate the prevalence and characteristics of narrative and systematic reviews in the five highest-ranked general medical journals and investigate the associations among type of review, number of citations, and impact factor (IF). METHODS: We surveyed the five highest-ranked medical journals (The New England Journal of Medicine, The Lancet, The Journal of the American Medical Association, The BMJ, and Annals of Internal Medicine) for narrative and systematic reviews published between June 2015 and June 2016. We independently selected and extracted the data from the reviews by strictly following the pre-determined eligibility criteria (Systematic and narrative reviews that focused on the management of diseases). We conducted regression analyses to investigate the associations among review type, number of citations, and IF. We also descriptively reported narrative reviews containing some methodology that might be reproducible. RESULTS: Two hundred seventy-five reviews were included: 75 (27%) systematic; 126 (46%) narrative with some methodology reported, and 74 (27%) narrative reviews. In comparison to systematic reviews, narrative reviews were more frequently published in journals with higher IF (risk ratio [RR] = 1.114 (95% CI 1.080 to 1.149). Systematic reviews received more citations than narrative reviews (group formed by narrative and narrative with some methodology reported (RR = 0.985 95% CI 0.978 to 0.991). CONCLUSIONS: Non-systematic evidence is the most prevalent type of evidence in reviews published in the five highest-ranked general medical journals. Narrative reviews were more frequently published in journals with higher IF. We recommend that journals limit their space for narrative information, and to address clinical research questions, these journals consider publishing systematic evidence exclusively.

Interventions for managing skeletal muscle spasticity following traumatic brain injury.

BACKGROUND: Skeletal muscle spasticity is a major physical complication resulting from traumatic brain injury (TBI), which can lead to muscle contracture, joint stiffness, reduced range of movement, broken skin and pain. Treatments for spasticity include a range of pharmacological and non-pharmacological interventions, often used in combination. Management of spasticity following TBI varies from other clinical populations because of the added complexity of behavioural and cognitive issues associated with TBI. OBJECTIVES: To assess the effects of interventions for managing skeletal muscle spasticity in people with TBI. SEARCH METHODS: In June 2017, we searched key databases including the Cochrane Injuries Group Specialised Register, CENTRAL, MEDLINE (Ovid), Embase (Ovid) and others, in addition to clinical trials registries and the reference lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cross-over RCTs evaluating any intervention for the management of spasticity in TBI. Only studies where at least 50% of participants had a TBI (or for whom separate data for participants with TBI were available) were included. The primary outcomes were spasticity and adverse effects. Secondary outcome measures were classified according to the World Health Organization International Classification of Functioning, Disability and Health including body functions (sensory, pain, neuromusculoskeletal and movement-related functions) and activities and participation (general tasks and demands; mobility; self-care; domestic life; major life areas; community, social and civic life). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Data were synthesised narratively; meta-analysis was precluded due to the paucity and heterogeneity of data. MAIN RESULTS: We included nine studies in this review which involved 134 participants with TBI. Only five studies reported between-group differences, yielding outcome data for 105 participants with TBI. These five studies assessed the effects of a range of pharmacological (baclofen, botulinum toxin A) and non-pharmacological (casting, physiotherapy, splints, tilt table standing and electrical stimulation) interventions, often in combination. The studies which tested the effect of baclofen and tizanidine did not report their results adequately. Where outcome data were available, spasticity and adverse events were reported, in addition to some secondary outcome measures.Of the five studies with results, three were funded by governments, charities or health services and two were funded by a pharmaceutical or medical technology company. The four studies without useable results were funded by pharmaceutical or medical technology companies.It was difficult to draw conclusions about the effectiveness of these interventions due to poor reporting, small study size and the fact that participants with TBI were usually only a proportion of the overall total. Meta-analysis was not feasible due to the paucity of data and heterogeneity of interventions and comparator groups. Some studies concluded that the intervention they tested had beneficial effects on spasticity, and others found no difference between certain treatments. The most common adverse event was minor skin damage in people who received casting. We believe it would be misleading to provide any further description of study results given the quality of the evidence was very low for all outcomes. AUTHORS' CONCLUSIONS: The very low quality and limited amount of evidence about the management of spasticity in people with TBI means that we are uncertain about the effectiveness or harms of these interventions. Well-designed and adequately powered studies using functional outcome measures to test the interventions used in clinical practice are needed.

Poor methodological quality and reporting standards of systematic reviews in burn care management.

The methodological and reporting quality of burn-specific systematic reviews has not been established. The aim of this study was to evaluate the methodological quality of systematic reviews in burn care management. Computerised searches were performed in Ovid MEDLINE, Ovid EMBASE and The Cochrane Library through to February 2016 for systematic reviews relevant to burn care using medical subject and free-text terms such as 'burn', 'systematic review' or 'meta-analysis'. Additional studies were identified by hand-searching five discipline-specific journals. Two authors independently screened papers, extracted and evaluated methodological quality using the 11-item A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool and reporting quality using the 27-item Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Characteristics of systematic reviews associated with methodological and reporting quality were identified. Descriptive statistics and linear regression identified features associated with improved methodological quality. A total of 60 systematic reviews met the inclusion criteria. Six of the 11 AMSTAR items reporting on 'a priori' design, duplicate study selection, grey literature, included/excluded studies, publication bias and conflict of interest were reported in less than 50% of the systematic reviews. Of the 27 items listed for PRISMA, 13 items reporting on introduction, methods, results and the discussion were addressed in less than 50% of systematic reviews. Multivariable analyses showed that systematic reviews associated with higher methodological or reporting quality incorporated a meta-analysis (AMSTAR regression coefficient 2.1; 95% CI: 1.1, 3.1; PRISMA regression coefficient 6·3; 95% CI: 3·8, 8·7) were published in the Cochrane library (AMSTAR regression coefficient 2·9; 95% CI: 1·6, 4·2; PRISMA regression coefficient 6·1; 95% CI: 3·1, 9·2) and included a randomised control trial (AMSTAR regression coefficient 1·4; 95%CI: 0·4, 2·4; PRISMA regression coefficient 3·4; 95% CI: 0·9, 5·8). The methodological and reporting quality of systematic reviews in burn care requires further improvement with stricter adherence by authors to the PRISMA checklist and AMSTAR tool.

The efficacy of hydrogel dressings as a first aid measure for burn wound management in the pre-hospital setting: a systematic review of the literature.

The aim of this systematic review was to determine the supporting evidence for the clinical use of hydrogel dressings as a first aid measure for burn wound management in the pre-hospital setting. Two authors searched three databases (Ovid Medline, Ovid Embase and The Cochrane Library) for relevant English language articles published through September 2014. Reference lists, conference proceedings and non-indexed academic journals were manually searched. A separate search was conducted using the Internet search engine Google to source additional studies from burns advisory agencies, first aid bodies, military institutions, manufacturer and paramedic websites. Two authors independently assessed study eligibility and relevance of non-traditional data forms for inclusion. Studies were independently assessed and included if Hydrogel-based burn dressings (HBD) were examined in first aid practices in the pre-hospital setting. A total of 129 studies were considered for inclusion, of which no pre-hospital studies were identified. The review highlights that current use of HBD in the pre-hospital setting appears to be driven by sources of information that do not reflect the paramedic environment. We recommend researchers in the pre-hospital settings undertake clinical trials in this field. More so, the review supports the need for expert consensus to identify key demographic, clinical and injury outcomes for clinicians and researchers undertaking further research into the use of dressings as a first aid measure.

Normobaric and hyperbaric oxygen therapy for the treatment and prevention of migraine and cluster headache.

BACKGROUND: Migraine and cluster headaches are severe and disabling. Migraine affects up to 18% of women, while cluster headaches are much less common (0.2% of the population). A number of acute and prophylactic therapies are available. Hyperbaric oxygen therapy (HBOT) is the therapeutic administration of 100% oxygen at environmental pressures greater than one atmosphere, while normobaric oxygen therapy (NBOT) is oxygen administered at one atmosphere. This is an updated version of the original Cochrane review published in Issue 3, 2008 under the title 'Normobaric and hyperbaric oxygen for migraine and cluster headache'. OBJECTIVES: To examine the efficacy and safety of normobaric oxygen therapy (NBOT) and hyperbaric oxygen therapy (HBOT) in the treatment and prevention of migraine and cluster headache. SEARCH METHODS: We updated searches of the following databases up to 15 June 2015: CENTRAL (the Cochrane Library), MEDLINE, EMBASE, and CINAHL. For the original review we searched the following databases up to May 2008: CENTRAL, MEDLINE, EMBASE, CINAHL, DORCTIHM, and reference lists from relevant articles. We handsearched relevant journals and contacted researchers to identify trials. SELECTION CRITERIA: Randomised controlled trials comparing HBOT or NBOT with one another, other active therapies, placebo (sham) interventions, or no treatment in participants with migraine or cluster headache. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data and assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: In this update, we included 11 trials with 209 participants. Five trials (103 participants) compared HBOT versus sham therapy for acute migraine, three trials compared NBOT to sham therapy or ergotamine tartrate for cluster headache (145 participants), two trials evaluated HBOT for cluster headache (29 participants), and one trial (56 participants) compared NBOT to sham for a mixed group of headache. The risk of bias varied considerably across these trials but in general trial quality was poor to moderate. One trial may not have been truly randomised and two included studies were reported as abstracts only. Seven trials did not indicate allocation concealment or randomisation method. Notably, 10 of the 11 trials used a sham comparator therapy and masked the outcome assessor to allocation.We pooled data from three trials, which suggested that HBOT was effective in relieving migraine headaches compared to sham therapy (risk ratio (RR) 6.21, 95% CI 2.41 to 16.00; 58 participants, three trials). The quality of evidence was low, having been downgraded for small crossover studies with incomplete reporting. There was no evidence that HBOT could prevent migraine episodes, reduce the incidence of nausea and vomiting, or reduce the requirement for rescue medication. There was no evidence that HBOT was effective for the termination of cluster headache (RR 11.38, 95% CI 0.77 to 167.85; P = 0.08) (one trial), but this trial had low power.NBOT was effective in terminating cluster headache compared to sham in a single small study (RR 7.88, 95% CI 1.13 to 54.66), but not superior to ergotamine administration in another small trial (RR 1.17, 95% CI 0.94 to 1.46; P = 0.16). A third trial reported a statistically significant difference in the proportion of attacks successfully treated with oxygen (117 of 150 attacks were successfully treated with NBOT (78%) versus 30 of 148 attacks treated with NBOT (20%)). The proportion of responders was consistent across these three trials, and suggested more than 75% of headaches were likely to respond to NBOT.No serious adverse events during HBOT or NBOT were reported. AUTHORS' CONCLUSIONS: Since the last version of this review, two new included studies have provided additional information to change the conclusions. There was some evidence that HBOT was effective for the termination of acute migraine in an unselected population, and some evidence that NBOT was similarly effective in cluster headache. Given the cost and poor availability of HBOT, more research should be done on patients unresponsive to standard therapy. NBOT is cheap, safe, and easy to apply, so will probably continue to be used despite the limited evidence in this review.

Effectiveness and risks of cricoid pressure during rapid sequence induction for endotracheal intubation.

BACKGROUND: Rapid sequence induction (RSI) for endotracheal intubation is a technique widely used in anaesthesia, emergency and intensive care medicine to secure an airway in patients deemed at risk of pulmonary aspiration. Cricoid pressure is conceptually used to reduce the risk of aspiration by compressing the oesophagus. OBJECTIVES: To identify and evaluate all randomized controlled trials (RCTs) involving participants undergoing elective or emergency airway management via RSI and compare participants who have cricoid pressure administered with participants who do not have cricoid pressure administered. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 4), MEDLINE via OvidSP (1946 to May 2015), EMBASE via OvidSP (1980 to May 2015), ISI Web of Science (from 1940 to May 2015) and CINAHL via EBSCOhost (1982 to May 2015). SELECTION CRITERIA: We included all RCTs comparing people undergoing RSI who have cricoid pressure applied, either intermittently or continuously, with people undergoing RSI who do not have cricoid pressure applied in the context of endotracheal intubation using a direct laryngoscopic technique. We included both elective and emergency cases. We included studies of blinded and unblinded participants. Participants (male or female) were involved in any type of procedure where general anaesthetic utilizing RSI or emergency airway management utilizing RSI and endotracheal intubation was undertaken. We expected the control arm to be the absence of cricoid pressure at any stage during RSI. The primary outcome of interest was the reported event rate or prevalence of aspiration determined by a) documented gastric aspiration determined by visual inspection of aspirated stomach contents on laryngoscopy; b) pepsin detection in tracheal aspirate using the Ufberg method; c) post-anaesthetic radiographic changes suggestive of aspiration pneumonitis or d) any combination of a to c. Secondary outcomes of interest included documented impaired visualization of the airway by a treating laryngoscopist, force applied during cricoid pressure, the direction of application of force of applied cricoid pressure, independent risk factors for aspiration and whether the person applying cricoid pressure had previously done so in an emergency airway context. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts of all the studies obtained from the search using recognition of words such as 'cricoid pressure', 'rapid sequence intubation', 'emergency airway management' and 'aspiration'. Two authors independently determined the study inclusion by using a study eligibility form that we developed for the purpose of this review. We also reported the decisions regarding inclusion and exclusion in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. We assumed that studies that did not describe the use of RSI in their title, abstract or methodology used an alternative method of anaesthetic induction or emergency airway management and thus we excluded them. Data extracted from included studies comprised study characteristics, participant demographics, intervention and comparison details plus outcome measures and results. We contacted primary authors of studies with missing or unreported but potentially relevant data to obtain missing data. MAIN RESULTS: Of 493 records that we identified from databases as a result of the search (excluding duplicates), we regarded 70 abstracts/titles as potentially relevant studies. Independent scrutiny of these 70 titles and abstracts identified 29 potentially relevant studies. Of the 29 potentially relevant studies, one study met the criteria for inclusion. This study was a RCT that compared participants undergoing RSI and endotracheal intubation in the context of elective surgery requiring a general anaesthetic. Forty participants were recruited, 20 of whom had cricoid pressure applied and 20 of whom had cricoid pressure simulated. The main outcomes reported were systolic arterial pressure and heart rate after laryngoscopy and tracheal intubation. We did not consider these outcomes relevant for the purposes of this systematic review. The search also identified one study that could potentially be included in an updated systematic review in the future, but was at the time of the search a proposal for a trial only and had no reported outcomes at this time. AUTHORS' CONCLUSIONS: There is currently no information available from published RCTs on clinically relevant outcome measures with respect to the application of cricoid pressure during RSI in the context of endotracheal intubation. On the basis of the findings of non-RCT literature, however, cricoid pressure may not be necessary to undertake RSI safely, and therefore well-designed and conducted RCTs should nonetheless be encouraged to properly assess the safety and effectiveness of cricoid pressure.

Interventions for reducing wrong-site surgery and invasive clinical procedures.

BACKGROUND: Specific clinical interventions are needed to reduce wrong-site surgery, which is a rare but potentially disastrous clinical error. Risk factors contributing to wrong-site surgery are variable and complex. The introduction of organisational and professional clinical strategies have a role in minimising wrong-site surgery. OBJECTIVES: To evaluate the effectiveness of organisational and professional interventions for reducing wrong-site surgery (including wrong-side, wrong-procedure and wrong-patient surgery), including non-surgical invasive clinical procedures such as regional blocks, dermatological, obstetric and dental procedures and emergency surgical procedures not undertaken within the operating theatre. SEARCH METHODS: For this update, we searched the following electronic databases: the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register (January 2014), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2014), MEDLINE (June 2011 to January 2014), EMBASE (June 2011 to January 2014), CINAHL (June 2011 to January 2014), Dissertations and Theses (June 2011 to January 2014), African Index Medicus, Latin American and Caribbean Health Sciences database, Virtual Health Library, Pan American Health Organization Database and the World Health Organization Library Information System. Database searches were conducted in January 2014. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs), non-randomised controlled trials, controlled before-after studies (CBAs) with at least two intervention and control sites, and interrupted-time-series (ITS) studies where the intervention time was clearly defined and there were at least three data points before and three after the intervention. We included two ITS studies that evaluated the effectiveness of organisational and professional interventions for reducing wrong-site surgery, including wrong-side and wrong-procedure surgery. Participants included all healthcare professionals providing care to surgical patients; studies where patients were involved to avoid the incorrect procedures or studies with interventions addressed to healthcare managers, administrators, stakeholders or health insurers. DATA COLLECTION AND ANALYSIS: Two review authors independently assesses the quality and abstracted data of all eligible studies using a standardised data extraction form, modified from the Cochrane EPOC checklists. We contacted study authors for additional information. MAIN RESULTS: In the initial review, we included one ITS study that evaluated a targeted educational intervention aimed at reducing the incidence of wrong-site tooth extractions. The intervention included examination of previous cases of wrong-site tooth extractions, educational intervention including a presentation of cases of erroneous extractions, explanation of relevant clinical guidelines and feedback by an instructor. Data were reported from all patients on the surveillance system of a University Medical centre in Taiwan with a total of 24,406 tooth extractions before the intervention and 28,084 tooth extractions after the intervention. We re-analysed the data using the Prais-Winsten time series and the change in level for annual number of mishaps was statistically significant at -4.52 (95% confidence interval (CI) -6.83 to -2.217) (standard error (SE) 0.5380). The change in slope was statistically significant at -1.16 (95% CI -2.22 to -0.10) (SE 0.2472; P < 0.05).This update includes an additional study reporting on the incidence of neurological WSS at a university hospital both before and after the Universal Protocol's implementation. A total of 22,743 patients undergoing neurosurgical procedures at the University of Illionois College of Medicine at Peoria, Illinois, United States of America were reported. Of these, 7286 patients were reported before the intervention and 15,456 patients were reported after the intervention. The authors found a significant difference (P < 0.001) in the incidence of WSS between the before period, 1999 to 2004, and the after period, 2005 to 2011.  Similarly, data were re-analysed using Prais-Winsten regression to correct for autocorrelation. As the incidences were reported by year only and the intervention occurred in July 2004, the intervention year 2004 was excluded from the analysis. The change in level at the point the intervention was introduced was not statistically significant at -0.078 percentage points (pp) (95% CI -0.176 pp to 0.02 pp; SE 0.042; P = 0.103). The change in slope was statistically significant at 0.031 (95% CI 0.004 to 0.058; SE 0.012; P < 0.05). AUTHORS' CONCLUSIONS: The findings of this update added one additional ITS study to the previous review which contained one ITS study. The original review suggested that the use of a specific educational intervention in the context of a dental outpatient setting, which targets junior dental staff using a training session that included cases of wrong-site surgery, presentation of clinical guidelines and feedback by an instructor, was associated with a reduction in the incidence of wrong-site tooth extractions. The additional study in this update evaluated the annual incidence rates of wrong-site surgery in a neurosurgical population before and after the implementation of the Universal Protocol. The data suggested a strong downward trend in the incidence of wrong-site surgery prior to the intervention with the incidence rate approaching zero. The effect of the intervention in these studies however remains unclear, as data reflect only two small low-quality studies in very specific population groups.

Synthetic devices for reconstructive surgery of the cruciate ligaments: a systematic review.

PURPOSE: The role of synthetic devices in the management of the cruciate ligament-injured knee remains controversial. The aim of this systematic review was to assess the safety and efficacy of synthetic devices in cruciate ligament surgery. METHODS: A systematic review of the electronic databases Medline, Embase, and The Cochrane Library (issue 1, 2014) on January 13, 2014, was performed to identify controlled and uncontrolled trials. Trials that assessed the safety and efficacy of synthetic devices for cruciate ligament surgery were included. The main variables assessed included rates of failure, revision, and noninfective effusion and synovitis. Patient-reported outcome assessments and complications were also assessed where reported. RESULTS: From 511 records screened, we included 85 articles published between 1985 and 2013 reporting on 6 synthetic devices (ligament augmentation and reconstruction system [Ligament Augmentation and Reconstruction System (LARS; Surgical Implants and Devices, Arc-sur-Tille, France)]; Leeds-Keio [Xiros (formerly Neoligaments), Leeds, England]; Kennedy ligament augmentation device [3M, St Paul, MN]; Dacron [Stryker, Kalamazoo, MI]; Gore-Tex [W.L. Gore and Associates, Flagstaff, AZ]; and Trevira [Telos (limited liability company), Marburg, Germany]). The heterogeneity of the included studies precluded meta-analysis. The results were analyzed by device and then type of reconstruction (anterior cruciate ligament [ACL]/posterior cruciate ligament [PCL]/combined ACL and PCL). The lowest cumulative rates of failure were seen with the LARS device (2.6% for ACL and 1% for PCL surgery). The highest failure rate was seen in the Dacron ACL group (cumulative rate, 33.6%). Rates of noninfective synovitis and effusion ranged from 0.2% in the LARS ACL group to 27.6% in the Gore-Tex ACL group. Revision rates ranged from 2.6% (LARS) to 11.8% (Trevira-Hochfest; Telos). Recent designs, specifically the LARS, showed good improvement in the outcome scores. The mean preoperative and postoperative Lysholm knee scores were 54 and 88, respectively; the mean preoperative and postoperative Tegner activity scale scores were 3.3 and 6, respectively. CONCLUSIONS: Preliminary results for newer-generation devices, specifically the LARS, show lower reported rates of failure, revision, and sterile effusion/synovitis when compared with older devices. LEVEL OF EVIDENCE: Level IV, systematic review of Level II through IV studies.

Bone grafts and bone substitutes for opening-wedge osteotomies of the knee: a systematic review.

PURPOSE: To establish the rate of use of various void fillers in the setting of opening-wedge osteotomy around the knee, the types of fixation used, and the rates of delayed union or nonunion related to these variables. In addition, this review addressed short-term to midterm outcomes and complication rates associated with such procedures. METHODS: The electronic databases Medline, Embase, and PubMed were searched using the methodology for systematic review as recommended by the Cochrane Collaboration. The search terms used were as follows: knee, osteotomy, knee joint, bone grafting, opening osteotomy, opening wedge, tibial osteotomy, femoral osteotomy, and bone substitute. We screened 1,383 articles and applied exclusion criteria. Fifty-six articles were included. RESULTS: We included 3,033 cases of osteotomy in 2,910 patients. The mean age of patients was 50 years, with a mean follow-up period of 42 months. Male patients comprised 52% of patients. The mean alignment change was 10.8°, shifting the mechanical axis to 5.1° valgus. Delayed union/nonunion rates were 2.6%, 4.6%, and 4.5% for autograft, allograft bone, and synthetic bone substitutes, respectively (P = .03). Delayed union/nonunion rates were significantly lower for autograft compared with allograft (P = .03) and for autograft and allograft compared with synthetic bone substitutes (P < .0001). Non-locking plates (n = 2,148) had a rate of delayed union/nonunion of 3.7% and a mean loss of correction over time of 0.5°. Locking plates (n = 681) had a rate of delayed union/nonunion of 2.6% and a loss of correction of 2.3°. All mean knee outcome scores improved, and an overall complication rate of 14% was found. CONCLUSIONS: Opening-wedge osteotomy had good short-term to midterm outcomes with acceptable complication rates. The lowest rates of delayed union/nonunion were in autograft bone-filled osteotomies. Plate type does not appear to affect osteotomy union or loss of correction. LEVEL OF EVIDENCE: Level IV, systematic review of Level I to IV studies.

Inpatient management of pyoderma gangrenosum: treatments, outcomes, and clinical implications.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare, ulcerative neutrophilic skin condition of unknown etiology. The disease continues to pose therapeutic challenges, with ongoing controversy regarding the role of surgery. METHODS: A retrospective medical records review was conducted for 29 patients who were diagnosed and treated for PG at an Australian tertiary center over 10 years, from 1 January 2000 to 31 December 2010. RESULTS: A total of 29 patients had a diagnosis of PG, with a total of 35 admissions. Nearly all patients had immunosuppressant therapy and 10 (35%) patients underwent surgery. Eight (28%) received hyperbaric oxygen therapy. Complications secondary to medical therapy occurred in 23 (66%) of admissions, with the commonest being poor blood sugar control in patients with diabetes (n = 6, 17%) and steroid-induced diabetes (n = 5, 14%). At discharge, 21 (72%) patients' ulcers had improved and there were 4 (14%) inpatient deaths. At 6 months, 3 of 10 cases with available follow-up showed complete ulcer healing. Most of the patients (n = 8, 80%) who underwent combined medical and surgical therapy had ulcers that had either completely healed or improved at 6 months after discharge. All 3 patients who underwent split skin grafting under immunosuppressive cover (with 2 having hyperbaric oxygen therapy) had no postoperative graft failure or pathergy. CONCLUSIONS: Pyoderma gangrenosum remains a therapeutic challenge, with significant complications and morbidity from long-term medical treatment. Surgery should be considered in conjunction with combined hyperbaric and immunosuppressive therapy once the disease is quiescent, to reduce disease-related comorbidity as well as the consequent adverse effects of long-term immunosuppressant therapy.

Stacked abdominal flap for unilateral breast reconstruction.

BACKGROUND: The abdominal flap can be used in a stacked, double-pedicle configuration for unilateral breast reconstruction. Aided by preoperative mapping, this is a good option when a single-pedicle flap is deemed unsuitable. We present reliable outcomes using the stacked flap and a logical classification system for its use. METHODS: From 2008 to 2013, 18 patients underwent a stacked abdominal flap for unilateral breast reconstruction. Flaps utilized deep inferior epigastric (D) and superficial inferior epigastric (S) pedicle combinations. Preoperative computed tomography angiogram was performed on all patients. Medical records were reviewed for complications and clinical data, and a thorough clinical evaluation was performed on all patients at follow-up. Flaps were all double-pedicled, with the secondary pedicle anastomosed onto the primary pedicle (type 1 to 3) or onto a second recipient vessel (type 4). Flaps were then classified into groups, based on pedicle dominance and intraflap anastomosis. RESULTS: Twelve reconstructions were immediate and six delayed. Mean operative time was 7 hours, the most frequently used configuration being a type 1 DD, that is, secondary pedicle (D) anastomosed end-to-end onto the superior continuation of the primary pedicle (D). Average hospital stay was 6 days. There were no flap losses and minimal complications, and mean follow-up was 20 months. CONCLUSION: Use of this flap poses a greater challenge to the microsurgical breast reconstruction. We demonstrate its reliable use in women deemed unsuitable for a single-pedicle flap. Our structured system clarifies vascular options, and preoperative perforator mapping tools are essential to the success of this technique.

Use of methodological tools for assessing the quality of studies in periodontology and implant dentistry: a systematic review.

OBJECTIVE: To evaluate the methodological approaches used to assess the quality of studies included in systematic reviews (SRs) in periodontology and implant dentistry. MATERIALS & METHODS: Two electronic databases (PubMed and Cochrane Database of Systematic Reviews) were searched independently to identify SRs examining interventions published through 2 September 2013. The reference lists of included SRs and records of 10 specialty dental journals were searched manually. Methodological approaches were assessed using seven criteria based on the Cochrane Handbook for Systematic Reviews of Interventions. Temporal trends in methodological quality were also explored. RESULTS: Of the 159 SRs with meta-analyses included in the analysis, 44 (28%) reported the use of domain-based tools, 15 (9%) reported the use of checklists and 7 (4%) reported the use of scales. Forty-two (26%) SRs reported use of more than one tool. Criteria were met heterogeneously; authors of 15 (9%) publications incorporated the quality of evidence of primary studies into SRs, whereas 69% of SRs reported methodological approaches in the Materials/Methods section. Reporting of four criteria was significantly better in recent (2010-2013) than in previous publications. CONCLUSION: The analysis identified several methodological limitations of approaches used to assess evidence in studies included in SRs in periodontology and implant dentistry.

Preoperative education for hip or knee replacement.

BACKGROUND: Hip or knee replacement is a major surgical procedure that can be physically and psychologically stressful for patients. It is hypothesised that education before surgery reduces anxiety and enhances clinically important postoperative outcomes. OBJECTIVES: To determine whether preoperative education in people undergoing total hip replacement or total knee replacement improves postoperative outcomes with respect to pain, function, health-related quality of life, anxiety, length of hospital stay and the incidence of adverse events (e.g. deep vein thrombosis). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (2013, Issue 5), MEDLINE (1966 to May 2013), EMBASE (1980 to May 2013), CINAHL (1982 to May 2013), PsycINFO (1872 to May 2013) and PEDro to July 2010. We handsearched the Australian Journal of Physiotherapy (1954 to 2009) and reviewed the reference lists of included trials and other relevant reviews. SELECTION CRITERIA: Randomised or quasi-randomised trials of preoperative education (verbal, written or audiovisual) delivered by a health professional within six weeks of surgery to people undergoing hip or knee replacement compared with usual care. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We analysed dichotomous outcomes using risk ratios. We combined continuous outcomes using mean differences (MD) or standardised mean differences (SMD) with 95% confidence intervals (CI). Where possible, we pooled data using a random-effects meta-analysis. MAIN RESULTS: We included 18 trials (1463 participants) in the review. Thirteen trials involved people undergoing hip replacement, three involved people undergoing knee replacement and two included both people with hip and knee replacements. Only six trials reported using an adequate method of allocation concealment, and only two trials blinded participants. Few trials reported sufficient data to analyse the major outcomes of the review (pain, function, health-related quality of life, global assessment, postoperative anxiety, total adverse events and re-operation rate). There did not appear to be an effect of time on any outcome, so we chose to include only the latest time point available per outcome in the review.In people undergoing hip replacement, preoperative education may not offer additional benefits over usual care. The mean postoperative anxiety score at six weeks with usual care was 32.16 on a 60-point scale (lower score represents less anxiety) and was 2.28 points lower with preoperative education (95% confidence interval (CI) -5.68 to 1.12; 3 RCTs, 264 participants, low-quality evidence), an absolute risk difference of -4% (95% CI -10% to 2%). The mean pain score up to three months postoperatively with usual care was 3.1 on a 10-point scale (lower score represents less pain) and was 0.34 points lower with preoperative education (95% CI -0.94 to 0.26; 3 RCTs, 227 participants; low-quality evidence), an absolute risk difference of -3% (95% CI -9% to 3%). The mean function score at 3 to 24 months postoperatively with usual care was 18.4 on a 68-point scale (lower score represents better function) and was 4.84 points lower with preoperative education (95% CI -10.23 to 0.66; 4 RCTs, 177 participants; low-quality evidence), an absolute risk difference of -7% (95% CI -15% to 1%). The number of people reporting adverse events, such as infection and deep vein thrombosis, did not differ between groups, but the effect estimates are uncertain due to very low quality evidence (23% (17/75) reported events with usual care versus 18% (14/75) with preoperative education; risk ratio (RR) 0.79; 95% CI 0.19 to 3.21; 2 RCTs, 150 participants). Health-related quality of life, global assessment of treatment success and re-operation rates were not reported.In people undergoing knee replacement, preoperative education may not offer additional benefits over usual care. The mean pain score at 12 months postoperatively with usual care was 80 on a 100-point scale (lower score represents less pain) and was 2 points lower with preoperative education (95% CI -3.45 to 7.45; 1 RCT, 109 participants), an absolute risk difference of -2% (95% CI -4% to 8%). The mean function score at 12 months postoperatively with usual care was 77 on a 100-point scale (lower score represents better function) and was no different with preoperative education (0; 95% CI -5.63 to 5.63; 1 RCT, 109 participants), an absolute risk difference of 0% (95% CI -6% to 6%). The mean health-related quality of life score at 12 months postoperatively with usual care was 41 on a 100-point scale (lower score represents worse quality of life) and was 3 points lower with preoperative education (95% CI -6.38 to 0.38; 1 RCT, 109 participants), an absolute risk difference of -3% (95% CI -6% to 1%). The number of people reporting adverse events, such as infection and deep vein thrombosis, did not differ between groups (18% (11/60) reported events with usual care versus 13% (7/55) with preoperative education; RR 0.69; 95% CI 0.29 to 1.66; 1 RCT, 115 participants), an absolute risk difference of -6% (-19% to 8%). Global assessment of treatment success, postoperative anxiety and re-operation rates were not reported. AUTHORS' CONCLUSIONS: Although preoperative education is embedded in the consent process, we are unsure if it offers benefits over usual care in terms of reducing anxiety, or in surgical outcomes, such as pain, function and adverse events. Preoperative education may represent a useful adjunct, with low risk of undesirable effects, particularly in certain patients, for example people with depression, anxiety or unrealistic expectations, who may respond well to preoperative education that is stratified according to their physical, psychological and social need.

Intravenous lidocaine for the treatment of background or procedural burn pain.

BACKGROUND: This is an update of the review on "Lidocaine for pain relief in burn injured patients" first published in Issue 3, 2007, and first updated in 2012. Pain is a major issue for people with many different types of wounds, in particular those people with burn injuries. Prompt, aggressive use of opioid analgesics such as morphine has been suggested as critical to avert the cycle of pain and anxiety, but adverse effects are encountered. It has been proposed that newer agents such as lidocaine could be effective in reducing pain and alleviating the escalating opioid dosage requirements in people with burn injury. OBJECTIVES: To assess the safety and effectiveness of intravenous lidocaine as a means of pain relief versus no therapy, placebo, other drugs, or a combination of these therapies in people with burn injury. SEARCH METHODS: For this third update, we searched the Cochrane Central Register of Controlled Trials (Issue 11, 2013), and Ovid MEDLINE, MEDLINE in Process and Ovid EMBASE (up to December 2013). SELECTION CRITERIA: We included randomised controlled trials (RCTs) and controlled clinical trials (CCTs), published and unpublished, which assessed the efficacy of intravenous lidocaine in varying doses as a single-agent therapy with no therapy, placebo, other analgesics (such as opioids), lidocaine plus another drug, or a combination of these therapies as a means of pain relief in people with burn injury. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed the risk of bias of the studies identified. MAIN RESULTS: In this 2014 update, we found no new studies. The one small randomised double-blind placebo-controlled cross-over trial found in 2012, which included only 45 participants and compared intravenous lidocaine against placebo as a means of pain relief in people with burns still remains central to this review. We assessed this study as being at a high risk of bias due to its small size (fewer than 50 participants per treatment arm). Subjective pain ratings, as measured by the verbal rating scale, increased during procedures for both treatment arms; however, the increase was less in the lidocaine treatment group. There were no significant clinical or statistical differences regarding the effects of lidocaine and placebo on opioid requests and consumption, anxiety or level of satisfaction during a wound care procedure, but the small included study provided insufficient data to draw any conclusions. AUTHORS' CONCLUSIONS: As current clinical evidence is based on only one RCT as well as case series and reports, intravenous lidocaine must be considered a pharmacological agent under investigation in burns care, the effectiveness of which is yet to be determined with further well-designed and conducted clinical trials.

Hyperbaric oxygen therapy for acute ischaemic stroke.

Background Most cases of stroke are caused by impairment of blood flow to the brain (ischaemia), which results in a reduction in available oxygen and subsequent cell death. It has been postulated that hyperbaric oxygen therapy (HBOT) may reduce the volume of brain that will die by greatly increasing available oxygen, and it may further improve outcomes by reducing brain swelling. Some centres are using HBOT routinely to treat people with stroke. This is an update of a Cochrane Review first published in 2005.Objectives To assess the effectiveness and safety of adjunctive HBOT in the treatment of people with acute ischaemic stroke.Search methods We searched the Cochrane Stroke Group Trials Register (last searched April 2014), the Cochrane Central Register of Controlled Trials(CENTRAL) (April 2014), MEDLINE (1966 to April 2014), EMBASE (1980 to April 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to April 2014), the Database of Randomised Controlled Trials in Hyperbaric Medicine(DORCTIHM) (searched April 2014) and the reference lists of articles.We handsearched relevant publications and contacted researchers to identify additional published and unpublished studies.Selection criteria Randomised controlled trials (RCTs) that compared the effects of adjunctive HBOT versus those of no HBOT (no treatment or sham).Data collection and analysis Three review authors independently extracted data, assessed each trial for internal validity and resolved differences by discussion.Main results We included 11 RCTs involving 705 participants. The methodological quality of the trials varied. We could pool data only for case fatalities. No significant differences were noted in the case fatality rate at six months in those receiving HBOT compared with the control group (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.34 to 2.75, P value 0.96). Four of 14 scale measures of disability and functional performance indicated improvement following HBOT, for example, the mean Trouillas Disability Scale score was lower with HBOT (mean difference (MD) 2.2 point reduction with HBOT, 95% CI 0.15 to 4.3, P value 0.04), and the mean Orgogozo Scale score was higher (MD 27.9 points, 95% CI 4.0 to 51.8, P value 0.02).Authors' conclusions We found no good evidence to show that HBOT improves clinical outcomes when applied during acute presentation of ischaemic stroke. Although evidence from the 11 RCTs is insufficient to provide clear guidelines for practice, the possibility of clinical benefit has not been excluded. Further research is required to better define the role of HBOT in this condition.

Immunonutrition as an adjuvant therapy for burns.

BACKGROUND: With burn injuries involving a large total body surface area (TBSA), the body can enter a state of breakdown, resulting in a condition similar to that seen with severe lack of proper nutrition. In addition, destruction of the effective skin barrier leads to loss of normal body temperature regulation and increased risk of infection and fluid loss. Nutritional support is common in the management of severe burn injury, and the approach of altering immune system activity with specific nutrients is termed immunonutrition. Three potential targets have been identified for immunonutrition: mucosal barrier function, cellular defence and local or systemic inflammation. The nutrients most often used for immunonutrition are glutamine, arginine, branched-chain amino acids (BCAAs), omega-3 (n-3) fatty acids and nucleotides. OBJECTIVES: To assess the effects of a diet with added immunonutrients (glutamine, arginine, BCAAs, n-3 fatty acids (fish oil), combined immunonutrients or precursors to known immunonutrients) versus an isonitrogenous diet (a diet wherein the overall protein content is held constant, but individual constituents may be changed) on clinical outcomes in patients with severe burn injury. SEARCH METHODS: The search was run on 12 August 2012. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, MEDLINE (OvidSP), Embase (OvidSP), ISI WOS SCI-EXPANDED & CPCI-S and four other databases. We handsearched relevant journals and conference proceedings, screened reference lists and contacted pharmaceutical companies. We updated this search in October 2014, but the results of this updated search have not yet been incorporated. SELECTION CRITERIA: Randomised controlled trials comparing the addition of immunonutrients to a standard nutritional regimen versus an isonitrogenated diet or another immunonutrient agent. DATA COLLECTION AND ANALYSIS: Two review authors were responsible for handsearching, reviewing electronic search results and identifying potentially eligible studies. Three review authors retrieved and reviewed independently full reports of these studies for inclusion. They resolved differences by discussion. Two review authors independently extracted and entered data from the included studies. A third review author checked these data. Two review authors independently assessed the risk of bias of each included study and resolved disagreements through discussion or consultation with the third and fourth review authors. Outcome measures of interest were mortality, hospital length of stay, rate of burn wound infection and rate of non-wound infection (bacteraemia, pneumonia and urinary tract infection). MAIN RESULTS: We identified 16 trials involving 678 people that met the inclusion criteria. A total of 16 trials contributed data to the analysis. Of note, most studies failed to report on randomisation methods and intention-to-treat principles; therefore study results should be interpreted with caution. Glutamine was the most common immunonutrient and was given in seven of the 16 included studies. Use of glutamine compared with an isonitrogenous control led to a reduction in length of hospital stay (mean stay -5.65 days, 95% confidence interval (CI) -8.09 to -3.22) and reduced mortality (pooled risk ratio (RR) 0.25, 95% CI 0.08 to 0.78). However, because of the small sample size, it is likely that these results reflect a false-positive effect. No study findings suggest that glutamine has an effect on burn wound infection or on non-wound infection. All other agents investigated showed no evidence of an effect on mortality, length of stay or burn wound infection or non-wound infection rates. AUTHORS' CONCLUSIONS: Although we found evidence of an effect of glutamine on mortality reduction, this finding should be taken with care. The number of study participants analysed in this systematic review was not sufficient to permit conclusions that recommend or refute the use of glutamine. Glutamine may be effective in reducing mortality, but larger studies are needed to determine the overall effects of glutamine and other immunonutrition agents.