Cochrane Clinical Trials Register Research Articles

Living with osteoarthritis: a systematic review and meta-ethnography

Objectives: To review and synthesize the existing literature on the experience of living with a diagnosis of hip and/or knee osteoarthritis (OA).Method: A systematic review was undertaken using meta-ethnography. A search of both published (AMED, CINAHL, EMBASE, PsychINFO, SportsDisc, MEDLINE, Cochrane Clinical Trials Registry, PubMed) and unpublished/trial registry databases [World Health Organization (WHO) International Clinical Trials Registry Platform, Current Controlled Trials, the United States National Institute of Health Trials Registry, National Institute for Health Research (NIHR) Clinical Research Portfolio Database] was undertaken from their inception to 5 June 2013.Results: Thirty-two studies formed the meta-ethnography of the lived experiences of people with OA. In total, 1643 people with OA were sampled, the majority diagnosed with knee OA. The evidence base was weak to moderate in quality. The majority of studies indicated that people viewed living with OA negatively. Four key factors influenced their attitudes to the condition: the severity of their symptoms; the impact of these symptoms on their functional capability; their attitude towards understanding their disease; and their perceptions of other people’s beliefs towards their disease.Conclusions: The current literature suggests that greater knowledge of the pathology of OA, management of symptoms, promotion of functional activity for patients and their family/friends networks, and understanding to better inform OA patient’s role in society are all important elements that affect a person’s attitude to OA. By better understanding these factors during future consultations, clinicians may forge stronger relationships with their patients to more effectively manage this long-term disabling condition.

Diagnostic accuracy of noninvasive markers of liver fibrosis in patients with psoriasis taking methotrexate: a systematic review and meta-analysis

People with psoriasis taking methotrexate may be at increased risk of developing liver fibrosis compared with the general population. Noninvasive methods of detecting fibrosis have been widely adopted but their clinical utility is uncertain. To evaluate the diagnostic accuracy of noninvasive methods to detect fibrosis compared with liver biopsy (reference standard) in people with psoriasis taking methotrexate. A systematic search using Ovid/Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library and Clinical Trials Register was performed. Diagnostic cohorts or case-control studies of adults taking or being considered for methotrexate therapy were considered. Study quality was evaluated using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2). Pooled data analysis was performed using RevMan 5.1. Bayesian meta-analysis was conducted using Markov chain Monte Carlo simulation. Seventeen studies were included. Sensitivity and specificity were 38% and 83% for standard liver function tests (LFTs), 74% and 77% for procollagen-3N-terminal peptide (P3NP), 60% and 80% for Fibroscan(®) (Echosens, France, www.echosens.com), and 55% and 49% for ultrasound. Confidence in these results is limited owing to low-quality data; old, small studies displayed significant selection bias and significant variation in the prevalence of fibrosis. No studies were identified evaluating recently developed markers. The clinical utility of LFTs, P3NP and liver ultrasound is poor. Therefore if these tests are used in isolation, a significant proportion of patients with liver fibrosis may remain unidentified. Larger prospective studies are required in this population to validate newer non-invasive methods.

The effects of lysine analogs during pelvic surgery: a systematic review and meta-analysis.

Pelvic vasculature is complex and inconsistent while pelvic bones impede access to pelvic organs. These anatomical characteristics render pelvic surgery inherently difficult, and some of these procedures are frequently associated with blood loss that necessitates blood transfusion. The aim of this study was to review the literature on the use of lysine analogs to prevent bleeding and blood transfusion during pelvic surgery. The objective of this study was to assess the safety and efficacy of lysine analogs during pelvic surgery. A systematic literature search was performed using Medline, Cochrane Register of Clinical Trials, Embase, and the reference lists of relevant articles. Randomized controlled trials or observational cohort studies comparing a lysine analog to placebo or standard care were included. Outcomes collected were blood transfusion, blood loss, thromboembolic adverse events (myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism), nonthromboembolic adverse events, and death. There were no language limitations. Fifty-six articles reported on 68 comparisons between a lysine analog and an inactive comparator, involving a total of 7244 patients published between 1961 and 2013. Thirty-nine studies evaluated urologic procedures, and 21 evaluated gynecologic procedures. Thirty-six studies (60%) were published before 1980. Of the 43 randomized comparisons, only 30 (44%) had a score of 3 or higher on Jadad's 5-point scale of methodological quality. Among randomized trials, lysine analogs reduced the risk of blood transfusion (pooled odds ratio [OR], 0.47; 95% confidence interval [CI], 0.35-0.64) and blood loss (pooled OR, 0.22; 95% CI, 0.18-0.27). There was a small statistically insignificant increased risk of thromboembolic events (pooled OR, 1.07; 95% CI, 0.72-1.59) and no-thrombotic serious adverse events (pooled OR, 1.11; 95% CI, 0.67-1.83). In the 17 randomized trials published since the year 2000, only 6 thrombotic events were reported, 4 of which occurred in the placebo arm. Lysine analogs did not increase risk of death (pooled OR, 0.91; 95% CI, 0.34-2.48). These results are significant as they indicate that lysine analogs significantly reduce blood loss and blood transfusion during pelvic surgery. Although there does not appear to be a large increase in the risk of thromboembolic and nonthrombotic adverse events, more data are required to definitively assess these outcomes. Based on this review, lysine analogs during pelvic surgery seem to reduce bleeding and blood transfusion requirements. Although there does not seem to be a significant risk of adverse effects, larger studies would help clarify risks, if any, associated with lysine analog use.

Lower-dose diclofenac capsules developed using solumatrix fine particle technology result in clinically meaningful improvements in pain in a phase 3 study of patients with osteoarthritis

Lower-dose diclofenac capsules developed using solumatrix fine particle technology result in clinically meaningful improvements in pain in a phase 3 study of patients with osteoarthritis

The Role of Mechanical Bowel Preparation before Ileal Urinary Diversion: A Systematic Review and Meta-Analysis

Background: Although the use of mechanical bowel preparation (MBP) is still widely promoted as the dogma before patients undergo ileal urinary diversion, an increasing number of clinical trials have suggested that there is no benefit. Thus, we performed a meta-analysis to evaluate the efficacy of MBP in ileal urinary diversion surgery. Methods: A literature search was performed in electronic databases, including PubMed, Embase, Science Citation Index Expanded as well as the Cochrane Library and the Cochrane Clinical Trials Registry, from 1966 to January 1, 2013. Clinical trials comparing outcomes of MBP versus no MBP for ileal urinary diversion surgery were included in the meta-analysis. Pooled odds ratios with 95% confidence intervals were calculated using the fixed- or random-effects models. Results: In total, two randomized controlled trials and five cohort studies were included in this meta-analysis. The primary outcomes, such as bowel leak and bowel obstruction, showed no statistical difference between the two groups. Additionally, the overall mortality rate and death rate related to operation also manifested that MBP does not offer an advantage over the no MBP. Conclusion: This meta-analysis suggests that MBP does not reduce the incidence of perioperative complications in urinary diversion compared with no MBP. However, large randomized controlled clinical trials are needed to confirm this finding.

Effect of B-type natriuretic peptide-guided treatment of chronic heart failure on total mortality and hospitalization: an individual patient meta-analysis

AimsNatriuretic peptide-guided (NP-guided) treatment of heart failure has been tested against standard clinically guided care in multiple studies, but findings have been limited by study size. We sought to perform an individual patient data meta-analysis to evaluate the effect of NP-guided treatment of heart failure on all-cause mortality.Methods and resultsEligible randomized clinical trials were identified from searches of Medline and EMBASE databases and the Cochrane Clinical Trials Register. The primary pre-specified outcome, all-cause mortality was tested using a Cox proportional hazards regression model that included study of origin, age (<75 or ≥75 years), and left ventricular ejection fraction (LVEF, ≤45 or >45%) as covariates. Secondary endpoints included heart failure or cardiovascular hospitalization. Of 11 eligible studies, 9 provided individual patient data and 2 aggregate data. For the primary endpoint individual data from 2000 patients were included, 994 randomized to clinically guided care and 1006 to NP-guided care. All-cause mortality was significantly reduced by NP-guided treatment [hazard ratio = 0.62 (0.45–0.86); P = 0.004] with no heterogeneity between studies or interaction with LVEF. The survival benefit from NP-guided therapy was seen in younger (<75 years) patients [0.62 (0.45–0.85); P = 0.004] but not older (≥75 years) patients [0.98 (0.75–1.27); P = 0.96]. Hospitalization due to heart failure [0.80 (0.67–0.94); P = 0.009] or cardiovascular disease [0.82 (0.67–0.99); P = 0.048] was significantly lower in NP-guided patients with no heterogeneity between studies and no interaction with age or LVEF.ConclusionNatriuretic peptide-guided treatment of heart failure reduces all-cause mortality in patients aged <75 years and overall reduces heart failure and cardiovascular hospitalization.

Predictors of chronic ankle instability after an index lateral ankle sprain: A systematic review

To identify the predictors of chronic ankle instability after an index lateral ankle sprain. Systematic review. The databases of MEDLINE, CINAHL, AMED, Scopus, SPORTDiscus, Embase, Web of Science, PubMed, PEDro, and Cochrane Register of Clinical Trials were searched from the earliest record until May 2013. Prospective studies investigating any potential intrinsic predictors of chronic ankle instability after an index ankle sprain were included. Eligible studies had a prospective design (follow-up of at least three months), participants of any age with an index ankle sprain, and had assessed ongoing impairments associated with chronic ankle instability. Eligible studies were screened and data extracted by two independent reviewers. Four studies were included. Three potential predictors of chronic ankle instability, i.e., postural control, perceived instability, and severity of the index sprain, were investigated. Decreased postural control measured by number of foot lifts during single-leg stance with eyes closed and perceived instability measured by Cumberland Ankle Instability Tool were not predictors of chronic ankle instability. While the results of one study showed that the severity of the initial sprain was a predictor of re-sprain, another study did not. Of the three investigated potential predictors of chronic ankle instability after an index ankle sprain, only severity of initial sprain (grade II) predicted re-sprain. However, concerns about validity of the grading system suggest that these findings should be interpreted with caution.

Intra-articular infiltration therapy for patients with glenohumeral osteoarthritis: A systematic review of the literature.

Background:Conservative treatments are especially in patients with glenohumeral osteoarthritis (GH-OA) important, since shoulder arthroplasty has its limitations. In this systematic review, we will evaluate the current evidence regarding the efficacy of intra-articular (IA) infiltration treatment options in patients with GH-OA.Materials and Methods:The following databases are searched: Pubmed/Medline, Cochrane Clinical Trial Register, Embase and the WHO clinical trial register. All IA injection products used for the treatment of shoulder OA in humans are included.Results:A total of 8 studies could be included in this review. Hyaluronic acid (HA) showed effect sizes of 2.07, 2.02 and 2.11 at 6, 12 and 26 weeks follow-up, respectively. Placebo (1.60, 1.82 and 1.68) also showed stable effect sizes at the same time points. The efficacy of corticosteroids (CS) decreased rapidly at follow-up (1.08, 0.43 and 0.19). Although statistical significant, the maximum difference in effect sizes between HA and placebo was only 0.43 with absolute values between 2.0 and 6.4 on a 100-point visual analogue score for pain.Conclusion:IA treatment with HA has a good efficacy at follow-up compared to baseline. However, the difference in efficacy between HA and placebo never reaches the minimal clinically important difference at any of the follow-up points. We are not able to give clear recommendations for the use of IA CS injections in patients with GH-OA. In future research, we recommend focusing on sufficiently powered randomized trials to compare the efficacies of HA, CS, placebo and other IA treatment options in patients with GH-OA.

Attitudes of people with osteoarthritis towards their conservative management: a systematic review and meta-ethnography

This paper determines the perceptions of people diagnosed with osteoarthritis towards their conservative management strategies. A systematic review of the published (AMED, CINAHL, EMBASE, PsychINFO, SportsDisc, MEDLINE, Cochrane Clinical Trials Registry, PubMed) and unpublished/trial registry databases (WHO International Clinical Trials Registry Platform, Current Controlled Trials, the United States National Institute of Health Trials Registry, NIHR Clinical Research Portfolio Database) searched from their inception to July 2013. Eligible studies included those which presented the attitudes or perceptions of people with osteoarthritis towards non-operative management strategies. Study quality was appraised using the CASP and the Gough's weight of evidence appraisal tools. Data were analysed through a meta-ethnography approach. Thirty-three studies including 1,314 people with osteoarthritis were sampled; the majority diagnosed with knee osteoarthritis. The overarching themes indicated people with osteoarthritis delay their diagnosis, opting for self-management and informal information gathering. This informal rather than health professional-led guidance is sought and maintained as an important resource throughout the care of this population and is valued. Diagnosis is sought at a 'critical point'. Healthcare interventions largely provided are poorly perceived. The period of subsequent self-management is an expectation before the inevitable requirement for joint replacement. There remains uncertainty regarding when this is required, but the expected failure of conservative treatment to manage pain and symptoms is common. In conclusion, patients should be enthused towards the principles of self-management and clinicians should not trivialise osteoarthritis. This may provide a more valuable perception of non-operative management to promote its adoption and adherence in managing osteoarthritis.

Stability and Performance of Rapid-Acting Insulin Analogs Used for Continuous Subcutaneous Insulin Infusion: A Systematic Review

We review and summarize the literature on the safety and stability of rapid-acting insulin analogs used for continuous subcutaneous insulin infusion (CSII) in patients with diabetes. Two predefined search strategies were systematically implemented to search Medline and the Cochrane Register of Clinical Trials for publications between 1996 and 2012. Twenty studies were included in the review: 13 in vitro studies and 7 clinical studies. In vitro studies investigated the effects of extreme CSII conditions (high temperature and mechanical agitation) on the risk of catheter occlusions and insulin stability factors, such as potency, purity, high molecular weight protein content, pH stability, and preservative content (m-cresol, phenol). Under these conditions, the overall stability of rapid-acting insulin analogs was similar for insulin lispro, insulin aspart, and insulin glulisine, although insulin glulisine showed greater susceptibility to insulin precipitation and catheter occlusions. A limited number of clinical trials were identified; this evidence-based information suggests that the rate of catheter occlusions in patients with type 1 diabetes using CSII treatment may vary depending on the rapid-acting analog used. Based on a limited amount of available data, the safety, stability, and performance of the three available rapid-acting insulin analogs available for use with CSII were similar. However, there is limited evidence suggesting that the risk of occlusion may vary with the insulin preparation under certain circumstances.

Therapeutic Mild Hypothermia and the Pharmacokinetics of Drugs in Trauma Brain Injury (TBI) Patients with a Focus on Sedation, Anticonvulsant and Antibiotic Therapy

Background: Therapeutic hypothermia may alter both the pharmacokinetic (PK) and dynamics (PD) of the commonly used drugs in critical care. To achieve maximum benefit, medication dosage and schedules should be optimized. Objective: To review the existing scientific evidence showing the effect of therapeutic hypothermia on the pharmacokinetics of drugs commonly used in the care of patients after Trauma Brain Injury (TBI); particularly including sedatives, anticonvulsants and antibiotics. Data Sources: Computerized searches of OVID MEDLINE, OVID EMBASE, Cochrane Clinical Trials Register to August 2013 and hand searching of references of retrieved articles and proceedings of meetings; associated reference lists; and articles identified by experts in the field. Study Selection: Inclusion criteria were as follows: a) population- humans or animals undergoing therapeutic hypothermia b) design-prospective, randomized controlled trial, c) intervention-hypothermia; measurement of PD and PK of different drugs. Data Extraction: A data extraction form was used and authors (CB & SP) reviewed all trials. Data Synthesis: We reviewed 30 trials that documented changes in PD and PK of sedatives (propofol and midazolam), opioids (fentanyl, remifentanil, alfentil and morphine), anticonvulsants (phenytoin) and antibiotics (aminoglycosides) conducted in human or animal models undergoing therapeutic hypothermia. Conclusion: Data show that therapeutic hypothermia significantly alters the pharmacokinetics of commonly used agents. Particular care should be taken to reduce sedatives once target temperature is reached. Further clinical studies are required to clarify the effect of hypothermia on the PD and PK of therapeutic agents to optimize the benefits of therapeutic hypothermia in the treatment of TBI patients.

Operative treatment for femoral shaft nonunions, a systematic review of the literature

The objective of this article is to systematically review the currently available literature to formulate evidence-based guidelines for the treatment of femoral shaft nonunions for clinical practice and to establish recommendations for future research. Articles from PubMed/MEDLINE, Cochrane Clinical Trial Register, and EMBASE, that presented data concerning treatment of nonunions of femoral shaft fractures in adult humans, were included for data extraction and analysis. The search was restricted to articles from January 1970 to March 2011 written in the English, German, or Dutch languages. Articles containing data that were thought to have been presented previously were used once. Reports on nonunion after periprosthetic fractures, review articles, expert opinions, abstracts from scientific meetings, and case reports on 5 or fewer patients were excluded. The data that were extracted from the relevant articles included: type of nonunion, type of initial and secondary treatments, follow-up, union rate, and general complications. Most studies had different inclusion criteria and outcome measures, thus prohibiting a proper meta-analysis. Therefore, only the union rate and number of complications were compared between the different treatments. Methodological quality was assessed by assigning levels of evidence as previously defined by the Centre for Evidence-Based Medicine. This systematic review provides evidence in favour of plating if a nail is the first treatment; after failed plate fixation, nailing has a 96 % union rate. After failed nailing, augmentative plating results in a 96 % union rate compared to 73 % in the exchange nailing group.

Comparative effectiveness of antiarrhythmic drugs on cardiovascular hospitalization and mortality in atrial fibrillation

To assess, through a systematic review, evidence for the effects of antiarrhythmic drugs (AADs) on cardiovascular (CV) hospitalization and mortality. English language articles were identified using MEDLINE, EMBASE and the Cochrane Clinical Trial Registry and were screened for study applicability and methodological quality. Out of 3526 identified studies, 38 were selected for analysis (19 evaluated individual AADs, 13 compared rate- versus rhythm-control strategies, and 6 evaluated multiple AADs but did not report outcomes for individual agents). None of the studies examining individual AADs employed the CV hospitalization end point used in ATHENA (the reference trial). There were no head-to-head comparisons of individual AADs on CV hospitalization. Most high-quality studies used multidrug rate- versus rhythm-control strategies. Assessment of the comparative effectiveness of individual AADs on CV hospitalization and mortality end points is not possible with the current evidence.

Low Glycemic Index Diets on Long‐term Blood Pressure Control: A Systematic Review and Meta‐analysis

OBJECTIVESWe conducted a systematic review and meta‐analysis to assess effectiveness of low GI diets on blood pressure (BP) in the long‐term.METHODSWe searched MEDLINE, EMBASE, and the Cochrane Register of Clinical Trials for clinical trials, 3 months or longer. Cochrane guidelines and the PRISMA methodologies were used. Results were pooled in Review Manager under generic inverse variance methods with random effects models and expressed as Mean Difference (MD) with 95% CI.RESULTS1290 reports were identified with 9 trials meeting eligibility criteria (7 parallel, 2 crossovers). 7 trials reported Systolic BP (SBP) (n=666, average duration= 27.7 weeks) while 6 had Diastolic BP (DBP) data (n=563, average duration= 23.2 weeks). The pooled effect of low GI diets was −0.17mmHg (95%CI: −1.07,0.74) for SBP and −2.26mmHg (95%CI: −4.17, − 0.35) for DBP, with significant heterogeneity for both (I2&gt;;86%, P&lt;0.00001).CONCLUSIONLow GI diets can lower DBP in T2D in the long‐term.Study Supported by Barilla

Systematic review and meta-analysis of the effect of perioperative steroids on ischaemia–reperfusion injury and surgical stress response in patients undergoing liver resection

Several therapeutic strategies, such as ischaemic preconditioning, intermittent or selective pedicle clamping and pharmacological interventions, have been explored to reduce morbidity caused by hepatic ischaemia-reperfusion injury and the surgical stress response. The role of steroids in this setting remains controversial. A comprehensive literature search in MEDLINE, Embase and the Cochrane Register of Clinical Trials (CENTRAL) was conducted (1966 onwards), identifying studies comparing perioperative administration of intravenous steroids with standard care or placebo, in the setting of liver surgery. Randomized Controlled trials (RCTs) and non-RCTs were included. Critical appraisal and meta-analysis were carried out according to the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) statement. Six articles were included; five were RCTs. Pooling the results revealed that patients receiving intravenous glucocorticoids were 24 per cent less likely to suffer postoperative morbidity compared with controls (risk ratio 0.76, 95 per cent confidence interval 0.57 to 0.99; P = 0.047). The treated group experienced a significantly greater rise in early postoperative interleukin (IL) 10 levels compared with controls. In addition, steroids significantly reduced postoperative blood levels of bilirubin, and of inflammatory markers such as IL-6 and C-reactive protein. There was no evidence supporting a risk difference in infectious complications and wound healing between study groups. Perioperative steroids have a favourable impact on postoperative outcomes after liver resection.

Orthostatic Hypotension in the Patient with Diabetes: A Broad Review of Pharmacologic Treatment Options

Objective:To provide an evidence-based broad review of the pharmacologic management of orthostatic hypotension (OH) in the patient with diabetes.Data Sources:A search of PubMed, MD Consult, International Pharmaceutical Abstracts, and the Cochrane Register of Clinical Trials and Systematic Reviews was performed using the key words diabetes, autonomic neuropathy, orthostatic hypotension, midodrine, fludrocortisone, pyridostigmine, xamoterol, octreotide, pindolol, dihydroergotamine, erythropoietin, clonidine, acarbose, desmopressin, and droxidopa. Literature published between 1976 and August 2012 was included.Study Selection and Data Extraction:All articles in English and studies in humans including clinical trials, meta-analyses, practice guidelines, randomized controlled trials, and review articles were identified and evaluated. Studies not including patients with diabetes were excluded. The selection of materials was focused on those that would aid the pharmacist in caring for patients with orthostatic hypotension resulting from diabetic neuropathy.Data Synthesis:Definitive guidelines on the pharmacologic management of OH in the patient with diabetes are not available and recommendations must be assessed from available evidence-based sources. Ten trials of medications used in the patient with diabetes were assessed for efficacy and safety. From these trials, evidence-based therapy options were recommended. If nonpharmacologic measures are insufficient in ameliorating symptoms, fludrocortisone or midodrine should be considered as first-line agents in the absence of contraindications. Pyridostigmine, octreotide, or recombinant erythropoietin may be useful as adjunct or alternative agents. Combination therapy may be considered, based on coexisting conditions or response. When recommending both nonpharmacologic and pharmacologic therapy, careful attention should be paid to comorbid conditions such as congestive heart failure, supine hypertension, and kidney disease.Conclusions:There is insufficient evidence to recommend the routine use of medications other than the first-line agents fludrocortisone or midodrine in this patient population. Further trials with existing and new therapeutic options in patients with diabetes are warranted.

Optimal dosing of antibiotics in critically ill patients by using continuous/extended infusions: a systematic review and meta-analysis

IntroductionThe aim of this study was to determine whether using pharmacodynamic-based dosing of antimicrobials, such as extended/continuous infusions, in critically ill patients is associated with improved outcomes as compared with traditional dosing methods.MethodsWe searched Medline, HealthStar, EMBASE, Cochrane Clinical Trial Registry, and CINAHL from inception to September 2013 without language restrictions for studies comparing the use of extended/continuous infusions with traditional dosing. Two authors independently selected studies, extracted data on methodology and outcomes, and performed quality assessment. Meta-analyses were performed by using random-effects models.ResultsOf 1,319 citations, 13 randomized controlled trials (RCTs) (n = 782 patients) and 13 cohort studies (n = 2,117 patients) met the inclusion criteria. Compared with traditional non-pharmacodynamic-based dosing, RCTs of continuous/extended infusions significantly reduced clinical failure rates (relative risk (RR) 0.68; 95% confidence interval (CI) 0.49 to 0.94, P = 0.02) and intensive care unit length of stay (mean difference, −1.5; 95% CI, −2.8 to −0.2 days, P = 0.02), but not mortality (RR, 0.87; 95% CI, 0.64 to 1.19; P = 0.38). No significant between-trial heterogeneity was found for these analyses (I2 = 0). Reduced mortality rates almost achieved statistical significance when the results of all included studies (RCTs and cohort studies) were pooled (RR, 0.83; 95% CI, 0.69 to 1.00; P = 0.054).ConclusionsPooled results from small RCTs suggest reduced clinical failure rates and intensive care unit length-of-stay when using continuous/extended infusions of antibiotics in critically ill patients. Reduced mortality rates almost achieved statistical significance when the results of RCTs were combined with cohort studies. These results support the conduct of adequately powered RCTs to define better the utility of continuous/extended infusions in the era of antibiotic resistance.

Flexible stabilization of the distal tibiofibular syndesmosis: clinical and biomechanical considerations: a review of the literature

Syndesmotic rupture is present in 10 % of ankle fractures and must be recognized and treated to prevent late complications. The method of fixation is classically rigid fixation with one or two screws. Knowledge of the biomechanics of the syndesmosis has led to the development of new dynamic implants to restore physiologic motion during walking. One of these implants is the suture-button system. The purpose of this paper is to review the orthopaedic trauma literature, both biomechanical and clinical, to present the current state of knowledge on the suture-button fixation and to put emphasis on the advantages and disadvantages of this technique. Two investigators searched the databases of Pubmed/Medline, Cochrane Clinical Trial Register and Embase independently. The search interval was from January 1980 to March 2011. The search keys comprised terms to identify articles on biomechanical and clinical issues of flexible fixation of syndesmotic ruptures. Ninety-nine publications met the search criteria. After filtering using the exclusion criteria, 11 articles (five biomechanical and six clinical) were available for review. The biomechanical studies involved 90 cadaveric ankles. The suture-button demonstrated good resistance to axial and rotational loads (equivalent to screws) and resistance to failure. Physiologic motion of the syndesmosis was restored in all directions. The clinical studies (149 ankles) demonstrated good functional results using the AOFAS score, indicating faster rehabilitation with flexible fixation than with screws. There were few complications. Preliminary results from the current literature support the use of suture-button fixation for syndesmotic ruptures. This method seems secure and safe. As there is no strong evidence for its use, prospective randomized controlled trials to compare the suture-button to the screw fixation for ankle syndesmotic ruptures are required.

A meta‐analysis of magnesium for tetanus

Uncontrolled studies suggest that magnesium sulphate controls spasms in patients with established tetanus. We performed a meta-analysis of controlled trials that compared magnesium sulphate with placebo or diazepam for the treatment of patients with tetanus. We searched PubMed, Scopus, Embase and the Cochrane clinical trials registry. Three studies met the inclusion criteria, containing 275 participants (199 male patients, 72.4%). Magnesium sulphate did not reduce mortality, relative risk (95% CI): vs placebo, 0.80 (0.41-1.58); vs diazepam, 1.11 (0.70-1.75). The data on duration of total intensive care unit stay, total hospital stay and the need for ventilatory support were conflicting and pooling of results could not be done due to methodological differences of individual trials. More controlled trials are needed to assess the effect of magnesium sulphate on reducing autonomic instability, spasms, duration of intensive care and hospital stays and the need for mechanical ventilation.

Acetazolamide for the Prevention of Acute Mountain Sickness—A Systematic Review and Meta‐analysis

Acetazolamide has been reported to be effective in the prevention of acute mountain sickness (AMS). Our aim was to conduct a systematic review of randomized, placebo-controlled trials of acetazolamide in the prevention of AMS. Studies were identified by searching the MEDLINE, Embase, Cochrane Clinical Trials Register, and ClinicalTrials.gov databases. Primary end point was difference in incidence of AMS between acetazolamide and placebo groups. Acetazolamide prophylaxis was associated with a 48% relative-risk reduction compared to placebo. There was no evidence of an association between efficacy and dose of acetazolamide. Adverse effects were often not systematically reported but appeared to be common but generally mild. One study found that adverse effects of acetazolamide were dose related. Acetazolamide is effective prophylaxis for the prevention of symptoms of AMS in those going to high altitude. A dose of 250 mg/day has similar efficacy to higher doses and may have a favorable side-effect profile.