Low Quality Randomized Controlled Trials Research Articles

Clinical Insights and Future Directions in Hypothermia for Severe Traumatic Brain Injury: A Narrative Review.

Fever control is essential in patients with severe traumatic brain injury (TBI). The efficacy of therapeutic hypothermia (TH) in severe TBI has been investigated over the last few decades; however, in contrast to experimental studies showing benefits, no evidence of efficacy has been demonstrated in clinical practice. In this review, the mechanisms and history of hypothermia were briefly outlined, while the results of major randomized controlled trials (RCTs) and meta-analyses investigating TH for adult TBI were introduced and discussed. The retrieved meta-analyses showed conflicting results, with a limited number of studies indicating the benefits of TH. Some studies have shown the benefits of long-term TH compared with short-term TH. Although TH is effective at lowering elevated intracranial pressure (ICP), reduced ICP does not lead to favorable outcomes. Low-quality RCTs overestimated the benefits of TH, while high-quality RCTs showed no difference or worse outcomes with TH. RCTs assessing standardized TH quality demonstrated the benefits of TH. As TBI has heterogeneous and complicated pathologies, applying a uniform treatment may not be ideal. A meta-analysis of young patients who underwent early cooling and hematoma removal showed better TH results. TH should not be abandoned, and its optimal usage should be advocated on an individual basis.

The efficacy and safety of oral antibiotic treatment in patients with chronic low back pain and Modic changes: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to summarize evidence regarding the effectiveness and safety of oral antibiotic intervention for chronic low back pain (CLBP) patients with/without type-1 Modic changes (MC1). AMED, CINAHL, Cochrane Library, Embase, and Medline were searched from inception to March 3, 2023. Randomized controlled trials (RCTs) or non-RCTs that investigated the effectiveness or safety of oral antibiotics in treating CLBP patients were eligible for inclusion. Two independent reviewers screened abstracts, full-text articles, and extracted data. The methodological quality of each included article were evaluated by RoB2 and NIH quality assessment tools. The quality of evidence was appraised by GRADE. Meta-analyses were performed, where applicable. A subgroup analysis was conducted to evaluate the RCTs and case series separately, and to evaluate the effect of removing a low-quality RCT. Three RCTs and four case series were included. All Amoxicillin-clavulanate/Amoxicillin treatments lasted for approximately 3 months. Moderate- and low-quality evidence suggested that antibiotic was significantly better than placebo in improving disability and quality of life in CLBP patients with MC1 at 12-month follow-up, respectively. Low-quality evidence from meta-analyses of RCTs showed that oral antibiotic was significantly better than placebo in improving pain and disability in CLBP patients with MC1 immediately post-treatment. Very low-quality evidence from the case series suggested that oral Amoxicillin-clavulanate significantly improved LBP/leg pain, and LBP-related disability. Conversely, low-quality evidence found that oral Amoxicillin alone was not significantly better than placebo in improving global perceived health in patients with CLBP at the 12-month follow-up. Additionally, oral antibiotic users had significantly more adverse effects than placebo users. Although oral antibiotics were statistically superior to placebo in reducing LBP-related disability in patients with CLBP and concomitant MC1, its clinical significance remains uncertain. Future large-scale high-quality RCTs are warranted to validate the effectiveness of antibiotics in individuals with CLBP.

Vitamin D Supplementation and Its Impact on Mortality and Cardiovascular Outcomes: Systematic Review and Meta-Analysis of 80 Randomized Clinical Trials.

The impact of vitamin D supplementation on cardiovascular outcomes and mortality risk reduction remains unclear due to conflicting study findings. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), published between 1983 and 2022, that reported the effect of vitamin D supplementation in adults versus placebo or no treatment on all-cause mortality (ACM), cardiovascular mortality (CVM), non-cardiovascular mortality (non-CVM), and cardiovascular morbidities. Only studies with a follow-up period longer than one year were included. The primary outcomes were ACM and CVM. Secondary outcomes were non-CVM, myocardial infarction, stroke, heart failure, and major or extended adverse cardiovascular events. Subgroup analyses were performed according to low-, fair- and good-quality RCTs. Eighty RCTs were assessed, including 82,210 participants receiving vitamin D supplementation and 80,921 receiving placebo or no treatment. The participants' mean (SD) age was 66.1 (11.2) years, and 68.6% were female. Vitamin D supplementation was associated with a lower risk of ACM (OR: 0.95 [95%CI 0.91-0.99] p = 0.013), was close to statistical significance for a lower risk of non-CVM (OR: 0.94 [95%CI 0.87-1.00] p = 0.055), and was not statistically associated with a lower risk of any cardiovascular morbi-mortality outcome. Meta-analysis of low-quality RCTs showed no association with cardiovascular or non-cardiovascular morbi-mortality outcomes. The emerging results of our meta-analysis present evidence that vitamin D supplementation appears to decrease the risk of ACM (especially convincing in the fair- and good-quality RCTs), while not showing a decrease in the specific cardiovascular morbidity and mortality risk. Thus, we conclude that further research is warranted in this area, with well-planned and executed studies as the basis for more robust recommendations.

Effects of neurofeedback in the management of chronic pain: A systematic review and meta-analysis of clinical trials.

Neurofeedback (NFB) provides real-time feedback about neurophysiological signals to patients, thereby encouraging modulation of pain-associated brain activity. This review aims to evaluate the effectiveness and safety of NFB in alleviating pain and pain-associated symptoms in chronic pain patients. MEDLINE, PUBMED, Web of Science and PsycINFO databases were searched using the strategy: ("Neurofeedback" OR "EEG Biofeedback" OR "fMRI Biofeedback") AND ("Pain" or "Chronic Pain"). Clinical trials reporting changes in pain following electroencephalogram (EEG) or functional magnetic resonance imaging (fMRI) NFB in chronic pain patients were included. Only Randomized-controlled trials (RCT), non-randomized controlled trials (NRCT) and case series were included. Effect size was pooled for all RCTs in a meta-analysis. Twenty-one studies were included. Reduction in pain following NFB was reported by one high-quality RCT, five of six low-quality RCT or NRCT and 13 of 14 case-series. Pain reduction reported by studies ranged from 6% to 82%, with 10 studies reporting a clinically significant reduction in pain of >30%. The overall effect size was medium (cohen's d -0.76, 95% confidence interval -1.31 to -0.20). Studies were highly heterogeneous (Q [df=5]=18.46, p=.002, I2 =73%). Improvements in depression, anxiety, fatigue and sleep were also seen in some studies. Common side-effects included headache, nausea and drowsiness. These generally did not lead to withdrawal of therapy except in one study. Neurofeedback is a safe and effective therapy with promising but largely low-quality evidence supporting its use in chronic pain. Further high-quality trials comparing different protocols is warranted to determine the most efficacious way to deliver NFB. Neurofeedback is a novel neuromodulatory approach which can be used to reduce the severity of pain and pain-associated symptoms such as sleep disturbances, mood disturbances, fatigue and anxiety in a number of chronic pain conditions. It has a potential to provide integrative non-pharmacological management for chronic pain patients with pain refractory to pharmacological agents with high side-effect profiles. Further high-quality double-blinded randomized sham-controlled trials are needed in order to fully explore the potential of this therapy.

Surgical wound closure by staples or sutures?: Systematic review.

To compare the effects of sutures and staples for skin closure of surgical wounds. We included published and unpublished randomized controlled trials (RCTs) and cluster-randomized trials comparing staples with sutures. Patients were adults (aged 18 years or over) who had undergone any type of surgery. The primary outcomes were risk of overall and severe wound infection. Secondary outcomes included length of hospital stay, readmission rate, adverse events, patient satisfaction with cosmetic results, postoperative pain. Forty-two very low to low quality RCTs with a total of 11,067 patients were included. Sutures resulted in slightly fewer overall wound infections (4.90%) compared to staples (6.75%) but it is uncertain whether there is a difference between the groups (risk ratio [RR] 1.20, 95% confidence intervals [CI] 0.80-1.79; patients = 9864; studies = 34; I = 70%). The evidence was also insufficient to state a difference in terms of severe wound infection (staples 1.4% vs sutures 1.3%; RR 1.08, 95% CI 0.61-1.89; patients = 3036; studies = 17; I = 0%), grade of satisfaction (RR 0.99, 95% CI 0.91-1.07; patients = 3243; studies = 14; I = 67%) and hospital stay. Staples may increase the risk of adverse events (7.3% for staples vs 3.5% for sutures; RR 2.00, 95% CI 1.44-2.79; patients = 6246; studies = 21; I = 33%), readmission rate (RR 1.28, 95% CI 0.18-9.05; patients = 2466; studies = 5; I = 66%) and postoperative pain (standardized mean difference [SMD] 0.41,95%CI -0.35 to 1.16; I = 88%, patients = 390 patients, studies = 5). Due to the lack of high quality evidence, we could not state if sutures are better than staples in terms of wound infection, readmission rate, adverse events, and postoperative pain. With a low quality of evidence, sutures reduce postoperative pain and improve grade of satisfaction with the cosmetic outcome.

Beta-blockers for preventing aortic dissection in Marfan syndrome.

Marfan syndrome is a hereditary disorder affecting the connective tissue and is caused by a mutation of the fibrillin-1 (FBN1) gene. It affects multiple systems of the body, most notably the cardiovascular, ocular, skeletal, dural and pulmonary systems. Aortic root dilatation is the most frequent cardiovascular manifestation and its complications, including aortic regurgitation, dissection and rupture are the main cause of morbidity and mortality. To assess the long-term efficacy and safety of beta-blocker therapy as compared to placebo, no treatment or surveillance only in people with Marfan syndrome. We searched the following databases on 28 June 2017; CENTRAL, MEDLINE, Embase, Science Citation Index Expanded and the Conference Proceeding Citation Index - Science in the Web of Science Core Collection. We also searched the Online Metabolic and Molecular Bases of Inherited Disease (OMMBID), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 30 June 2017. We did not impose any restriction on language of publication. All randomised controlled trials (RCTs) of at least one year in duration assessing the effects of beta-blocker monotherapy compared with placebo, no treatment or surveillance only, in people of all ages with a confirmed diagnosis of Marfan syndrome were eligible for inclusion. Two review authors independently screened titles and abstracts for inclusion, extracted data and assessed trial quality. Trial authors were contacted to obtain missing data. Dichotomous outcomes will be reported as relative risk and continuous outcomes as mean differences with 95% confidence intervals. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. One open-label, randomised, single-centre trial including 70 participants with Marfan syndrome (aged 12 to 50 years old) met the inclusion criteria. Participants were randomly assigned to propranolol (N = 32) or no treatment (N = 38) for an average duration of 9.3 years in the control group and 10.7 years in the treatment group. The initial dose of propranolol was 10 mg four times daily and the optimal dose was reached when the heart rate remained below 100 beats per minute during exercise or the systolic time interval increased by 30%. The mean (± standard error (SE)) optimal dose of propranolol was 212 ± 68 mg given in four divided doses daily.Beta-blocker therapy did not reduce the incidence of all-cause mortality (RR 0.24, 95% CI 0.01 to 4.75; participants = 70; low-quality evidence). Mortality attributed to Marfan syndrome was not reported. Non-fatal serious adverse events were also not reported. However, study authors report on pre-defined, non-fatal clinical endpoints, which include aortic dissection, aortic regurgitation, cardiovascular surgery and congestive heart failure. Their analysis showed no difference between the treatment and control groups in these outcomes (RR 0.79, 95% CI 0.37 to 1.69; participants = 70; low-quality evidence).Beta-blocker therapy did not reduce the incidence of aortic dissection (RR 0.59, 95% CI 0.12 to 3.03), aortic regurgitation (RR 1.19, 95% CI 0.18 to 7.96), congestive heart failure (RR 1.19, 95% CI 0.18 to 7.96) or cardiovascular surgery, (RR 0.59, 95% CI 0.12 to 3.03); participants = 70; low-quality evidence.The study reports a reduced rate of aortic dilatation measured by M-mode echocardiography in the treatment group (aortic ratio mean slope: 0.084 (control) vs 0.023 (treatment), P < 0.001). The change in systolic and diastolic blood pressure, total adverse events and withdrawal due to adverse events were not reported in the treatment or control group at study end point.We judged this study to be at high risk of selection (allocation concealment) bias, performance bias, detection bias, attrition bias and selective reporting bias. The overall quality of evidence was low. We do not know whether a statistically significant reduced rate of aortic dilatation translates into clinical benefit in terms of aortic dissection or mortality. Based on only one, low-quality RCT comparing long-term propranolol to no treatment in people with Marfan syndrome, we could draw no definitive conclusions for clinical practice. High-quality, randomised trials are needed to evaluate the long-term efficacy of beta-blocker treatment in people with Marfan syndrome. Future trials should report on all clinically relevant end points and adverse events to evaluate benefit versus harm of therapy.

Negative Pressure Wound Therapy: Randomised Controlled Trials from 2000 to 2015

Background Negative pressure wound therapy is believed to promote wound healing. However, the results from randomised controlled trials (RCTs) are inconsistent. Systematic reviews indicate unclear evidence, due in part to low-quality RCTs, calling for more RCTs of higher quality. Methods This study aimed to ascertain the number of RCTs as well as systematic reviews on RCTs published during the time period from 2000 to 2015. Various search strategies were used to identify studies in PubMed, Cochrane Library, Google, references lists of retrieved articles, and institutions that issue evidence reports. The study also aimed to investigate the quality of included RCTs. It evaluated whether or not the randomisation methodology was comprehensibly described and conclusions were based on acceptable endpoints. Results The search for studies resulted in 456 different references, which included a total of 49 RCTs and 81 systematic reviews. Randomisation was comprehensibly described in 37% (18 out of 49 RCTs) and concealment of allocation in 10% (5’out of 49 RCTs). Conclusions were based on acceptable endpoints in 55% (27 out of 49 RCTs). A superior efficacy of NPWT versus standard was stated in 65% (32 out of 49 RCTs). In studies based on acceptable endpoints, this proportion was 16% (8 out of 49 RCTs). Systematic reviews repeatedly included identical study data. Conclusion The published literature, reviewed over a period of more than 16 years, contains more systematic reviews incorporating secondary data from other RCTs than actual RCTs reporting primary clinical data. Many RCTs seem to be of low quality, which considerably limits the validity of the corresponding conclusions. The ongoing production of potentially unreliable RCTs and redundant systematic reviews does not seem to provide convincing answers to crucial clinical research questions. Therefore, a change in strategy should be contemplated to observe individual characteristics of the respective persons and the wounds in question.

Interventions for dysphagia in long-term, progressive muscle disease.

Normal swallowing function is divided into oral, pharyngeal, and oesophageal phases. The anatomy and physiology of the oral cavity facilitates an oral preparatory phase of swallowing, in which food and liquid are pushed towards the pharynx by the tongue. During pharyngeal and oesophageal phases of swallowing, food and liquid are moved from the pharynx to the stomach via the oesophagus. Our understanding of swallowing function in health and disease has informed our understanding of how muscle weakness can disrupt swallowing in people with muscle disease. As a common complication of long-term, progressive muscle disease, there is a clear need to evaluate the current interventions for managing swallowing difficulties (dysphagia). This is an update of a review first published in 2004. To assess the effects of interventions for dysphagia in people with long-term, progressive muscle disease. On 11 January 2016, we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED, LILACS, and CINAHL. We checked references in the identified trials for additional randomised and quasi-randomised controlled trials. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform on 12 January 2016 for ongoing or completed but unpublished clinical trials. We included randomised and quasi-randomised controlled trials that assessed the effect of interventions for managing dysphagia in adults and children with long-term, progressive muscle disease, compared to other interventions, placebo, no intervention, or standard care. Quasi-randomised controlled trials are trials that used a quasi-random method of allocation, such as date of birth, alternation, or case record number. Review authors previously excluded trials involving people with muscle conditions of a known inflammatory or toxic aetiology. In this review update, we decided to include trials of people with sporadic inclusion body myositis (IBM) on the basis that it presents as a long-term, progressive muscle disease with uncertain degenerative and inflammatory aetiology and is typically refractory to treatment. We applied standard Cochrane methodological procedures. There were no randomised controlled trials (RCTs) that reported results in terms of the review's primary outcome of interest, weight gain or maintenance. However, we identified one RCT that assessed the effect of intravenous immunoglobulin on swallowing function in people with IBM. The trial authors did not specify the number of study participants who had dysphagia. There was also incomplete reporting of findings from videofluoroscopic investigations, which was one of the review's secondary outcome measures. The study did report reductions in the time taken to swallow, as measured using ultrasound. No serious adverse events occurred during the study, although data for the follow-up period were lacking. It was also unclear whether the non-serious adverse events reported occurred in the treatment group or the placebo group. We assessed this study as having a high risk of bias and uncertain confidence intervals for the review outcomes, which limited the overall quality of the evidence. Using GRADE criteria, we downgraded the quality of the evidence from this RCT to 'low' for efficacy in treating dysphagia, due to limitations in study design and implementation, and indirectness in terms of the population and outcome measures. Similarly, we assessed the quality of the evidence for adverse events as 'low'. From our search for RCTs, we identified two other non-randomised studies, which reported the effects of long-term intravenous immunoglobulin therapy in adults with IBM and lip-strengthening exercises in children with myotonic dystrophy type 1. Headaches affected two participants treated with long-term intravenous immunoglobulin therapy, who received a tailored dose reduction; there were no adverse events associated with lip-strengthening exercises. Both non-randomised studies identified improved outcomes for some participants following the intervention, but neither study specified the number of participants with dysphagia or demonstrated any group-level treatment effect for swallowing function using the outcomes prespecified in this review. There is insufficient and low-quality RCT evidence to determine the effect of interventions for dysphagia in long-term, progressive muscle disease. Clinically relevant effects of intravenous immunoglobulin for dysphagia in inclusion body myositis can neither be confirmed or excluded using the evidence presented in this review. Standardised, validated, and reliable outcome measures are needed to assess dysphagia and any possible treatment effect. Clinically meaningful outcomes for dysphagia may require a shift in focus from measures of impairment to disability associated with oral feeding difficulties.

The Relationship Between Training Load and Injury, Illness and Soreness: A Systematic and Literature Review.

Clinically it is understood that rapid increases in training loads expose an athlete to an increased risk of injury; however, there are no systematic reviews to qualify this statement. The aim of this systematic review was to determine training and competition loads, and the relationship between injury, illness and soreness. The MEDLINE, SPORTDiscus, CINAHL and EMBASE databases were searched using a predefined search strategy. Studies were included if they analysed the relationship between training or competition loads and injury or illness, and were published prior to October 2015. Participants were athletes of any age or level of competition. The quality of the studies included in the review was evaluated using the Newcastle-Ottawa Scale (NOS). The level of evidence was defined as strong, 'consistent findings among multiple high-quality randomised controlled trials (RCTs)'; moderate, 'consistent findings among multiple low-quality RCTs and/or non-randomised controlled trials (CCTs) and/or one high-quality RCT'; limited, 'one low-quality RCT and/or CCTs, conflicting evidence'; conflicting, 'inconsistent findings among multiple trials (RCTs and/or CCTs)'; or no evidence, 'no RCTs or CCTs'. A total of 799 studies were identified; 23 studies met the inclusion criteria, and a further 12 studies that were not identified in the search but met the inclusion criteria were subsequently added to the review. The largest number of studies evaluated the relationship between injuries and training load in rugby league players (n=9) followed by cricket (n=5), football (n=3), Australian Football (n=3), rugby union (n=2),volleyball (n=2), baseball (n=2), water polo (n=1), rowing (n=1), basketball (n=1), swimming (n=1), middle-distance runners (n=1) and various sports combined (n=1). Moderate evidence for a significant relationship was observed between training loads and injury incidence in the majority of studies (n=27, 93%). In addition, moderate evidence exists for a significant relationship between training loads and illness incidence (n=6, 75%). Training loads were reported to have a protective effect against injury (n=9, 31%) and illness (n=1, 13%). The median (range) NOS score for injury and illness was 8 (5-9) and 6 (5-9), respectively. A limitation of this systematic review was the a priori search strategy. Twelve further studies were included that were not identified in the search strategy, thus potentially introducing bias. The quality assessment was completed by only one author. The results of this systematic review highlight that there is emerging moderate evidence for the relationship between the training load applied to an athlete and the occurrence of injury and illness. The training load applied to an athlete appears to be related to their risk of injury and/or illness. Sports science and medicine professionals working with athletes should monitor this load and avoid acute spikes in loads. It is recommended that internal load as the product of the rate of perceived exertion (10-point modified Borg) and duration be used when determining injury risk in team-based sports. External loads measured as throw counts should also be monitored and collected across a season to determine injury risk in throwing populations. Global positioning system-derived distances should be utilised in team sports, and injury monitoring should occur for at least 4weeks after spikes in loads.

Effectiveness of tranexamic acid in reducing blood loss during cytoreductive surgery for advanced ovarian cancer.

Ovarian cancer is the third most common gynaecological cancer worldwide, with an age-standardised incidence rate of 6.1 per 10,000 women. Standard therapy for advanced epithelial ovarian cancer (EOC) includes a combination of cytoreductive surgery and platinum-based chemotherapy. Cytoreductive surgery aims to remove as much of the visible tumour as possible. As extensive intraperitoneal metastases are typical of advanced EOC, cytoreductive surgery is usually an extensive procedure with the risk of excessive bleeding. Tranexamic acid given perioperatively is effective in reducing blood loss and allogeneic blood transfusion requirements in a variety of surgical settings. Therefore, tranexamic acid seems to be a promising agent for minimising blood loss and the need for blood transfusion among women with advanced EOC undergoing cytoreductive surgery. To assess the effects of tranexamic acid for reducing blood loss associated with cytoreductive surgery in women with advanced EOC (stage III to IV). We searched the Cochrane Gynaecological, Neuro-oncology and Orphan Cancers Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 5, 2015), MEDLINE, EMBASE and conference proceedings to May 2015. We also checked registers of clinical trials, citation lists of included studies, key textbooks and previous systematic reviews for potentially relevant studies. We included randomised controlled trials (RCTs) comparing tranexamic acid given during surgery versus placebo or no treatment, in adult women diagnosed with advanced EOC. Two review authors (CK, AS) independently selected potentially relevant trials, extracted data, assessed risk of bias, compared results and resolved disagreements by discussion. We found only one study that met our inclusion criteria. This was a randomised double blind, placebo-controlled multicentre study conducted to evaluate the effectiveness of a single dose of intravenous tranexamic acid (15 mg/kg body weight) versus placebo, given immediately before surgery for reducing blood loss and the need for red blood cell transfusion. The mean total estimated blood loss was 668.34 mL and 916.93 mL for participants assigned to tranexamic acid and placebo groups, respectively. The mean difference (MD) of total estimated blood loss between the groups did not show a clinically important effect (MD - 248.59 mL; 95% confidence interval (CI) - 550.9 to 53.79; one study, 100 participants; moderate quality evidence). The mean number of transfused units of blood components was not different between the two groups (low quality evidence). There were no noted differences in the incidence of reoperation, readmission or thromboembolic events (very low quality evidence). We considered the methodology of the included study to be at low risk of selection, detection, and reporting biases. However, we were concerned about an imbalance of some baseline characteristics between the groups, and as there was no protocol for blood transfusion, the rate of blood transfusion may vary depending on the practice of each participating hospital. Currently, there is insufficient evidence to recommend the routine use of tranexamic acid for reducing blood loss in women undergoing cytoreductive surgery for advanced EOC, as only limited data are available from a single, low quality RCT at low overall risk of bias.

Effectiveness of posterior decompression techniques compared with conventional laminectomy for lumbar stenosis.

The gold standard treatment for symptomatic lumbar stenosis refractory to conservative management is a facet-preserving laminectomy. New techniques of posterior decompression have been developed to preserve spinal integrity and to minimise tissue damage by limiting bony decompression and avoiding removal of the midline structures (i.e. spinous process, vertebral arch and interspinous and supraspinous ligaments). To compare the effectiveness of techniques of posterior decompression that limit the extent of bony decompression or avoid removal of posterior midline structures of the lumbar spine versus conventional facet-preserving laminectomy for the treatment of patients with degenerative lumbar stenosis. An experienced librarian conducted a comprehensive electronic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science, and the clinical trials registries ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) for relevant literature up to June 2014. We included prospective controlled studies comparing conventional facet-preserving laminectomy versus a posterior decompressive technique that avoids removal of posterior midline structures or a technique involving only partial resection of the vertebral arch. We excluded studies describing techniques of decompression by means of interspinous process devices or concomitant (instrumented) fusion procedures. Participants included individuals with symptomatic degenerative lumbar stenosis only. Two review authors independently assessed risk of bias using the Cochrane Back Review Group criteria for randomised controlled trials (RCTs) and the Newcastle-Ottawa Scale for non-randomised studies. We extracted data regarding demographics, intervention details and outcome measures. A total of four high-quality RCTs and six low-quality RCTs met the search criteria of this review. These studies included a total of 733 participants. Investigators compared three different posterior decompression techniques versus conventional laminectomy. Three studies (173 participants) compared unilateral laminotomy for bilateral decompression versus conventional laminectomy. Four studies (382 participants) compared bilateral laminotomy versus conventional laminectomy (one study included three treatment groups and compared unilateral and bilateral laminotomy vs conventional laminectomy). Finally, four studies (218 participants) compared a split-spinous process laminotomy versus conventional laminectomy.Evidence of low or very low quality suggests that different techniques of posterior decompression and conventional laminectomy have similar effects on functional disability and leg pain. Only perceived recovery at final follow-up was better in people who underwent bilateral laminotomy compared with conventional laminectomy (two RCTs, 223 participants, odds ratio 5.69, 95% confidence interval (CI) 2.55 to 12.71).Among the secondary outcome measures, unilateral laminotomy for bilateral decompression and bilateral laminotomy resulted in numerically fewer cases of iatrogenic instability, although in both cases, the incidence of instability was low (three RCTs, 166 participants, odds ratio 0.28, 95% CI 0.07 to 1.15; three RCTs, 294 participants, odds ratio 0.10, 95% CI 0.02 to 0.55, respectively). The difference in severity of postoperative low back pain following bilateral laminotomy (two RCTs, 223 participants, mean difference -0.51, 95% CI -0.80 to -0.23) and split-spinous process laminotomy compared with conventional laminectomy (two RCTs, 97 participants, mean difference -1.07, 95% CI -2.15 to -0.00) was significantly less, but was too small to be clinically important. A quantitative comparison between unilateral laminotomy and conventional laminectomy was not possible because of different reporting of outcome measures. We found no evidence to show that the incidence of complications, length of the procedure, length of hospital stay and postoperative walking distance differed between techniques of posterior decompression. The evidence provided by this systematic review for the effects of unilateral laminotomy for bilateral decompression, bilateral laminotomy and split-spinous process laminotomy compared with conventional laminectomy on functional disability, perceived recovery and leg pain is of low or very low quality. Therefore, further research is necessary to establish whether these techniques provide a safe and effective alternative for conventional laminectomy. Proposed advantages of these techniques regarding the incidence of iatrogenic instability and postoperative back pain are plausible, but definitive conclusions are limited by poor methodology and poor reporting of outcome measures among included studies. Future research is necessary to establish the incidence of iatrogenic instability using standardised definitions of radiological and clinical instability at comparable follow-up intervals. Long-term results with these techniques are currently lacking.

Acupuncture and moxibustion for lateral elbow pain: a systematic review of randomized controlled trials.

BackgroundAcupuncture and moxibustion have widely been used to treat lateral elbow pain (LEP). A comprehensive systematic review of randomized controlled trials (RCTs) including both English and Chinese databases was conducted to assess the efficacy of acupuncture and moxibustion in the treatment of LEP.MethodsRevised STRICTA (2010) criteria were used to appraise the acupuncture procedures, the Cochrane risk of bias tool was used to assess the methodological quality of the studies. A total of 19 RCTs that compared acupuncture and/or moxibustion with sham acupuncture, another form of acupuncture, or conventional treatment were included.ResultsAll studies had at least one domain rated as high risk or uncertain risk of bias in the Cochrane risk of bias tool. Results from three RCTs of moderate quality showed that acupuncture was more effective than sham acupuncture. Results from 10 RCTs of mostly low quality showed that acupuncture or moxibustion was superior or equal to conventional treatment, such as local anesthetic injection, local steroid injection, non-steroidal anti- inflammatory drugs, or ultrasound. There were six low quality RCTs that compared acupuncture and moxibustion combined with manual acupuncture alone, and all showed that acupuncture and moxibustion combined was superior to manual acupuncture alone.ConclusionModerate quality studies suggest that acupuncture is more effective than sham acupuncture. Interpretations of findings regarding acupuncture vs. conventional treatment, and acupuncture and moxibustion combined vs. manual acupuncture alone are limited by the methodological qualities of these studies. Future studies with improved methodological design are warranted to confirm the efficacy of acupuncture and moxibustion for LEP.

Do Epidural Injections Provide Short- and Long-term Relief for Lumbar Disc Herniation? A Systematic Review.

As part of a comprehensive nonsurgical approach, epidural injections often are used in the management of lumbar disc herniation. Recent guidelines and systematic reviews have reached different conclusions about the efficacy of epidural injections in managing lumbar disc herniation. In this systematic review, we determined the efficacy (pain relief and functional improvement) of the three anatomic approaches (caudal, lumbar interlaminar, and transforaminal) for epidural injections in the treatment of disc herniation. We performed a literature search from 1966 to June 2013 in PubMed, Cochrane library, US National Guideline Clearinghouse, previous systematic reviews, and cross-references for trials studying all types of epidural injections in managing chronic or chronic and subacute lumbar disc herniation. We wanted only randomized controlled trials (RCTs) (either placebo or active controlled) to be included in our analysis, and 66 studies found in our search fulfilled these criteria. We then assessed the methodologic quality of these 66 studies using the Cochrane review criteria for RCTs. Thirty-nine studies were excluded, leaving 23 RCTs of high and moderate methodologic quality for analysis. Evidence for the efficacy of all three approaches for epidural injection under fluoroscopy was strong for short-term (<6months) and moderate for long-term (≥6months) based on the Cochrane rating system with five levels of evidence (best evidence synthesis), with strong evidence denoting consistent findings among multiple high-quality RCTs and moderate evidence denoting consistent findings among multiple low-quality RCTs or one high-quality RCT. The primary outcome measure was pain relief, defined as at least 50% improvement in pain or 3-point improvement in pain scores in at least 50% of the patients. The secondary outcome measure was functional improvement, defined as 50% reduction in disability or 30% reduction in the disability scores. Based on strong evidence for short-term efficacy from multiple high-quality trials and moderate evidence for long-term efficacy from at least one high quality trial, we found that fluoroscopic caudal, lumbar interlaminar, and transforaminal epidural injections were efficacious at managing lumbar disc herniation in terms of pain relief and functional improvement. The available evidence suggests that epidural injections performed under fluoroscopy by trained physicians offer improvement in pain and function in well-selected patients with lumbar disc herniation.

Fusion Rates of Instrumented Lumbar Spinal Arthrodesis according to Surgical Approach: A Systematic Review of Randomized Trials

BackgroundLumbar spine fusion rates can vary according to the surgical technique. Although many studies on spinal fusion have been conducted and reported, the heterogeneity of the study designs and data handling make it difficult to identify which approach yields the highest fusion rate. This paper reviews studies that compared the lumbosacral fusion rates achieved with different surgical techniques.MethodsRelevant randomized trials comparing the fusion rates of different surgical approaches for instrumented lumbosacral spinal fusion surgery were identified through highly sensitive and targeted keyword search strategies. A methodological quality assessment was performed according to the checklist suggested by the Cochrane Collaboration Back Review Group. Qualitative analysis was performed.ResultsA literature search identified six randomized controlled trials (RCTs) comparing the fusion rates of different surgical approaches. One trial compared anterior lumbar interbody fusion (ALIF) plus adjunctive posterior transpedicular instrumentation with circumferential fusion and posterolateral fusion (PLF) with posterior lumbar interbody fusion (PLIF). Three studies compared PLF with circumferential fusion. One study compared three fusion approaches: PLF, PLIF and circumferential fusion.ConclusionsOne low quality RCT reported no difference in fusion rate between ALIF with posterior transpedicular instrumentation and circumferential fusion, and PLIF and circumferential fusion. There is moderate evidence suggesting no difference in fusion rate between PLF and PLIF. The evidence on the fusion rate of circumferential fusion compared to PLF from qualitative analysis was conflicting. However, no general conclusion could be made due to the scarcity of data, heterogeneity of the trials included, and some methodological defects of the six studies reviewed.

Systematic Review on the Safety of Concomitant Use of Hypoglycemia-Inducing Drugs and Non-Steroidal Anti-Inflammatory Drugs in Patients With Musculoskeletal Pathology

ObjectivesTo analyze the safety of combining non-steroidal anti-inflammatory drugs (NSAID) and hypoglycemia-inducing drugs. MethodsA systematic review following a sensitive search strategy was performed. All articles published in MEDLINE (since 1961), EMBASE (since 1961), and Cochrane Library, up to December 2007, were examined. Selection criteria: the population (subjects taking hypoglycemia-inducing drugs: insulin or oral antidiabetic drugs [OAD]), the intervention (concomitantly use of NSAID), and the outcomes related to safety (gastrointestinal, renal, cardiovascular toxicity) and glycemic control. Titles and abstracts of retrieved articles meeting inclusion criteria from the search were reviewed. Only randomized controlled trials (RCT), or cohort studies were included. ResultsA total of 33 studies were reviewed in detail, and 11 were finally included, 10 low quality RCT, and 1 prospective cohort study with moderate quality, which included 199 patients. All patients were diabetics; mostly young or middle aged men, on different NSAID and hypoglycemic drugs. There was no evidence of important changes in patient's glycemic controls, nor in their renal function, when combining NSAID with hypoglycemia-inducing drugs. Moreover, there is no clear increase in the number of serious side effects. ConclusionsAccording to the published evidence, there are not enough arguments to contraindicate the use of NSAID with hypoglycemia-inducing drugs (insulin or OAD).

Rifampicin-impregnated central venous catheters: a meta-analysis of randomized controlled trials

The use of antimicrobial-impregnated central venous catheters (CVCs) for the prevention of CVC microbial colonization and catheter-related bloodstream infection (CRBSI) remains controversial. We performed a meta-analysis of randomized controlled trials (RCTs) evaluating CRBSI and colonization of CVCs impregnated with rifampicin-based antimicrobial combinations. Our main analysis compared the occurrence of CRBSI with rifampicin/minocycline-impregnated CVCs with that of non-rifampicin-impregnated CVCs. The PubMed and Cochrane Central Register of Controlled Trials databases were searched (until October 2006). Eight RCTs were included in the analysis. The main analysis (seven RCTs) demonstrated that rifampicin/minocycline-impregnated CVCs were associated with fewer CRBSIs compared with catheters not impregnated with rifampicin/minocycline (OR 0.23, 95% CI 0.14-0.40). The same was true regarding colonization (OR 0.46, 95% CI 0.31-0.69). Further analysis, comparing rifampicin-based CVCs with non-rifampicin-impregnated CVCs, demonstrated superiority of rifampicin-based CVCs in reducing colonization (OR 0.38, 95% CI 0.24-0.62) and CRBSI (OR 0.24, 95% CI 0.14-0.40). Similar results, suggesting superiority of rifampicin/minocycline-impregnated CVCs, were noted in a subgroup analysis of colonization and CRBSIs in which rifampicin/minocycline-impregnated CVCs were compared with simple, non-tunnelled, non-antimicrobially impregnated CVCs, a subgroup analysis that was performed by excluding low quality RCTs, and a subgroup analysis for colonization comprising studies in which the sonication technique was used. No serious adverse events and no difference in mortality between the two treatment groups were reported. No clear conclusions can be made regarding the impact of the use of rifampicin/minocycline-impregnated CVCs on the development of antimicrobial resistance based on the available data. The available evidence suggests that rifampicin/minocycline-impregnated CVCs are safe and effective in reducing the rate of catheter colonization and CRBSI. Further research should focus on the possible development of resistance and on pharmacoeconomic issues related to the use of rifampicin/minocycline-impregnated CVCs.

The effectiveness of bone density measurement and associated treatments for prevention of fractures. An international collaborative review.

This review assesses the evidence regarding the effectiveness of bone density measurement (BDM) screening and related interventions--hormone replacement therapy (HRT) and intranasal salmon calcitonin (SCT[N])--in menopausal women to prevent fractures in later life. Data sources included systematic reviews of evidence and relevant primary studies identified through literature searches on MEDLINE and EMBASE. Study selection included trials of BDM screening programs, prospective studies examining the predictive value of BDM, randomized controlled trials, cohort studies, and case-control studies of HRT and SCT (N). The evidence was evaluated using a classification system incorporating study design and quality. Outcomes were measured in terms of relative risk of fracture for a 1 SD decrease in bone mineral density below the age-adjusted mean, relative risks or odds ratios for fractures associated with treatments, and proportion of hip fractures potentially prevented by BDM screening linked to treatments. Fair evidence from prospective cohort studies suggests that BDM can predict the risk of fractures, but not with high accuracy. Fair evidence from low-quality randomized controlled trials and observational studies suggests that HRT and SCT(N) are efficacious in preventing fractures. Good evidence supports the efficacy of these treatments in preserving bone mass, but there is fair evidence that the effect wears off after cessation of therapy. There is little evidence on the impact of screening menopausal women with BDM in association with HRT or SCT(N) treatment. Estimates based on combining existing evidence regarding the predictive value of BDM and efficacy of HRT suggests that 1-7% of hip fractures might be prevented.