RCT Evidence Research Articles

Surgical Management of Lumbar Radiculopathy: a Systematic Review.

Lumbar radiculopathy is characterized by radiating pain with or without motor weakness or sensory disturbances; the point prevalence ranges from 1.6 to 13.4%. The objective of this review was to determine the efficacy, safety, and cost of surgical versus nonsurgical management of symptomatic lumbar radiculopathy in adults. We searched PubMed from January 1, 2007, to April 10, 2019 with hand searches of systematic reviews for studies prior to 2007. One reviewer extracted data and a second checked for accuracy. Two reviewers completed independent risk of bias and strength of evidence ratings. We included seven RCTs (N = 1158) and three cost-effectiveness analysis. Surgery reduced leg pain by 6 to 26 points more than nonsurgical interventions as measured on a 0- to 100-point visual analog scale of pain at up to 26 weeks follow-up; differences between groups did not persist at 1 year or later. The evidence was somewhat mixed for function and disability in follow-up through 26 weeks (standardized mean difference [SMD] - 0.16 (95% CI, - 0.30 to - 0.03); minimal differences were observed at 2 years (SMD - 0.06 (95% CI, - 0.20 to 0.07). There were similar improvements in quality of life, neurologic symptoms, and return to work. No surgical deaths occurred and surgical morbidity was infrequent. The incidence of reoperations ranged from 0 to 10%. The average cost per quality-adjusted life year gained from a healthcare payor perspective ranged from $51,156 to $83,322 for surgery compared to nonsurgical interventions. Most findings are based on a body of RCT evidence graded as low to very low certainty. Compared with nonsurgical interventions, surgery probably reduces pain and improves function in the short- and medium-term, but this difference does not persist in the long-term. Although surgery appears to be safe, it may or may not be cost-effective depending on a decision maker's willingness to pay threshold.

Can smokers be helped to reduce the harm caused by cigarette smoking by smoking fewer cigarettes or using different tobacco products?

Some people may be willing to cut down the number of cigarettes smoked but may not be ready to quit completely. Long‐term change in health status would be a direct indicator of whether cutting down reduces long‐term smoking‐related harm, but no RCT evidence investigating this was found. Reviewers instead found studies looking at smoking reduction and/or cessation rates and found that people can be helped to reduce the number of cigarettes and to quit over the long term by using nicotine replacement therapy (NRT). However, findings were based on a relatively small number of trials and do not directly show the harm reduction and evidence is of low or very low certainty.

Is there RCT evidence to support using the larvicide pyriproxyfen to prevent malaria transmission?

Is there RCT evidence to support using the larvicide pyriproxyfen to prevent malaria transmission?

Is there RCT evidence showing the effects of antigen-specific active immunotherapy in women with ovarian cancer?

Is there RCT evidence showing the effects of antigen-specific active immunotherapy in women with ovarian cancer?

52. Not every rheumatologic headache is giant cell arteritis: a case of aseptic meningitis on a background of rheumatoid arthritis

IntroductionA 65-year-old Caucasian lady had a background of longstanding seropositive rheumatoid arthritis (RA) for which multiple disease modifying drugs and biologics had been tried, but then stopped due to either inefficacy or intolerance. She presented with possible vasculitis and was initially treated and investigated for giant cell arteritis (GCA).Case descriptionThis patient presented with temporal headache and right-sided visual field loss, with tenderness over a weakly palpable right temporal artery. No jaw claudication or other cranial nerve abnormality and peripheral nervous system examination was normal. She was commenced on prednisolone and the ophthalmologist decided against temporal artery biopsy. She subsequently developed episodes of tonic-clonic seizure and reduced consciousness, which would be unexplained by GCA.ESR 70 and CRP 28. ANCA and ANA negative, rheumatoid factor positive and anti-CCP antibodies >600.Gadolinium-enhanced MRI brain showed subdural effusions in the left frontal/parietal lobes alongside effacement of the gyri, indicating lepatomeningitis. Lumbar puncture showed increased cerebral spinal fluid (CSF) protein of 1.25g/L (0.1-0.4) and mildly reduced glucose of 2.1mmol/L (2.2-3.9). CSF was negative for acid fast bacilli, lyme disease, cryptococcal antigen, PCR for viruses and TB, culture and extensive immunological screening. Tuberculosis T-Spot test was negative whilst PET-CT demonstrated widespread polyarthropathy but no evidence of an underlying malignancy. The patient was referred for meningeal biopsy; however it was considered too high-risk given her medical co-morbidities.As an inpatient, she developed pneumonia and two myocardial infarctions. For the next four months, she was seizure-free on levetiracetam, but still experienced right-sided facial twitching. She was commenced on a reducing regime of prednisolone on the assumption of rheumatoid meningitis and also given 12-month empirical therapy to cover for possibility of TB meningitis, although this was deemed less likely. Initially she responded to prednisolone but upon dose reduction, she noticed worsening incoordination and unsteadiness, with simultaneous joint flare-up, indicating that immunosuppression was beneficial to her neurological status. Azathioprine was introduced as a steroid-sparing agent but she developed abnormal liver function and hence mycophenolate has been used instead. No side effects have been reported; she has remained seizure-free and reports an improvement in her neurological status. DiscussionInitially it was appropriate to treat as GCA given very typical history. However, the presence of other unexplained symptoms and MRI findings led the decision that the diagnosis was not purely vasculitic in origin. MRI brain and CSF findings were consistent with aseptic meningitis, typically where there is meningeal inflammation with negative Gram stain and culture of CSF, often with pleocytosis. Although predominantly caused by enteroviruses; it can occur secondary to malignancy, drugs and autoimmune disease. These causes were considered, however the presence of active rheumatoid arthritis made a diagnosis of rheumatoid meningitis likely. This uncommon complication of seropositive rheumatoid arthritis was described by Bathon et al as having three hallmark neuropathological findings; rheumatoid nodules, pachymeningitis and vasculitis. A diagnostic challenge is the lack of correlation between synovitis and neurological presentation. Presentation ranges from cranial/peripheral nerve dysfunction to seizures and altered mental state. In the CSF we expect to find high protein and reduced glucose with sporadic pleocytosis. Findings from MRI and CSF analysis can be variable. Ultimately rheumatoid meningitis as described in the literature is diagnosed by histopathology at biopsy, but this is not always available in clinical practice, and sometimes empirical treatment has to be given.Key learning pointsRheumatoid meningitis is a rare complication of RA, but can present with stroke-like episodes or seizures, so this diagnosis should always be considered in RA patients presenting in such a way. Despite high mortality and the lack of any evidence-based guidelines, combinations of steroids alongside cyclophosphamide, azathioprine and methotrexate are reported to have improved prognosis in some patients. The lack of any RCT evidence means the condition has to be managed according to expert opinion, which may require close co-operation between specialties such as neurology, infectious diseases and rheumatology to achieve a good outcome.Conflicts of interestThe authors have declared no conflicts of interest.

087 Endovascular clot retrieval (ECR) in the elderly. For better or worse in the real world?

IntroductionAcross multicentre trials ECR is safe and effective in octogenarians. Despite RCT evidence elderly patients may be denied ECR due to perceived poor risk-benefit. We examine impact of age on ECR outcomes and outcomes in transcatheter aortic valve implantation (TAVI) cases (where stroke risk is high), in a real world setting.MethodsWe analysed 311 consecutive ECR cases between 2016 and 2019 in 10 year age bands for ECR outcomes including 90 day mRS and mortality. Impact of premorbid function (mRS), NIHSS, recorded co-morbidities, and aetiology was assessed. TAVI case outcomes were examined.ResultsThirty one percent of ECR outcome cases were over 79 years of age; 90 day mortality was 34%; 25% had a 90 day mRS 0–2. Early NIHSS improvement was 5. Ninety-day mortality and mRS 0–2 for 10–19 (n=3), 20–29 (n=2), 30–39 (n=4), 40–49 (n=23), 50–59 (n=27), 60–69 (n=69), 70–79 (n=84),80–89 (n=62) and 90–99 (n=11) years were 0 and 100%, 0 and 100%, 33 and 67%, 4 and 78%, 15 and 52%, 13 and 49%, 17 and 33%, 24 and 2% and 55 and 18%, respectively. There was 9% lost to follow-up.Six TAVI cases had a NIHSS of 8–20 and pre-morbid mRS<3, four with mRS 0. Mean 24 hour NIHSS improvement was 8.ConclusionWithout age exclusions older patients had worse unadjusted outcomes. However, patients over 79 years had clinically important early improvement in NIHSS score and ninety day outcomes were comparable to favourable RCT data and TAVI patients also had early improvement.

Does ambulatory oxygen improve quality of life in patients with fibrotic lung disease? Results from the AmbOx trial.

The AmbOx trial provides RCT evidence for ambulatory oxygen therapy improving HRQoL in patients with fibrotic ILD http://ow.ly/uHC030nEzsz

PO-1132 RCT evidence in 2018 ASTRO/ASCO/AUA guidelines for hypofractionated radiotherapy in prostate cancer

PO-1132 RCT evidence in 2018 ASTRO/ASCO/AUA guidelines for hypofractionated radiotherapy in prostate cancer

Is there RCT evidence to support the use of uterine artery embolization (UAE) in women with symptomatic uterine fibroids?

Is there RCT evidence to support the use of uterine artery embolization (UAE) in women with symptomatic uterine fibroids?

Effectiveness of dietetic consultation for lowering blood lipid levels in the management of cardiovascular disease risk: A systematic review and meta-analysis of randomised controlled trials.

AimEvidence of the effectiveness of dietetic consultation for the management of cardiovascular disease (CVD) risk factors has not been previously synthesised. A systematic review and four meta‐analyses evaluated the effectiveness of dietetic consultation for lowering blood lipid levels in high‐risk individuals in primary health‐care settings.MethodsOf the 4860 records identified, 10 eligible randomised controlled trials (RCTs, n = 1530) were evaluated for reporting blood lipid outcomes following dietetic consultation (DN)—defined as at least one exclusive individual face‐to‐face consultation with a dietitian and comparators (C)—defined as no nutrition intervention or usual or minimal care provided by physicians and/or nurses.ResultsDN groups were effective for lowering blood lipid levels across nine studies reporting total cholesterol (TC) and LDL; and across five of six studies reporting triglycerides (TG). Between‐group differences were not consistently assessed, with significance levels reported in four studies all in favour of DN, P < 0.05. Meta‐analyses for TC and LDL (seven studies) confirmed DN and C groups were equally effective, P > 0.05; and for TG (six studies) DN groups were significantly more effective than C groups, P < 0.05).ConclusionsThis review provides RCT evidence that dietetic counselling is effective for lowering TG levels and at least as effective as usual and minimal care for improving cholesterol levels in high‐risk individuals in primary health care. However, more adequate reporting of methods and greater consistency in timing interventions and data collection will enhance the quality of the evidence and increase confidence in the health benefits of dietetic counselling for the management of CVD risk.

Is there RCT evidence to support the use of antihypertensive drugs over placebo/no treatment for primary prevention in adults with mild to moderate hypertension?

Is there RCT evidence to support the use of antihypertensive drugs over placebo/no treatment for primary prevention in adults with mild to moderate hypertension?

Is there RCT evidence to support the use of transmyocardial laser revascularization compared with medical therapy for the treatment of refractory angina?

Is there RCT evidence to support the use of transmyocardial laser revascularization compared with medical therapy for the treatment of refractory angina?

Evidence into practice: protocol for a new mixed-methods approach to explore the relationship between trials evidence and clinical practice through systematic identification and analysis of articles citing randomised controlled trials

IntroductionRandomised controlled trials (RCTs) provide high-quality evidence to inform practice. However, much routine care is not based on available RCT evidence. Understanding this disconnect may improve trial design, reporting and...

Which anticoagulants should be used for stroke prevention in non-valvular atrial fibrillation and severe chronic kidney disease?

Non-valvular atrial fibrillation is common in patients with severe chronic kidney disease (CKD) and historically patients have been treated with vitamin K antagonists (VKA). However, these agents have questionable efficacy and are associated with increased bleeding risk. Non-vitamin K oral anticoagulants (NOAC) have advantages over VKA in early stage CKD. In this review, we sought to establish evidence for best practice in patients with severe CKD (creatinine clearance <30 ml/min including dialysis patients) and nonvalvular atrial fibrillation. Registry studies have shown that the relative risk of stroke in untreated atrial fibrillation in dialysis patients is lower than in patients in the general population, but VKA are associated with increased haemorrhagic stroke in this high-risk population. A large meta-analysis of dialysis patients found no benefit of VKA in reducing stroke, but an increased bleeding risk. However, studies from Scandinavia have emphasized that risk of VKA are mitigated by increasing the time in anticoagulant therapeutic range (TTR). The consensus from the Kidney Disease: Improving Global Outcomes conference on arrhythmia in CKD was that if dialysis patients required OAC for atrial fibrillation then apixaban could be considered in preference to VKA. Best practice prophylaxis against stroke risk in dialysis patients with atrial fibrillation is still an area of uncertainty. If OAC is indicated because of high risk, then treatment options include VKA with careful attention to increased TTR, or reduced dose apixaban, which would be off label in Europe. No RCT evidence currently exists to guide therapy, but RCTS of apixaban versus VKA in dialysis patients are currently underway.

Evaluation of organized cancer screening programs: general aspects and current status in Germany

In the past decades, it has been increasingly recognized that cancer screening is not always or not exclusively beneficial and, in the case of some measures, the negative effects may even outweigh the benefits. This has fundamentally changed the significance and emphasis placed on the evaluation of cancer screening programs. Generally, there is adistinction between an endpoint evaluation, which assesses the effectiveness or risk/benefit ratio, and aprocess evaluation, which aims to ensure optimum implementation of the program.Prior to the nationwide introduction of ascreening measure, proof of effectiveness should ideally be provided by arandomized controlled trial (RCT), in which persons without ascreening offer form the control group. From ascientific point of view, this study design is by far the best method to evaluate the endpoint, as it avoids biases that may distort the results in observational studies. RCT evidence on cancer screening measures currently offered by statutory health insurance providers in Germany - if available at all - originates exclusively from other countries.When mammography screening was introduced as the first organized screening program in Germany, comprehensive measures for process evaluation were taken. In April 2013, the legal basis for the transfer of colorectal and cervical cancer screening into organized programs was created. According to the legal provisions, both aprocess and an endpoint evaluation are planned for the new programs. It remains to be seen how the necessary data flows will be conceptualized and later implemented in practice.

PRM261 - INCORPORATION OF OBSERVATIONAL DATA INTO NETWORK META-ANALYSIS: A CASE STUDY

The RCT represents the ‘gold standard’ for generating estimates of relative treatment effect. However observational data are considered more direct, relevant and generalisable to the wider population. Meta-analyses are usually conducted based on RCT evidence but interest in the inclusion of observational data in the decision-making process is growing. A case study that incorporates observational data in a network meta-analysis (NMA) is presented. A previously conducted systematic review and NMA based on RCT data of treatments for stroke prevention in atrial fibrillation was updated. A single comparative observational study (comparing 110/150 mg dabigatran versus vitamin K antagonist [VKA]) was identified and incorporated into the NMA analysis for the outcome of mortality by i) using this study to inform prior distributions and ii) using a design-adjusted analysis; adjusting the estimates from the observational data for potential bias. The inclusion of the observational data in the NMA at face value resulted in lower odds of mortality of 150 mg/110 mg dabigatran versus VKA. In comparison, the associated 95% CrIs of the same treatment comparison estimates did not include the null value when the NMA was restricted to RCT evidence only. When 30% overestimation of observational evidence is assumed in the analysis, the observational evidence requires further discounting (adjustment for overprecision) before it could be concluded that the 110 mg or 150 mg dose of dabigatran does not decrease the odds of mortality compared with adjusted dose VKA. In the exploratory analyses the conclusions around the relative efficacy of the NOACs are robust to the beliefs around the bias in terms of overprecision and overestimation within the observational data. Observational data can provide additional information on relative treatment effects and it may be relevant to include such data in meta-analyses to allow a decision-making process which includes all available data.

Bowel Cancer Screening in Australia: Research and Tactics to Achieve an Advocacy Goal

Background and context: Bowel cancer is the second leading cause of cancer death in Australia, yet survival is above 90% if it is detected at stage one. Cancer Council Australia has advocated since 1997 (when RCT evidence was published) for a national government-run screening program—a challenge to any government, given the costs and changes across the health system, irrespective of the health benefits. Cancer Council Australia has advocated at every step in the program’s development, from pilot studies to securing bipartisan political support for the program´s introduction to funding allocations linked to our budget submissions. Yet cost pressures restricted the Australian Government in 2013 to implementation by 2034 - an unacceptable timeframe in view of preventable deaths over that period. To find a peer-reviewed “big number” to convince candidates in Australia´s 2013 federal election to support full implementation by 2020, Cancer Council commissioned a study of multiple screening scenarios submitted to a leading medical journal, showing our implementation plan would prevent 35,000 bowel cancer deaths by 2040. The incoming government, despite campaigning on national debt-reduction, allocated almost $100 million dollars—the centrepiece of its first health budget—to Cancer Council Australia´s plan, attributing the decision to our advice. Subsequent Cancer Council Australia research has shown the program´s life-saving benefits to be even greater if participation can be increased, and that it would achieve net savings. We continue to push for program promotion, with our peer-reviewed research showing 60% participation would prevent 84,000 bowel cancer deaths by 2040. Aim: To highlight how political advocacy and scientific research can work together by ensuring the advocacy is based on the best available evidence, with that evidence collected through a peer-reviewed study designed to deliver major policy reform. Strategy/Tactics: The key strategy/tactics were basic but often overlooked: collect the most compelling evidence of benefit, thereby making it difficult for politicians to dismiss the advocacy. The example of bowel cancer screening advocacy in Australia since 2012-13 has been presented in Australian research institutes to highlight how studies can be designed expressly to translate to a major policy outcome. Program/Policy process: Cancer Council Australia adhered to all government processes within its advocacy remit (budget submissions, being appointed to government committees, producing clinical practice guidelines) while working independently to drive the research and public policy agenda. Outcomes: The accelerated implementation of a landmark national screening program. What was learned: That even politicians obsessed with budget cuts can´t always argue with the best evidence—and that researchers can design studies that change policy and practice, if guided by political pragmatists.

Moving beyond RCT evidence in mental health?

Moving beyond RCT evidence in mental health?

Health Technology Assessments for Flash Glucose Monitoring and How to Use Them in Everyday Clinical Practice.

Various health technology assessment (HTA) agencies review new medical devices worldwide, and their recommendations can be useful in guiding clinical decision making. However, different agencies use different processes and methodologies, resulting in variation in recommendations. The objectives were to review full HTAs for a new technology for diabetes management, flash glucose monitoring (FGM), with the aim of summarizing similarities/differences in processes, methodologies, and recommendations from the perspective of everyday clinical practice. A literature review was conducted using online HTA resources. Four full HTAs were identified (Canary Islands, France, Catalunya, and Norway); one issued a conditional recommendation for patients with type 1 diabetes mellitus (T1DM) with controlled glycated hemoglobin (HbA1c) (Spain; Canary Islands), one issued a broader recommendation for patients with T1DM and T2DM (France), and two reported that there was insufficient evidence to support a recommendation (Spain [Catalunya] and Norway). The most comprehensive and stringent of the available HTAs were those in the Canary Islands and Norway, which included systematic literature reviews (SLRs), consultation with patient groups and clinicians, GRADE evidence quality assessments, and full economic models. Comprehensive HTAs either did not recommend FGM (Norway) or restricted the recommendation to a small subpopulation of the overall diabetes population (Canary Islands). HTAs represent a valuable additional resource for clinicians to consider alongside clinical evidence, guidelines, and consensus papers; however, interpreting recommendations requires an understanding of the processes behind these recommendations. In this review, comprehensive HTAs either recommended for a selected subpopulation based on RCT evidence or found insufficient evidence for a recommendation.

Cost-effectiveness of treatments for superficial venous reflux in patients with chronic venous ulceration.

BackgroundVenous leg ulcers impair quality of life significantly, with substantial costs to health services. The aim of this study was to estimate the cost‐effectiveness of interventional procedures alongside compression therapy versus compression therapy alone for the treatment of chronic venous leg ulceration.MethodsA Markov decision analytical model was developed. The main outcome measures were quality‐adjusted life‐years (QALYs) and lifetime costs per patient, from the perspective of the UK National Health Service at 2015 prices. Resource use included the initial procedures, compression therapy, primary care and outpatient consultations. The interventional procedures included superficial venous surgery, endothermal ablation and ultrasound‐guided foam sclerotherapy (UGFS). The study population was patients with a chronic venous ulcer who were eligible for either compression therapy or an interventional procedure. Data were obtained from systematic review and meta‐analysis of RCTs.ResultsSurgery gained 0·112 (95 per cent c.i. −0·011 to 0·213) QALYs compared with compression therapy alone, with a difference in lifetime costs of €−1330 (−3570 to 1262). Given the expected savings in community care, the procedure would pay for itself within 4 years. There was insufficient evidence regarding endothermal ablation and UGFS to draw conclusions.DiscussionThis modelling study found surgery to be more effective and less costly than compression therapy alone. Further RCT evidence is required for both endothermal ablation and UGFS.