The breast cancer screening programmes in the United Kingdom currently invite women aged 50-70 years for screening mammography every 3 years. Since the time the screening programmes were established, ...there has been debate, at times sharply polarised, over the magnitude of their benefit and harm, and the balance between them. The expected major benefit is reduction in mortality from breast cancer. The major harm is overdiagnosis and its consequences; overdiagnosis refers to the detection of cancers on screening, which would not have become clinically apparent in the woman's lifetime in the absence of screening. Professor Sir Mike Richards, National Cancer Director, England, and Dr Harpal Kumar, Chief Executive Officer of Cancer Research UK, asked Professor Sir Michael Marmot to convene and chair an independent panel to review the evidence on benefits and harms of breast screening in the context of the UK breast screening programmes. The panel, authors of this report, reviewed the extensive literature and heard testimony from experts in the field who were the main contributors to the debate. 85 references
Recent genetic and morphologic studies have challenged the traditional view on the pathogenesis of ovarian cancer; suggesting that ovarian cancer predominantly arises within the fallopian tubes or ...the uterus. We hypothesize that surgical removal of the fallopian tubes is associated with a reduced risk for ovarian cancer.
In this population-based cohort study, we used data on women with previous surgery on benign indication (sterilization, salpingectomy, hysterectomy, and bilateral salpingo-oophorectomy BSO, hysterectomy; n = 251465) compared with the unexposed population (n = 5449119) between 1973 and 2009 and analyzed with Cox regression models. The effects of one- and two-sided salpingectomy were considered in a subanalysis. All statistical tests were two-sided.
There was a statistically significantly lower risk for ovarian cancer among women with previous salpingectomy (HR = 0.65, 95% CI = 0.52 to 0.81) when compared with the unexposed population. In addition, statistically significant risk reductions were observed among women with previous hysterectomy (HR = 0.79, 95% CI = 0.70 to 0.88), sterilization (HR = 0.72, 95% CI = 0.64 to 0.81), and hysterectomy with BSO (HR = 0.06, 95% CI = 0.03 to 0.12). Bilateral salpingectomy was associated with a 50% decrease in risk of ovarian cancer compared with the unilateral procedure (HR = 0.35, 95% CI = 0.17 to 0.73, and 0.71, 95% CI = 0.56 to 0.91, respectively).
Salpingectomy on benign indication is associated with reduced risk of ovarian cancer. These data support the hypothesis that a substantial fraction of ovarian cancer arises in the fallopian tube. Our results suggest that removal of the fallopian tubes by itself, or concomitantly with other benign surgery, is an effective measure to reduce ovarian cancer risk in the general population.
Knee osteoarthritis (OA) is one of the leading causes of disability within the adult population. Current treatment options for OA of the knee include intra-articular (IA) hyaluronic acid (HA), a ...molecule found intrinsically within the knee joint that provides viscoelastic properties to the synovial fluid. A variety of mechanisms in which HA is thought to combat knee OA are reported in the current basic literature.
We conducted a comprehensive literature search to identify currently available primary non-clinical basic science articles focussing on the mechanism of action of IA-HA treatment. Included articles were assessed and categorized based on the mechanism of action described within them. The key findings and conclusions from each included article were obtained and analyzed in aggregate with studies of the same categorical assignment.
Chondroprotection was the most frequent mechanism reported within the included articles, followed by proteoglycan and glycosaminoglycan synthesis, anti-inflammatory, mechanical, subchondral, and analgesic actions. HA-cluster of differentiation 44 (CD44) receptor binding was the most frequently reported biological cause of the mechanisms presented. High molecular weight HA was seen to be superior to lower molecular weight HA products. HA derived through a biological fermentation process is also described as having favorable safety outcomes over avian-derived HA products.
The non-clinical basic science literature provides evidence for numerous mechanisms in which HA acts on joint structures and function. These actions provide support for the purported clinical benefit of IA-HA in OA of the knee. Future research should not only focus on the pain relief provided by IA-HA treatment, but the disease modification properties that this treatment modality possesses as well.
GRIPP2 (short form and long form) is the first international guidance for reporting of patient and public involvement in health and social care research. This paper describes the development of the ...GRIPP2 reporting checklists, which aim to improve the quality, transparency, and consistency of the international patient and public involvement (PPI) evidence base, to ensure that PPI practice is based on the best evidence
Background
Prediction models are developed to aid healthcare providers in estimating the probability or risk that a specific disease or condition is present (diagnostic models) or that a specific ...event will occur in the future (prognostic models), to inform their decision‐making. However, the overwhelming evidence shows that the quality of reporting of prediction model studies is poor. Only with full and clear reporting of information on all aspects of a prediction model can risk of bias and potential usefulness of prediction models be adequately assessed. The Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) Initiative developed a set of recommendations for the reporting of studies developing, validating or updating a prediction model, whether for diagnostic or prognostic purposes. This article describes how the TRIPOD Statement was developed.
Methods
An extensive list of items based on a review of the literature was created, which was reduced after a web‐based survey and revised during a 3‐day meeting in June 2011 with methodologists, healthcare professionals and journal editors. The list was refined during several meetings of the steering group and in e‐mail discussions with the wider group of TRIPOD contributors.
Results
The resulting TRIPOD Statement is a checklist of 22 items, deemed essential for transparent reporting of a prediction model study.
Conclusion
The TRIPOD Statement aims to improve the transparency of the reporting of a prediction model study regardless of the study methods used. The TRIPOD Statement is best used in conjunction with the TRIPOD explanation and elaboration document. A complete checklist is available at http://www.tripod‐statement.org.
Background:
Knee osteoarthritis (OA) is a common and often disabling joint disorder among adults that may result in impaired activity and daily function. A variety of treatment options are currently ...available and prescribed for knee OA depending on the severity of the disorder and physician preference. Intra-articular hyaluronic acid (IA-HA) injection is a treatment for knee OA that reportedly provides numerous biochemical and biological benefits, including shock absorption, chondroprotection, and anti-inflammatory effects within the knee. Clarity is needed as to whether the available IA-HA products should be considered for therapy as a group or whether there are significant differences in the products that need to be considered in treatment of OA of the knee.
Purpose:
To determine whether there are differences in efficacy and safety with respect to intrinsic properties of available IA-HA injections for knee OA.
Study Design:
Meta-analysis.
Methods:
A comprehensive literature search of the Medline, EMBASE, and PubMed databases was conducted for all existing randomized trials of IA-HA. The primary outcome measure analyzed was the mean pain score at the reported follow-up nearest to 26 weeks after injection. Pooled efficacy and safety results were recorded for subgroupings of HA product characteristics.
Results:
A total of 68 studies were included for analysis. Products with an average molecular weight ≥3000 kDa provided favorable efficacy results when compared with products of an average molecular weight <3000 kDa. Products with a molecular weight ≥3000 kDa demonstrated significantly fewer discontinuations due to treatment-related adverse events than did ≤1500 kDa counterparts, while trial discontinuation rates were similar between biological fermentation–derived HA products and avian-derived HA. The results did not demonstrate a significant difference in the occurrence of effusion across molecular weight subgroups. Additionally, biological fermentation–derived HA had a significantly smaller incidence of effusion than did avian-derived HA. Biological fermentation–derived HA demonstrated fewer acute flare-ups at the injection site than did avian-derived HA products, while high-molecular-weight products demonstrated the highest rate of injection site flare-up.
Conclusion:
Despite similarities, IA-HA products should not be treated as a group, as there are differences in IA-HA products that influence both efficacy and safety. In the available literature, IA-HA products with a molecular weight ≥3000 kDa and those derived from biological fermentation relate to superior efficacy and safety—factors that may influence selection an IA-HA product for OA of the knee.
Objective
To develop an evidence‐based guideline for the comprehensive management of osteoarthritis (OA) as a collaboration between the American College of Rheumatology (ACR) and the Arthritis ...Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA.
Methods
We identified clinically relevant population, intervention, comparator, outcomes questions and critical outcomes in OA. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available educational, behavioral, psychosocial, physical, mind‐body, and pharmacologic therapies for OA. Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. A Voting Panel, including rheumatologists, an internist, physical and occupational therapists, and patients, achieved consensus on the recommendations.
Results
Based on the available evidence, either strong or conditional recommendations were made for or against the approaches evaluated. Strong recommendations were made for exercise, weight loss in patients with knee and/or hip OA who are overweight or obese, self‐efficacy and self‐management programs, tai chi, cane use, hand orthoses for first carpometacarpal (CMC) joint OA, tibiofemoral bracing for tibiofemoral knee OA, topical nonsteroidal antiinflammatory drugs (NSAIDs) for knee OA, oral NSAIDs, and intraarticular glucocorticoid injections for knee OA. Conditional recommendations were made for balance exercises, yoga, cognitive behavioral therapy, kinesiotaping for first CMC OA, orthoses for hand joints other than the first CMC joint, patellofemoral bracing for patellofemoral knee OA, acupuncture, thermal modalities, radiofrequency ablation for knee OA, topical NSAIDs, intraarticular steroid injections and chondroitin sulfate for hand OA, topical capsaicin for knee OA, acetaminophen, duloxetine, and tramadol.
Conclusion
This guideline provides direction for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision‐making that accounts for patients’ values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.
Objective
To develop an evidence‐based guideline for the comprehensive management of osteoarthritis (OA) as a collaboration between the American College of Rheumatology (ACR) and the Arthritis ...Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA.
Methods
We identified clinically relevant population, intervention, comparator, outcomes questions and critical outcomes in OA. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available educational, behavioral, psychosocial, physical, mind‐body, and pharmacologic therapies for OA. Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. A Voting Panel, including rheumatologists, an internist, physical and occupational therapists, and patients, achieved consensus on the recommendations.
Results
Based on the available evidence, either strong or conditional recommendations were made for or against the approaches evaluated. Strong recommendations were made for exercise, weight loss in patients with knee and/or hip OA who are overweight or obese, self‐efficacy and self‐management programs, tai chi, cane use, hand orthoses for first carpometacarpal (CMC) joint OA, tibiofemoral bracing for tibiofemoral knee OA, topical nonsteroidal antiinflammatory drugs (NSAIDs) for knee OA, oral NSAIDs, and intraarticular glucocorticoid injections for knee OA. Conditional recommendations were made for balance exercises, yoga, cognitive behavioral therapy, kinesiotaping for first CMC OA, orthoses for hand joints other than the first CMC joint, patellofemoral bracing for patellofemoral knee OA, acupuncture, thermal modalities, radiofrequency ablation for knee OA, topical NSAIDs, intraarticular steroid injections and chondroitin sulfate for hand OA, topical capsaicin for knee OA, acetaminophen, duloxetine, and tramadol.
Conclusion
This guideline provides direction for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision‐making that accounts for patients’ values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.
While the patient and public involvement (PPI) evidence base has expanded over the past decade, the quality of reporting within papers is often inconsistent, limiting our understanding of how it ...works, in what context, for whom, and why.
To develop international consensus on the key items to report to enhance the quality, transparency, and consistency of the PPI evidence base. To collaboratively involve patients as research partners at all stages in the development of GRIPP2.
The EQUATOR method for developing reporting guidelines was used. The original GRIPP (Guidance for Reporting Involvement of Patients and the Public) checklist was revised, based on updated systematic review evidence. A three round Delphi survey was used to develop consensus on items to be included in the guideline. A subsequent face-to-face meeting produced agreement on items not reaching consensus during the Delphi process.
One hundred forty-three participants agreed to participate in round one, with an 86% (123/143) response for round two and a 78% (112/143) response for round three. The Delphi survey identified the need for long form (LF) and short form (SF) versions. GRIPP2-LF includes 34 items on aims, definitions, concepts and theory, methods, stages and nature of involvement, context, capture or measurement of impact, outcomes, economic assessment, and reflections and is suitable for studies where the main focus is PPI. GRIPP2-SF includes five items on aims, methods, results, outcomes, and critical perspective and is suitable for studies where PPI is a secondary focus.
GRIPP2-LF and GRIPP2-SF represent the first international evidence based, consensus informed guidance for reporting patient and public involvement in research. Both versions of GRIPP2 aim to improve the quality, transparency, and consistency of the international PPI evidence base, to ensure PPI practice is based on the best evidence. In order to encourage its wide dissemination this article is freely accessible on The BMJ and
journal websites.
Background Randomized trials without reported adequate allocation concealment have been shown to overestimate the benefit of experimental interventions. We investigated the robustness of conclusions ...drawn from meta-analyses to exclusion of such trials. Material Random sample of 38 reviews from The Cochrane Library 2003, issue 2 and 32 other reviews from PubMed accessed in 2002. Eligible reviews presented a binary effect estimate from a meta-analysis of randomized controlled trials as the first statistically significant result that supported a conclusion in favour of one of the interventions. Methods We assessed the methods sections of the trials in each included meta-analysis for adequacy of allocation concealment. We replicated each meta-analysis using the authors' methods but included only trials that had adequate allocation concealment. Conclusions were defined as not supported if our result was not statistically significant. Results Thirty-four of the 70 meta-analyses contained a mixture of trials with unclear or inadequate concealment as well as trials with adequate allocation concealment. Four meta-analyses only contained trials with adequate concealment, and 32, only trials with unclear or inadequate concealment. When only trials with adequate concealment were included, 48 of 70 conclusions (69%; 95% confidence interval: 56–79%) lost support. The loss of support mainly reflected loss of power (the total number of patients was reduced by 49%) but also a shift in the point estimate towards a less beneficial effect. Conclusion Two-thirds of conclusions in favour of one of the interventions were no longer supported if only trials with adequate allocation concealment were included.
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