Objective To determine the diagnostic accuracy of tuning fork tests for detecting fractures. Design Systematic review of primary studies evaluating the diagnostic accuracy of tuning fork tests for ...the presence of fracture. Data source We searched MEDLINE, CINAHL, AMED, EMBASE, Sports Discus, CAB Abstracts and Web of Science from commencement to November 2012. We manually searched the reference lists of any review papers and any identified relevant studies. Study selection and data extraction Two reviewers independently reviewed the list of potentially eligible studies and rated the studies for quality using the QUADAS-2 tool. Data were extracted to form 2×2 contingency tables. The primary outcome measure was the accuracy of the test as measured by its sensitivity and specificity with 95% CIs. Data synthesis We included six studies (329 patients), with two types of tuning fork tests (pain induction and loss of sound transmission). The studies included patients with an age range 7–60 years. The prevalence of fracture ranged from 10% to 80%. The sensitivity of the tuning fork tests was high, ranging from 75% to 100%. The specificity of the tests was highly heterogeneous, ranging from 18% to 95%. Conclusions Based on the studies in this review, tuning fork tests have some value in ruling out fractures, but are not sufficiently reliable or accurate for widespread clinical use. The small sample size of the studies and the observed heterogeneity make generalisable conclusion difficult.
For at least 25 years, hypertension guidelines have suggested measuring blood pressure in both arms, but GPs' acceptance of this is low. Current and past versions of major guidelines were identified ...to review and assess the degree to which they provided justification, evidence, and a description of dual-arm measurement techniques. It is suggested that if guidelines better justified recommendations and cited primary literature to support claims, a greater percentage of practitioners might accept and adhere to such guidance.
BackgroundPolypharmacy interventions are resource-intensive and should be targeted to those at risk of negative health outcomes. Our aim was to develop and internally validate prognostic models to ...predict health-related quality of life (HRQoL) and the combined outcome of falls, hospitalisation, institutionalisation and nursing care needs, in older patients with multimorbidity and polypharmacy in general practices.MethodsDesign: two independent data sets, one comprising health insurance claims data (n=592 456), the other data from the PRIoritising MUltimedication in Multimorbidity (PRIMUM) cluster randomised controlled trial (n=502). Population: ≥60 years, ≥5 drugs, ≥3 chronic diseases, excluding dementia. Outcomes: combined outcome of falls, hospitalisation, institutionalisation and nursing care needs (after 6, 9 and 24 months) (claims data); and HRQoL (after 6 and 9 months) (trial data). Predictor variables in both data sets: age, sex, morbidity-related variables (disease count), medication-related variables (European Union-Potentially Inappropriate Medication list (EU-PIM list)) and health service utilisation. Predictor variables exclusively in trial data: additional socio-demographics, morbidity-related variables (Cumulative Illness Rating Scale, depression), Medication Appropriateness Index (MAI), lifestyle, functional status and HRQoL (EuroQol EQ-5D-3L). Analysis: mixed regression models, combined with stepwise variable selection, 10-fold cross validation and sensitivity analyses.ResultsMost important predictors of EQ-5D-3L at 6 months in best model (Nagelkerke’s R² 0.507) were depressive symptoms (−2.73 (95% CI: −3.56 to −1.91)), MAI (−0.39 (95% CI: −0.7 to −0.08)), baseline EQ-5D-3L (0.55 (95% CI: 0.47 to 0.64)). Models based on claims data and those predicting long-term outcomes based on both data sets produced low R² values. In claims data-based model with highest explanatory power (R²=0.16), previous falls/fall-related injuries, previous hospitalisations, age, number of involved physicians and disease count were most important predictor variables.ConclusionsBest trial data-based model predicted HRQoL after 6 months well and included parameters of well-being not found in claims. Performance of claims data-based models and models predicting long-term outcomes was relatively weak. For generalisability, future studies should refit models by considering parameters representing well-being and functional status.
The translation of evidence from clinical trials into practice is complex. One approach to facilitating this translation is to consider the 'implementability' of trials as they are designed and ...conducted. Implementability of trials refers to characteristics of the design, execution and reporting of a late-phase clinical trial that can influence the capacity for the evidence generated by that trial to be implemented. On behalf of the Australian Clinical Trials Alliance (ACTA), the national peak body representing networks of clinician researchers conducting investigator-initiated clinical trials, we conducted a pragmatic literature review to develop a concept map of implementability.
Documents were included in the review if they related to the design, conduct and reporting of late-phase clinical trials; described factors that increased or decreased the capacity of trials to be implemented; and were published after 2009 in English. Eligible documents included systematic reviews, guidance documents, tools or primary studies (if other designs were not available). With an expert reference group, we developed a preliminary concept map and conducted a snowballing search based on known relevant papers and websites of key organisations in May 2019.
Sixty-five resources were included. A final map of 38 concepts was developed covering the domains of validity, relevance and usability across the design, conduct and reporting of a trial. The concepts drew on literature relating to implementation science, consumer engagement, pragmatic trials, reporting, research waste and other fields. No single resource addressed more than ten of the 38 concepts in the map.
The concept map provides trialists with a tool to think through a range of areas in which practical action could enhance the implementability of their trials. Future work could validate the strength of the associations between the concepts identified and implementability of trials and investigate the effectiveness of steps to address each concept. ACTA will use this concept map to develop guidance for trialists in Australia.
This review did not include health-related outcomes and was therefore not eligible for registration in the PROSPERO register.
Blood pressure-lowering treatment reduces cardiovascular risk in patients with diabetes mellitus, but the effect varies between individuals. We sought to identify which patients benefit most from ...such treatment in a large clinical trial in type 2 diabetes mellitus. In Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) participants (n=11 140), we estimated the individual patient 5-year absolute risk of major adverse cardiovascular events with and without treatment by perindopril-indapamide (4/1.25 mg). The difference between treated and untreated risk is the estimated individual patient's absolute risk reduction (ARR). Predictions were based on a Cox proportional hazards model inclusive of demographic and clinical characteristics together with the observed relative treatment effect. The group-level effect of selectively treating patients with an estimated ARR above a range of decision thresholds was compared with treating everyone or those with a blood pressure >140/90 mm Hg using net benefit analysis. In ADVANCE, there was wide variation in treatment effects across individual patients. According to the algorithm, 43% of patients had a large predicted 5-year ARR of ≥1% (number-needed-to-treat NNT5 ≤100) and 40% had an intermediate predicted ARR of 0.5% to 1% (NNT5=100-`200). The proportion of patients with a small ARR of ≤0.5% (NNT5≥200) was 17%. Provided that one is prepared to treat at most 200 patients for 5 years to prevent 1 adverse outcome, prediction-based treatment yielded the highest net benefit. In conclusion, a multivariable treatment algorithm can identify those individuals who benefit most from blood pressure-lowering therapy in terms of ARR of major adverse cardiovascular events and may be used to guide treatment decisions in individual patients with diabetes.
http://www.clinicaltrials.gov. Unique identifier: NCT00145925.
We review controversies associated with randomized controlled trials (RCTs) stopped early for apparent benefit (truncated RCTs or tRCTs) and present our groups’ perspective. Long-established theory, ...simulations and recent empirical evidence demonstrate that tRCTs will on average overestimate treatment effects, and this overestimation may be large, particularly when tRCTs have small number of events. Theoretical considerations and simulations demonstrate that on average, meta-analyses of RCTs with appropriate stopping rules will lead to only trivial overestimation of treatment effects. However, tRCTs will disproportionally contribute to meta-analytic estimates when tRCTs occur early in the sequence of trials with few subsequent studies, publication of nontruncated RCTs is delayed, there is publication bias, or tRCTs result in a ‘freezing’ effect in which ‘correcting’ trials are never undertaken. To avoid applying overestimates of effect to clinical decision-making, clinicians should view the results of individual tRCTs with small sample sizes and small number of events with skepticism. Pooled effects from meta-analyses including tRCTs are likely to overestimate effect when there is a substantial difference in effect estimates between the tRCTs and the nontruncated RCTs, and in which the tRCTs have a substantial weight in the meta-analysis despite themselves having a relatively small number of events. Such circumstances call for sensitivity analyses omitting tRCTs.
Abbreviations: CCTR, Cochrane Central Register of Controlled Trials; FDA, US Food and Drug Administration; HTA, health technology assessment; IQWiG, Institute for Quality and Efficiency in Health ...Care; NICE, National Institute for Health and Clinical Excellence; NLM, US National Library of Medicine; SIGN, Scottish Intercollegiate Guidelines Network Provenance: Not commissioned; externally peer reviewed. ...clinicians and patients require open access to these important resources. ...although more funding for evaluative clinical research internationally remains a priority, more international collaboration could result in better use being made of resources for systematic reviewing and HTAs.
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