Rating of Included Trials on the Efficacy-Effectiveness Spectrum (RITES): development of a new tool for systematic reviews

AbstractBackground Randomized trials may be designed to provide evidence more strongly related to efficacy or effectiveness of an intervention. When systematic reviews are used to inform clinical or policy decisions, it is important to know the efficacy-effectiveness nature of the included trials. Objective To develop a tool to characterize randomized trials included in a systematic review on an efficacy-effectiveness continuum. Methods We extracted rating domains and descriptors from existing tools, and used a modified Delphi procedure to condense the domains and develop a new tool. The feasibility and inter-rater reliability of the tool was tested on trials from 4 systematic reviews. Results The RITES (Rating of Included Trials on the Efficacy-effectiveness Spectrum) tool rates clinical trials on a 5-point Likert scale in four domains: (1) participant characteristics, (2) trial setting, (3) flexibility of interventions, and (4) clinical relevance of interventions. When RITES was piloted on trials from 3 reviews by unaffiliated raters, ratings were variable (Intraclass Correlation Coefficient 0.25-0.66 for the four domains), but when RITES was used on 1 review by the review authors with expertise on the topic the ratings were consistent (ICCs >0.80. Conclusion RITES may help to characterize the efficacy-effectiveness nature of trials included in systematic reviews

Development and validation of a pain monitoring app for patients with musculoskeletal conditions (The Keele pain recorder feasibility study).

BACKGROUND: Assessing daily change in pain and related symptoms help in diagnosis, prognosis, and monitoring response to treatment. However, such changes are infrequently assessed, and usually reviewed weeks or months after the start of treatment. We therefore developed a smartphone application (Keele Pain Recorder) to record information on the severity and impact of pain on daily life. Specifically, the study goal was to assess face, content and construct validity of data collection using the Pain Recorder in primary care patients receiving new analgesic prescriptions for musculoskeletal pain, as well as to assess its acceptability and clinical utility. METHODS: The app was developed with Keele's Research User Group (RUG), a clinical advisory group (CAG) and software developer for use on Android devices. The app recorded pain levels, interference, sleep disturbance, analgesic use, mood and side effects. In a feasibility study, patients aged >?18 attending their general practitioner (GP) with a painful musculoskeletal condition were recruited to use the app twice per day for 28?days. Face and construct validity were assessed through baseline and post-study questionnaires (Spearman's rank correlation coefficient). Usability and acceptability were determined through post-study questionnaires, and patient, GP, RUG and CAG interviews. RESULTS: An app was developed which was liked by both patients and GPs. It was felt that it offered the opportunity for GPs to discuss pain control with their patients in a new way. All participants found the app easy to use (it did not interfere with their activities) and results easy to interpret. Strong associations existed between the first 3?days (Spearman r?=?0.79) and last 3?days (r?=?0.60) of pain levels and intensity scores on the app with the validated questionnaires. CONCLUSIONS: Collaborating with patient representatives and clinical stakeholders, we developed an app which can be used to help clinicians and patients monitor painful musculoskeletal conditions in response to analgesic prescribing. Recordings were accurate and valid, especially, for pain intensity ratings, and it was easy to use. Future work needs to examine how pain trajectories can help manage changes in a patient's condition, ultimately assisting in self-management

Critical items for assessing risk of lung and colorectal cancer in primary care: a Delphi study

Background Patients with lung or colorectal cancer often present late and have a poor prognosis. Identifying diagnostic indicators to optimally assess the risk of these cancers in primary care would support early identification and timely referral for patients at increased risk. Aim To obtain consensus regarding potential diagnostic indicators that are important for assessing the risk of lung or colorectal cancer in primary care consulters presenting with lung or abdominal symptoms. Design and setting A Delphi study was conducted with 28 participants from primary and secondary care and academic settings in the UK and Europe. Method Indicators were obtained from systematic reviews, recent primary studies and consultation with experts prior to the Delphi study being conducted. Over three rounds, participants rated each diagnostic indicator in terms of its importance, ranked them in order of importance, and rated each item as crucial or not crucial to assess during a GP consultation. Results The final round resulted in 25 items remaining for each type of cancer, including established cancer symptoms such as rectal bleeding for colorectal cancer and haemoptysis for lung cancer, but also less frequently used indicators such as patients’ concerns about cancer. Conclusion This study highlights the items clinicians feel would be most crucial to include in the clinical assessment of primary care patients, a number of which have rarely been noted in the previous literature. Their importance in assessing the risk of lung or colorectal cancer will be tested as part of a large prospective cohort study (CANDID)

Exercise for lower limb osteoarthritis : systematic review incorporating trial sequential analysis and network meta-analysis

Objective: To determine whether there is sufficient evidence to conclude that exercise interventions are more effective than no exercise control and to compare the effectiveness of different exercise interventions in relieving pain and improving function in patients with lower limb osteoarthritis. Data sources: Nine electronic databases searched from inception to March 2012. Study selection: Randomised controlled trials comparing exercise interventions with each other or with no exercise control for adults with knee or hip osteoarthritis. Data extraction: Two reviewers evaluated eligibility and methodological quality. Main outcomes extracted were pain intensity and limitation of function. Trial sequential analysis was used to investigate reliability and conclusiveness of available evidence for exercise interventions. Bayesian network meta-analysis was used to combine both direct (within trial) and indirect (between trial) evidence on treatment effectiveness. Results: 60 trials (44 knee, two hip, 14 mixed) covering 12 exercise interventions and with 8218 patients met inclusion criteria. Sequential analysis showed that as of 2002 sufficient evidence had been accrued to show significant benefit of exercise interventions over no exercise control. For pain relief, strengthening, flexibility plus strengthening, flexibility plus strengthening plus aerobic, aquatic strengthening, and aquatic strengthening plus flexibility, exercises were significantly more effective than no exercise control. A combined intervention of strengthening, flexibility, and aerobic exercise was also significantly more effective than no exercise control for improving limitation in function (standardised mean difference −0.63, 95% credible interval −1.16 to −0.10). Conclusions: As of 2002 sufficient evidence had accumulated to show significant benefit of exercise over no exercise in patients with osteoarthritis, and further trials are unlikely to overturn this result. An approach combining exercises to increase strength, flexibility, and aerobic capacity is likely to be most effective in the management of lower limb osteoarthritis. The evidence is largely from trials in patients with knee osteoarthritis

Corticosteroid injection for de Quervain's tenosynovitis

Back ground De Quervain's tenosynovitis is a disorder characterised by pain on the radial (thumb) side of the wrist and functional disability of the hand. It can be treated by corticosteroid injection, splinting and surgery. Objectives To summarise evidence on the efficacy and safety of corticosteroid injections for de Quervain's tenosynovitis. Search strategy We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 2), MEDLINE (1966 to April 2009), EMBASE (1956 to April 2009), CINAHL (1982 to April 2009), AMED (1985 to April 2009), DARE, Dissertation Abstracts and PEDro (physiotherapy evidence database). Selection criteria Randomised and controlled clinical trials evaluating the efficacy and safety of corticosteroid injections for de Quervain's tenosynovitis. Data collection and analysis After screening abstracts of studies identified by the search we obtained full text articles of studies which fulfilled the selection criteria. We extracted data using a predefined electronic form. We assessed the methodological quality of included trials by using the checklist developed by Jadad and the Delphi list. We extracted data on the primary outcome measures: treatment success; severity of pain or tenderness at the radial styloid; functional impairment of the wrist or hand; and outcome of Finkelstein's test, and the secondary outcome measures: proportion of patients with side effects; type of side effects and patient satisfaction with injection treatment. Main results We found one controlled clinical trial of 18 participants (all pregnant or lactating women) that compared one steroid injection with methylprednisolone and bupivacaine to splinting with a thumb spica. All patients in the steroid injection group (9/9) achieved complete relief of pain whereas none of the patients in the thumb spica group (0/9) had complete relief of pain, one to six days after intervention (number needed to treat to benefit (NNTB) = 1, 95% confidence interval (CI) 0.8 to 1.2). No side effects or local complications of steroid injection were noted. Authors' conclusions The efficacy of corticosteroid injections for de Quervain's tenosynovitis has been studied in only one small controlled clinical trial, which found steroid injections to be superior to thumb spica splinting. However, the applicability of our findings to daily clinical practice is limited, as they are based on only one trial with a small number of included participants, the methodological quality was poor and only pregnant and lactating women participated in the study. No adverse effects were observed

Prognostic factors for persistent pain after a distal radius fracture: A systematic review

Introduction: The aim of this systematic review was to synthesize the evidence regarding prognostic factors for persistent pain, including Complex Regional Pain Syndrome (CRPS), after a distal radius fracture (DRF), a common condition after which persistent pain can develop. Methods: Medline, Pubmed, Embase, Psychinfo, CINAHL, BNI, AMED and the Cochrane Register of Clinical Trials were searched from inception to May 2021 for prospective longitudinal prognostic factor studies investigating persistent pain in adults who had sustained a DRF. The Quality in Prognostic Studies (QUIPS) tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework were used to assess the strength of evidence. Results: A search yielded 440 studies of which 7 studies met full eligibility criteria. From five studies we found low evidence for high baseline pain or an ulnar styloid fracture as prognostic factors for persistent pain, and very low evidence for diabetes or older age. From two studies, investigating an outcome of CRPS, there was low evidence for high baseline pain, slow reaction time, dysynchiria, swelling and catastrophising as prognostic factors, and very low evidence for depression. Sex was found not to be a prognostic factor for CRPS or persistent pain. Conclusions: The associations between prognostic factors and persistent pain following a DRF are unclear. The small number of factors investigated in more than one study, along with poor reporting and methodological limitations contributed to an assessment of low to very low strength of evidence. Further prospective studies, investigating psychosocial factors as candidate predictors of multidimensional pain outcomes are recommended

Does metformin protect against osteoarthritis? An electronic health record cohort study

BackgroundObesity is a major risk factor for osteoarthritis (OA) whilst there is some evidence that diabetes also increases risk. Metformin is a common oral treatment for those with diabetes.ObjectiveThe aim is to investigate whether metformin reduces the risk of OA.MethodsThis was a cohort study set within the Consultations in Primary Care Archive, with 3217 patients with type 2 diabetes. Patients at 13 general practices with recorded type 2 diabetes in the baseline period (2002–2003) and no prior record of OA were identified. Exposure was a prescription for metformin. Outcome was an OA record during follow up. Cox proportional hazard models with Gamma frailty term were fitted: adjusted for age, gender, deprivation, and comorbidity.ResultsThere was no association between prescribed metformin treatment at baseline and OA (adjusted HR: 1.02, 95% CI: 0.91, 1.15). A similar non- significant association was found when allowing exposure status of prescription of metformin to vary over time

GRAPPA Treatment Recommendations: An Update From the 2020 GRAPPA Annual Meeting

Throughout 2020, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has been working to update the GRAPPA treatment recommendations for psoriasis and psoriatic arthritis (PsA). The planned methodology for this update was published previously, and herein we provide an update on progress so far, including details of the systematic literature searches undertaken. GRAPPA is committed to regular updates of its treatment recommendations to incorporate the many significant therapeutic advances that have taken place in the PsA literature since the previous recommendation publication in 2015. The development and updating of treatment recommendations for optimal treatment approaches for patients with PsA has been an important mission of the GRAPPA since its inception. GRAPPA is currently finalizing domain-specific recommendations with an aim to produce updated treatment recommendations for publication in 2021

Study protocol for the development and internal validation of Schizophrenia Prediction of Resistance to Treatment (SPIRIT): a clinical tool for predicting risk of treatment resistance to antipsychotics in first-episode schizophrenia

INTRODUCTION: Treatment-resistant schizophrenia (TRS) is associated with significant impairment of functioning and high treatment costs. Identification of patients at high risk of TRS at the time of their initial diagnosis may significantly improve clinical outcomes and minimise social and functional disability. We aim to develop a prognostic model for predicting the risk of developing TRS in patients with first-episode schizophrenia and to examine its potential utility and acceptability as a clinical decision tool. METHODS AND ANALYSIS: We will use two well-characterised longitudinal UK-based first-episode psychosis cohorts: Aetiology and Ethnicity in Schizophrenia and Other Psychoses and Genetics and Psychosis for which data have been collected on sociodemographic and clinical characteristics. We will identify candidate predictors for the model based on current literature and stakeholder consultation. Model development will use all data, with the number of candidate predictors restricted according to available sample size and event rate. A model for predicting risk of TRS will be developed based on penalised regression, with missing data handled using multiple imputation. Internal validation will be undertaken via bootstrapping, obtaining optimism-adjusted estimates of the model's performance. The clinical utility of the model in terms of clinically relevant risk thresholds will be evaluated using net benefit and decision curves (comparative to competing strategies). Consultation with patients and clinical stakeholders will determine potential thresholds of risk for treatment decision-making. The acceptability of embedding the model as a clinical tool will be explored using qualitative focus groups with up to 20 clinicians in total from early intervention services. Clinicians will be recruited from services in Stafford and London with the focus groups being held via an online platform. ETHICS AND DISSEMINATION: The development of the prognostic model will be based on anonymised data from existing cohorts, for which ethical approval is in place. Ethical approval has been obtained from Keele University for the qualitative focus groups within early intervention in psychosis services (ref: MH-210174). Suitable processes are in place to obtain informed consent for National Health Service staff taking part in interviews or focus groups. A study information sheet with cover letter and consent form have been prepared and approved by the local Research Ethics Committee. Findings will be shared through peer-reviewed publications, conference presentations and social media. A lay summary will be published on collaborator websites