Quality of stepped-wedge trial reporting can be reliably assessed using an updated CONSORT::crowd-sourcing systematic review

ObjectivesThe Consolidated Standards of Reporting Trials extension for the stepped-wedge cluster randomized trial (SW-CRT) is a recently published reporting guideline for SW-CRTs. We assess the quality of reporting of a recent sample of SW-CRTs.Study Design and SettingQuality of reporting was asssessed according to the 26 items in the new guideline using a novel crowd sourcing methodology conducted independently and in duplicate, with random assignment, by 50 reviewers. We assessed reliability of the quality assessments, proposing this as a novel way to assess robustness of items in reporting guidelines.ResultsSeveral items were well reported. Some items were very poorly reported, including several items that have unique requirements for the SW-CRT, such as the rationale for use of the design, description of the design, identification and recruitment of participants within clusters, and concealment of cluster allocation (not reported in more than 50% of the reports). Agreement across items was moderate (median percentage agreement was 76% [IQR 64 to 86]). Agreement was low for several items including the description of the trial design and why trial ended or stopped for example.ConclusionsWhen reporting SW-CRTs, authors should pay particular attention to ensure clear reporting on the exact format of the design with justification, as well as how clusters and individuals were identified for inclusion in the study, and whether this was done before or after randomization of the clusters, which are crucial for risk of bias assessments. Some items, including why the trial ended, might either not be relevant to SW-CRTs or might be unclearly described in the statement

Overdiagnosis and overtreatment of breast cancer: Overdiagnosis in randomised controlled trials of breast cancer screening

Data from randomised controlled trials of mammographic screening can be used to determine the extent of any overdiagnosis, as soon as either a time equivalent to the lead-time has elapsed after the final screen, or the control arm has been offered screening. This paper reviews those randomised trials for which breast cancer incidence data are available. In recent trials in which the control group has not been offered screening, an excess incidence of breast cancer remains after many years of follow-up. In those trials in which the control arm has been offered screening, although there is a possible shift from invasive to in situ disease, there is no evidence of overdiagnosis as a result of incident screens

Health-related quality of life of children born very preterm: a multinational European cohort study

Purpose This study aims to (1) describe the health-related quality of life (HRQoL) outcomes experienced by children born very preterm (28–31 weeks’ gestation) and extremely preterm (< 28 weeks’ gestation) at five years of age and (2) explore the mediation effects of bronchopulmonary dysplasia (BPD) and severe non-respiratory neonatal morbidity on those outcomes. Methods This investigation was based on data for 3687 children born at < 32 weeks’ gestation that contributed to the EPICE and SHIPS studies conducted in 19 regions across 11 European countries. Descriptive statistics and multi-level ordinary linear squares (OLS) regression were used to explore the association between perinatal and sociodemographic characteristics and PedsQL™ GCS scores. A mediation analysis that applied generalised structural equation modelling explored the association between potential mediators and PedsQL™ GCS scores. Results The multi-level OLS regression (fully adjusted model) revealed that birth at < 26 weeks’ gestation, BPD status and experience of severe non-respiratory morbidity were associated with mean decrements in the total PedsQL™ GCS score of 0.35, 3.71 and 5.87, respectively. The mediation analysis revealed that the indirect effects of BPD and severe non-respiratory morbidity on the total PedsQL™ GCS score translated into decrements of 1.73 and 17.56, respectively, at < 26 weeks’ gestation; 0.99 and 10.95, respectively, at 26–27 weeks’ gestation; and 0.34 and 4.80, respectively, at 28–29 weeks’ gestation (referent: birth at 30–31 weeks’ gestation). Conclusion The findings suggest that HRQoL is particularly impaired by extremely preterm birth and the concomitant complications of preterm birth such as BPD and severe non-respiratory morbidity.This study was supported by a grant from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No 633724. Prof Petrou receives support as a National Institute for Health Research (NIHR) Senior Investigator (NF-SI-0616-10103) and from the NIHR Applied Research Collaboration Oxford and Thames Valley

Visual fields in patients who have undergone vitrectomy for complications of diabetic retinopathy. A prospective study

BACKROUND: To determine the extent of visual field loss in patients who had required a pars plana vitrectomy secondary to complications of proliferative diabetic retinopathy. METHODS: Patients that had undergone a vitrectomy on at least one eye for treatment of either vitreous haemorrhage or tractional retinal detachment were selected for study. ETDRS acuity and Humphrey binocular Esterman visual field testing were performed and compared to the minimum standards for safe driving as defined by the Royal College of Ophthalmologists in 1999. In addition to this Goldman kinetic visual fields using a III4e and V4e stimulus size and central 24-2 threshold test with the SITA-fast strategy were performed on the vitrectomised eye. RESULTS: 20 patients (n = 20) were recruited. Mean visual acuity in the eye being tested was 0.20 (Snellen 6/9.5). Results from the Humphrey field analyzer showed a mean number of abnormal stimulus locations of 71.2% (p < 0.005). 70% of patients had sufficient binocular acuity to drive and of these 71.4% were shown not to have a minimum visual field for safe driving on binocular Esterman field analysis. CONCLUSION: Vitrectomy potentially allows retention/restoration of good visual acuity in patients with complications of proliferative diabetic retinopathy. However patients may be suffering from unrecognized visual impairment consequent upon extensive visual field loss which in over two thirds of patients may be sufficiently severe to preclude safe driving

Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain

Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS) to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR), and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The process and experiences described provide a model for development of other DSSs that translate written guidelines into actionable, real-time clinical recommendations.http://deepblue.lib.umich.edu/bitstream/2027.42/78267/1/1748-5908-5-26.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/2/1748-5908-5-26.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/3/1748-5908-5-26-S3.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/4/1748-5908-5-26-S2.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/5/1748-5908-5-26-S1.TIFFPeer Reviewe

Increased Indoleamine-2,3-Dioxygenase Activity Is Associated With Poor Clinical Outcome in Adults Hospitalized With Influenza in the INSIGHT FLU003Plus Study

BACKGROUND: Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections. METHODS: We performed a case-control (1:2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1)pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression. RESULTS: We included 32 cases and 64 controls with a median age of 52 years; 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M; IQR, 0.13–0.40) than controls (0.12; IQR, 0.09–0.17; P ≤ .001). When divided into tertiles, 59% of cases vs 20% of controls had KT ratios in the highest tertile (0.21–0.84 mM/M). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95% CI, 2.25–43.90). CONCLUSIONS: High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The clinical utility of this biomarker in this setting merits further exploration. CLINICALTRIALS.GOV IDENTIFIER: NCT01056185

Overdiagnosis and overtreatment of breast cancer: Overdiagnosis and overtreatment in service screening

Screening mammography has been shown to be effective for reducing breast cancer mortality. According to screening theory, the first expected consequence of mammography screening is the detection of the disease at earlier stages and this diagnostic anticipation changes the population incidence curve, with an observed increase in incidence rates at earlier ages. It is unreasonable to expect that the age-specific incidence will ever return to pre-screening levels or to anticipate a significant reduction of incidence at older ages immediately after the first screening round. The interpretation of incidence trends, especially in the short term, is difficult. Methodology for quantification of overdiagnosis and statistical modelling based on service screening data is not well developed and few population-based studies are available. The overtreatment issue is discussed in terms of appropriateness of effective treatment considering the question of chemotherapy in very early stages and the use of breast conserving surgery

Timely digital patient-clinician communication in specialist clinical services for young people : a mixed-methods study (the LYNC study)

BACKGROUND: Young people (aged 16-24 years) with long-term health conditions can disengage from health services, resulting in poor health outcomes, but clinicians in the UK National Health Service (NHS) are using digital communication to try to improve engagement. Evidence of effectiveness of this digital communication is equivocal. There are gaps in evidence as to how it might work, its cost, and ethical and safety issues. OBJECTIVE: Our objective was to understand how the use of digital communication between young people with long-term conditions and their NHS specialist clinicians changes engagement of the young people with their health care; and to identify costs and necessary safeguards. METHODS: We conducted mixed-methods case studies of 20 NHS specialist clinical teams from across England and Wales and their practice providing care for 13 different long-term physical or mental health conditions. We observed 79 clinical team members and interviewed 165 young people aged 16-24 years with a long-term health condition recruited via case study clinical teams, 173 clinical team members, and 16 information governance specialists from study NHS Trusts. We conducted a thematic analysis of how digital communication works, and analyzed ethics, safety and governance, and annual direct costs. RESULTS: Young people and their clinical teams variously used mobile phone calls, text messages, email, and voice over Internet protocol. Length of clinician use of digital communication varied from 1 to 13 years in 17 case studies, and was being considered in 3. Digital communication enables timely access for young people to the right clinician at the time when it can make a difference to how they manage their health condition. This is valued as an addition to traditional clinic appointments and can engage those otherwise disengaged, particularly at times of change for young people. It can enhance patient autonomy, empowerment and activation. It challenges the nature and boundaries of therapeutic relationships but can improve trust. The clinical teams studied had not themselves formally evaluated the impact of their intervention. Staff time is the main cost driver, but offsetting savings are likely elsewhere in the health service. Risks include increased dependence on clinicians, inadvertent disclosure of confidential information, and communication failures, which are mostly mitigated by young people and clinicians using common-sense approaches. CONCLUSIONS: As NHS policy prompts more widespread use of digital communication to improve the health care experience, our findings suggest that benefit is most likely, and harms are mitigated, when digital communication is used with patients who already have a relationship of trust with the clinical team, and where there is identifiable need for patients to have flexible access, such as when transitioning between services, treatments, or lived context. Clinical teams need a proactive approach to ethics, governance, and patient safety

Averages of bb-hadron, cc-hadron, and τ\tau-lepton properties as of summer 2014

This article reports world averages of measurements of $b$-hadron, $c$-hadron, and $\tau$-lepton properties obtained by the Heavy Flavor Averaging Group (HFAG) using results available through summer 2014. For the averaging, common input parameters used in the various analyses are adjusted (rescaled) to common values, and known correlations are taken into account. The averages include branching fractions, lifetimes, neutral meson mixing parameters, $CP$ violation parameters, parameters of semileptonic decays and CKM matrix elements.Comment: 436 pages, many figures and tables. Online updates available at http://www.slac.stanford.edu/xorg/hfag

Additional consensus recommendations for conducting complex innovative trials of oncology agents: a post-pandemic perspective

In our 2020 consensus paper, we devised ten recommendations for conducting Complex Innovative Design (CID) trials to evaluate cancer drugs. Within weeks of its publication, the UK was hit by the first wave of the SARS-CoV-2 pandemic. Large CID trials were prioritised to compare the efficacy of new and repurposed COVID-19 treatments and inform regulatory decisions. The unusual circumstances of the pandemic meant studies such as RECOVERY were opened almost immediately and recruited record numbers of participants. However, trial teams were required to make concessions and adaptations to these studies to ensure recruitment was rapid and broad. As these are relevant to cancer trials that enrol patients with similar risk factors, we have added three new recommendations to our original ten: employing pragmatism such as using focused information sheets and collection of only the most relevant data; minimising negative environmental impacts with paperless systems; and using direct-to-patient communication methods to improve uptake. These recommendations can be applied to all oncology CID trials to improve their inclusivity, uptake and efficiency. Above all, the success of CID studies during the COVID-19 pandemic underscores their efficacy as tools for rapid treatment evaluation