Multiple Imputation of Missing Composite Outcomes in Longitudinal Data.

In longitudinal randomised trials and observational studies within a medical context, a composite outcome-which is a function of several individual patient-specific outcomes-may be felt to best represent the outcome of interest. As in other contexts, missing data on patient outcome, due to patient drop-out or for other reasons, may pose a problem. Multiple imputation is a widely used method for handling missing data, but its use for composite outcomes has been seldom discussed. Whilst standard multiple imputation methodology can be used directly for the composite outcome, the distribution of a composite outcome may be of a complicated form and perhaps not amenable to statistical modelling. We compare direct multiple imputation of a composite outcome with separate imputation of the components of a composite outcome. We consider two imputation approaches. One approach involves modelling each component of a composite outcome using standard likelihood-based models. The other approach is to use linear increments methods. A linear increments approach can provide an appealing alternative as assumptions concerning both the missingness structure within the data and the imputation models are different from the standard likelihood-based approach. We compare both approaches using simulation studies and data from a randomised trial on early rheumatoid arthritis patients. Results suggest that both approaches are comparable and that for each, separate imputation offers some improvement on the direct imputation of a composite outcome

Rugby (the religion of Wales) and its influence on the Catholic church: should Pope Benedict XVI be worried?

Objective To explore the perceived wisdom that papal mortality is related to the success of the Welsh rugby union team

Potential impact of the validated Predicting Abusive Head Trauma (PredAHT) clinical prediction tool: A clinical vignette study

Background The validated Predicting Abusive Head Trauma (PredAHT) tool estimates the probability of abusive head trauma (AHT) in children <3 years old with intracranial injury. Objective To explore the impact of PredAHT on clinicians’ AHT probability estimates and child protection (CP) actions, and assess inter-rater agreement between their estimates and between their CP actions, before and after PredAHT. Participants and Setting Twenty-nine clinicians from different specialties, at teaching and community hospitals. Methods Clinicians estimated the probability of AHT and indicated their CP actions in six clinical vignettes. One vignette described a child with AHT, another described a child with non-AHT, and four represented “gray” cases, where the diagnosis was uncertain. Clinicians calculated the PredAHT score, and reported whether this altered their estimate/actions. The ‘think-aloud’ method was used to capture the reasoning behind their responses. Analysis included linear modelling, linear mixed-effects modelling, chi-square tests, Fisher’s exact tests, intraclass correlation, Gwet’s AC1 coefficient and thematic analysis. Results Overall, PredAHT significantly influenced clinicians’ probability estimates in all vignettes (p < 0.001), although the impact on individual clinicians varied. However, the influence of PredAHT on clinicians’ CP actions was limited; after using PredAHT, 9/29 clinicians changed their CP actions in only 11/174 instances. Clinicians’ AHT probability estimates and CP actions varied somewhat both before and after PredAHT. Qualitative data suggested that PredAHT may increase clinicians’ confidence in their decisions when considered alongside other associated clinical, historical and social factors. Conclusions PredAHT significantly influenced clinicians’ AHT probability estimates, but had minimal impact on their CP actions

Incidence and antibiotic prescribing for clinically diagnosed urinary tract infection in older adults in UK primary care, 2004-2014

Funding: This report is independent research arising from a National Institute of Health Research (NIHR) Doctoral Research Fellowship awarded to Haroon Ahmed, and supported by Health and Care Research Wales (HCRW) (Grant number: DRF-2014-07-010). The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS Wales, HCRW or the Welsh Government. Hywel Jones is supported by The Farr Institute @ CIPHER, a Medical Research Council led multi-funder initiative for e-health research, MRC Grant Number: MR/K006525/1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of this manuscript.Peer reviewedPublisher PD

Acceptability of the Predicting Abusive Head Trauma (PredAHT) clinical prediction tool: A qualitative study with child protection professionals

The validated Predicting Abusive Head Trauma (PredAHT) tool estimates the probability of abusive head trauma (AHT) based on combinations of six clinical features: head/neck bruising; apnea; seizures; rib/long-bone fractures; retinal hemorrhages. We aimed to determine the acceptability of PredAHT to child protection professionals. We conducted qualitative semi-structured interviews with 56 participants: clinicians (25), child protection social workers (10), legal practitioners (9, including 4 judges), police officers (8), and pathologists (4), purposively sampled across southwest United Kingdom. Interviews were recorded, transcribed and imported into NVivo for thematic analysis (38% double-coded). We explored participants’ evaluations of PredAHT, their opinions about the optimal way to present the calculated probabilities, and their interpretation of probabilities in the context of suspected AHT. Clinicians, child protection social workers and police thought PredAHT would be beneficial as an objective adjunct to their professional judgment, to give them greater confidence in their decisions. Lawyers and pathologists appreciated its value for prompting multidisciplinary investigations, but were uncertain of its usefulness in court. Perceived disadvantages included: possible over-reliance and false reassurance from a low score. Interpretations regarding which percentages equate to ‘low’, ‘medium’ or ‘high’ likelihood of AHT varied; participants preferred a precise % probability over these general terms. Participants would use PredAHT with provisos: if they received multi-agency training to define accepted risk thresholds for consistent interpretation; with knowledge of its development; if it was accepted by colleagues. PredAHT may therefore increase professionals’ confidence in their decision-making when investigating suspected AHT, but may be of less value in court

Factors influencing child protection professionals' decision-making and multidisciplinary collaboration in suspected abusive head trauma cases: a qualitative study

Clinicians face unique challenges when assessing suspected child abuse cases. The majority of the literature exploring diagnostic decision-making in this field is anecdotal or survey-based and there is a lack of studies exploring decision-making around suspected abusive head trauma (AHT). We aimed to determine factors influencing decision-making and multidisciplinary collaboration in suspected AHT cases, amongst 56 child protection professionals. Semi-structured interviews were conducted with clinicians (25), child protection social workers (10), legal practitioners (9, including 4 judges), police officers (8), and pathologists (4), purposively sampled across southwest United Kingdom. Interviews were recorded, transcribed and imported into NVivo for thematic analysis (38% double-coded). We identified six themes influencing decision-making: ‘professional’, ‘medical’, ‘circumstantial’, ‘family’, ‘psychological’ and ‘legal’ factors. Participants diagnose AHT based on clinical features, the history, and the social history, after excluding potential differential diagnoses. Participants find these cases emotionally challenging but are aware of potential biases in their evaluations and strive to overcome these. Barriers to decision-making include lack of experience, uncertainty, the impact on the family, the pressure of making the correct diagnosis, and disagreements between professionals. Legal barriers include alternative theories of causation proposed in court. Facilitators include support from colleagues and knowledge of the evidence-base. Participants’ experiences with multidisciplinary collaboration are generally positive, however child protection social workers and police officers are heavily reliant on clinicians to guide their decision-making, suggesting the need for training on the medical aspects of physical abuse for these professionals and multidisciplinary training that provides knowledge about the roles of each agency

Defining criteria for rheumatoid arthritis patient-derived disease activity score that correspond to Disease Activity Score 28 and Clinical Disease Activity Index based disease states and response criteria

Objective. Two versions of a patient-based DAS (PDAS) 1 and 2 (with and without ESR) have been developed and validated in RA. The objective of this study was to define PDAS1- and PDAS2-based criteria for remission, low, moderate and high disease activity and responses to treatment. Method. Using receiver operating characteristic curves, the optimal thresholds for PDAS1 and PDAS2 that correspond to validated assessor-based DAS (DAS28) and Clinical Disease Activity Index (CDAI) disease statuses were determined. Data from RA patients initiated on disease-modifying drugs were used to determine optimal thresholds for PDAS1 and PDAS2 that corresponded to EULAR good and moderate responses. Agreement with DAS28, CDAI and EULAR response criteria was assessed by Cohen’s κ statistic. Results. Threshold for PDAS1 and PDAS2 demonstrated fair to moderate agreement with DAS28 [κ = 0.44 (95% CI: 0.40, 0.50) and 0.31 (95% CI: 0.25, 0.38)] and CDAI [κ = 0.27 (95% CI: 0.22, 0.33) and 0.42 (95% CI: 0.35, 0.49)] disease statuses, respectively, which was similar to agreement between DAS28 and CDAI [κ = 0.54 (95% CI: 0.46, 0.61)] within this group. Agreement of EULAR good and moderate response with PDAS1 and PDAS2 was κ = 0.46 (95% CI: 0.27, 0.64) and 0.38 (95% CI: 0.20, 0.56), respectively. Conclusion. Thresholds for disease activity statuses and response to treatment for PDAS1 and PDAS2 have been established. They have comparable agreement to assessor-based criteria

Antibiotic prophylaxis and clinical outcomes among older adults with recurrent urinary tract infection: cohort study

Background clinical guidelines recommend antibiotic prophylaxis for preventing recurrent urinary tract infections (UTIs), but there is little evidence for their effectiveness in older adults. Methods this was a retrospective cohort study of health records from 19,696 adults aged ≥65 with recurrent UTIs. We used prescription records to ascertain ≥3 months’ prophylaxis with trimethoprim, cefalexin or nitrofurantoin. We used random effects Cox recurrent event models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for risks of clinical recurrence (primary outcome), acute antibiotic prescribing and hospitalisation. Results of 4,043 men and 15,653 women aged ≥65 with recurrent UTIs, 508 men (12.6%) and 2,229 women (14.2%) were prescribed antibiotic prophylaxis. In men, prophylaxis was associated with a reduced risk of clinical recurrence (HR, 0.49; 95% CI, 0.45–0.54), acute antibiotic prescribing (HR, 0.54; 95% CI, 0.51–0.57) and UTI-related hospitalisation (HR, 0.78; 95% CI, 0.64–0.94). In women, prophylaxis was also associated with a reduced risk of clinical recurrence (HR, 0.57; 95% CI, 0.55–0.59) and acute antibiotic prescribing (HR, 0.61; 95% CI, 0.59–0.62), but estimates of the risk of UTI-related hospitalisation were inconsistent between our main analysis (HR, 1.16; 95% CI, 1.05–1.28) and sensitivity analysis (HR, 0.82; 95% CI, 0.72–0.94). Conclusions antibiotic prophylaxis was associated with lower rates of UTI recurrence and acute antibiotic prescribing in older adults. To fully understand the benefits and harms of prophylaxis, further research should determine the frequency of antibiotic-related adverse events and the impact on antimicrobial resistance and quality of life

Burden of nosocomial COVID-19 in Wales: results from a multicentre retrospective observational study of 2508 hospitalised adults

The burden of nosocomial SARS-CoV-2 infection remains poorly defined. We report on the outcomes of 2508 adults with molecularly-confirmed SARS-CoV-2 admitted across 18 major hospitals, representing over 60% of those hospitalised across Wales between 1 March and 1 July 2020. Inpatient mortality for nosocomial infection ranged from 38% to 42%, consistently higher than participants with community-acquired infection (31%–35%) across a range of case definitions. Those with hospital-acquired infection were older and frailer than those infected within the community. Nosocomial diagnosis occurred a median of 30 days following admission (IQR 21–63), suggesting a window for prophylactic or postexposure interventions, alongside enhanced infection control measures