Can analyses of electronic patient records be independently and externally validated? The effect of statins on the mortality of patients with ischaemic heart disease: a cohort study with nested case-control analysis

Objective To conduct a fully independent and external validation of a research study based on one electronic health record database, using a different electronic database sampling the same population. Design Using the Clinical Practice Research Datalink (CPRD), we replicated a published investigation into the effects of statins in patients with ischaemic heart disease (IHD) by a different research team using QResearch. We replicated the original methods and analysed all-cause mortality using: (1) a cohort analysis and (2) a case-control analysis nested within the full cohort. Setting Electronic health record databases containing longitudinal patient consultation data from large numbers of general practices distributed throughout the UK. Participants CPRD data for 34 925 patients with IHD from 224 general practices, compared to previously published results from QResearch for 13 029 patients from 89 general practices. The study period was from January 1996 to December 2003. Results We successfully replicated the methods of the original study very closely. In a cohort analysis, risk of death was lower by 55% for patients on statins, compared with 53% for QResearch (adjusted HR 0.45, 95% CI 0.40 to 0.50; vs 0.47, 95% CI 0.41 to 0.53). In case-control analyses, patients on statins had a 31% lower odds of death, compared with 39% for QResearch (adjusted OR 0.69, 95% CI 0.63 to 0.75; vs OR 0.61, 95% CI 0.52 to 0.72). Results were also close for individual statins. Conclusions Database differences in population characteristics and in data definitions, recording, quality and completeness had a minimal impact on key statistical outputs. The results uphold the validity of research using CPRD and QResearch by providing independent evidence that both datasets produce very similar estimates of treatment effect, leading to the same clinical and policy decisions. Together with other non-independent replication studies, there is a nascent body of evidence for wider validity

Withdrawing performance indicators: retrospective analysis of general practice performance under UK Quality and Outcomes Framework.

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.OBJECTIVES: To investigate the effect of withdrawing incentives on recorded quality of care, in the context of the UK Quality and Outcomes Framework pay for performance scheme. DESIGN: Retrospective longitudinal study. SETTING: Data for 644 general practices, from 2004/05 to 2011/12, extracted from the Clinical Practice Research Datalink. PARTICIPANTS: All patients registered with any of the practices over the study period-13,772,992 in total. INTERVENTION: Removal of financial incentives for aspects of care for patients with asthma, coronary heart disease, diabetes, stroke, and psychosis. MAIN OUTCOME MEASURES: Performance on eight clinical quality indicators withdrawn from a national incentive scheme: influenza immunisation (asthma) and lithium treatment monitoring (psychosis), removed in April 2006; blood pressure monitoring (coronary heart disease, diabetes, stroke), cholesterol concentration monitoring (coronary heart disease, diabetes), and blood glucose monitoring (diabetes), removed in April 2011. Multilevel mixed effects multiple linear regression models were used to quantify the effect of incentive withdrawal. RESULTS: Mean levels of performance were generally stable after the removal of the incentives, in both the short and long term. For the two indicators removed in April 2006, levels in 2011/12 were very close to 2005/06 levels, although a small but statistically significant drop was estimated for influenza immunisation. For five of the six indicators withdrawn from April 2011, no significant effect on performance was seen following removal and differences between predicted and observed scores were small. Performance on related outcome indicators retained in the scheme (such as blood pressure control) was generally unaffected. CONCLUSIONS: Following the removal of incentives, levels of performance across a range of clinical activities generally remained stable. This indicates that health benefits from incentive schemes can potentially be increased by periodically replacing existing indicators with new indicators relating to alternative aspects of care. However, all aspects of care investigated remained indirectly or partly incentivised in other indicators, and further work is needed to assess the generalisability of the findings when incentives are fully withdrawn.National Institute for Health Research (NIHR

I Believe, Therefore I Do

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Development of machine learning support for reading whole body diffusion-weighted MRI (WB-MRI) in myeloma for the detection and quantification of the extent of disease before and after treatment (MALIMAR): protocol for a cross-sectional diagnostic test accuracy study.

INTRODUCTION: Whole-body MRI (WB-MRI) is recommended by the National Institute of Clinical Excellence as the first-line imaging tool for diagnosis of multiple myeloma. Reporting WB-MRI scans requires expertise to interpret and can be challenging for radiologists who need to meet rapid turn-around requirements. Automated computational tools based on machine learning (ML) could assist the radiologist in terms of sensitivity and reading speed and would facilitate improved accuracy, productivity and cost-effectiveness. The MALIMAR study aims to develop and validate a ML algorithm to increase the diagnostic accuracy and reading speed of radiological interpretation of WB-MRI compared with standard methods. METHODS AND ANALYSIS: This phase II/III imaging trial will perform retrospective analysis of previously obtained clinical radiology MRI scans and scans from healthy volunteers obtained prospectively to implement training and validation of an ML algorithm. The study will comprise three project phases using approximately 633 scans to (1) train the ML algorithm to identify active disease, (2) clinically validate the ML algorithm and (3) determine change in disease status following treatment via a quantification of burden of disease in patients with myeloma. Phase 1 will primarily train the ML algorithm to detect active myeloma against an expert assessment ('reference standard'). Phase 2 will use the ML output in the setting of radiology reader study to assess the difference in sensitivity when using ML-assisted reading or human-alone reading. Phase 3 will assess the agreement between experienced readers (with and without ML) and the reference standard in scoring both overall burden of disease before and after treatment, and response. ETHICS AND DISSEMINATION: MALIMAR has ethical approval from South Central-Oxford C Research Ethics Committee (REC Reference: 17/SC/0630). IRAS Project ID: 233501. CPMS Portfolio adoption (CPMS ID: 36766). Participants gave informed consent to participate in the study before taking part. MALIMAR is funded by National Institute for Healthcare Research Efficacy and Mechanism Evaluation funding (NIHR EME Project ID: 16/68/34). Findings will be made available through peer-reviewed publications and conference dissemination. TRIAL REGISTRATION NUMBER: NCT03574454

Unintended Consequences of Incentive Provision for Behaviour Change and Maintenance around Childbirth

Financial (positive or negative) and non-financial incentives or rewards are increasingly used in attempts to influence health behaviours. While unintended consequences of incentive provision are discussed in the literature, evidence syntheses did not identify any primary research with the aim of investigating unintended consequences of incentive interventions for lifestyle behaviour change. Our objective was to investigate perceived positive and negative unintended consequences of incentive provision for a shortlist of seven promising incentive strategies for smoking cessation in pregnancy and breastfeeding. A multi-disciplinary, mixed-methods approach included involving two service-user mother and baby groups from disadvantaged areas with experience of the target behaviours as study co-investigators. Systematic reviews informed the shortlist of incentive strategies. Qualitative semi-structured interviews and a web-based survey of health professionals asked open questions on positive and negative consequences of incentives. The participants from three UK regions were a diverse sample with and without direct experience of incentive interventions: 88 pregnant women/recent mothers/partners/family members; 53 service providers; 24 experts/decision makers and interactive discussions with 63 conference attendees. Maternity and early years health professionals (n = 497) including doctors, midwives, health visitors, public health and related staff participated in the survey. Qualitative analysis identified ethical, political, cultural, social and psychological implications of incentive delivery at population and individual levels. Four key themes emerged: how incentives can address or create inequalities; enhance or diminish intrinsic motivation and wellbeing; have a positive or negative effect on relationships with others within personal networks or health providers; and can impact on health systems and resources by raising awareness and directing service delivery, but may be detrimental to other health care areas. Financial incentives are controversial and generated emotive and oppositional responses. The planning, design and delivery of future incentive interventions should evaluate unexpected consequences to inform the evidence for effectiveness, cost-effectiveness and future implementation

Haploinsufficiency for Translation Elongation Factor eEF1A2 in Aged Mouse Muscle and Neurons Is Compatible with Normal Function

Translation elongation factor isoform eEF1A2 is expressed in muscle and neurons. Deletion of eEF1A2 in mice gives rise to the neurodegenerative phenotype "wasted" (wst). Mice homozygous for the wasted mutation die of muscle wasting and neurodegeneration at four weeks post-natal. Although the mutation is said to be recessive, aged heterozygous mice have never been examined in detail; a number of other mouse models of motor neuron degeneration have recently been shown to have similar, albeit less severe, phenotypic abnormalities in the heterozygous state. We therefore examined the effects of ageing on a cohort of heterozygous +/wst mice and control mice, in order to establish whether a presumed 50% reduction in eEF1A2 expression was compatible with normal function. We evaluated the grip strength assay as a way of distinguishing between wasted and wild-type mice at 3-4 weeks, and then performed the same assay in older +/wst and wild-type mice. We also used rotarod performance and immunohistochemistry of spinal cord sections to evaluate the phenotype of aged heterozygous mice. Heterozygous mutant mice showed no deficit in neuromuscular function or signs of spinal cord pathology, in spite of the low levels of eEF1A2

FIRE (facilitating implementation of research evidence) : a study protocol

Research evidence underpins best practice, but is not always used in healthcare. The Promoting Action on Research Implementation in Health Services (PARIHS) framework suggests that the nature of evidence, the context in which it is used, and whether those trying to use evidence are helped (or facilitated) affect the use of evidence. Urinary incontinence has a major effect on quality of life of older people, has a high prevalence, and is a key priority within European health and social care policy. Improving continence care has the potential to improve the quality of life for older people and reduce the costs associated with providing incontinence aids

Improving outcomes for people with COPD by developing networks of general practices: evaluation of a quality improvement project in east London

BACKGROUND: Structured care for people with chronic obstructive pulmonary disease (COPD) can improve outcomes. Delivering care in a deprived ethnically diverse area can prove challenging. AIMS: Evaluation of a system change to enhance COPD care delivery in a primary care setting between 2010 and 2013 using observational data. METHODS: All 36 practices in one inner London primary care trust were grouped geographically into eight networks of 4-5 practices, each supported by a network manager, clerical staff and an educational budget. A multidisciplinary group, including a respiratory specialist and the community respiratory team, developed a 'care package' for COPD management, with financial incentives based on network achievements of clinical targets and supported case management and education. Monthly electronic dashboards enabled networks to track and improve performance. RESULTS: The size of network COPD registers increased by 10% in the first year. Between 2010 and 2013 completed care plans increased from 53 to 86.5%, pulmonary rehabilitation referrals rose from 45 to 70% and rates of flu immunisation from 81 to 83%, exceeding London and England figures. Hospital admissions decreased in Tower Hamlets from a historic high base. CONCLUSIONS: Investment of financial, organisational and educational resource into general practice networks was associated with clinically important improvements in COPD care in socially deprived, ethnically diverse communities. Key behaviour change included the following: collaborative working between practices driven by high-quality information to support performance review; shared financial incentives; and engagement between primary and secondary care clinicians

Gliding Motility of Babesia bovis Merozoites Visualized by Time-Lapse Video Microscopy

BACKGROUND: Babesia bovis is an apicomplexan intraerythrocytic protozoan parasite that induces babesiosis in cattle after transmission by ticks. During specific stages of the apicomplexan parasite lifecycle, such as the sporozoites of Plasmodium falciparum and tachyzoites of Toxoplasma gondii, host cells are targeted for invasion using a unique, active process termed "gliding motility". However, it is not thoroughly understood how the merozoites of B. bovis target and invade host red blood cells (RBCs), and gliding motility has so far not been observed in the parasite. METHODOLOGY/PRINCIPAL FINDINGS: Gliding motility of B. bovis merozoites was revealed by time-lapse video microscopy. The recorded images revealed that the process included egress of the merozoites from the infected RBC, gliding motility, and subsequent invasion into new RBCs. The gliding motility of B. bovis merozoites was similar to the helical gliding of Toxoplasma tachyzoites. The trails left by the merozoites were detected by indirect immunofluorescence assay using antiserum against B. bovis merozoite surface antigen 1. Inhibition of gliding motility by actin filament polymerization or depolymerization indicated that the gliding motility was driven by actomyosin dependent process. In addition, we revealed the timing of breakdown of the parasitophorous vacuole. Time-lapse image analysis of membrane-stained bovine RBCs showed formation and breakdown of the parasitophorous vacuole within ten minutes of invasion. CONCLUSIONS/SIGNIFICANCE: This is the first report of the gliding motility of B. bovis. Since merozoites of Plasmodium parasites do not glide on a substrate, the gliding motility of B. bovis merozoites is a notable finding

Metacarpal trabecular bone varies with distinct hand-positions used in hominid locomotion

Trabecular bone remodels during life in response to loading and thus should, at least in part, reflect potential variation in the magnitude, frequency and direction of joint loading across different hominid species. Here we analyse the trabecular structure across all non-pollical metacarpal distal heads (Mc2-5) in extant great apes, expanding on previous volume of interest and whole-epiphysis analyses that have largely focussed on only the first or third metacarpal. Specifically, we employ both a univariate statistical mapping and a multivariate approach to test for both inter-ray and interspecific differences in relative trabecular bone volume fraction (RBV/TV) and degree of anisotropy (DA) in Mc2-5 subchondral trabecular bone. Results demonstrate that while DA values only separate Pongo from African apes (Pan troglodytes, Pan paniscus, Gorilla gorilla), RBV/TV distribution varies with the predicted loading of the metacarpophalangeal (McP) joints during locomotor behaviours in each species. Gorilla exhibits a relatively dorsal distribution of RBV/TV consistent with habitual hyper-extension of the McP joints during knuckle-walking, whereas Pongo has a palmar distribution consistent with flexed McP joints used to grasp arboreal substrates. Both Pan species possess a disto-dorsal distribution of RBV/TV, compatible with multiple hand postures associated with a more varied locomotor regime. Further inter-ray comparisons reveal RBV/TV patterns consistent with varied knuckle-walking postures in Pan species in contrast to higher RBV/TV values toward the midline of the hand in Mc2 and Mc5 of Gorilla, consistent with habitual palm-back knuckle-walking. These patterns of trabecular bone distribution and structure reflect different behavioural signals that could be useful for determining the behaviours of fossil hominins