Effect of a model consultation informed by guideline on recorded quality of care of osteoarthritis (MOSAICS): a cluster randomised controlled trial in primary care

Objective To determine the effect of a model osteoarthritis (OA) consultation (MOAC) informed by National Institute for Health and Care Excellence (NICE) recommendations compared with usual care on recorded quality of care of clinical OA in general practice. Design Two-arm cluster randomised controlled trial. Setting Eight general practices in Cheshire, Shropshire, or Staffordshire UK. Participants General practitioners and nurses with patients consulting with clinical OA. Intervention Following six-month baseline period practices were randomised to intervention (n = 4) or usual care (n = 4). Intervention practices delivered MOAC (enhanced initial GP consultation, nurse-led clinic, OA guidebook) to patients aged ≥45 years consulting with clinical OA. An electronic (e-)template for consultations was used in all practices to record OA quality care indicators. Outcomes Quality of OA care over six months recorded in the medical record. Results 1851 patients consulted in baseline period (1015 intervention; 836 control); 1960 consulted following randomisation (1118 intervention; 842 control). At baseline wide variations in quality of care were noted. Post-randomisation increases were found for written advice on OA (4–28%), exercise (4–22%) and weight loss (1–15%) in intervention practices but not controls (1–3%). Intervention practices were more likely to refer to physiotherapy (10% vs 2%, odds ratio 5.30; 95% CI 2.11, 13.34), and prescribe paracetamol (22% vs 14%, 1.74; 95% CI 1.27, 2.38). Conclusions The intervention did not improve all aspects of care but increased core NICE recommendations of written advice on OA, exercise and weight management. There remains a need to reduce variation and uniformly enhance improvement in recorded OA care

The dipole of the galaxy bispectrum

The bispectrum will play an important role in future galaxy surveys. On large scales it is a key probe for measuring primordial non-Gaussianity which can help differentiate between different inflationary models and other theories of the early universe. On these scales a variety of relativistic effects come into play once the galaxy number-count fluctuation is projected onto our past lightcone. We show for the first time that the leading relativistic correction from these distortions in the galaxy bispectrum generates a significant dipole, mainly from relativistic redshift space distortions. The amplitude of the dipole can be more than 10% of the monopole even on equality scales. Such a dipole is absent in the Newtonian approximation to the redshift space bispectrum, so it offers a clear signature of relativistic effects on cosmological scales in large scale structure.Comment: 5 pages, 2 figures. v2 has slight changes to the figures and is the version to appear in MNRAS Letter

Theories of behaviour change synthesised into a set of theoretical groupings: Introducing a thematic series on the Theoretical Domains Framework

Behaviour change is key to increasing the uptake of evidence into healthcare practice. Designing behaviour-change interventions first requires problem analysis, ideally informed by theory. Yet the large number of partly overlapping theories of behaviour makes it difficult to select the most appropriate theory. The need for an overarching theoretical framework of behaviour change was addressed in research in which 128 explanatory constructs from 33 theories of behaviour were identified and grouped. The resulting Theoretical Domains Framework (TDF) appears to be a helpful basis for investigating implementation problems. Research groups in several countries have conducted TDF-based studies. It seems timely to bring together the experience of these teams in a thematic series to demonstrate further applications and to report key developments. This overview article describes the TDF, provides a brief critique of the framework, and introduces this thematic series. In a brief review to assess the extent of TDF-based research, we identified 133 papers that cite the framework. Of these, 17 used the TDF as the basis for empirical studies to explore health professionals’ behaviour. The identified papers provide evidence of the impact of the TDF on implementation research. Two major strengths of the framework are its theoretical coverage and its capacity to elicit beliefs that could signify key mediators of behaviour change. The TDF provides a useful conceptual basis for assessing implementation problems, designing interventions to enhance healthcare practice, and understanding behaviour-change processes. We discuss limitations and research challenges and introduce papers in this series

A 30-Min Nucleic Acid Amplification Point-of-Care Test for Genital Chlamydia trachomatis Infection in Women: A Prospective, Multi-center Study of Diagnostic Accuracy.

BACKGROUND: Rapid Point-Of-Care Tests for Chlamydia trachomatis (CT) may reduce onward transmission and reproductive sexual health (RSH) sequelae by reducing turnaround times between diagnosis and treatment. The io® single module system (Atlas Genetics Ltd.) runs clinical samples through a nucleic acid amplification test (NAAT)-based CT cartridge, delivering results in 30min. METHODS: Prospective diagnostic accuracy study of the io® CT-assay in four UK Genito-Urinary Medicine (GUM)/RSH clinics on additional-to-routine self-collected vulvovaginal swabs. Samples were tested "fresh" within 10days of collection, or "frozen" at -80°C for later testing. Participant characteristics were collected to assess risk factors associated with CT infection. RESULTS: CT prevalence was 7.2% (51/709) overall. Sensitivity, specificity, positive and negative predictive values of the io® CT assay were, respectively, 96.1% (95% Confidence Interval (CI): 86.5-99.5), 97.7% (95%CI: 96.3-98.7), 76.6% (95%CI: 64.3-86.2) and 99.7% (95%CI: 98.9-100). The only risk factor associated with CT infection was being a sexual contact of an individual with CT. CONCLUSIONS: The io® CT-assay is a 30-min, fully automated, high-performing NAAT currently CE-marked for CT diagnosis in women, making it a highly promising diagnostic to enable specific treatment, initiation of partner notification and appropriately intensive health promotion at the point of care

A 30-minute nucleic acid amplification point-of-care test for genital<i>Chlamydia trachomatis</i>infection in women: a prospective, multi-centre study of diagnostic accuracy

ABSTRACTBackgroundRapid Point-Of-Care Tests (POCTs) forChlamydia trachomatis(CT) may reduce onward transmission and reproductive sexual health (RSH) sequelae by reducing turnaround times between diagnosis and treatment. The io®single module system (Atlas Genetics Ltd) runs clinical samples through a microfluidic CT cartridge, delivering results in 30 minutes. We evaluated its performance on female genital samples in four UK Genito-Urinary Medicine (GUM)/RSH clinics.MethodsProspective diagnostic accuracy study, using BD ProbeTec CT/GC assay as the routine clinic nucleic acid amplification test (NAAT) as the initial comparator test, and the QIAgen Artus CT assay to resolve discrepancies. In these instances, the reference standard was defined as the resolved result when two out of three assay results concurred. Female participants aged ≥16 provided additional-to-routine self-collected vulvovaginal swabs. Samples were tested fresh with the io®CT assay within 7 days of collection, or were frozen at −80°C for later testing. Participant clinical, demographic and behavioural characteristics were collected to assess risk factors associated with CT infection.ResultsOf 785 participants recruited, final analyses were conducted on 709 (90.3%). CT prevalence was 7.2% (51/709) overall. Sensitivity, specificity, positive and negative predictive values of the io®CT assay were, respectively, 96.1% (95% Confidence Interval (CI): 86.5-99.5), 97.7% (95%CI: 96.3-98.7), 76.6% (95%CI: 64.3-86.2) and 99.7% (95%CI: 98.9-100). There was no significant difference in performance measures between fresh and frozen samples, or between symptomatic and asymptomatic participants (p&gt;0.05). The only risk factor associated with CT infection was being a sexual contact of an individual with CT.ConclusionsThe io®CT-assay is the only 30-minute, fully automated, high-performing NAAT currently CE-marked for CT diagnosis in women, making it a highly promising diagnostic to enable specific treatment, initiation of partner notification and appropriately intensive health promotion at the point of care. Future research is required to evaluate acceptability by clinicians and patients in GUM/RSH clinics, impact on clinical pathways and patient management, and cost-effectiveness.</jats:sec

Efficient Information-Flow Verification under Speculative Execution

We study the formal verification of information-flow properties in the presence of speculative execution and side-channels. First, we present a formal model of speculative execution semantics. This model can be parameterized by the depth of speculative execution and is amenable to a range of verification techniques. Second, we introduce a novel notion of information leakage under speculation, which is parameterized by the information that is available to an attacker through side-channels. Finally, we present one verification technique that uses our formalism and can be used to detect information leaks under speculation through cache side-channels, and can decide whether these are only possible under speculative execution. We implemented an instance of this verification technique that combines taint analysis and safety model checking. We evaluated this approach on a range of examples that have been proposed as benchmarks for mitigations of the Spectre vulnerability, and show that our approach correctly identifies all information leaks

Recessive mutations in SPTBN2 implicate β-III spectrin in both cognitive and motor development

β-III spectrin is present in the brain and is known to be important in the function of the cerebellum. Heterozygous mutations in SPTBN2, the gene encoding β-III spectrin, cause Spinocerebellar Ataxia Type 5 (SCA5), an adult-onset, slowly progressive, autosomal-dominant pure cerebellar ataxia. SCA5 is sometimes known as "Lincoln ataxia," because the largest known family is descended from relatives of the United States President Abraham Lincoln. Using targeted capture and next-generation sequencing, we identified a homozygous stop codon in SPTBN2 in a consanguineous family in which childhood developmental ataxia co-segregates with cognitive impairment. The cognitive impairment could result from mutations in a second gene, but further analysis using whole-genome sequencing combined with SNP array analysis did not reveal any evidence of other mutations. We also examined a mouse knockout of β-III spectrin in which ataxia and progressive degeneration of cerebellar Purkinje cells has been previously reported and found morphological abnormalities in neurons from prefrontal cortex and deficits in object recognition tasks, consistent with the human cognitive phenotype. These data provide the first evidence that β-III spectrin plays an important role in cortical brain development and cognition, in addition to its function in the cerebellum; and we conclude that cognitive impairment is an integral part of this novel recessive ataxic syndrome, Spectrin-associated Autosomal Recessive Cerebellar Ataxia type 1 (SPARCA1). In addition, the identification of SPARCA1 and normal heterozygous carriers of the stop codon in SPTBN2 provides insights into the mechanism of molecular dominance in SCA5 and demonstrates that the cell-specific repertoire of spectrin subunits underlies a novel group of disorders, the neuronal spectrinopathies, which includes SCA5, SPARCA1, and a form of West syndrome

Evaluating an audit and feedback intervention for reducing antibiotic prescribing behaviour in general dental practice (the RAPiD trial): a partial factorial cluster randomised trial protocol

BACKGROUND: Antibiotic prescribing in dentistry accounts for 9% of total antibiotic prescriptions in Scottish primary care. The Scottish Dental Clinical Effectiveness Programme (SDCEP) published guidance in April 2008 (2nd edition, August 2011) for Drug Prescribing in Dentistry, which aims to assist dentists to make evidence-based antibiotic prescribing decisions. However, wide variation in prescribing persists and the overall use of antibiotics is increasing. METHODS: RAPiD is a 12-month partial factorial cluster randomised trial conducted in NHS General Dental Practices across Scotland. Its aim is to compare the effectiveness of individualised audit and feedback (A&F) strategies for the translation into practice of SDCEP recommendations on antibiotic prescribing. The trial uses routinely collected electronic healthcare data in five aspects of its design in order to: identify the study population; apply eligibility criteria; carry out stratified randomisation; generate the trial intervention; analyse trial outcomes. Eligibility was determined on contract status and a minimum level of recent NHS treatment provision. All eligible dental practices in Scotland were simultaneously randomised at baseline either to current audit practice or to an intervention group. Randomisation was stratified by single-handed/multi-handed practices. General dental practitioners (GDPs) working at intervention practices will receive individualised graphical representations of their antibiotic prescribing rate from the previous 14 months at baseline and an update at six months. GDPs could not be blinded to their practice allocation. Intervention practices were further randomised using a factorial design to receive feedback with or without: a health board comparator; a supplementary text-based intervention; additional feedback at nine months. The primary outcome is the total antibiotic prescribing rate per 100 courses of treatment over the year following delivery of the baseline intervention. A concurrent qualitative process evaluation will apply theory-based approaches using the Consolidated Framework for Implementation Research to explore the acceptability of the interventions and the Theoretical Domains Framework to identify barriers and enablers to evidence-based antibiotic prescribing behaviour by GDPs. DISCUSSION: RAPiD will provide a robust evaluation of A&F in dentistry in Scotland. It also demonstrates that linked administrative datasets have the potential to be used efficiently and effectively across all stages of an randomised controlled trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN49204710

Loss of protein kinase C delta alters mammary gland development and apoptosis

As apoptotic pathways are commonly deregulated in breast cancer, exploring how mammary gland cell death is regulated is critical for understanding human disease. We show that primary mammary epithelial cells from protein kinase C delta (PKCδ) −/− mice have a suppressed response to apoptotic agents in vitro. In the mammary gland in vivo, apoptosis is critical for ductal morphogenesis during puberty and involution following lactation. We have explored mammary gland development in the PKCδ −/− mouse during these two critical windows. Branching morphogenesis was altered in 4- to 6-week-old PKCδ −/− mice as indicated by reduced ductal branching; however, apoptosis and proliferation in the terminal end buds was unaltered. Conversely, activation of caspase-3 during involution was delayed in PKCδ −/− mice, but involution proceeded normally. The thymus also undergoes apoptosis in response to physiological signals. A dramatic suppression of caspase-3 activation was observed in the thymus of PKCδ −/− mice treated with irradiation, but not mice treated with dexamethasone, suggesting that there are both target- and tissue-dependent differences in the execution of apoptotic pathways in vivo. These findings highlight a role for PKCδ in both apoptotic and nonapoptotic processes in the mammary gland and underscore the redundancy of apoptotic pathways in vivo

Open-label randomised pragmatic trial (CONTACT) comparing naproxen and low-dose colchicine for the treatment of gout flares in primary care

OBJECTIVES: To compare the effectiveness and safety of naproxen and low-dose colchicine for treating gout flares in primary care. METHODS: This was a multicentre open-label randomised trial. Adults with a gout flare recruited from 100 general practices were randomised equally to naproxen 750 mg immediately then 250 mg every 8 hours for 7 days or low-dose colchicine 500 mcg three times per day for 4 days. The primary outcome was change in worst pain intensity in the last 24 hours (0-10 Numeric Rating Scale) from baseline measured daily over the first 7 days: mean change from baseline was compared between groups over days 1-7 by intention to treat. RESULTS: Between 29 January 2014 and 31 December 2015, we recruited 399 participants (naproxen n=200, colchicine n=199), of whom 349 (87.5%) completed primary outcome data at day 7. There was no significant between-group difference in average pain-change scores over days 1-7 (colchicine vs naproxen: mean difference -0.18; 95% CI -0.53 to 0.17; p=0.32). During days 1-7, diarrhoea (45.9% vs 20.0%; OR 3.31; 2.01 to 5.44) and headache (20.5% vs 10.7%; 1.92; 1.03 to 3.55) were more common in the colchicine group than the naproxen group but constipation was less common (4.8% vs 19.3%; 0.24; 0.11 to 0.54). CONCLUSION: We found no difference in pain intensity over 7 days between people with a gout flare randomised to either naproxen or low-dose colchicine. Naproxen caused fewer side effects supporting naproxen as first-line treatment for gout flares in primary care in the absence of contraindications. TRIAL REGISTRATION NUMBER: ISRCTN (69836939), clinicaltrials.gov (NCT01994226), EudraCT (2013-001354-95)