Designing an intervention for improving primary care management of sleep problems (REST: Resources for Effective Sleep Treatment)

Brief outline of context An improvement project was begun in a Primary Care Trust in Lincolnshire a large rural county in the East Midlands of the United Kingdom comprising almost 700,000 patients. The projects included patients, general practitioners and their primary care teams, pharmacists and research and audit teams. Brief outline of problem Hypnotic prescribing rates from general practice Prescribing Analysis and Cost Data was identified by the executive as high in Lincolnshire compared to the rest of the East Midlands and the United Kingdom. Published research has shown that the clinical benefits of hypnotic drugs are small with significant risks of complications from adverse cognitive, psychiatric or psychomotor effects which may persist for several months after stopping the drug. The extent of the problem, its nature and the barriers to improvement were not well understood given that previous attempts to improve prescribing rates in this area of practice had failed. Assessment of problem and analysis of its causes Previous efforts to improve this aspect of quality and safety in healthcare in Lincolnshire and nationally have been hampered because of practitioner and patient attitudes, lack of organisational support or systems for change and an emphasis on other areas of healthcare. To understand the barriers to improving prescribing more fully we used questionnaires to general practitioners and patients and measured variation in prescribing rates across practices. Unforeseen and hitherto invisible problems were revealed by the responses. In addition, the views of patients prescribed hypnotics in the previous six months exposed high rates of inappropriate long term prescribing (94.9%had taken benzodiazepine or Z drug hypnotics for four weeks or more), side effects (41.8%reported at least one side effect), a wish to stop taking drugs (Z-drugs vs. benzodiazepines: 22.7 vs. 12.3%; p=0.001) and previous attempts by patients to come off medication (Z-drugs vs. benzodiazepines: 52.4% vs. 41.0%; p=0.001). Potential barriers to improvement included attitudes of general practitioners which supported prescribing of newer (Z drug) hypnotics for the majority of indications. More positively, practitioners were aware of their practice prescribing rates to the extent that they were able to identify whether they were in a high, intermediate or low prescribing practice. Most doctors held a negative perception of hypnotics and were positive to the idea of reducing prescribing in this area. Practitioners’ favoured methods for reducing prescribing helped inform potential strategies for change and will be presented. On the basis of these results it was felt that systematic efforts at implementation and improvement were likely to be successful given appropriate organisational support from the Primary Care Trust. Strategy for change: How did you implement the proposed change? What staff or other groups were involved? How did you disseminate the results of your analysis and your plans for change to the groups involved with/affected by the planned change? What was the timetable for change? A change project was developed, Resources for Effective Sleep Treatment (REST), with a number of stakeholders including partner organisation and patients. The aims of this project are to produce measurable improvements in the management of insomnia, specifically to: a. Reduce rate and (costs) of z-drug prescribing by 50% in 3 years b. Reduce the rate (costs) of benzodiazepine hypnotic prescribing by 25% in 3 years c. Increase use of recorded non-pharmacological measures in insomnia by at least 100% in 3 years. d. Improve the user experience of management of insomnia. We will use evidence based methods to develop an effective spread and adoption strategy to effect a sustained and sustainable change in practice in relation to management of insomnia. We will initially work with 10 pilot practices (10% of the total) using rapid experimentation (plan, do, study, act) cycles. We plan to work with these willing adopter practices and practitioners to develop a network of good practice, measurement and improvement tools, opinion leaders and champions for good practice using rapid cycle of change. We will also undertake focus groups with prescribing practitioners and patients to help understand more fully the barriers and facilitators, to identify good practice and to design appropriate improvement methods and interventions in this area of practice. Tailored interventions for practices involving clinician, pharmacy, secondary care and administrative support could help bring about change in clinical management. Measurement of improvement We will gather and analyse prescribing and improvement data from all practices in the county to enable systematic spread and adoption of improvements in prescribing and improvement methods more generally in the county. Lessons learned This project has emphasised the importance of gathering data at the onset of quality improvement initiatives to understand invisible barriers or facilitators for change and of involvement of patients and practitioners in their initial and ongoing development. Message for others Quality improvement projects benefit from research as well as quality improvement expertise in order to analyse, present and utilise information for their appropriate design

Policing and Health Collaboration in England and Wales. Landscape review.

The links between health, offending and policing are complex but inextricable. Collaborative working between the police and health has a long history but is still not commonplace. This landscape review aims to consider the breadth of the subject, and also to look at emerging themes and to influence future approaches

Inter-individual Differences in Tolerance to a Simulated Hemorrhage Challenge During Heat Stress: Cerebrovascular Control

A high degree of inter-individual variability exists in heat stress (HS) -induced reductions in orthostatic tolerance relative to normothermia (NT), which may be associated with HS-mediated reductions in cerebral perfusion, and thus mechanisms of cerebrovascular control during hypotensive challenges. This study tested two hypotheses; 1) the magnitude of increase in cerebral autoregulation (CA) would be negatively correlated with the difference in tolerance to graded lower body negative pressure (LBNP) 30 [assessed with a cumulative stress index (CSI)] during HS relative to NT (CSIdiff), and 2) cerebrovascular sensitivity to HS-induced hypocapnia would be positively correlated with CSIdiff. Subjects (N=13) were exposed to LBNP on two occasions (NT and HS) separated by \u3e72h to assess CSI. On a third day, indices of CA were assessed during NT and HS by spectral and transfer function analyses, and cerebrovascular sensitivity to changes in PaCO2 was determined during NT, HS, and HS+LBNP (-20 mm Hg; HSLBNP). Estimates of CA were improved during HS compared to NT (P0.05). Hyperventilation-induced hypocapnia reduced cerebral vascular conductance (CVCi) during HS and HSLBNP relative to NT (P0.05 for all). In summary, HS augments mechanisms of cerebrovascular control to protect against orthostatic challenges; however, individual differences in these responses do not predict tolerance to a simulated hemorrhage when internal temperature is elevated

A psychometric evaluation of the Defence Style Questionnaire-40 in a UK forensic patient population

Psychological defence mechanisms have been considered important personality processes in the onset, maintenance and recovery of mental disorders. More recently, their application to understanding presenting problems and as potential outcome indicators for forensic patients has been recommended. However, to date there have been no investigations into the reliability and factor structure of defence mechanism assessments for this population. The current study investigated the factor structure, internal consistency and test-retest reliability of the Defence Style Questionnaire-40 (DSQ) for 160 adult male UK forensic patients. The three-factor model of defences proposed by the DSQ-40 developers was not confirmed in the study sample. Reliability indices of the three factors indicated that the Immature factor was the most ‘acceptable’ in terms of internal consistency. Test-retest reliability coefficients ranged from .70 to .91. A revised three-factor structure that closely corresponds to the original validation study is recommended following an exploratory factor analysis. The findings are compared with previous reliability and factor analytic evaluations of the DSQ-40, and recommendations for its use with forensic patients are discussed

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

The voice of detainees in a high security setting on services for people with personality disorder

BACKGROUND: British government Home and Health Departments have been consulting widely about service development for people with ' dangerous severe personality disorder' (DSPD). There has, however, been no consultation with service users, nor is there any user view literature in this area. METHODS: All people detained in one high security hospital under the legal classification of psychopathic disorder were eligible but those on the admission or intensive care wards were not approached. Views of service were elicited using a purpose designed semi-structured interview. The principal researcher was independent of all clinical teams. Confidentiality about patients' views was assured. AIMS: To establish views on services from one subgroup of people nominated by the government department as having 'DSPD'. RESULTS: Sixty-one of 89 agreed to interview. With security a given, about half expressed a preference for a high security hospital setting, 20% prison and 25% elsewhere, generally medium secure hospitals. Participants most valued caring, understanding and 'experience' among staff. An ideal service was considered to be one within small, domestic living units, providing group and individual therapies. Some found living with people with mental illness difficult, but some specified not wanting segregated units. Views were affected by gender and comorbidity. CONCLUSIONS: As the sample were all in hospital, the emphasis on treatment may reflect a placement bias. All but five participants, however, had had experience of both health and criminal justice services, so were well placed to talk with authority about preferences