Acceptability and necessity of HIV and other blood-borne virus testing in a psychiatric setting.

Studies in North America and Europe indicate that the prevalence of blood-borne viruses (BBVs) is elevated in individuals with severe mental illness; there are no comparable data for the UK. We offered routine testing for HIV, and hepatitis B and C in an inner-London in-patient psychiatric unit as a service improvement. Of the patients approached 83% had mental capacity to provide informed consent for testing and 66% of patients offered testing accepted. Although it was not our objective to establish the prevalence of BBVs, 18% of patients had serological evidence of a current or previous BBV infection. We found that offering routine testing in an in-patient psychiatric setting is both practical and acceptable to patients.

Socio-economic deprivation and risk of emergency readmission and inpatient mortality in people with sickle cell disease in England: observational study.

BACKGROUND: Sickle cell disease (SCD) is a cause of frequent emergency readmissions. We examined trends in SCD emergency readmissions and inpatient mortality in England in relation to socio-economic status. METHODS: Data from Hospital Episode Statistics were extracted for all SCD patients admitted in 2005/06. The financial year 2005/06 was taken as the index year for analysis. We calculated readmission rates and inpatient mortality for patients admitted with a primary or secondary diagnosis of sickle cell anaemia with crisis and without crisis in the index year during the subsequent 5 years (2006/07-2010/11). Charlson Score was used to measure comorbidity. Using Cox proportional hazards models, we also examined the relationship between patient characteristics and both emergency readmissions and inpatient mortality. RESULTS: In 2005/06, there were 7679 SCD index admissions. Over the subsequent 5-year period, patients living in the most socio-economically deprived areas were at highest risk of readmission (54.2% readmitted over the study period compared with 28% of the least deprived group). Inpatient mortality amongst readmissions was highest in patients living in the most deprived areas [hazard ratio (HR) 2.34, 95% CI 1.41-3.90]. CONCLUSION: SCD patients from the most socio-economically deprived areas and with comorbidities are at highest risk of both SCD readmissions and in-hospital mortality, suggesting that there are inequalities in healthcare access and health outcomes amongst people with SCD.

Trends in hospital admissions for sickle cell disease in England, 2001/02-2009/10.

BACKGROUND: Sickle cell disease (SCD) is a rising cause of mortality and morbidity in England and consequently an important policy issue for the National Health Service. There has been no previous study that has examined SCD admission rates in England. METHODS: Data from Hospital Episode Statistics were analysed for all hospital episodes (2001/10) in England with a primary diagnosis of sickle cell anaemia with crisis (D57.0) or without crisis (D57.1). Secondary and tertiary diagnoses were examined among those patients admitted with either of these codes as their primary diagnosis. RESULTS: The overall SCD admission rate per 100 000 has risen from 21.2 in 2001/02 to 33.5 in 2009/10, a rise of over 50%. London accounts for 74.9% of all SCD admissions in England. 57.9% of patients admitted are discharged within 24 h. The largest rise in admission rates was seen among males aged 40-49 years where admission rates per 100 000 increased from 7.6 to 26.8 over the study period. CONCLUSIONS: Our data show that SCD admissions are rising in England, particularly in London. Over half of patients admitted with SCD were discharged within 24 h, suggesting that some of these admissions could be prevented through better ambulatory care of patients.

The addition of cyclophosphamide to lenalidomide and dexamethasone in multiply relapsed/refractory myeloma patients; a phase I/II study.

We report the results of a Phase I/II dose escalation study to determine the maximum tolerated dose (MTD) of cyclophosphamide when combined with lenalidomide and dexamethasone in relapsed/refractory myeloma. Thirty-one patients were enrolled in cohorts of 3, at five dose levels of cyclophosphamide to a maximum of 700 mg on days 1 and 8 of a 28-d cycle. Patients received lenalidomide 25 mg days 1-21 and dexamethasone 20 mg orally days 1-4 and 8-11. The MTD was 600 mg cyclophosphamide, days 1 and 8. Grade 3/4 haematological complications occurred in 26% of patients, grade 3/4 infection in 3% (both at 700 mg cyclophosphamide), with thromboembolic complications in 6% of patients. Overall complete response (CR) rate was 29%, very good partial response rate 7% and partial response rate 45% giving an overall response rate of 81%. After 21 months median follow-up, projected 2-year progression-free survival was 56%, with 80% overall survival at 30 months. Ten further patients were treated at MTD with a 40% CR rate. No dose reductions for any study drugs or deaths occurred during cycles 1-9. Lenalidomide, cyclophosphamide and dexamethasone is a safe, effective combination in relapsed myeloma inducing a high response rate, warranting further investigation in phase III trials.

ACCORD: A Multicentre, Seamless, Phase 2 Adaptive Randomisation Platform Study to Assess the Efficacy and Safety of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalised Patients: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Stage 1: To evaluate the safety and efficacy of candidate agents as add-on therapies to standard of care (SoC) in patients hospitalised with COVID-19 in a screening stage. Stage 2: To confirm the efficacy of candidate agents selected on the basis of evidence from Stage 1 in patients hospitalised with COVID-19 in an expansion stage. TRIAL DESIGN: ACCORD is a seamless, Phase 2, adaptive, randomised controlled platform study, designed to rapidly test candidate agents in the treatment of COVID-19. Designed as a master protocol with each candidate agent being included via its own sub-protocol, initially randomising equally between each candidate and a single contemporaneous SoC arm (which can adapt into 2:1). Candidate agents currently include bemcentinib, MEDI3506, acalabrutinib, zilucoplan and nebulised heparin. For each candidate a total of 60 patients will be recruited in Stage 1. If Stage 1 provides evidence of efficacy and acceptable safety the candidate will enter Stage 2 where a total of approximately 126 patients will be recruited into each study arm sub-protocol. Enrollees and outcomes will not be shared across the Stages; the endpoint, analysis and sample size for Stage 2 may be adjusted based on evidence from Stage 1. Additional arms may be added as new potential candidate agents are identified via candidate agent specific sub-protocols. PARTICIPANTS: The study will include hospitalised adult patients (≥18 years) with confirmed SARS-CoV-2 infection, the virus that causes COVID-19, that clinically meet Grades 3 (hospitalised - mild disease, no oxygen therapy), Grades 4 (hospitalised, oxygen by mask or nasal prongs) and 5 (hospitalised, non-invasive ventilation or high flow oxygen) of the WHO Working Group on the Clinical Characteristics of COVID-19 9-point category ordinal scale. Participants will be recruited from England, Northern Ireland, Wales and Scotland. INTERVENTION AND COMPARATOR: Comparator is current standard of care (SoC) for the treatment of COVID-19. Current candidate experimental arms include bemcentinib, MEDI3506, acalabrutinib, zilucoplan and nebulised heparin with others to be added over time. Bemcentinib could potentially reduce viral infection and blocks SARS-CoV-2 spike protein; MEDI3506 is a clinic-ready anti-IL-33 monoclonal antibody with the potential to treat respiratory failure caused by COVID; acalabrutinib is a BTK inhibitor which is anti-viral and anti-inflammatory; zilucoplan is a complement C5 inhibitor which may block the severe inflammatory response in COVID-19 and; nebulised heparin has been shown to bind with the spike protein. ACCORD is linked with the UK national COVID therapeutics task force to help prioritise candidate agents. MAIN OUTCOMES: Time to sustained clinical improvement of at least 2 points (from randomisation) on the WHO 9-point category ordinal scale, live discharge from the hospital, or considered fit for discharge (a score of 0, 1, or 2 on the ordinal scale), whichever comes first, by Day 29 (this will also define the "responder" for the response rate analyses). RANDOMISATION: An electronic randomization will be performed by Cenduit using Interactive Response Technology (IRT). Randomisation will be stratified by baseline severity grade. Randomisation will proceed with an equal allocation to each arm and a contemporaneous SoC arm (e.g. 1:1 if control and 1 experimental arm; 1:1:1 if two experimental candidate arms etc) but will be reviewed as the trial progresses and may be changed to 2:1 in favour of the candidate agents. BLINDING (MASKING): The trial is open label and no blinding is currently planned in the study. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): This will be in the order of 60 patients per candidate agent for Stage 1, and 126 patients for Stage 2. However, sample size re-estimation may be considered after Stage 1. It is estimated that up to 1800 patients will participate in the overall study. TRIAL STATUS: Master protocol version ACCORD-2-001 - Master Protocol (Amendment 1) 22nd April 2020, the trial has full regulatory approval and recruitment is ongoing in the bemcentinib (first patient recruited 6/5/2020), MEDI3506 (first patient recruited 19/5/2020), acalabrutinib (first patient recruited 20/5/2020) and zilucoplan (first patient recruited 19/5/2020) candidates (and SoC). The recruitment dates of each arm will vary between candidate agents as they are added or dropped from the trial, but will have recruited and reported within a year. TRIAL REGISTRATION: EudraCT 2020-001736-95 , registered 28th April 2020. FULL PROTOCOL: The full protocol (Master Protocol with each of the candidate sub-protocols) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

The incidence and outcome of myeloid malignancies in 2,112 adult patients in southeast England.

There is a paucity of epidemiological data on chronic myeloproliferative disorders and myelodysplastic syndromes (MDS), while subtypes of acute myeloid leukemia (AML) are rarely defined. We identified 2,112 adult myeloid malignancies in the South Thames area between 1999 and 2000. The incidence (European standard population) of AML was 3.00/100,000, that of MDS 3.47/100,000, chronic myelomonocytic leukemia (CMML) 0.46/100,000, idiopathic myelofibrosis (IMF) 0.37/100,000, polycythemia vera (PV) 1.08/100,000, primary thrombocythemia (PT) 1.65/100,000 and chronic myeloid leukemia (CML) 1.09/100,000. The 3-year survival for AML was 15%, MDS 45%, CMML 29%, IMF 48%, PV 80%, PT 81% and CML 50% We believe this study reflects the true incidence and outcome of myeloid malignancies in South East England.

An identification and brief advice programme for low-risk alcohol consumption in an acute medical setting: an implementation study.

OBJECTIVES: To implement an identification and brief advice (IBA) intervention to detect low-risk/hazardous alcohol consumption. DESIGN: Implementation was guided through the use of quality improvement tools and training. SETTING: This study was conducted over an 18-month period from April 2010 to September 2011 on a 42-bed acute medical unit at a central London acute hospital. PARTICIPANTS: All medical patients over the age of 18 admitted to the acute assessment unit were eligible; any patient unable to provide a medical history either through language barriers or due to illness was excluded. MAIN OUTCOME MEASURES: Percentage of medical patients admitted each week to the acute assessment unit who were screened for low-risk/hazardous alcohol consumption. RESULTS: Weekly data were analysed in time series run charts and cross-referenced to the date of educational sessions and their effect on the uptake of screening monitored. A demonstrable change in the mean percentage number of patients screened was observed in different time periods, 67.3-80.1%, following targeted teaching on the AAU. CONCLUSIONS: Our study demonstrates the successful use of quality improvement methodology to guide the implementation of Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), an IBA intervention, in the acute medical setting. The incorporation of the AUDIT-C into an admission document has been well accepted by the junior doctors, attaining an average (mean) of 80% of patients being screened using the tool. Targeted teaching of clinical staff involved in admitting patients appears to be the most effective method in improving uptake of IBA by junior doctors.

Making change last: applying the NHS institute for innovation and improvement sustainability model to healthcare improvement.

The implementation of evidence-based treatments to deliver high-quality care is essential to meet the healthcare demands of aging populations. However, the sustainable application of recommended practice is difficult to achieve and variable outcomes well recognised. The NHS Institute for Innovation and Improvement Sustainability Model (SM) was designed to help healthcare teams recognise determinants of sustainability and take action to embed new practice in routine care. This article describes a formative evaluation of the application of the SM by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Northwest London (CLAHRC NWL). Data from project teams' responses to the SM and formal reviews was used to assess acceptability of the SM and the extent to which it prompted teams to take action. Projects were classified as 'engaged,' 'partially engaged' and 'non-engaged.' Quarterly survey feedback data was used to explore reasons for variation in engagement. Score patterns were compared against formal review data and a 'diversity of opinion' measure was derived to assess response variance over time. Of the 19 teams, six were categorized as 'engaged,' six 'partially engaged,' and seven as 'non-engaged.' Twelve teams found the model acceptable to some extent. Diversity of opinion reduced over time. A minority of teams used the SM consistently to take action to promote sustainability but for the majority SM use was sporadic. Feedback from some team members indicates difficulty in understanding and applying the model and negative views regarding its usefulness. The SM is an important attempt to enable teams to systematically consider determinants of sustainability, provide timely data to assess progress, and prompt action to create conditions for sustained practice. Tools such as these need to be tested in healthcare settings to assess strengths and weaknesses and findings disseminated to aid development. This study indicates the SM provides a potentially useful approach to measuring teams' views on the likelihood of sustainability and prompting action. Securing engagement of teams with the SM was challenging and redesign of elements may need to be considered. Capacity building and facilitation appears necessary for teams to effectively deploy the SM.

Characterizing emergency admissions of patients with sickle cell crisis in NHS brent: observational study.

OBJECTIVES: To characterize emergency admissions for patients with sickle cell crisis in NHS Brent and to determine which patients and practices may benefit most from primary care intervention. DESIGN: Observational study SETTING: Emergency departments attended by residents of the London borough of Brent PARTICIPANTS: Patients with sickle cell disease registered with a general practitioner (GP) in the borough of Brent MAIN OUTCOME MEASURES: Analysis of admissions between January 2008 and July 2010 that included length of stay (average and <2 days versus ≥2 days) by age group and registered GP practice. RESULTS: Thirty six percent of sickle cell disease admission spells resulted in a length of stay of less than two days. Seventy four percent of total bed days are associated with patients with more than one admission during the period of analysis, i.e. multiple admissions. Two general practices in Brent were identified as having the highest number of patients admitted to the emergency department for sickle cell crisis and may benefit most from primary care intervention. DISCUSSION: Patients with short length of stay and multiple admissions may be potentially amenable to primary care intervention. The practices which have the highest numbers of sickle cell disease patients who frequently seek emergency care will be earmarked for an education intervention designed to help further engage general practitioners in the care and management of their sickle cell patients.

Patients' views on improving sickle cell disease management in primary care: focus group discussion.

OBJECTIVES: To assess sickle cell disease (SCD) patient and carer perspectives on the primary care services related to SCD that they receive from their general practitioner (GP). DESIGN: A focus group discussion was used to elicit the views of patients about the quality of care they receive from their primary health-care providers and what they thought was the role of primary care in SCD management. The focus group discussion was video recorded. The recording was then examined by the project team and recurring themes were identified. A comparison was made with notes made by two scribes also present at the discussion. SETTING: Sickle Cell Society in Brent, UK. PARTICIPANTS: Ten participants with SCD or caring for someone with SCD from Northwest London, UK. MAIN OUTCOME MEASURES: Patients' perceptions about the primary care services they received, and a list of key themes and suggestions. RESULTS: Patients and carers often bypassed GPs for acute problems but felt that GPs had an important role to play around repeat prescriptions and general health care. These service users believed SCD is often ignored and deemed unimportant by GPs. CONCLUSION: Participants wanted the health service to support primary health-care providers to improve their knowledge and understanding of SCD. Key themes and suggestions from this focus group have been used to help develop an educational intervention for general practice services that will be used to improve SCD management in primary care.

Making a jigsaw puzzle in 10 minutes: is case management feasible in general practice?

Background Case management has been advocated as a method of optimising the care of patients with complex problems and reducing inappropriate use of hospital services, but its impact to date has been limited. It is not known whether case management earlier in the development of complex problems will be more effective. Aim To develop a case management protocol usable in general practice. Design Co-designed by practitioners using a technology development approach. Setting General practices and community nursing teams in one primary care trust (PCT). Method Nominal group techniques applied to six multidisciplinary workshops held over nine months, in order to design and refine a case management protocol. Then field testing of the protocol with selected patients in four practices. Results A modular case management protocol has been designed that can be used in routine practice and completed over successive consultations. The protocol asks the practitioner and patient about their different perspectives on need, and about mental health, social care needs, nutritional status, vision and hearing, bone fragility, pain, continence and where appropriate end-of-life plans. An electronic version can be partially populated automatically, from the existing medical record. Field testing suggests that a paper version can also be used as a patient-held record for other professionals to use. Conclusion This study has created a model of case management for general practice that appears to be useable in general practice. A wider feasibility study is now needed to test uptake of the protocol by practices.

Comparison of a specialist haematological malignancy database against a regional cancer registry: case ascertainment and diagnostic accuracy.

No large-scale study has been performed to assess the problem of registering all subtypes of haematological malignancies. We compared registration of haematological malignancies between 1994 and 1996 by haematologists in 14 National Health Service Trusts in the Eastern part of the South Thames Region with data for the same area recorded by the Thames Cancer Registry (TCR). Case ascertainment and diagnostic accuracy were the two main outcome measures. A combined total of 4714 haematological malignancies were recorded over the 3-year period. Of these, 1329 (28%) were common to both databases, 1975 (42%) were recorded only by the TCR and 1410 (30%) were recorded only by the haematologists. Nearly one-third (31%) of all cases recorded by the TCR were death certificate-only registrations. The TCR records were obtained from 30 clinical specialities. Haematology only accounted for 35% of these cases. Discordant diagnoses were recorded in 20% of the cases that were recorded in both databases. Our data suggests that both registers have deficiencies in collecting and validating data on the incidence of haematological malignancies. To address this, a partnership was established in 1998 between haematologists in the South Thames Region and the Thames Cancer Registry. It is anticipated that engaging clinicians in the collection and validation of data will enhance the completeness of case ascertainment and improve the quality of data on haematological malignancies.