Evaluating the efficacy of the Thai Health Improvement Profile intervention for preventing weight gain in people with early stage psychosis: A randomized controlled trial.

OBJECTIVES: To investigate the efficacy of the Thai Health Improvement Profile intervention for preventing clinically significant weight gain in people with early stage psychosis. METHODS: We undertook a randomised controlled trial from 10/2018 to 05/2021. Participants with early stage psychosis (<5 year duration) were recruited using convenience sampling from the caseloads of community psychiatric nurses in Thailand and randomly allocated to either the Thai Health Improvement Profile intervention or treatment as usual group following baseline assessment. Outcome assessors were blind to group allocation, whereas participants were not. Participants in the intervention group received three monthly (five in total) systematic health checks using the Thai Health Improvement Profile tool, which was used to develop a personal health plan in collaboration with a family member/carer. Nurses supported participants to implement the health plan using behaviour change techniques derived from motivational interviewing. The treatment as usual group consisted of medication and psychosocial support, and no additional intervention was provided. The primary outcome was weight gain (defined as a greater or equal to 7 % increase in weight against baseline) within 1 year. RESULTS: Fifty-three participants were allocated to the intervention and an equal number to the treatment as usual group. Primary outcome data were available for 30 participants in each group at the 12 month follow-up. We undertook an intention to treat analysis with multiple imputation (to handle the missing data) for the primary outcome. The treatment as usual group was found to have higher odds than the Thai Health Improvement Profile intervention group of gaining ≥7 % of baseline body weight (OR = 6.52; 95 % CI: 1.88-22.65, p = 0.004). CONCLUSIONS: The Thai Health Improvement Profile intervention was effective at preventing weight gain in people with early stage psychosis at one year, though attrition was relatively high. The results highlight the need for community mental health nurses to adopt a holistic approach, the potential benefits of conducting regular comprehensive health checks and the importance of involving family members when aiming to improve the physical health of people diagnosed with early stage psychosis. A large definitive multi-site randomised controlled trial of the Thai Health Improvement Profile with a longer follow-up is now justified. TRIAL REGISTRATION: Prospectively registered with the Thai Clinical Trials Registry (reference: TCTR20180305002).

Midwife led randomised controlled trials in Australia and New Zealand: A scoping review.

BACKGROUND: Midwives are the largest workforce involved in caring for pregnant women and their babies, and are well placed to translate research into practice and ensure midwifery priorities are appropriately targeted in researched. Currently, the number and focus of randomised controlled trials led by midwives in Australia and New Zealand is unknown. The Australasian Nursing and Midwifery Clinical Trials Network was established in 2020 to build nursing and midwifery research capacity. To aid this, scoping reviews of the quality and quantity of nurse and midwife led trials were undertaken. AIM: To identify midwife led trials conducted between 2000 and 2021 in Australia and New Zealand. METHODS: This review was informed by the JBI scoping review framework. Medline, Emcare, and Scopus were searched from 2000-August 2021. ANZCTR, NHMRC, MRFF, and HRC (NZ) registries were searched from inception to July 2021. FINDINGS: Of 26,467 randomised controlled trials registered on the Australian and New Zealand Clinical Trials Registry, 50 midwife led trials, and 35 peer-reviewed publications were identified. Publications were of moderate to high quality with scores limited due to an inability to blind participants or clinicians. Blinding of assessors was included in 19 published trials. DISCUSSION: Additional support for midwives to design and conduct trials and publish findings is required. Further support is needed to translate registration of trial protocols into peer reviewed publications. CONCLUSION: These findings will inform the Australasian Nursing and Midwifery Clinical Trials Network plans to promote quality midwife led trials.

A scoping review of nurse-led randomised controlled trials.

BACKGROUND: Nurses comprise the largest portion of the healthcare workforce worldwide. However, nurse representation in the leadership of clinical research and research funding is largely unknown. The Australasian Nursing and Midwifery Clinical Trials Network was established to provide a coordinated network, focussed on building research capacity in nursing and midwifery. To support this work, this scoping review of nurse-led randomised controlled trials was conducted to summarise research activity, as well as highlight future research directions, gaps and resources. Midwife-led trials will be reported elsewhere. AIM: To quantify number, type and quality of nurse-led randomised controlled trials registered between 2000-2021. DESIGN: A scoping review of RCTs. DATA SOURCES: Medline, Emcare and Scopus were searched from 2000 to August 2021. ANZCTR, NHMRC, MRFF and HRC (NZ) registries were searched from inception to July 2021. REVIEW METHODS: This review was informed by the JBI scoping review framework using the PRISMA-ScR. RESULTS: Our search yielded 188 nurse-led publications and 279 registered randomised controlled trials. Multiple trials had the same nurse leaders. There were more registrations than publications. Publications were predominantly of high methodological quality; however, there was a reliance on active controls and blinding was low. Trial registrations indicate that universities and hospital/healthcare organisations were the major sources of funding, while publications indicate that Governments and the National Health and Medical Research Council were the main funding bodies. CONCLUSION: A small number of high-quality, large-scale, nationally funded randomised controlled trials were identified, with a larger number of locally funded small trials. There was a disparity between the number of registered trials and those published. Additional infrastructure, funding and career frameworks are needed to enable nurses to design, conduct and publish clinical trials that inform the health system and improve health outcomes. RELEVANCE TO CLINICAL PRACTICE: Research initiated and led by nurses has the potential to improve the health and well-being of individuals and communities, and current nurse-led research is of high methodological quality; however, there were very few nurse-led RCTs, conducted by a small pool of nurse researchers. This gap highlights the need for support in the design, conduct and publishing of nurse-led RCTs. PATIENT OR PUBLIC CONTRIBUTION: This is a scoping review; therefore, patient or public contribution is not applicable.

Preoperative Chemotherapy for Operable Colon Cancer: Mature Results of an International Randomized Controlled Trial.

PURPOSE: Neoadjuvant chemotherapy (NAC) has potential advantages over standard postoperative chemotherapy for locally advanced colon cancer but requires formal evaluation. METHODS: Patients with radiologically staged T3-4, N0-2, M0 colon cancer were randomly allocated (2:1) to 6 weeks oxaliplatin-fluoropyrimidine preoperatively plus 18 postoperatively (NAC group) or 24 weeks postoperatively (control group). Patients with RAS-wildtype tumors could also be randomly assigned 1:1 to receive panitumumab or not during NAC. The primary end point was residual disease or recurrence within 2 years. Secondary outcomes included surgical morbidity, histopathologic stage, regression grade, completeness of resection, and cause-specific mortality. Log-rank analyses were by intention-to-treat. RESULTS: Of 699 patients allocated to NAC, 674 (96%) started and 606 (87%) completed NAC. In total, 686 of 699 (98.1%) NAC patients and 351 of 354 (99.2%) control patients underwent surgery. Thirty patients (4.3%) allocated to NAC developed obstructive symptoms requiring expedited surgery, but there were fewer serious postoperative complications with NAC than with control. NAC produced marked T and N downstaging and histologic tumor regression (all P < .001). Resection was more often histopathologically complete: 94% (648/686) versus 89% (311/351), P < .001. Fewer NAC than control patients had residual or recurrent disease within 2 years (16.9% [118/699] v 21.5% [76/354]; rate ratio, 0.72 [95% CI, 0.54 to 0.98]; P = .037). Tumor regression correlated strongly with freedom from recurrence. Panitumumab did not enhance the benefit from NAC. Little benefit from NAC was seen in mismatch repair-deficient tumors. CONCLUSION: Six weeks of preoperative oxaliplatin-fluoropyrimidine chemotherapy for operable colon cancer can be delivered safely, without increasing perioperative morbidity. This chemotherapy regimen, when given preoperatively, produces marked histopathologic down-staging, fewer incomplete resections, and better 2-year disease control. Histologic regression after NAC is a strong predictor of lower postoperative recurrence risk so has potential use as a guide for postoperative therapy. Six weeks of NAC should be considered as a treatment option for locally advanced colon cancer.

Evaluation of the effect of a Nursing System Framework on Nurse Sensitive Indicators, mortality and readmission in an NHS Trust.

In 2018, an NHS Trust (UK) implemented an innovative Nursing System Framework (NSF). The NSF formalized a two-year strategy, which provided teams with clear aims and measurable objectives to deliver care. Failures of coordination of nursing services are well-recognized threats to the quality, safety and sustainability of care provision. AIM: To evaluate the efficacy of introducing a NSF in an NHS Trust, using nursing sensitive indicators and pre-selected mortality, data outcome measures. DESIGN: A before and after implementation, observational study. METHODS: 105,437 admissions were extracted at an admission record level. Data was extracted from 1st September 2018 through to the 31st August 2019. RESULTS: Using SQUIRE guidelines to report the study, insufficient evidence was found to reject a null hypothesis with a chi-squared test of association between in-hospital death and the NSF intervention period, with a p-value of .091. However, trends were seen in the data, which suggested a positive association. CONCLUSION: The NSF is a complex intervention, which provides direction for improvements but requires further research to understand the benefits for nurses, Midwives, Health Visitors and patients.

Experiences and views of carers regarding the physical health care of people with severe mental illness: An integrative thematic review of qualitative research.

WHAT IS KNOWN ON THE SUBJECT?: People with severe mental illness (SMI) have high rates of physical illnesses, and carers are core partners in managing their physical health. Qualitative research on carers' views/experiences of physical health care is limited, and there is no published systematic review that synthesizes the current evidence. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: Carers' views from seven articles were synthesised into nine themes and six subthemes describing their perceived facilitators, barriers and roles regarding the physical health care of people with SMI. Carers' voiced similar concerns to those previously identified by professionals and service users, particularly in relation to poor service access/responsiveness and communication difficulties with healthcare professionals. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Mental health nurses should be aware of the risk of diagnostic overshadowing and ensure they are both responsive and sensitive to carers concerns about the physical health of people with SMI. It is essential for mental health nurses to actively involve carers in managing physical health, especially in formulating physical healthcare plans and providing clear practical advice/information. ABSTRACT: Introduction People with severe mental illness (SMI) have high rates of physical illnesses. Informal carers are core partners in addressing these issues, however research on their views/experiences is limited and there is no systematic review published on the topic. Aim This integrative thematic review explored the experiences and views of carers on physical health care in SMI by synthesizing the existing qualitative research findings. Methods Six databases were searched from 2000 to 2021. Data were extracted and synthesised using thematic integrative analysis. The quality of included studies was assessed with the JBI Critical Appraisal Checklist. Results Five studies were included. Nine themes were identified conceptualising carers' perceived facilitators, barriers and roles regarding physical health care for people with SMI. Discussion Carers felt that receiving practical help and a specialised role for mental health nurses would facilitate better physical health care. Lack of coordination/communication and poor service access/responsiveness were common barriers, often compounded by diagnostic overshadowing. Carers are involved in promoting healthy lifestyles, monitoring physical health and supporting access to services. Implications for Practice Mental health nurses should ensure they are responsive to carers' concerns and proactively support them to promote the physical health of people with SMI.

How prospective trial registration can prevent selective outcome reporting and salami slicing?

BACKGROUND: Pre-registration of a clinical trial before the first participant is recruited can help to prevent selective outcome reporting and salami-slicing that can distort the evidence base for an intervention and result in people being offered care or treatment that is not effective. Rates of clinical trial registration in nursing and midwifery are low. AIM: To use a hypothetical example from midwifery practice to illustrate how selective outcome reporting and salami-slicing can distort the evidence base. FINDINGS: A trial of immersion in water during labour and birth is used to consider issues in outcome selection and how researchers may be drawn to switch primary outcomes or report different outcomes across multiple papers. DISCUSSION: In nursing and midwifery science, selective outcome and salami reporting are seemingly common. Prospective trial registration is intended to prevent these practices, enhancing the quality and integrity of the work. CONCLUSION: Clinical trials are a robust form of primary research evidence and directly impact clinical practice. Researchers must ensure their trials are correctly registered and editors need to reconcile submitted papers and registration entries as part of the review process.

A reflection on the impact of COVID-19 on primary care in the United Kingdom.

The COVID-19 pandemic has presented both challenges and opportunities for those working in health and social care in the United Kingdom (UK). With much focus on secondary and acute care at this time, there has been less communication and understanding about the impact on primary care. This discussion paper is based on the experience of one of the authors working as a general practitioner/family doctor during the pandemic and rapid changes are described during this time (April 2020). Two important themes emerged from this experience focusing on the importance of supporting one another and new roles and ways of working. It can be argued that the challenges presented by COVID-19 have expedited positive and potentially sustainable change in UK primary care that has been needed for some time. The authors discuss the implications for future working and make a series of recommendations for primary care relating to the importance of supporting the workforce, remote consultations and communication, regular team meetings, and development of integrated care. It is suggested that many of the challenges highlighted can be addressed by placing a greater emphasis on the use of interprofessional education (IPE) to underpin and support effective collaborative working.

Gaps in the HIV diagnosis and care cascade for migrants in Australia, 2013-2017: A cross-sectional study.

BACKGROUND: Globally, few studies compare progress toward the Joint United Nations Program on HIV/AIDS (UNAIDS) Fast-Track targets among migrant populations. Fast-Track targets are aligned to the HIV diagnosis and care cascade and entail achieving 90-90-90 (90% of people living with HIV [PLHIV] diagnosed, 90% of those diagnosed on treatment, and 90% of those on treatment with viral suppression [VS]) by 2020 and 95-95-95 by 2030. We compared cascades between migrant and nonmigrant populations in Australia. METHODS AND FINDINGS: We conducted a serial cross-sectional survey for HIV diagnosis and care cascades using modelling estimates for proportions diagnosed combined with a clinical database for proportions on treatment and VS between 2013-2017. We estimated the number of PLHIV and number diagnosed using New South Wales (NSW) and Victorian (VIC) data from the Australian National HIV Registry. Cascades were stratified by migration status, sex, HIV exposure, and eligibility for subsidised healthcare in Australia (reciprocal healthcare agreement [RHCA]). We found that in 2017, 17,760 PLHIV were estimated in NSW and VIC, and 90% of them were males. In total, 90% of estimated PLHIV were diagnosed. Of the 9,391 who were diagnosed and retained in care, most (85%; n = 8,015) were males. We excluded 38% of PLHIV with missing data for country of birth, and 41% (n = 2,408) of eligible retained PLHIV were migrants. Most migrants were from Southeast Asia (SEA; 28%), northern Europe (12%), and eastern Asia (11%). Most of the migrants and nonmigrants were males (72% and 83%, respectively). We found that among those retained in care, 90% were on antiretroviral therapy (ART), and 95% of those on ART had VS (i.e., 90-90-95). Migrants had larger gaps in their HIV diagnosis and care cascade (85-85-93) compared with nonmigrants (94-90-96). Similarly, there were larger gaps among migrants reporting male-to-male HIV exposure (84-83-93) compared with nonmigrants reporting male-to-male HIV exposure (96-92-96). Large gaps were also found among migrants from SEA (72-87-93) and sub-Saharan Africa (SSA; 89-93-91). Migrants from countries ineligible for RHCA had lower cascade estimates (83-85-92) than RHCA-eligible migrants (96-86-95). Trends in the HIV diagnosis and care cascades improved over time (2013 and 2017). However, there was no significant increase in ART coverage among migrant females (incidence rate ratio [IRR]: 1.03; 95% CI 0.99-1.08; p = 0.154), nonmigrant females (IRR: 1.01; 95% CI 0.95-1.07; p = 0.71), and migrants from SEA (IRR: 1.03; 95% CI 0.99-1.07; p = 0.06) and SSA (IRR: 1.03; 95% CI 0.99-1.08; p = 0.11). Additionally, there was no significant increase in VS among migrants reporting male-to-male HIV exposure (IRR: 1.02; 95% CI 0.99-1.04; p = 0.08). The major limitation of our study was a high proportion of individuals missing data for country of birth, thereby limiting migrant status categorisation. Additionally, we used a cross-sectional instead of a longitudinal study design to develop the cascades and used the number retained as opposed to using all individuals diagnosed to calculate the proportions on ART. CONCLUSIONS: HIV diagnosis and care cascades improved overall between 2013 and 2017 in NSW and VIC. Cascades for migrants had larger gaps compared with nonmigrants, particularly among key migrant populations. Tracking subpopulation cascades enables gaps to be identified and addressed early to facilitate achievement of Fast-Track targets.

Implementation of an Enhanced Recovery After Surgery (ERAS) Program is Associated with Improved Outcomes in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been associated with increased postoperative complications and a prolonged length of stay (LOS). We report on our experience following implementation of an Enhanced Recovery After Surgery (ERAS) program for CRS and HIPEC. METHODS: Patients were divided into pre- and post-ERAS groups. Modifications in the ERAS group included routine use of transversus abdominis plane blocks, intra- and postoperative fluid restriction, and minimizing the use of narcotics, drains, and nasogastric tubes. RESULTS: Of a total of 130 procedures, 49 (38%) were in the pre-ERAS group and 81 (62%) were in the ERAS group. Mean LOS was reduced from 10.3 ± 8.9 days to 6.9 ± 5.0 days (p = 0.007) and the rate of grade III/IV complications was reduced from 24 to 15% (p = 0.243) following ERAS implementation. The ERAS group received less intravenous fluid during hospitalization (19.2 ± 18.7 L vs. 32.8 ± 32.5 L, p = 0.003) and used less opioids than the pre-ERAS group (median of 159.7 mg of oral morphine equivalents vs. 272.6 mg). There were no significant changes in the rates of 30-day readmission or acute kidney injury between the two groups (p = non-significant). On multivariable analyses, ERAS was significantly associated with a reduction in LOS (- 2.89 days, 95% CI - 4.84 to - 0.94) and complication rates (odds ratio 0.22, 95% CI 0.08-0.57). CONCLUSIONS: Implementation of an ERAS program for CRS and HIPEC is associated with a reduction in overall intravenous fluids, postoperative narcotic use, complication rates, and LOS.

Therapeutic Dancing for Frail Older People in Residential Aged Care: A Thematic Analysis of Barriers and Facilitators to Implementation.

BACKGROUND: Adults who live in residential aged care can have reduced participation in physical activities and sit for prolonged periods. Therapeutic dancing aims to optimize movement, creative expression, well-being, and social interaction. OBJECTIVES: To investigate the benefits, challenges, and facilitators to implementing therapeutic dancing in residential aged care. METHODS: Thematic analysis of semistructured interviews of residential aged care staff and therapists. Interviews were digitally audio-recorded and thematically analyzed. Findings: Four main themes were identified: (a) despite frailty, dancing classes afforded motor and nonmotor benefits, (b) music and dance genre selections were key to success, (c) the skills of the dance instructor were associated with successful outcomes, and (d) there were modifiable and nonmodifiable facilitators and barriers to implementation. CONCLUSION: Enablers included support from management, resident supervision, age-appropriate music with a strong rhythmical beat, and a dance instructor skilled in comprehensive care. Barriers included multimorbidity, frailty, severe cognitive impairment, and funding.

Comparison of 99mTc-Sestamibi Molecular Breast Imaging and Breast MRI in Patients With Invasive Breast Cancer Receiving Neoadjuvant Chemotherapy.

OBJECTIVE. The purpose of this study is to prospectively compare the size of invasive breast cancer before and after neoadjuvant chemotherapy (NAC) at breast MRI and molecular breast imaging (MBI) and to assess the accuracy of post-NAC MBI and MRI relative to pathologic analysis. SUBJECTS AND METHODS. Women with invasive breast cancer greater than or equal to 1.5 cm were enrolled to compare the longest dimension before and after NAC at MRI and MBI. MBI was performed on a dual-detector cadmium zinc telluride system after administration of 6.5 mCi (240 MBq) 99mTc-sestamibi. The accuracy of MRI and MBI in assessing residual disease (invasive disease or ductal carcinoma in situ) was determined relative to pathologic examination. RESULTS. The longest dimension at MRI was within 1.0 cm of that at MBI in 72.3% of cases before NAC and 70.1% of cases after NAC. The difference between the longest dimension at imaging after NAC and pathologic tumor size was within 1 cm for 58.7% of breast MRI cases and 59.6% of MBI cases. Ninety patients underwent both MRI and MBI after NAC. In the 56 patients with invasive residual disease, 10 (17.9%) cases were negative at MRI and 23 (41.1%) cases were negative at MBI. In the 34 patients with breast pathologic complete response, there was enhancement in 10 cases (29.4%) at MRI and uptake in six cases (17.6%) at MBI. Sensitivity, specificity, positive predictive value, and negative predictive value after NAC were 82.8%, 69.4%, 81.4%, and 71.4%, respectively, for MRI and 58.9%, 82.4%, 84.6%, and 54.9%, respectively, for MBI. CONCLUSION. Breast MRI and MBI showed similar disease extent before NAC. MBI may be an alternative to breast MRI in patients with a contraindication to breast MRI. Neither modality showed sufficient accuracy after NAC in predicting breast pathologic complete response to obviate tissue diagnosis to assess for residual invasive disease. Defining the extent of residual disease compared with pathologic evaluation was also limited after NAC for both breast MRI and MBI.

Amisulpride for very late-onset schizophrenia-like psychosis: the ATLAS three-arm RCT.

BACKGROUND: Very late-onset (aged ≥ 60 years) schizophrenia-like psychosis (VLOSLP) occurs frequently but no placebo-controlled, randomised trials have assessed the efficacy or risks of antipsychotic treatment. Most patients are not prescribed treatment. OBJECTIVES: The study investigated whether or not low-dose amisulpride is superior to placebo in reducing psychosis symptoms over 12 weeks and if any benefit is maintained by continuing treatment thereafter. Treatment safety and cost-effectiveness were also investigated. DESIGN: Three-arm, parallel-group, placebo-controlled, double-blind, randomised controlled trial. Participants who received at least one dose of study treatment were included in the intention-to-treat analyses. SETTING: Secondary care specialist old age psychiatry services in 25 NHS mental health trusts in England and Scotland. PARTICIPANTS: Patients meeting diagnostic criteria for VLOSLP and scoring > 30 points on the Brief Psychiatric Rating Scale (BPRS). INTERVENTION: Participants were randomly assigned to three arms in a two-stage trial: (1) 100 mg of amisulpride in both stages, (2) amisulpride then placebo and (3) placebo then amisulpride. Treatment duration was 12 weeks in stage 1 and 24 weeks (later reduced to 12) in stage 2. Participants, investigators and outcome assessors were blind to treatment allocation. MAIN OUTCOME MEASURES: Primary outcomes were psychosis symptoms assessed by the BPRS and trial treatment discontinuation for non-efficacy. Secondary outcomes were extrapyramidal symptoms measured with the Simpson-Angus Scale, quality of life measured with the World Health Organization's quality-of-life scale, and cost-effectiveness measured with NHS, social care and carer work loss costs and EuroQol-5 Dimensions. RESULTS: A total of 101 participants were randomised. Ninety-two (91%) participants took the trial medication, 59 (64%) completed stage 1 and 33 (56%) completed stage 2 treatment. Despite suboptimal compliance, improvements in BPRS scores at 12 weeks were 7.7 points (95% CI 3.8 to 11.5 points) greater with amisulpride than with placebo (11.9 vs. 4.2 points; p = 0.0002). In stage 2, BPRS scores improved by 1.1 point in those who continued with amisulpride but deteriorated by 5.2 points in those who switched from amisulpride to placebo, a difference of 6.3 points (95% CI 0.9 to 11.7 points; p = 0.024). Fewer participants allocated to the amisulpride group stopped treatment because of non-efficacy in stages 1 (p = 0.01) and 2 (p = 0.031). The number of patients stopping because of extrapyramidal symptoms and other side effects did not differ significantly between groups. Amisulpride treatment in the base-case analyses was associated with non-significant reductions in combined NHS, social care and unpaid carer costs and non-significant reductions in quality-adjusted life-years (QALYs) in both stages. Including patients who were intensive users of inpatient services in sensitivity analyses did not change the QALY result but resulted in placebo dominance in stage 1 and significant reductions in NHS/social care (95% CI -£8923 to -£122) and societal costs (95% CI -£8985 to -£153) for those continuing with amisulpride. LIMITATIONS: The original recruitment target of 300 participants was not achieved and compliance with trial medication was highly variable. CONCLUSIONS: Low-dose amisulpride is effective and well tolerated as a treatment for VLOSLP, with benefits maintained by prolonging treatment. Potential adverse events include clinically significant extrapyramidal symptoms and falls. FUTURE WORK: Trials should examine the longer-term effectiveness and safety of antipsychotic treatment in this patient group, and assess interventions to improve their appreciation of potential benefits of antipsychotic treatment and compliance with prescribed medication. TRIAL REGISTRATION: Current Controlled Trials ISRCTN45593573 and EudraCT2010-022184-35. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 67. See the NIHR Journals Library website for further project information.