Engagement With Stop Smoking Services After Referral or Signposting: A Mixed Methods Study.

INTRODUCTION: Screening for smoking when people interact with healthcare services and referral of those who smoke to stop smoking services (SSSs) is a key component of efforts to tackle tobacco use. However, little is known about what happens after someone is referred or signposted to SSSs. METHODS: As part of the Cessation of Smoking Trial in the Emergency Department (NCT04854616), those randomised to intervention (n= 505) were referred to local SSSs (along with receiving brief advice and an e-cigarette starter kit) and those randomised to control (n= 502) were given contact details for the same services (signposted). SSS engagement data was collected: 1) directly from participants and 2) from SSS, additional qualitative data came from 33 participant interviews. RESULTS: Engagement with SSSs was very low. 3.2% (n=16) of those in the intervention group and 2.4% (n=12) in the control group reported attending a one-to-one support session. From SSS data, engagement was also low with 8.9% (n=43) of those referred engaging and 3.1% (n=15) going on to quit with SSS support. The majority of the 24 intervention participants interviewed did not recall being contacted by an SSS. CONCLUSION: Referral or signposting to stop smoking services within an Emergency Department based trial resulted in very low levels of engagement. Barriers to engagement identified included participants not being contacted by SSSs and the support offered not meeting their needs. IMPLICATIONS: Referral or signposting of those who smoke to Stop smoking services from the Emergency Department resulted in low rates of engagement in this large multi-centre randomised controlled trial. In order to better support those who smoke it may be more effective for smoking cessation advice to be offered 'in the moment' within clinical settings, and follow-up to be proactively offered rather than relying on people being motivated to contact the services themselves or engaging when contacted.

Cessation of Smoking Trial in the Emergency Department (COSTED): a multicentre randomised controlled trial.

BACKGROUND: Supporting people to quit smoking is one of the most powerful interventions to improve health. The Emergency Department (ED) represents a potentially valuable opportunity to deliver a smoking cessation intervention if it is sufficiently resourced. The objective of this trial was to determine whether an opportunistic ED-based smoking cessation intervention can help people to quit smoking. METHODS: In this multicentre, parallel-group, randomised controlled superiority trial conducted between January and August 2022, adults who smoked daily and attended one of six UK EDs were randomised to intervention (brief advice, e-cigarette starter kit and referral to stop smoking services) or control (written information on stop smoking services). The primary outcome was biochemically validated abstinence at 6 months. RESULTS: An intention-to-treat analysis included 972 of 1443 people screened for inclusion (484 in the intervention group, 488 in the control group). Of 975 participants randomised, 3 were subsequently excluded, 17 withdrew and 287 were lost to follow-up. The 6-month biochemically-verified abstinence rate was 7.2% in the intervention group and 4.1% in the control group (relative risk 1.76; 95% CI 1.03 to 3.01; p=0.038). Self-reported 7-day abstinence at 6 months was 23.3% in the intervention group and 12.9% in the control group (relative risk 1.80; 95% CI 1.36 to 2.38; p<0.001). No serious adverse events related to taking part in the trial were reported. CONCLUSIONS: An opportunistic smoking cessation intervention comprising brief advice, an e-cigarette starter kit and referral to stop smoking services is effective for sustained smoking abstinence with few reported adverse events. TRIAL REGISTRATION NUMBER: NCT04854616.

Study of mirtazapine for agitated behaviours in dementia (SYMBAD): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Agitation is common in people with dementia and negatively affects the quality of life of both people with dementia and carers. Non-drug patient-centred care is the first-line treatment, but there is a need for other treatment when this care is not effective. Current evidence is sparse on safer and effective alternatives to antipsychotics. We assessed the efficacy and safety of mirtazapine, an antidepressant prescribed for agitation in dementia. METHODS: This parallel-group, double-blind, placebo-controlled trial-the Study of Mirtazapine for Agitated Behaviours in Dementia trial (SYMBAD)-was done in 26 UK centres. Participants had probable or possible Alzheimer's disease, agitation unresponsive to non-drug treatment, and a Cohen-Mansfield Agitation Inventory (CMAI) score of 45 or more. They were randomly assigned (1:1) to receive either mirtazapine (titrated to 45 mg) or placebo. The primary outcome was reduction in CMAI score at 12 weeks. This trial is registered with ClinicalTrials.gov, NCT03031184, and ISRCTN17411897. FINDINGS: Between Jan 26, 2017, and March 6, 2020, 204 participants were recruited and randomised. Mean CMAI scores at 12 weeks were not significantly different between participants receiving mirtazapine and participants receiving placebo (adjusted mean difference -1·74, 95% CI -7·17 to 3·69; p=0·53). The number of controls with adverse events (65 [64%] of 102 controls) was similar to that in the mirtazapine group (67 [66%] of 102 participants receiving mirtazapine). However, there were more deaths in the mirtazapine group (n=7) by week 16 than in the control group (n=1), with post-hoc analysis suggesting this difference was of marginal statistical significance (p=0·065). INTERPRETATION: This trial found no benefit of mirtazapine compared with placebo, and we observed a potentially higher mortality with use of mirtazapine. The data from this study do not support using mirtazapine as a treatment for agitation in dementia. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Cost-effectiveness of mirtazapine for agitated behaviors in dementia: findings from a randomized controlled trial.

OBJECTIVES: To examine the costs and cost-effectiveness of mirtazapine compared to placebo over 12-week follow-up. DESIGN: Economic evaluation in a double-blind randomized controlled trial of mirtazapine vs. placebo. SETTING: Community settings and care homes in 26 UK centers. PARTICIPANTS: People with probable or possible Alzheimer's disease and agitation. MEASUREMENTS: Primary outcome included incremental cost of participants' health and social care per 6-point difference in CMAI score at 12 weeks. Secondary cost-utility analyses examined participants' and unpaid carers' gain in quality-adjusted life years (derived from EQ-5D-5L, DEMQOL-Proxy-U, and DEMQOL-U) from the health and social care and societal perspectives. RESULTS: One hundred and two participants were allocated to each group; 81 mirtazapine and 90 placebo participants completed a 12-week assessment (87 and 95, respectively, completed a 6-week assessment). Mirtazapine and placebo groups did not differ on mean CMAI scores or health and social care costs over the study period, before or after adjustment for center and living arrangement (independent living/care home). On the primary outcome, neither mirtazapine nor placebo could be considered a cost-effective strategy with a high level of confidence. Groups did not differ in terms of participant self- or proxy-rated or carer self-rated quality of life scores, health and social care or societal costs, before or after adjustment. CONCLUSIONS: On cost-effectiveness grounds, the use of mirtazapine cannot be recommended for agitated behaviors in people living with dementia. Effective and cost-effective medications for agitation in dementia remain to be identified in cases where non-pharmacological strategies for managing agitation have been unsuccessful.

Implementing supportive exercise interventions in the colorectal cancer care pathway: a process evaluation of the PREPARE-ABC randomised controlled trial.

BACKGROUND: A colorectal resection is standard treatment for patients with colorectal cancer (CRC). However, the procedure results in significant post-operative mortality and reduced quality of life. Maximising pre-operative cardiopulmonary fitness could improve post-surgical outcomes. PREPARE-ABC is a multi-centre, three-armed, randomised controlled trial investigating the effects of exercise interventions, with motivational support on short and longer-term recovery outcomes in CRC patients undergoing major lower-gastrointestinal surgery. The trial included an internal pilot phase with parallel process evaluation. The aim of the process evaluation was to optimise intervention implementation for the main trial. METHODS: Mixed methods process evaluation conducted in 14 UK hospitals between November 2016 and March 2018. Data included a site profile questionnaire and telephone scoping interview with hospital staff, 34 qualitative observations of standard care and 14 observations of intervention delivery, 13 semi-structured interviews with healthcare professionals (HCPs) and 28 semi-structured interviews with patients. Data analysis focused on describing intervention delivery within each arm, assessing fidelity, acceptability and how variation in delivery was linked to contextual characteristics. RESULTS: Standard care exercise advice was typically limited to maintaining current activity levels, and with lead-in time to surgery affecting whether any exercise advice was provided. Variation in HCP capacity affected the ability of colorectal units to deploy staff to deliver the intervention. Patients' exercise history and motivation prior to surgery influenced HCP perceptions and delivery of the motivational components. Observations indicated a high level of fidelity to delivery of the exercise interventions. All but one of the 28 interviewed patients reported increasing exercise levels as a result of receiving the intervention, with most finding them motivational and greatly valuing the enhanced level of social support (versus standard care) provided by staff. CONCLUSION: Hospital-supervised and home-based exercise interventions were highly acceptable for most patients undergoing surgery for CRC. Delivery of pre- and post-operative exercise within the CRC care pathway is feasible but systematic planning of capacity and resources is required to optimise implementation.

Effect of Co-trimoxazole (Trimethoprim-Sulfamethoxazole) vs Placebo on Death, Lung Transplant, or Hospital Admission in Patients With Moderate and Severe Idiopathic Pulmonary Fibrosis: The EME-TIPAC Randomized Clinical Trial.

Importance: Idiopathic pulmonary fibrosis (IPF) has a poor prognosis and limited treatment options. Patients with IPF have altered lung microbiota, with bacterial burden within the lungs associated with mortality; previous studies have suggested benefit with co-trimoxazole (trimethoprim-sulfamethoxazole). Objective: To determine the efficacy of co-trimoxazole in patients with moderate and severe IPF. Design, Setting, and Participants: Double-blind, placebo-controlled, parallel randomized trial of 342 patients with IPF, breathlessness (Medical Research Council dyspnea scale score >1), and impaired lung function (forced vital capacity ≤75% predicted) conducted in 39 UK specialist interstitial lung disease centers between April 2015 (first patient visit) and April 2019 (last patient follow-up). Interventions: Study participants were randomized to receive 960 mg of oral co-trimoxazole twice daily (n = 170) or matched placebo (n = 172) for between 12 and 42 months. All patients received 5 mg of folic acid orally once daily. Main Outcomes and Measures: The primary outcome was time to death (all causes), lung transplant, or first nonelective hospital admission. There were 15 secondary outcomes, including the individual components of the primary end point respiratory-related events, lung function (forced vital capacity and gas transfer), and patient-reported outcomes (Medical Research Council dyspnea scale, 5-level EuroQol 5-dimension questionnaire, cough severity, Leicester Cough Questionnaire, and King's Brief Interstitial Lung Disease questionnaire scores). Results: Among 342 individuals who were randomized (mean age, 71.3 years; 46 [13%] women), 283 (83%) completed the trial. The median (interquartile range) duration of follow-up was 1.02 (0.35-1.73) years. Events per person-year of follow-up among participants randomized to the co-trimoxazole and placebo groups were 0.45 (84/186) and 0.38 (80/209), respectively, with a hazard ratio of 1.2 ([95% CI, 0.9-1.6]; P = .32). There were no statistically significant differences in other event outcomes, lung function, or patient-reported outcomes. Patients in the co-trimoxazole group had 696 adverse events (nausea [n = 89], diarrhea [n = 52], vomiting [n = 28], and rash [n = 31]) and patients in the placebo group had 640 adverse events (nausea [n = 67], diarrhea [n = 84], vomiting [n = 20], and rash [n = 20]). Conclusions and Relevance: Among patients with moderate or severe IPF, treatment with oral co-trimoxazole did not reduce a composite outcome of time to death, transplant, or nonelective hospitalization compared with placebo. Trial Registration: ISRCTN Identifier: ISRCTN17464641.

Association of increasing age with receipt of specialist care and long-term mortality in patients with non-ST elevation myocardial infarction.

BACKGROUND: observational studies suggest that older patients are less likely to receive secondary prevention medicines following acute coronary syndrome (ACS). OBJECTIVES: to examine the association of increasing age with receipt of specialist care and influence of specialist care on long-term mortality in patients with non-ST elevation myocardial infarction (NSTEMI). DESIGN: a cohort study. SETTING: National ACS registry of England and Wales. SUBJECTS: a total of 85,183 patients admitted with NSTEMI between 2006 and 2010. METHODS: logistic regression analyses to assess receipt of secondary prevention medicines (ACE inhibitor, ß-blocker, statin, aspirin) by age group; multivariate Cox regression models to examine longitudinal effect of cardiologist care on all-cause mortality by age group. RESULTS: mean age 72.0 years (SD 13.0 years), mean follow-up was 2.13 years. Older patients received less cardiologist care (70.2% of NSTEMI patients ≥85 years compared with 94.7% of patients <65) years and had more co-morbidity. Cardiologists prescribed more secondary prevention in all age groups than generalists, but this was mostly explained away by co-morbidity (receipt of statin crude OR 1.51 (1.27,1.80), fully adjusted OR 1.11 (0.92,1.33) in patients ≥85 years). Receiving cardiologist care compared with generalist care was associated with a decreased risk of death in all even after adjustment for co-morbidity, disease severity and secondary prevention; this benefit reduced incrementally with older age group (adjusted hazard ratio (HR) 0.58 (0.49,0.68) aged <65; 0.87 (0.82,0.92) aged ≥85). CONCLUSION: older patients with NSTEMI were less likely to see a cardiologist, but reduced treatment by generalists was explained away by co-morbidity. Cardiologist care was associated with lower mortality in all age groups than a generalist, but this survival benefit was less pronounced in older patients.

The association between older age and receipt of care and outcomes in patients with acute coronary syndromes: a cohort study of the Myocardial Ischaemia National Audit Project (MINAP).

AIMS: Older people increasingly constitute a large proportion of the acute coronary syndrome (ACS) population. We examined the relationship of age with receipt of more intensive management and secondary prevention medicine. Then, the comparative association of intensive management (reperfusion/angiography) over a conservative strategy on time to death was investigated by age. METHODS AND RESULTS: Using data from 155 818 patients in the national registry for ACS in England and Wales [the Myocardial Ischaemia National Audit Project (MINAP)], we found that older patients were incrementally less likely to receive secondary prevention medicines and intensive management for both ST-elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI). In STEMI patients ≥85 years, 55% received reperfusion compared with 84% in those aged 18 to <65 [odds ratio 0.22 (95% CI 0.21, 0.24)]. Not receiving intensive management was associated with worse survival [mean follow-up 2.29 years (SD 1.42)] in all age groups (adjusted for sex, cardiovascular risk factors, co-morbidities, healthcare factors, and case severity), but there was an incremental reduction in survival benefit from intensive management with increasing age. In STEMI patients aged 18-64, 65-74, 75-84, and ≥85, adjusted hazard ratios (HRs) for all-cause mortality comparing conservative treatment to intensive management were 1.98 (1.78, 2.19), 1.65 (1.51, 1.80), 1.62 (1.52, 1.72), and 1.36 (1.27, 1.47), respectively. In NSTEMI patients, the respective HRs were 4.37 (4.00, 4.78), 3.76 (3.54, 3.99), 2.79 (2.67, 2.91), and 1.90 (1.77, 2.04). CONCLUSION: We found an incremental reduction in the use of evidence-based therapies with increasing age using a national ACS registry cohort. While survival benefit from more intensive management reduced with older age, better survival was associated with intensive management at all ages highlighting the requirement to improve standard of care in older patients with ACS.

How do people quit smoking using e-cigarettes? A mixed-methods exploration of participant smoking pathways following receiving an opportunistic e-cigarette-based smoking cessation intervention.

BACKGROUND AND AIMS: Pathways of transitioning from tobacco smoking to vaping after receiving an e-cigarette-based smoking cessation intervention have been minimally explored. STUDY AIMS: 1) identify pathways between intervention delivery and final follow-up; 2) describe baseline and post-intervention statistical data in relation to smoking/vaping behaviour of the different pathway groups; 3) explore qualitative participant perspectives contextualising pathway groups. DESIGN: Embedded mixed-methods analysis of data collected for the Cessation of Smoking Trial in the Emergency Department (COSTED) randomised controlled trial. SETTING: Recruitment from 6 Emergency Departments (5 in England and 1 in Scotland) between January and August 2022. PARTICIPANTS: 366 adult smokers who were randomised to receive the COSTED intervention and provided data at 6-month follow-up. Qualitative subsample of 24 participants interviewed after follow-up. INTERVENTIONS: Brief smoking cessation advice, provision of an e-cigarette starter kit and referral to the local Stop Smoking Service. MEASUREMENTS: Descriptive statistical reporting of identified pathways and smoking/vaping behaviour at baseline and 6-month follow-up. Semi-structured phone/video interviews analysed thematically. FINDINGS: 13.4% (n = 49) of participants quit smoking within 1 month of receiving the intervention, 19.1% (n = 70) quit between 1 and 6 months, 24.9% (n = 91) reduced cigarettes per day (CPD) by at least 50%, and 42.6% did not experience a significant smoking reduction. Approximately a third of participants who quit reported not vaping at follow-up. Reporting dual use was associated with a reduction in CPD. Appoximately a third reported experimenting with a different device to the one provided as part of the intervention. Quitters reported themes of satisfaction with vaping, changes in environment facilitating quitting and motivation to quit. CONCLUSIONS: Dual use of cigarettes and e-cigarettes can result in a reduction of smoking and may preclude quitting smoking. Sustained e-cigarette use is not always necessary for quitting success. Success depends on personal context as well satisfaction with vaping.

Predictors of Successful Tobacco Cessation After Receiving an E-Cigarette Based Smoking Cessation Intervention.

Introduction: E-cigarettes have been shown to be effective for tobacco smoking cessation. Predicting those who are most likely to achieve smoking abstinence after receiving an e-cigarette based smoking cessation intervention could help to target interventions more efficiently. Methods: A secondary analysis of baseline characteristics of 505 people who received an emergency department based smoking cessation intervention incorporating brief advice, provision of an e-cigarette starter kit and referral to stop smoking services. Gender, ethnicity, age, employment status, deprivation, partner smoking status, cigarettes per day, motivation to quit, cigarette dependence and previous e-cigarette use were assessed as predictors of abstinence. Self-reported smoking status was collected 6 months after intervention delivery. Results: At 6 months 169/505 (33%) of those who received the intervention self-reported abstinence. The groups that were more likely to report having quit were females (37.4% of females vs 31.0% of males), older people (41.1% of over 50s vs 33.3% of under 35s), lighter smokers (36.4% of those who smoked less than 10 cigarettes per day vs 30.7% for those who smoked over 20) and more motivated quitters (35.6% for those with high motivation vs 29.2% for those with low motivation). However, in multiple logistic regression, when adjusting for the other factors, no factors significantly predicted smoking abstinence. Degree of nicotine dependence was very similar between those who quit and those who did not. Conclusion: The study found no baseline factors that could predict successful smoking cessation with e-cigarettes. Consequently, this study does not support the use of a targeted e-cigarette-based smoking cessation intervention, suggesting the adoption of a more universal approach.

Cost-utility analysis of provision of e-cigarette starter kits for smoking cessation in emergency departments: An economic evaluation of a randomized controlled trial.

AIMS: To assess the cost-effectiveness of the Cessation of Smoking Trial in Emergency Department (COSTED) intervention compared with signposting to local stop smoking service (SSS) from the National Health Service (NHS) and personal social services (PSS) perspective. DESIGN, SETTING AND PARTICIPANTS: This was a two-group, multi-centre, pragmatic, individually randomized controlled trial set in six Emergency Departments (EDs) in urban and rural areas in the United Kingdom. Adult (≥ 18 years) daily smokers (at least one cigarette or equivalent per day) but not daily e-cigarette users, with carbon monoxide reading ≥ 8 parts per million, attending the ED (n = 972) were included. The intervention consisted of provision of an e-cigarette starter kit plus brief smoking cessation advice and referral to a local SSS. Control was an information card on how to access local SSS. MEASUREMENTS: Intervention costs included costs of training and delivery. Control costs included costs of printing information cards. Costs of smoking cessation and health-care services were estimated based on quantities reported by participants and unit costs extracted from secondary sources. The effects were measured by quality-adjusted life years (QALYs) derived from EQ-5D-5L. Other outcomes were smoking cessation measures. The primary outcome was incremental cost-effectiveness ratio (ICER), which was calculated by dividing the difference in costs by the difference in QALYs between groups. FINDINGS: The mean intervention costs were £48 [standard error (SE) = £0] per participant and the mean control costs were £0.2 (SE = £0) per participant. Using regression estimates, total costs were £31 [95% confidence interval (CI) = -£341 to £283] higher and 6-month QALYs were 0.004 (95% CI = -0.004 to 0.014) higher in the intervention group than in the control group. The ICER was calculated at £7750 (probability of cost-effective at range £20 000-30 000: 72.2-76.5%). CONCLUSIONS: The UK Cessation of Smoking Trial in Emergency Department (COSTED) intervention (provision of an e-cigarette starter kit plus brief smoking cessation advice) was cost-effective compared with signposting to local stop smoking services under the current recommendations of the maximum acceptable thresholds.

A pragmatic, multicentre, double-blind, placebo-controlled randomised trial to assess the safety, clinical and cost-effectiveness of mirtazapine and carbamazepine in people with Alzheimer's disease and agitated behaviours: the HTA-SYMBAD trial.

Background: Agitation is common and impacts negatively on people with dementia and carers. Non-drug patient-centred care is first-line treatment, but we need other treatment when this fails. Current evidence is sparse on safer and effective alternatives to antipsychotics. Objectives: To assess clinical and cost-effectiveness and safety of mirtazapine and carbamazepine in treating agitation in dementia. Design: Pragmatic, phase III, multicentre, double-blind, superiority, randomised, placebo-controlled trial of the clinical effectiveness of mirtazapine over 12 weeks (carbamazepine arm discontinued). Setting: Twenty-six UK secondary care centres. Participants: Eligibility: probable or possible Alzheimer's disease, agitation unresponsive to non-drug treatment, Cohen-Mansfield Agitation Inventory score ≥ 45. Interventions: Mirtazapine (target 45 mg), carbamazepine (target 300 mg) and placebo. Outcome measures: Primary: Cohen-Mansfield Agitation Inventory score 12 weeks post randomisation. Main economic outcome evaluation: incremental cost per six-point difference in Cohen-Mansfield Agitation Inventory score at 12 weeks, from health and social care system perspective. Data from participants and informants at baseline, 6 and 12 weeks. Long-term follow-up Cohen-Mansfield Agitation Inventory data collected by telephone from informants at 6 and 12 months. Randomisation and blinding: Participants allocated 1 : 1 : 1 ratio (to discontinuation of the carbamazepine arm, 1 : 1 thereafter) to receive placebo or carbamazepine or mirtazapine, with treatment as usual. Random allocation was block stratified by centre and residence type with random block lengths of three or six (after discontinuation of carbamazepine, two or four). Double-blind, with drug and placebo identically encapsulated. Referring clinicians, participants, trial management team and research workers who did assessments were masked to group allocation. Results: Two hundred and forty-four participants recruited and randomised (102 mirtazapine, 102 placebo, 40 carbamazepine). The carbamazepine arm was discontinued due to slow overall recruitment; carbamazepine/placebo analyses are therefore statistically underpowered and not detailed in the abstract. Mean difference placebo-mirtazapine (-1.74, 95% confidence interval -7.17 to 3.69; p = 0.53). Harms: The number of controls with adverse events (65/102, 64%) was similar to the mirtazapine group (67/102, 66%). However, there were more deaths in the mirtazapine group (n = 7) by week 16 than in the control group (n = 1). Post hoc analysis suggests this was of marginal statistical significance (p = 0.065); this difference did not persist at 6- and 12-month assessments. At 12 weeks, the costs of unpaid care by the dyadic carer were significantly higher in the mirtazapine than placebo group [difference: £1120 (95% confidence interval £56 to £2184)]. In the cost-effectiveness analyses, mean raw and adjusted outcome scores and costs of the complete cases samples showed no differences between groups. Limitations: Our study has four important potential limitations: (1) we dropped the proposed carbamazepine group; (2) the trial was not powered to investigate a mortality difference between the groups; (3) recruitment beyond February 2020, was constrained by the COVID-19 pandemic; and (4) generalisability is limited by recruitment of participants from old-age psychiatry services and care homes. Conclusions: The data suggest mirtazapine is not clinically or cost-effective (compared to placebo) for agitation in dementia. There is little reason to recommend mirtazapine for people with dementia with agitation. Future work: Effective and cost-effective management strategies for agitation in dementia are needed where non-pharmacological approaches are unsuccessful. Study registration: This trial is registered as ISRCTN17411897/NCT03031184. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 23. See the NIHR Journals Library website for further project information.

It is common for people with Alzheimer's disease to experience agitation, for example feeling restless or unsettled. If left untreated, agitation can lead to poorer quality of life and increased hospitalisation and strain for family carers. Often these symptoms are treated with medications that are usually used to manage psychosis (antipsychotic drugs), but such medication has limited effectiveness and can cause serious adverse effects to patients, including risk of increased death. Two medications that are already commonly prescribed for other health issues, mirtazapine (an antidepressant) and carbamazepine (a drug used to treat epilepsy), had been identified as a possible alternative way of treating agitation in Alzheimer's disease that might not have the harms associated with antipsychotic medication. In this study, we compared the effects of giving mirtazapine or carbamazepine with a dummy drug (placebo) in people with Alzheimer's disease who were experiencing agitation. The results of the study showed that neither medication was any more effective than the placebo in reducing agitation over 12 weeks in terms of improving symptoms, or in economic terms. Mirtazapine may lead to additional carer costs as compared to placebo. The study findings are stronger for mirtazapine than carbamazepine because the carbamazepine arm was stopped when it had recruited less than half the numbers needed. That was done because the study was not recruiting quickly enough to support both the mirtazapine and the carbamazepine arms. The findings from this study show that mirtazapine should not be recommended to treat agitation in Alzheimer's disease. More work is needed to formulate effective ways and to test new drug and non-drug treatments for agitation in dementia.

A multidomain decision support tool to prevent falls in older people: the FinCH cluster RCT.

BACKGROUND: Falls in care home residents are common, unpleasant, costly and difficult to prevent. OBJECTIVES: The objectives were to evaluate the clinical effectiveness and cost-effectiveness of the Guide to Action for falls prevention in Care Homes (GtACH) programme. DESIGN: A multicentre, cluster, parallel, 1 : 1 randomised controlled trial with embedded process evaluation and economic evaluation. Care homes were randomised on a 1 : 1 basis to the GtACH programme or usual care using a secure web-based randomisation service. Research assistants, participating residents and staff informants were blind to allocation at recruitment; research assistants were blind to allocation at follow-up. NHS Digital data were extracted blindly. SETTING: Older people's care homes from 10 UK sites. PARTICIPANTS: Older care home residents. INTERVENTION: The GtACH programme, which includes care home staff training, systematic use of a multidomain decision support tool and implementation of falls prevention actions, compared to usual falls prevention care. OUTCOMES: The primary trial outcome was the rate of falls per participating resident occurring during the 90-day period between 91 and 180 days post randomisation. The primary outcome for the cost-effectiveness analysis was the cost per fall averted, and the primary outcome for the cost-utility analysis was the incremental cost per quality adjusted life-year. Secondary outcomes included the rate of falls over days 0-90 and 181-360 post randomisation, activity levels, dependency and fractures. The number of falls per resident was compared between arms using a negative binomial regression model (generalised estimating equation). RESULTS: A total of 84 care homes were randomised: 39 to the GtACH arm and 45 to the control arm. A total of 1657 residents consented and provided baseline measures (mean age 85 years, 32% men). GtACH programme training was delivered to 1051 staff (71% of eligible staff) over 146 group sessions. Primary outcome data were available for 630 GtACH participants and 712 control participants. The primary outcome result showed an unadjusted incidence rate ratio of 0.57 (95% CI 0.45 to 0.71; p < 0.01) in favour of the GtACH programme. Falls rates were lower in the GtACH arm in the period 0-90 days. There were no other differences between arms in the secondary outcomes. Care home staff valued the training, systematic strategies and specialist peer support, but the incorporation of the GtACH programme documentation into routine care home practice was limited. No adverse events were recorded. The incremental cost was £20,889.42 per Dementia Specific Quality of Life-based quality-adjusted life-year and £4543.69 per quality-adjusted life-year based on the EuroQol-5 dimensions, five-level version. The mean number of falls was 1.889 (standard deviation 3.662) in the GtACH arm and 2.747 (standard deviation 7.414) in the control arm. Therefore, 0.858 falls were averted. The base-case incremental cost per fall averted was £190.62. CONCLUSION: The GtACH programme significantly reduced the falls rate in the study care homes without restricting residents' activity levels or increasing their dependency, and was cost-effective at current thresholds in the NHS. FUTURE WORK: Future work should include a broad implementation programme, focusing on scale and sustainability of the GtACH programme. LIMITATIONS: A key limitation was the fact that care home staff were not blinded, although risk was small because of the UK statutory requirement to record falls in care homes. TRIAL REGISTRATION: This trial is registered as ISRCTN34353836. 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. 26, No. 9. See the NIHR Journals Library website for further project information.

Falls in care home residents are common, unpleasant, costly and hard to prevent. We tested whether or not the Guide to Action for falls prevention in Care Homes (GtACH) programme was effective in preventing falls. In this programme, care home staff were systematically trained and supported in the assessment of residents' risk of falling and the generation of a falls reduction care plan. We undertook a randomised controlled trial comparing the GtACH programme with usual care, which does not involve this systematic attention to falls prevention. We also undertook a process evaluation, observing organisational and care processes, and an economic study to evaluate value for money. A total of 39 care homes were randomly allocated to the GtACH programme and 45 care homes were randomly allocated to usual care, involving a total of 1657 residents. The main comparison between the two arms was the rate of falls during months 4­6 after randomisation, when we expected any effect to be at its peak. We also assessed the falls rates before and 6 months after this period. We measured activity and dependency levels, as it was important to be sure that any reduction in the rate of falls was not achieved through restrictive care practices. We saw a 43% reduction in the falls rates of the GtACH programme participants during months 4­6, without observing any reduction in residents' activity or dependency. Care home staff and relatives were positive about the GtACH programme. The GtACH programme was good value for money, as it was likely to be cost-effective. The effect of the programme waned over months 6­12, which may be because some staff did not embed the GtACH programme in their usual practice routines, and awareness levels may have dropped.

Predicting asthma-related crisis events using routine electronic healthcare data: a quantitative database analysis study.

BACKGROUND: There is no published algorithm predicting asthma crisis events (accident and emergency [A&E] attendance, hospitalisation, or death) using routinely available electronic health record (EHR) data. AIM: To develop an algorithm to identify individuals at high risk of an asthma crisis event. DESIGN AND SETTING: Database analysis from primary care EHRs of people with asthma across England and Scotland. METHOD: Multivariable logistic regression was applied to a dataset of 61 861 people with asthma from England and Scotland using the Clinical Practice Research Datalink. External validation was performed using the Secure Anonymised Information Linkage Databank of 174 240 patients from Wales. Outcomes were ≥1 hospitalisation (development dataset) and asthma-related hospitalisation, A&E attendance, or death (validation dataset) within a 12-month period. RESULTS: Risk factors for asthma-related crisis events included previous hospitalisation, older age, underweight, smoking, and blood eosinophilia. The prediction algorithm had acceptable predictive ability with a receiver operating characteristic of 0.71 (95% confidence interval [CI] = 0.70 to 0.72) in the validation dataset. Using a cut-point based on the 7% of the population at greatest risk results in a positive predictive value of 5.7% (95% CI = 5.3% to 6.1%) and a negative predictive value of 98.9% (95% CI = 98.9% to 99.0%), with sensitivity of 28.5% (95% CI = 26.7% to 30.3%) and specificity of 93.3% (95% CI = 93.2% to 93.4%); those individuals had an event risk of 6.0% compared with 1.1% for the remaining population. In total, 18 people would need to be followed to identify one admission. CONCLUSION: This externally validated algorithm has acceptable predictive ability for identifying patients at high risk of asthma-related crisis events and excluding those not at high risk.

Perspectives on Bioengineering Clinical Immersion: History, Innovation, and Impact.

Opportunities to provide clinical immersion experiences to bioengineering undergraduate students have expanded over the last several years. These programs allow students to observe the clinical environment in order to better understand workflow processes, the context in which medical equipment is used, and identify unmet needs firsthand. While each program focuses on identifying unmet needs, these experiences vary in content and implementation. Here we discuss features of clinical immersion programs, share details of our program after six years, and present data regarding post-graduation employment of our participants. Students who participated in the University of Illinois at Chicago Clinical Immersion Program are not more likely to pursue careers in industry as compared to non-participants, nor do they demonstrate an ability to find a job more quickly than non-participants. However, participants who did enter into industry self-reported that the program was impactful to both their career interests and ability to find their first employment position.

The Efficacy and Mechanism Evaluation of Treating Idiopathic Pulmonary fibrosis with the Addition of Co-trimoxazole (EME-TIPAC): study protocol for a randomised controlled trial.

BACKGROUND: We hypothesise, based upon the findings from our previous trial, that the addition of co-trimoxazole to standard therapy is beneficial to patients with moderate to severe idiopathic pulmonary fibrosis (IPF). We aim to investigate this by assessing unplanned hospitalisation-free survival (defined as time from randomisation to first non-elective hospitalisation, lung transplant or death) and to determine whether any effect relates to changes in infection and/or markers of disease control and neutrophil activity. METHODS/DESIGN: The EME-TIPAC trial is a double-blind, placebo-controlled, randomised, multicentre clinical trial. A total of 330 symptomatic patients, aged 40 years old or older, with IPF diagnosed by a multidisciplinary team (MDT) according to international guidelines and a FVC ≤ 75% predicted will be enrolled. Patients are randomised equally to receive either two tablets of co-trimoxazole 480 mg or two placebo tablets twice daily over a median treatment period of 27 (range 12-42) months. All patients receive folic acid 5 mg daily whilst on the trial IMP to reduce the risk of bone marrow depression. The primary outcome for the trial is a composite endpoint consisting of the time to death, transplant or first non-elective hospital admission and will be determined from adverse event reporting, hospital databases and the Office of National Statistics with active tracing of patients missing appointments. Secondary outcomes include the individual components of the primary outcome, (1) King's Brief Interstitial Lung Disease Questionnaire, (2) MRC Dyspnoea Score, (3) EQ5D, (4) spirometry, (5) total lung-diffusing capacity and (6) routine sputum microbiology. Blood will be taken for cell count, biochemistry and analysis of biomarkers including C-reactive protein and markers of disease. The trial will last for 4 years. Recruitment will take place in a network of approximately 40 sites throughout the UK (see Table 1 for a full list of participating sites). We expect recruitment for 30 months, follow-up for 12 months and trial analysis and reporting to take 4 months. DISCUSSION: The trial is designed to test the hypothesis that treating IPF patients with co-trimoxazole will increase the time to death (all causes), lung transplant or first non-elective hospital admission compared to standard care ( https://www.nice.org.uk/guidance/cg163 ), in patients with moderate to severe disease. The mechanistic aims are to investigate the effect on lung microbiota and other measures of infection, markers of epithelial injury and markers of neutrophil activity. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 17464641 . Registered on 29 January 2015.

Severe hypercalcaemia and hypophosphataemia with an optimised preterm parenteral nutrition formulation in two epochs of differing phosphate supplementation.

OBJECTIVE: To compare in two epochs of differing phosphate provision serum calcium, phosphate, potassium, and sodium concentrations and the frequency of abnormality of these electrolytes and of sepsis in preterm infants who received an optimised higher amino acid-content formulation. DESIGN AND SETTING: Retrospective cohort study at a single tertiary-level neonatal unit. PATIENTS: Preterm infants given parenteral nutrition (PN) in the first postnatal week during two discrete 6-month epochs in 2013-2014. INTERVENTIONS: In epoch 1 the Ca2+:PO4 molar ratio of the PN formulation was ~1.3-1.5:1 (1.7 mmol Ca2+ and 1.1 mmol PO4 per 100 mL aqueous phase) and in epoch 2 was 1.0:1 via extra phosphate supplementation (1.7 mmol Ca2+ and 1.7 mmol PO4 per 100 mL). MAIN OUTCOME MEASURES: Peak calcium and nadir phosphate and potassium concentrations, and proportions with severe hypercalcaemia (Ca2+ >3.0 mmol/L), hypophosphataemia (PO4<1.5 mmol/L), and hypokalaemia (K+ <3.5 mmol/L) within the first postnatal week. RESULTS: In epoch 2, peak calcium concentrations were lower than in epoch 1 (geometric means: 2.83 mmol/L vs 3.09 mmol/L, p value<0.0001), fewer babies were severely hypercalcaemic (10/49, 20%, vs 31/51, 61%, p value<0.0001); nadir plasma phosphate concentrations were higher (means: 1.54 mmol/L vs 1.32 mmol/L, p value=0.006), and there were fewer cases of hypophosphataemia (17/49, 35% vs 31/51, 61%, p value=0.009) and hypokalaemia (12/49, 25% vs 23/51, 45%, p value=0.03). CONCLUSIONS: Reverting from a PN Ca2+:PO4 molar ratio of 1.3-1.5:1 to a ratio of 1.0:1 was associated with a lower incidence and severity of hypophosphataemia and hypercalcaemia. For preterm infants given higher concentrations of amino acids (≥2.5 g/kg/day) from postnatal day 1, an equimolar Ca2+:PO4 ratio may be preferable during the first postnatal week.

Effect of age on the prognostic value of left ventricular function in patients with acute coronary syndrome: A prospective registry study.

OBJECTIVE: This study aims to study the prognostic impact of left ventricular function on mortality and examine the effect of age on the prognostic value of left ventricular function. METHODS: We examined the myocardial ischaemia national audit project registry (2006-2010) data with a mean follow-up of 2.1 years. Left ventricular function was categorised into good (ejection fraction ⩾50%), moderate (ejection fraction 30-49%) and poor (ejection fraction <30%) categories. Cox proportional hazards models were constructed to examine the prognostic significance of left ventricular function in different age groups (<65, 65-74, 75-84 and ⩾85 years) on all-cause mortality adjusting for baseline variables. RESULTS: Out of 424,848 patients, left ventricular function data were available for 123,609. Multiple imputations were used to impute missing values of left ventricular function and the final sample for analyses was drawn from 414,305. After controlling for confounders, 339,887 participants were included in the regression models. For any age group, mortality was higher with a worsening degree of left ventricular impairment. Increased age reduced the adverse prognosis associated with reduced left ventricular function (hazard ratios of death comparing poor left ventricular function to good left ventricular function were 2.11, 95% confidence interval 1.88-2.37 for age <65 years and 1.28, 95% confidence interval 1.20-1.36 for age ⩾85 years). Older patients had a high mortality risk even in those with good left ventricular function. Hazard ratios of mortality for ⩾85 compared to <65 years (hazard ratio = 1.00) within good, moderate and poor ejection fraction groups were 5.89, 4.86 and 3.43, respectively. CONCLUSIONS: In patients with acute coronary syndrome, clinicians should interpret the prognostic value of left ventricular function taking into account the patient's age.

Population-based multidimensional assessment of older people in UK general practice: a cluster-randomised factorial trial.

BACKGROUND: The benefit of multidimensional assessment and management of older people remains controversial. Most trials have been too small to produce adequate evidence to inform policy. We aimed to measure the effects of different approaches to assessment and management of older people. METHODS: We undertook a cluster-randomised factorial trial in 106 general practices (43219 eligible patients aged 75 years and older, 78% participation), comparing (1) universal versus targeted assessment and (2) subsequent management by hospital outpatient geriatric team versus the primary-care team. All participants received a brief multidimensional assessment followed by a nurse-led in-depth assessment in the universal group, whereas in the targeted group the in-depth assessment was offered only to those with problems established at the brief assessment. Referrals to the randomised team (geriatric management or primary care), other medical or social services, health-care workers, or agencies, and emergency referrals to the general practitioner were based on a standard protocol at the in-depth assessment. The primary endpoints were mortality, admissions to hospital and institution, and quality of life. Analysis was by intention to treat and per protocol. This trial has been assigned the International Standardised Randomised Controlled Trial Number ISRCTN23494848. FINDINGS: Mortality and hospital or institutional admissions did not differ between groups. During 3 years' follow-up, significant improvements in quality of life resulted from universal versus targeted assessment in terms of homecare, and from management by geriatric team versus primary-care team, in terms of mobility, social interaction, and morale. However, only the result for social interaction was consistent with a small but important effect. INTERPRETATION: The different forms of multidimensional assessment offered almost no differences in patient outcome.

Prognostic value of troponins in acute coronary syndrome depends upon patient age.

OBJECTIVE: This study aims to determine whether the prognostic significance of troponins in acute coronary syndrome in predicting mortality varies by age, and if so, to what extent when other prognostic indicators are considered. METHODS: We analysed Myocardial Ischemia National Audit Project registry data collected between January 2006 and December 2010 and followed up this cohort for all-cause mortality until August 2011. Relationships between peak troponin levels (types I and T) and time to death in different age groups, and between age and time to death at different troponin levels were investigated using multiple variable adjusted Cox regression models. RESULTS: Of the 322 617 patients with acute coronary syndromes included, a third (n=106 365, 33%) died during 695 334 person-years of follow-up. Within each troponin category, older age was associated with a higher mortality even in those with a troponin <0.01 ng/mL for both troponin types (HR ~10-12 in ≥85 years cf. HR of 1.0 in <65 years). The relative potency of an elevated troponin to predict an adverse outcome compared with a low troponin attenuated with increased age (for troponin I ≥15.0 compared with troponin I <0.01 in age <65, adjusted HR 2.41 (95% CI 1.80 to 3.24); age ≥85 HR 2.01 (1.62 to 2.52)). Similar but less consistent results were observed with troponin T elevation at the higher levels. CONCLUSIONS: Clinicians should interpret the prognostic value of troponin taking into account the patient's age.