A Bayesian spatio-temporal study of the association between meteorological factors and the spread of COVID-19.

BACKGROUND: The spread of COVID-19 has brought challenges to health, social and economic systems around the world. With little to no prior immunity in the global population, transmission has been driven primarily by human interaction. However, as with common respiratory illnesses such as influenza some authors have suggested COVID-19 may become seasonal as immunity grows. Despite this, the effects of meteorological conditions on the spread of COVID-19 are poorly understood. Previous studies have produced contrasting results, due in part to limited and inconsistent study designs. METHODS: This study investigates the effects of meteorological conditions on COVID-19 infections in England using a Bayesian conditional auto-regressive spatio-temporal model. Our data consists of daily case counts from local authorities in England during the first lockdown from March-May 2020. During this period, legal restrictions limiting human interaction remained consistent, minimising the impact of changes in human interaction. We introduce a lag from weather conditions to daily cases to accommodate an incubation period and delays in obtaining test results. By modelling spatio-temporal random effects we account for the nature of a human transmissible virus, allowing the model to isolate meteorological effects. RESULTS: Our analysis considers cases across England's 312 local authorities for a 55-day period. We find relative humidity is negatively associated with COVID-19 cases, with a 1% increase in relative humidity corresponding to a reduction in relative risk of 0.2% [95% highest posterior density (HPD): 0.1-0.3%]. However, we find no evidence for temperature, wind speed, precipitation or solar radiation being associated with COVID-19 spread. The inclusion of weekdays highlights systematic under reporting of cases on weekends with between 27.2-43.7% fewer cases reported on Saturdays and 26.3-44.8% fewer cases on Sundays respectively (based on 95% HPDs). CONCLUSION: By applying a Bayesian conditional auto-regressive model to COVID-19 case data we capture the underlying spatio-temporal trends present in the data. This enables us to isolate the main meteorological effects and make robust claims about the association of weather variables to COVID-19 incidence. Overall, we find no strong association between meteorological factors and COVID-19 transmission.

Cluster randomized controlled trial analysis at the cluster level: The clan command.

In this article, we introduce a new command, clan, that conducts a cluster-level analysis of cluster randomized trials. The command simplifies adjusting for individual- and cluster-level covariates and can also account for a stratified design. It can be used to analyze a continuous, binary, or rate outcome.

Linear mixed models to handle missing at random data in trial-based economic evaluations.

Trial-based cost-effectiveness analyses (CEAs) are an important source of evidence in the assessment of health interventions. In these studies, cost and effectiveness outcomes are commonly measured at multiple time points, but some observations may be missing. Restricting the analysis to the participants with complete data can lead to biased and inefficient estimates. Methods, such as multiple imputation, have been recommended as they make better use of the data available and are valid under less restrictive Missing At Random (MAR) assumption. Linear mixed effects models (LMMs) offer a simple alternative to handle missing data under MAR without requiring imputations, and have not been very well explored in the CEA context. In this manuscript, we aim to familiarize readers with LMMs and demonstrate their implementation in CEA. We illustrate the approach on a randomized trial of antidepressants, and provide the implementation code in R and Stata. We hope that the more familiar statistical framework associated with LMMs, compared to other missing data approaches, will encourage their implementation and move practitioners away from inadequate methods.

The EmpaTeach intervention for reducing physical violence from teachers to students in Nyarugusu Refugee Camp: A cluster-randomised controlled trial.

BACKGROUND: School-based violence prevention interventions offer enormous potential to reduce children's experience of violence perpetrated by teachers, but few have been rigorously evaluated globally and, to the best of our knowledge, none in humanitarian settings. We tested whether the EmpaTeach intervention could reduce physical violence from teachers to students in Nyarugusu Refugee Camp, Tanzania. METHODS AND FINDINGS: We conducted a 2-arm cluster-randomised controlled trial with parallel assignment. A complete sample of all 27 primary and secondary schools in Nyarugusu Refugee Camp were approached and agreed to participate in the study. Eligible students and teachers participated in cross-sectional baseline, midline, and endline surveys in November/December 2018, May/June 2019, and January/February 2020, respectively. Fourteen schools were randomly assigned to receive a violence prevention intervention targeted at teachers implemented in January-March 2019; 13 formed a wait-list control group. The EmpaTeach intervention used empathy-building exercises and group work to equip teachers with self-regulation, alternative discipline techniques, and classroom management strategies. Allocation was not concealed due to the nature of the intervention. The primary outcome was students' self-reported experience of physical violence from teachers, assessed at midline using a modified version of the ISPCAN Child Abuse Screening Tool-Child Institutional. Secondary outcomes included student reports of emotional violence, depressive symptoms, and school attendance. Analyses were by intention to treat, using generalised estimating equations adjusted for stratification factors. No schools left the study. In total, 1,493 of the 1,866 (80%) randomly sampled students approached for participation took part in the baseline survey; at baseline 54.1% of students reported past-week physical violence from school staff. In total, 1,619 of 1,978 students (81.9%) took part in the midline survey, and 1,617 of 2,032 students (79.6%) participated at endline. Prevalence of past-week violence at midline was not statistically different in intervention (408 of 839 students, 48.6%) and control schools (412 of 777 students, 53.0%; risk ratio = 0.91, 95% CI 0.80 to 1.02, p = 0.106). No effect was detected on secondary outcomes. A camp-wide educational policy change during intervention implementation resulted in 14.7% of teachers in the intervention arm receiving a compressed version of the intervention, but exploratory analyses showed no difference in our primary outcome by school-level adherence to the intervention. Main study limitations included the small number of schools in the camp, which limited statistical power to detect small differences between intervention and control groups. We also did not assess the test-retest reliability of our outcome measures, and interviewers were unmasked to intervention allocation. CONCLUSIONS: There was no evidence that the EmpaTeach intervention effectively reduced physical violence from teachers towards primary or secondary school students in Nyarugusu Refugee Camp. Further research is needed to develop and test interventions to prevent teacher violence in humanitarian settings. TRIAL REGISTRATION: clinicaltrials.gov (NCT03745573).

Reference-based multiple imputation for missing data sensitivity analyses in trial-based cost-effectiveness analysis.

Missing data are a common issue in cost-effectiveness analysis (CEA) alongside randomised trials and are often addressed assuming the data are 'missing at random'. However, this assumption is often questionable, and sensitivity analyses are required to assess the implications of departures from missing at random. Reference-based multiple imputation provides an attractive approach for conducting such sensitivity analyses, because missing data assumptions are framed in an intuitive way by making reference to other trial arms. For example, a plausible not at random mechanism in a placebo-controlled trial would be to assume that participants in the experimental arm who dropped out stop taking their treatment and have similar outcomes to those in the placebo arm. Drawing on the increasing use of this approach in other areas, this paper aims to extend and illustrate the reference-based multiple imputation approach in CEA. It introduces the principles of reference-based imputation and proposes an extension to the CEA context. The method is illustrated in the CEA of the CoBalT trial evaluating cognitive behavioural therapy for treatment-resistant depression. Stata code is provided. We find that reference-based multiple imputation provides a relevant and accessible framework for assessing the robustness of CEA conclusions to different missing data assumptions.

Drug therapy for delirium in terminally ill adults.

BACKGROUND: Delirium is a syndrome characterised by an acute disturbance of attention and awareness which develops over a short time period and fluctuates in severity over the course of the day. It is commonly experienced during inpatient admission in the terminal phase of illness. It can cause symptoms such as agitation and hallucinations and is distressing for terminally ill people, their families and staff. Delirium may arise from any number of causes and treatment should aim to address these causes. When this is not possible, or treatment is unsuccessful, drug therapy to manage the symptoms may become necessary. This is the second update of the review first published in 2004. OBJECTIVES: To evaluate the effectiveness and safety of drug therapies to manage delirium symptoms in terminally ill adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL and PsycINFO from inception to July 2019, reference lists of retrieved papers, and online trial registries. SELECTION CRITERIA: We included randomised controlled trials of drug therapies in any dose by any route, compared to another drug therapy, a non-pharmacological approach, placebo, standard care or wait-list control, for the management of delirium symptoms in terminally ill adults (18 years or older). DATA COLLECTION AND ANALYSIS: We independently screened citations, extracted data and assessed risk of bias. Primary outcomes were delirium symptoms; agitation score; adverse events. Secondary outcomes were: use of rescue medication; cognitive status; survival. We applied the GRADE approach to assess the overall quality of the evidence for each outcome and we include eight 'Summary of findings' tables. MAIN RESULTS: We included four studies (three new to this update), with 399 participants. Most participants had advanced cancer or advanced AIDS, and mild- to moderate-severity delirium. Meta-analysis was not possible because no two studies examined the same comparison. Each study was at high risk of bias for at least one criterion. Most evidence was low to very low quality, downgraded due to very serious study limitations, imprecision or because there were so few data. Most studies reported delirium symptoms; two reported agitation scores; three reported adverse events with data on extrapyramidal effects; and none reported serious adverse events. 1. Haloperidol versus placebo There may be little to no difference between placebo and haloperidol in delirium symptoms within 24 hours (mean difference (MD) 0.34, 95% confidence interval (CI) -0.07 to 0.75; 133 participants). Haloperidol may slightly worsen delirium symptoms compared with placebo at 48 hours (MD 0.49, 95% CI 0.10 to 0.88; 123 participants with mild- to moderate-severity delirium). Haloperidol may reduce agitation slightly compared with placebo between 24 and 48 hours (MD -0.14, 95% -0.28 to -0.00; 123 participants with mild- to moderate-severity delirium). Haloperidol probably increases extrapyramidal adverse effects compared with placebo (MD 0.79, 95% CI 0.17 to 1.41; 123 participants with mild- to moderate-severity delirium). 2. Haloperidol versus risperidone There may be little to no difference in delirium symptoms with haloperidol compared with risperidone within 24 hours (MD -0.42, 95% CI -0.90 to 0.06; 126 participants) or 48 hours (MD -0.36, 95% CI -0.92 to 0.20; 106 participants with mild- to moderate-severity delirium). Agitation scores and adverse events were not reported for this comparison. 3. Haloperidol versus olanzapine We are uncertain whether haloperidol reduces delirium symptoms compared with olanzapine within 24 hours (MD 2.36, 95% CI -0.75 to 5.47; 28 participants) or 48 hours (MD 1.90, 95% CI -1.50 to 5.30, 24 participants). Agitation scores and adverse events were not reported for this comparison. 4. Risperidone versus placebo Risperidone may slightly worsen delirium symptoms compared with placebo within 24 hours (MD 0.76, 95% CI 0.30 to 1.22; 129 participants); and at 48 hours (MD 0.85, 95% CI 0.32 to 1.38; 111 participants with mild- to moderate-severity delirium). There may be little to no difference in agitation with risperidone compared with placebo between 24 and 48 hours (MD -0.05, 95% CI -0.19 to 0.09; 111 participants with mild- to moderate-severity delirium). Risperidone may increase extrapyramidal adverse effects compared with placebo (MD 0.73 95% CI 0.09 to 1.37; 111 participants with mild- to moderate-severity delirium). 5. Lorazepam plus haloperidol versus placebo plus haloperidol We are uncertain whether lorazepam plus haloperidol compared with placebo plus haloperidol improves delirium symptoms within 24 hours (MD 2.10, 95% CI -1.00 to 5.20; 50 participants with moderate to severe delirium), reduces agitation within 24 hours (MD 1.90, 95% CI 0.90 to 2.80; 52 participants), or increases adverse events (RR 0.70, 95% CI -0.19 to 2.63; 31 participants with moderate to severe delirium). 6. Haloperidol versus chlorpromazine We are uncertain whether haloperidol reduces delirium symptoms compared with chlorpromazine at 48 hours (MD 0.37, 95% CI -4.58 to 5.32; 24 participants). Agitation scores were not reported. We are uncertain whether haloperidol increases adverse events compared with chlorpromazine (MD 0.46, 95% CI -4.22 to 5.14; 24 participants). 7. Haloperidol versus lorazepam We are uncertain whether haloperidol reduces delirium symptoms compared with lorazepam at 48 hours (MD -4.88, 95% CI -9.70 to 0.06; 17 participants). Agitation scores were not reported. We are uncertain whether haloperidol increases adverse events compared with lorazepam (MD -6.66, 95% CI -14.85 to 1.53; 17 participants). 8. Lorazepam versus chlorpromazine We are uncertain whether lorazepam reduces delirium symptoms compared with chlorpromazine at 48 hours (MD 5.25, 95% CI 0.38 to 10.12; 19 participants), or increases adverse events (MD 7.12, 95% CI 1.08 to 15.32; 18 participants). Agitation scores were not reported. SECONDARY OUTCOMES: use of rescue medication, cognitive impairment, survival There were insufficient data to draw conclusions or assess GRADE. AUTHORS' CONCLUSIONS: We found no high-quality evidence to support or refute the use of drug therapy for delirium symptoms in terminally ill adults. We found low-quality evidence that risperidone or haloperidol may slightly worsen delirium symptoms of mild to moderate severity for terminally ill people compared with placebo. We found moderate- to low-quality evidence that haloperidol and risperidone may slightly increase extrapyramidal adverse events for people with mild- to moderate-severity delirium. Given the small number of studies and participants on which current evidence is based, further research is essential.

An Intervention Delivered by Mobile Phone Instant Messaging to Increase Acceptability and Use of Effective Contraception Among Young Women in Bolivia: Randomized Controlled Trial.

BACKGROUND: Although the most effective methods of contraception are available in Bolivia, unmet need for contraception among women aged 15 to 19 years is estimated to be 38% (2008), and the adolescent fertility rate is 71 per 1000 women (2016). Mobile phones are a popular mode to deliver health behavior support. We developed a contraceptive behavioral intervention for young Bolivian women delivered by mobile phone and guided by behavioral science. The intervention consists of short instant messages sent through an app over 4 months. OBJECTIVE: This trial aimed to evaluate the effect of the intervention on young Bolivian women's use of and attitudes toward the effective contraceptive methods available in Bolivia. METHODS: This was a parallel group, individually randomized superiority trial with a 1:1 allocation ratio. Women were eligible if they were aged 16 to 24 years, owned a personal Android mobile phone, lived in La Paz or El Alto, reported an unmet need for contraception, and could read Spanish. The target sample size was 1310 participants. Participants allocated to the intervention had access to an app with standard family planning information and intervention messages. Participants allocated to the control group had access to the same app and control messages. Coprimary outcomes were use of effective contraception and acceptability of at least one method of effective contraception at 4 months. Secondary outcomes were use of effective contraception during the study, acceptability of the individual methods, service uptake, unintended pregnancy, and abortion. Process outcomes included knowledge, perceived norms, personal agency, and intention. Outcomes were analyzed using logistic and linear regression. We also asked participants about physical violence. RESULTS: A total of 640 participants were enrolled, and 67.0% (429) of them contributed follow-up data for the coprimary outcome, the use of effective contraception. There was no evidence that use differed between the groups (33% control vs 37% intervention; adjusted odds ratio [OR] 1.19, 95% CI 0.80 to 1.77; P=.40). There was a borderline significant effect regarding acceptability (63% control vs 72% intervention; adjusted OR 1.49, 95% CI 0.98 to 2.28; P=.06). There were no statistically significant differences in any of the secondary or process outcomes. The intervention dose received was low. In the control group, 2.8% (6/207) reported experiencing physical violence compared with 1.9% (4/202) in the intervention group (Fisher exact test P=.75). CONCLUSIONS: This trial was unable to provide definitive conclusions regarding the effect of the intervention on use and acceptability of effective contraception because of under recruitment. Although we cannot strongly recommend implementation, the results suggest that it would be safe and may increase the acceptability of effective contraception if the intervention messages were offered alongside the download of the app. TRIAL REGISTRATION: ClinicalTrials.gov NCT02905526; https://clinicaltrials.gov/ct2/show/NCT02905526.

Missing data in trial-based cost-effectiveness analysis: An incomplete journey.

Cost-effectiveness analyses (CEA) conducted alongside randomised trials provide key evidence for informing healthcare decision making, but missing data pose substantive challenges. Recently, there have been a number of developments in methods and guidelines addressing missing data in trials. However, it is unclear whether these developments have permeated CEA practice. This paper critically reviews the extent of and methods used to address missing data in recently published trial-based CEA. Issues of the Health Technology Assessment journal from 2013 to 2015 were searched. Fifty-two eligible studies were identified. Missing data were very common; the median proportion of trial participants with complete cost-effectiveness data was 63% (interquartile range: 47%-81%). The most common approach for the primary analysis was to restrict analysis to those with complete data (43%), followed by multiple imputation (30%). Half of the studies conducted some sort of sensitivity analyses, but only 2 (4%) considered possible departures from the missing-at-random assumption. Further improvements are needed to address missing data in cost-effectiveness analyses conducted alongside randomised trials. These should focus on limiting the extent of missing data, choosing an appropriate method for the primary analysis that is valid under contextually plausible assumptions, and conducting sensitivity analyses to departures from the missing-at-random assumption.

Correction to: A randomized controlled trial of an intervention delivered by mobile phone app instant messaging to increase the acceptability of effective contraception among young people in Tajikistan.

After publication of the original article [1], it came to the authors' attention that there is a typo in the Results section.

A randomized controlled trial of an intervention delivered by mobile phone app instant messaging to increase the acceptability of effective contraception among young people in Tajikistan.

BACKGROUND: Unintended pregnancy is associated with poorer health outcomes for women and their families. In Tajikistan, around 26% of married 15-24 year old women have an unmet need for contraception. There is some evidence that interventions delivered by mobile phone can affect contraceptive-related behaviour and knowledge. We developed an intervention delivered by mobile phone app instant messaging to improve acceptability of effective contraceptive methods among young people in Tajikistan. METHODS: This was a randomized controlled trial among Tajik people aged 16-24. Participants allocated to the intervention arm had access to an app plus intervention messages. Participants allocated to the control arm had access to the app plus control messages. The primary outcome was acceptability of at least one method of effective contraception at 4 months. Secondary outcomes were use of effective contraception at 4 months and during the study, acceptability of individual methods, service uptake, unintended pregnancy and induced abortion. Process outcomes were knowledge, perceived norms, personal agency and intention. Outcomes were analysed using logistic and linear regression. We conducted a pre-specified subgroup analysis and a post-hoc analysis of change in acceptability from baseline to follow-up. RESULTS: Five hundred and seventy-three participants were enrolled. Intervention content was included on the app, causing contamination. Four hundred and seventy-two (82%) completed follow-up for the primary outcome. There was no evidence of a difference in acceptability of effective contraception between the groups (66% in the intervention arm vs 64% in the control arm, adjusted OR 1.21, 95% CI .80-1.83, p = 0.36). There were no differences in the secondary or process outcomes between groups. There was some evidence that the effect of the intervention was greater among women compared to men (interaction test p = 0.03). There was an increase in acceptability of effective contraception from baseline to follow-up (2% to 65%, p < 0.001). CONCLUSIONS: The whole intervention delivered by instant messaging provided no additional benefit over a portion of the intervention delivered by app pages. The important increase in contraceptive acceptability from baseline to follow-up suggests that the intervention content included on the app may influence attitudes. Further research is needed to establish the effect of the intervention on attitudes towards and use of effective contraception among married/sexually active young people. TRIAL REGISTRATION: Clinicaltrial.gov NCT02905513 . Date of registration: 14 September 2016.

The management of behavioural and psychological symptoms of dementia in the acute general medical hospital: a longitudinal cohort study.

BACKGROUND: The acute hospital is a challenging place for a person with dementia. Behavioural and psychological symptoms of dementia (BPSD) are common and may be exacerbated by the hospital environment. Concerns have been raised about how BPSD are managed in this setting and about over reliance on neuroleptic medication. This study aimed to investigate how BPSD are managed in UK acute hospitals. METHOD(S): A longitudinal cohort of 230 patients with dementia admitted to two acute NHS hospitals. BPSD were measured every four days (Behave-AD scale), as well as documentation of pharmacological prescriptions and non-pharmacological management. RESULTS: The overall prevalence of BPSD was 75%, with aggression and activity disturbance being the most common. Antipsychotics were prescribed for 28 (12%) patients; 70% of these prescriptions were new on admission. Benzodiazepines were prescribed for 27 (12%) patients, antidepressants were prescribed for 37 (16%) patients, and sedatives were prescribed for 14 (3%) patients. Patients who were prescribed antipsychotics, after adjusting for end of life medication, age and dementia severity, were significantly more likely to die (adjusted hazard ratio 5.78, 95% CI 1.57, 21.26, p = 0.008). Non-pharmacological management was used in 55% of participants, most commonly psychosocial interventions (36%) with little evidence of monitoring their effectiveness. A form of restraint was used during 50 (22%) patients' admissions. CONCLUSIONS: Antipsychotic medications and psychosocial interventions were the main methods used to manage BPSD; however, these were not implemented or monitored in a systematic fashion.

Monitoring patient care through health facility exit interviews: an assessment of the Hawthorne effect in a trial of adherence to malaria treatment guidelines in Tanzania.

BACKGROUND: Survey of patients exiting health facilities is a common way to assess consultation practices. It is, however, unclear to what extent health professionals may change their practices when they are aware of such interviews taking place, possibly paying more attention to following recommended practices. This so-called Hawthorne effect could have important consequences for interpreting research and programme monitoring, but has rarely been assessed. METHODS: A three-arm cluster-randomised trial of interventions to improve adherence to guidelines for the use of anti-malarial drugs was conducted in Tanzania. Patient interviews were conducted outside health facilities on two randomly-selected days per week. Health workers also routinely documented consultations in their ledgers. The Hawthorne effect was investigated by comparing routine data according to whether exit interviews had been conducted on three key indicators of malaria care. Adjusted logistic mixed-effects models were used, taking into account the dependencies within health facilities and calendar days. RESULTS: Routine data were collected on 19,579 consultations in 18 facilities. The odds of having a malaria rapid diagnostic test (RDT) result reported were 11 % higher on days when exit surveys were conducted (adjusted odds ratio 95 % CI: 0.98-1.26, p = 0.097), 17 % lower for prescribing an anti-malarial drug to patients with a negative RDT result (0.56-1.23, p = 0.343), and 27 % lower for prescribing an anti-malarial when no RDT result was reported (0.53-1.00, p = 0.052). The effect varied with time, with a U-shaped association over the study period (p < 0.001). We also observed a higher number of consultations recorded on days when exit-interviews were conducted (adjusted mean difference = 2.03, p < 0.001). CONCLUSIONS: Although modest, there was some suggestion of better practice by health professionals on days when exit interviews were conducted. Researchers should be aware of the potential Hawthorne effect, and take into account assessment methods when generalising findings to the 'real word' setting. This effect is, however, likely to be context dependent, and further controlled evaluation across different settings should be conducted. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01292707 . Registered on 29th January 2011.

The clinical and cost-effectiveness of brief advice for excessive alcohol consumption among people attending sexual health clinics: a randomised controlled trial.

OBJECTIVES: To examine the clinical and cost-effectiveness of brief advice for excessive alcohol consumption among people who attend sexual health clinics. METHODS: Two-arm, parallel group, assessor blind, pragmatic, randomised controlled trial. 802 people aged 19 years or over who attended one of three sexual health clinics and were drinking excessively were randomised to either brief advice or control treatment. Brief advice consisted of feedback on alcohol and health, written information and an offer of an appointment with an Alcohol Health Worker. Control participants received a leaflet on health and lifestyle. The primary outcome was mean weekly alcohol consumption during the previous 90 days measured 6 months after randomisation. The main secondary outcome was unprotected sex during this period. RESULTS: Among the 402 randomised to brief advice, 397 (99%) received it. The adjusted mean difference in alcohol consumption at 6 months was -2.33 units per week (95% CI -4.69 to 0.03, p=0.053) among those in the active compared to the control arm of the trial. Unprotected sex was reported by 154 (53%) of those who received brief advice, and 178 (59%) controls (adjusted OR=0.89, 95% CI 0.63 to 1.25, p=0.496). There were no significant differences in costs between study groups at 6 months. CONCLUSIONS: Introduction of universal screening and brief advice for excessive alcohol use among people attending sexual health clinics does not result in clinically important reductions in alcohol consumption or provide a cost-effective use of resources. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN 99963322.

Behavioural and psychiatric symptoms in people with dementia admitted to the acute hospital: prospective cohort study.

BACKGROUND: Dementia is common in older people admitted to acute hospitals. There are concerns about the quality of care they receive. Behavioural and psychiatric symptoms of dementia (BPSD) seem to be particularly challenging for hospital staff. AIMS To define the prevalence of BPSD and explore their clinical associations. METHOD: Longitudinal cohort study of 230 people with dementia, aged over 70, admitted to hospital for acute medical illness, and assessed for BPSD at admission and every 4 (± 1) days until discharge. Other measures included length of stay, care quality indicators, adverse events and mortality. RESULTS: Participants were very impaired; 46% at Functional Assessment Staging Scale (FAST) stage 6d or above (doubly incontinent), 75% had BPSD, and 43% had some BPSD that were moderately/severely troubling to staff. Most common were aggression (57%), activity disturbance (44%), sleep disturbance (42%) and anxiety (35%). CONCLUSIONS: We found that BPSD are very common in older people admitted to an acute hospital. Patients and staff would benefit from more specialist psychiatric support.

Composite endpoints for malaria case-management: not simplifying the picture?

Rapid diagnostic tests (RDTs) for infection with Plasmodium spp. offer two main potential advantages related to malaria treatment: 1) ensuring that individuals with malaria are promptly treated with an effective artemisinin-based combination therapy, and 2) ensuring that individuals without malaria do not receive an anti-malarial they do not need (and instead receive a more appropriate treatment). Some studies of the impact of RDTs on malaria case management have combined these two different successes into a binary outcome describing 'correct management'. However combining correct management of positives and negatives into a single summary measure can be misleading. The problems, which are analogous to those encountered in the evaluation of diagnostic tests, can largely be avoided if data for patients with and without malaria are presented and analysed separately. Where a combined metric is necessary, then one of the established approaches to summarise the performance of diagnostic tests could be considered, although these are not without their limitations. Two graphical approaches to help understand case management performance are illustrated.

Cost-effectiveness of computer-tailored smoking cessation advice in primary care: a randomized trial (ESCAPE).

INTRODUCTION: Smoking remains a significant public health problem and is a leading cause of preventable morbidity and mortality around the world. By combining the behavioral intervention principles used in specialist services with the high reach rates of public health interventions, personal tailored self-help cessation intervention provides a potential economical method for improving reach and effectiveness. METHODS: Cost-effectiveness analysis is performed alongside a randomized controlled trial to compare the computer-tailored self-help intervention with a generic self-help intervention in smoking cessation. A Markov model was developed to extrapolate lifetime cost-effectiveness by combining trial data with estimates from the literature. FINDINGS: In the short term, smokers in the intervention group gained 0.0006 (95% CI = -0.0024 to 0.0036) quality-adjusted life years (QALYs) more than those in the control group at an increased cost of about £9 per person (95% CI = £5-£12). This yielded an incremental cost-effectiveness ratio (ICER) of £14,432/QALY. Precision of the ICER estimates was assessed by 5,000 bootstrapping replications. The probability that the intervention was cost effective was 54% (58%) at a cost-effectiveness threshold of £20,000(£30,000) per QALY. The Markov model showed that simulating lifetime outcomes improved the cost-effectiveness ratio (£9,700/QALY) in favor of the tailored intervention. The intervention would have a 55%-57% chance of being more cost effective than nontailored intervention at the willingness-to-pay threshold of £20,000-30,000/QALY. CONCLUSIONS: The computer-tailored intervention appears slightly more likely to be cost effective than the generic self-help intervention in smoking cessation, in both the short term and the long term, but caution is required given the considerable uncertainty surrounding the estimates.

Risk factors for incident delirium among older people in acute hospital medical units: a systematic review and meta-analysis.

BACKGROUND: delirium affects up to 40% of older hospitalised patients, but there has been no systematic review focussing on risk factors for incident delirium in older medical inpatients. We aimed to synthesise data on risk factors for incident delirium and where possible conduct meta-analysis of these. METHODS: PubMed and Web of Science databases were searched (January 1987-August 2013). Studies were quality rated using the Newcastle-Ottawa Scale. We used the Mantel-Haenszel and inverse variance method to estimate the pooled odds ratio (OR) or mean difference for individual risk factors. RESULTS: eleven articles met inclusion criteria and were included for review. Total study population 2338 (411 patients with delirium/1927 controls). The commonest factors significantly associated with delirium were dementia, older age, co-morbid illness, severity of medical illness, infection, 'high-risk' medication use, diminished activities of daily living, immobility, sensory impairment, urinary catheterisation, urea and electrolyte imbalance and malnutrition. In pooled analyses, dementia (OR 6.62; 95% CI (confidence interval) 4.30, 10.19), illness severity (APACHE II) (MD (mean difference) 3.91; 95% CI 2.22, 5.59), visual impairment (OR 1.89; 95% CI 1.03, 3.47), urinary catheterisation (OR 3.16; 95% CI 1.26, 7.92), low albumin level (MD -3.14; 95% CI -5.99, -0.29) and length of hospital stay (OR 4.85; 95% CI 2.20, 7.50) were statistically significantly associated with delirium. CONCLUSION: we identified risk factors consistently associated with incident delirium following admission. These factors help to highlight older acute medical inpatients at risk of developing delirium during their hospital stay.

Moderating factors for the effectiveness of group art therapy for schizophrenia: secondary analysis of data from the MATISSE randomised controlled trial.

PURPOSE: Although some studies suggest that art therapy may be useful in the treatment of negative symptoms of schizophrenia, a recent large trial of group art therapy found no clinical advantage over standard care, but the study population was heterogeneous and uptake of the intervention was poor. This study aimed to investigate whether art therapy was more effective for specific subgroups of patients. METHODS: Secondary analysis of data from a randomised controlled trial of group art therapy as an adjunctive treatment for schizophrenia (n = 140) versus standard care alone (n = 137). Positive and Negative Syndrome Scale scores at 12 months were compared between trial arms. Interaction between intervention effect and different subgroups, including those with more severe negative symptoms of schizophrenia, and those who expressed a preference for art therapy prior to randomisation, was tested using a linear mixed model. RESULTS: The clinical effectiveness of group art therapy did not significantly differ between participants with more or less severe negative symptoms [interaction for difference in PANSS = 1.7, 95 % CI (-8.6 to 12.1), P = 0.741], or between those who did and did not express a preference for art therapy [interaction = 3.9, 95 % CI (-6.7 to 14.5), P = 0.473]. None of the other exploratory subgroups suggested differences in intervention effect. CONCLUSIONS: There was no evidence of greater improvement in clinical symptoms of schizophrenia for those with more severe negative symptoms or those with a preference for art therapy. Identification of patients with schizophrenia who may benefit most from group art therapy remains elusive.

A cost-utility analysis of a rehabilitation service for people living with and beyond cancer.

BACKGROUND: We conducted a wait-list control randomised trial of an outpatient rehabilitation service for people living with and beyond cancer, delivered in a hospice day care unit. We report the results of an economic evaluation undertaken using the trial data. METHODS: Forty-one participants were recruited into the study. A within-trial stochastic cost-utility analysis was undertaken using Monte-Carlo simulation. The outcome measure for the economic evaluation was quality adjusted life years (QALYs). Costs were measured from the perspective of the NHS and personal social services. Uncertainty in the observed data was captured through probabilistic sensitivity analysis. Scenario analysis was conducted to explore the effects of changing the way QALYs were estimated and adjusting for baseline difference in the population. We also explore assumptions about the length of treatment benefit being maintained. RESULTS: The incremental cost-effectiveness ratio (ICER) for the base-case analysis was £14,231 per QALY. When QALYs were assumed to change linearly over time, this increased to £20,514 per QALY at three months. Adjusting the estimate of QALYs to account for differences in the population at baseline increased the ICER to £94,748 per QALY at three months. Increasing the assumed length of treatment benefit led to reduced ICERs in all scenarios. CONCLUSIONS: Although the intervention is likely to be cost-effective in some circumstances, there is considerable uncertainty surrounding the decision to implement the service. Further research, informed by a formal value of information analysis, would reduce this uncertainty.

Activity groups for people with schizophrenia: a randomized controlled trial.

BACKGROUND: UK guidelines recommend that patients with schizophrenia are offered access to social activities, however, the impact of such interventions have not been examined in a large randomized trial. AIMS: To investigate the effect of an activity group intervention on mental health and global functioning 12 months after randomization compared to standard care alone. METHODS: Secondary analysis of data from the MATISSE study. Primary outcomes were global functioning, assessed using the Global Assessment of Functioning (GAF), and mental health symptoms measured using the Positive and Negative Syndrome Scale (PANSS). RESULTS: About 140 participants were randomized to activity groups and 137 to standard care alone. Follow-up data were collected from 242 (87%) participants. Mental health improved significantly among those offered activity groups (change in PANSS score = -6.0, 95% CI -2.3 to -9.8) but global functioning did not (change in GAF score = 0.8, 95% CI -1.7 to 3.3). No significant differences were found between treatment arms. CONCLUSIONS: Offering activity groups to patients with schizophrenia was not associated with any additional clinical benefits. There was poor uptake and attendance at activity groups. Interventions that aim to improve negative symptoms may be useful in enabling engagement in psychosocial interventions.