Study protocol for a randomised placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment resistant bipolar depression (the PAX-BD study).

BACKGROUND: Treatment Resistant Bipolar Depression (TRBD) is a major contributor to the burden of disease associated with Bipolar Disorder (BD). Treatment options for people experiencing bipolar depression are limited to three interventions listed by National Institute for Health and Care: lamotrigine, quetiapine and olanzapine, of which the latter two are often not well tolerated. The majority of depressed people with BD are therefore prescribed antidepressants despite limited efficacy. This demonstrates an unmet need for additional interventions. Pramipexole has been shown to improve mood symptoms in animal models of depression, in people with Parkinson's Disease and two proof of principle trials of pramipexole for people with BD who are currently depressed. METHODS: The PAX-BD study, funded by the United Kingdom (UK) National Institute for Health Research, aims to extend previous findings by assessing the efficacy, safety and health economic impact of pramipexole in addition to mood stabilisers for patients with TRBD. A randomised, double-blind, placebo controlled design is conducted in a naturalistic UK National Health Service setting. An internal pilot study to examine feasibility and acceptability of the study design is included. Participants with TRBD are screened from National Health Service secondary care services in up to 40 mental health trusts in the UK, with the aim of recruiting approximately 414 participants into a pre-randomisation phase to achieve a target of 290 randomised participants. Primary safety and efficacy measures are at 12 weeks following randomisation, with follow up of participants to 52 weeks. The primary outcome is depressive symptoms as measured by Quick Inventory for Depressive Symptomatology - Self Report. Secondary outcomes include changes in anxiety, manic symptoms, tolerability, acceptability, quality of life and cost-effectiveness. Outcome measures are collected remotely using self-report tools implemented online, and observer-rated assessments conducted via telephone. ANCOVA will be used to examine the difference in rating scale scores between treatment arms, and dependent on compliance in completion of weekly self-report measures. A mixed effects linear regression model may also be used to account for repeated measures. TRIAL REGISTRATION: ISRCTN72151939. Registered on 28 August 2019, http://www.isrctn.com/ISRCTN72151939 Protocol Version: 04-FEB-2021, Version 9.0.

Prevalence of alcohol related attendance at an inner city emergency department and its impact: a dual prospective and retrospective cohort study.

BACKGROUND: Alcohol related hospital attendances are a potentially avoidable burden on emergency departments (EDs). Understanding the number and type of patients attending EDs with alcohol intoxication is important in estimating the workload and cost implications. We used best practice from previous studies to establish the prevalence of adult alcohol related ED attendances and estimate the costs of clinical management and subsequent health service use. METHODS: The setting was a large inner city ED in northeast England, UK. Data were collected via (i) retrospective review of hospital records for all ED attendances for four pre-specified weeks in 2010/2011 to identify alcohol related cases along with 12 months of follow-up of the care episode and (ii) prospective 24/7 assessment via breath alcohol concentration testing of patients presenting to the ED in the corresponding weeks in 2012/2013. RESULTS: The prevalence rates of alcohol related attendances were 12% and 15% for the retrospective and prospective cohorts, respectively. Prospectively, the rates ranged widely from 4% to 60% across week days, rising to over 70% at weekends. Younger males attending in the early morning hours at weekends made up the largest proportion of alcohol related attendances. The mean cost per attendance was £249 (SD £1064); the mean total cost for those admitted was £851 (SD £2549). The most common reasons for attending were trauma related injuries followed by psychiatric problems. CONCLUSIONS: Alcohol related attendances are a major and avoidable burden on emergency care. However, targeted interventions at weekends and early morning hours could capture the majority of cases and help prevent future re-attendance.

Validation of a home safety questionnaire used in a series of case-control studies.

OBJECTIVE: To measure the validity of safety behaviours, safety equipment use and hazards reported on a questionnaire by parents/carers with children aged under 5 years participating in a series of home safety case-control studies. METHODS: The questionnaire measured safety behaviours, safety equipment use and hazards being used as exposures in five case-control studies. Responses to questions were compared with observations made during a home visit. The researchers making observations were blind to questionnaire responses. RESULTS: In total, 162 families participated in the study. Overall agreement between reported and observed values of the safety practices ranged from 48.5% to 97.3%. Only 3 safety practices (stair gate at the top of stairs, stair gate at the bottom of stairs, stairs are carpeted) had substantial agreement based on the κ statistic (k=0.65, 0.72, 0.74, respectively). Sensitivity was high (≥70%) for 19 of the 30 safety practices, and specificity was high (≥70%) for 20 of the 30 practices. Overall for 24 safety practices, a higher proportion of respondents over-reported than under-reported safe practice (negative predictive value>positive predictive value). For six safety practices, a higher proportion of respondents under-reported than over-reported safe practice (negative predictive value

Modifiable risk factors for scald injury in children under 5 years of age: A Multi-centre Case-Control Study.

OBJECTIVE: To determine the relationship between a range of modifiable risk factors and medically attended scalds in children under the age of 5 years. METHODS: Multicentre matched case-control study in acute hospitals, minor injury units and GP practices in four study centres in England. Cases comprised 338 children under 5 presenting with a scald, and 1438 control participants matched on age, gender, date of event and study centre. Parents/caregivers completed questionnaires on safety practices, safety equipment use, home hazards and potential confounders. Odds ratios were estimated using conditional logistic regression. RESULTS: Parents of cases were significantly more likely than parents of controls to have left hot drinks within reach of their child (adjusted odds ratio (AOR) 2.33, 95%CI 1.63 to 3.31; population attributable fraction (PAF) 31%). They were more likely not to have taught children rules about climbing on kitchen objects (AOR 1.66, 95%CI 1.12 to 2.47; PAF 20%); what to do or not do when parents are cooking (AOR 1.95, 95%CI 1.33 to 2.85; PAF 26%); and about hot things in the kitchen (AOR 1.89, 95%CI 1.30 to 2.75; PAF 26%). CONCLUSIONS: Some scald injuries may be prevented by parents keeping hot drinks out of reach of children and by teaching children rules about not climbing on objects in the kitchen, what to do or not do whilst parents are cooking using the top of the cooker and about hot objects in the kitchen. Further studies, providing a more sophisticated exploration of the immediate antecedents of scalds are required to quantify associations between other hazards and behaviours and scalds in young children.

Risk and protective factors for falls from furniture in young children: multicenter case-control study.

IMPORTANCE: Falls from furniture are common in young children but there is little evidence on protective factors for these falls. OBJECTIVE: To estimate associations for risk and protective factors for falls from furniture in children aged 0 to 4 years. DESIGN, SETTING, AND PARTICIPANTS: Multicenter case-control study at hospitals, minor injury units, and general practices in and around 4 UK study centers. Recruitment commenced June 14, 2010, and ended April 27, 2012. Participants included 672 children with falls from furniture and 2648 control participants matched on age, sex, calendar time, and study center. Thirty-five percent of cases and 33% of control individuals agreed to participate. The mean age was 1.74 years for cases and 1.91 years for control participants. Fifty-four percent of cases and 56% of control participants were male. Exposures included safety practices, safety equipment use, and home hazards. MAIN OUTCOMES AND MEASURES: Falls from furniture occurring at the child's home resulting in attendance at an emergency department, minor injury unit, or hospital admission. RESULTS: Compared with parents of control participants, parents of cases were significantly more likely not to use safety gates in the home (adjusted odds ratio [AOR], 1.65; 95% CI, 1.29-2.12) and not to have taught their children rules about climbing on kitchen objects (AOR, 1.58; 95% CI, 1.16-2.15). Cases aged 0 to 12 months were significantly more likely to have been left on raised surfaces (AOR, 5.62; 95% CI, 3.62-8.72), had their diapers changed on raised surfaces (AOR, 1.89; 95% CI, 1.24-2.88), and been put in car/bouncing seats on raised surfaces (AOR, 2.05; 95% CI, 1.29-3.27). Cases 3 years and older were significantly more likely to have played or climbed on furniture (AOR, 9.25; 95% CI, 1.22-70.07). Cases were significantly less likely to have played or climbed on garden furniture (AOR, 0.74; 95% CI, 0.56-0.97). CONCLUSIONS AND RELEVANCE: If estimated associations are causal, some falls from furniture may be prevented by incorporating advice into child health contacts, personal child health records, and home safety assessments about use of safety gates; not leaving children, changing diapers, or putting children in car/bouncing seats on raised surfaces; allowing children to play or climb on furniture; and teaching children safety rules about climbing on objects.

Preventing childhood scalds within the home: Overview of systematic reviews and a systematic review of primary studies.

OBJECTIVE: To synthesise and evaluate the evidence of the effectiveness of interventions to prevent scalds in children. METHODS: An overview of systematic reviews (SR) and a SR of primary studies were performed evaluating interventions to prevent scalds in children. A comprehensive literature search was conducted covering various resources up to October 2012. Experimental and controlled observational studies reporting scald injuries, safety practices and safety equipment use were included. RESULTS: Fourteen systematic reviews and 39 primary studies were included. There is little evidence that interventions are effective in reducing the incidence of scalds in children. More evidence was found that inventions are effective in promoting safe hot tap water temperature, especially when home safety education, home safety checks and discounted or free safety equipment including thermometers and thermostatic mixing valves were provided. No consistent evidence was found for the effectiveness of interventions on the safe handling of hot food or drinks nor improving kitchen safety practices. CONCLUSION: Education, home safety checks along with thermometers or thermostatic mixing valves should be promoted to reduce tap water scalds. Further research is needed to evaluate the effectiveness of interventions on scald injuries and to disentangle the effects of multifaceted interventions on scald injuries and safety practices.

Recruitment and retention strategies and the examination of attrition bias in a randomised controlled trial in children's centres serving families in disadvantaged areas of England.

BACKGROUND: Failure to retain participants in randomised controlled trials and longitudinal studies can cause significant methodological problems. We report the recruitment and retention strategies of a randomised controlled trial to promote fire-related injury prevention in families with pre-school children attending children's centres in disadvantaged areas in England. METHODS: Thirty-six children's centres were cluster randomised into one of three arms of a 12-month fire-related injury prevention trial. Two arms delivered safety interventions and there was one control arm. Retention rates compared the numbers of participants responding to the 12-month questionnaire to the number recruited to the trial. Multivariable random effects logistic regression was used to explore factors independently associated with participant retention. RESULTS: The trial exceeded its required sample size through the use of multiple recruitment strategies. All children's centres remained in the study, despite increased reorganisation. Parent retention was 68% at 12 months, ranging from 65% to 70% across trial arms and from 62% to 74% across trial sites. There was no significant difference in the rates of retention between trial arms (p = 0.58) or between trial sites (p = 0.16). Retention was significantly lower amongst mothers aged 16-25 years than older mothers [adjusted odds ratio (AOR) 0.57, 95% CI 0.41, 0.78], those living in non-owner occupied accommodation than in owner occupied accommodation (AOR 0.53, 95% CI 0.38, 0.73) and those living in more disadvantaged areas (most versus least disadvantaged quintiles AOR 0.50, 95% CI 0.30, 0.82). CONCLUSIONS: Studies recruiting disadvantaged populations should measure and report attrition by socioeconomic factors to enable determination of the extent of attrition bias and estimation of its potential impact on findings. Where differential attrition is anticipated, consideration should be given to over-sampling during recruitment and targeted and more intensive strategies of participant retention in these sub-groups. In transient populations collection of multiple sources of contact information at recruitment and throughout the study may aid retention. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01452191 ; Date of registration: 10 October 2011, ISRCTN65067450.

Emergency physicians' opinions on the use of intravenous fluids to treat patients intoxicated with ethanol (alcohol): attitudes of emergency medicine physicians in the North East of England toward the use of intravenous fluids to treat individuals intoxicated with ethanol (alcohol) attending the emergency department compared with the scientific evidence.

OBJECTIVES: There is an apparent conflict between published evidence and UK emergency medicine (EM) physician practice with regard to the use of intravenous fluids to treat patients intoxicated with alcohol. We conducted a survey of all EM physicians in North East (NE) England to determine opinion with regard to this therapy, and compared this with the available evidence for its benefit. METHODS: We identified 136 EM consultants and trainees in NE England. Each one was contacted and asked to complete a questionnaire with regard to their opinion on the use of intravenous fluids for intoxicated patients, both with and without head injury. RESULTS: The majority (73%) of EM physicians in the NE England use intravenous fluids in their treatment of intoxicated patients. The treatment used varies, but the most commonly used fluid is 0.9% saline (volume range, 500-3000 ml; mean, 1300 ml). Fewer respondents (52%) would use intravenous fluids if the patient had suffered an apparent head injury. CONCLUSION: The use of intravenous fluids to treat intoxication is common practice among EM physicians in NE England. The available literature states that this practice is futile. However, there are significant limitations in these studies. This suggests that EM physicians might be using intravenous fluids therapy (IVT) because they are finding in their own practice it is effective. We hypothesize that IVT should improve care in most intoxicated patients as the result of a direct dilutional effect. Further research is required to establish the validity of existing EM physician's practice of using IVT.