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Background: Following the COVID-19 pandemic, millions of people continue to experience ongoing physical and mental health sequelae after recovery from acute infection. There is currently no specific treatment for the diverse symptoms associated with post-COVID-19 condition. Physical and mental health rehabilitation may help improve quality of life in such patients. This study reports the cost-effectiveness of a programme of physical and mental health rehabilitation compared to best practice usual care in people with post-COVID-19 condition who were previously hospitalised., Methods: We conducted an economic evaluation within a randomised controlled trial from the perspective of the UK national health service (NHS) and personnel social services perspective (PSS). Resource used and health-related quality of life were collected using bespoke questionnaire and the EQ-5D-5 L questionnaire at three, six, and 12 months. Incremental costs and quality adjusted life years accrued over the follow-up period were estimated and reported as the incremental cost-effectiveness ratio. Estimate uncertainty was managed by multiple imputation and bootstrapping cost-effectiveness estimates; and displayed graphically on the cost-effectiveness plane., Results: Over a 12-month time horizon, incremental costs and QALYs were £305 (95% CI: -123 to 732) and 0.026 (95% CI: -0.005 to 0.052) respectively. The ICER was £11,941 per QALY indicating cost-effective care. Sensitivity analyses supported the base case findings. The probability of the intervention being cost-effective at a £30,000 per QALY willingness-to-pay threshold was 84%., Conclusion: The within-trial economic evaluation suggested that people with post-COVID-19 condition after hospitalisation should be offered a programme of physical and mental health rehabilitation as it likely reflects a cost-effective use of NHS resources. Hospitalisation for COVID-19 has become less commonplace: further evaluation in non-hospitalised patients may be worthwhile., Trial Registration: ISRCTN registry ISRCTN11466448 23rd November 2020., (© 2024. The Author(s).)

Background: The SPHERe (Supervised Pulmonary Hypertension Exercise Rehabilitation) trial is a multi-centre, pragmatic, randomised controlled trial assessing the clinical and cost-effectiveness of supervised exercise rehabilitation with psychosocial and motivational support compared to best-practice usual care for people with pulmonary hypertension (PH). The original protocol was published in BMC Pulmonary Medicine (accessible online). We randomised our first participant in January 2020. In response to the COVID-19 pandemic, the trial was stopped in March 2020. In person delivery of the SPHERe intervention to a vulnerable population was not possible during the COVID-19 pandemic. We describe here how trial procedures and intervention delivery were adapted in response to the COVID-19 pandemic., Methods: Restrictions imposed by the COVID-19 pandemic on the clinically vulnerable PH population meant that trial delivery was changed from a centre-based rehabilitation programme to remotely delivered group online sessions. This led to minor alterations to the eligibility criteria. These changes followed a consultation process with stakeholders and people with PH and were approved by the funder and independent trial committees., Conclusions: We describe the modified SPHERe trial protocol in response to restrictions imposed by the COVID-19 pandemic. SPHERe is the first randomised controlled trial to assess the clinical and cost-effectiveness of an online group rehabilitation programme for people with PH compared to usual care., Trial Registration: ISRCTN no. 10608766. Prospectively registered on 18th March 2019, updated 16th August 2023., (© 2024. The Author(s).)

Background: Prehospital analgesia is often required after traumatic injury, currently morphine is the strongest parenteral analgesia routinely available for use by paramedics in the United Kingdom (UK) when treating patients with severe pain. This protocol describes a multi-centre, randomised, double blinded trial comparing the clinical and cost-effectiveness of ketamine and morphine for severe pain following acute traumatic injury., Methods: A two arm pragmatic, phase III trial working with two large NHS ambulance services, with an internal pilot. Participants will be randomised in equal numbers to either (1) morphine or (2) ketamine by IV/IO injection. We aim to recruit 446 participants over the age of 16 years old, with a self-reported pain score of 7 or above out of 10. Randomised participants will receive a maximum of 20 mg of morphine, or a maximum of 30 mg of ketamine, to manage their pain. The primary outcome will be the sum of pain intensity difference. Secondary outcomes measure the effectiveness of pain relief and overall patient experience from randomisation to arrival at hospital as well as monitoring the adverse events, resource use and cost-effectiveness outcomes., Discussion: The PACKMAN study is the first UK clinical trial addressing the clinical and cost-effectiveness of ketamine and morphine in treating acute severe pain from traumatic injury treated by NHS paramedics. The findings will inform future clinical practice and provide insights into the effectiveness of ketamine as a prehospital analgesia., Trial Registration: ISRCTN, ISRCTN14124474. Registered 22 October 2020, https://www.isrctn.com/ISRCTN14124474., (© 2023. The Author(s).)

Background: Fractures are rare events and can occur because of a fall. Fracture counts are distinct from other count data in that these data are positively skewed, inflated by excess zero counts, and events can recur over time. Analytical methods used to assess fracture data and account for these characteristics are limited in the literature., Methods: Commonly used models for count data include Poisson regression, negative binomial regression, hurdle regression, and zero-inflated regression models. In this paper, we compare four alternative statistical models to fit fracture counts using data from a large UK based clinical trial evaluating the clinical and cost-effectiveness of alternative falls prevention interventions in older people (Prevention of Falls Injury Trial; PreFIT)., Results: The values of Akaike information criterion and Bayesian information criterion, the goodness-of-fit statistics, were the lowest for negative binomial model. The likelihood ratio test of no dispersion in the data showed strong evidence of dispersion (chi-square = 225.68, p-value < 0.001). This indicates that the negative binomial model fits the data better compared to the Poisson regression model. We also compared the standard negative binomial regression and mixed effects negative binomial models. The LR test showed no gain in fitting the data using mixed effects negative binomial model (chi-square = 1.67, p-value = 0.098) compared to standard negative binomial model., Conclusions: The negative binomial regression model was the most appropriate and optimal fit model for fracture count analyses., Trial Registration: The PreFIT trial was registered as ISRCTN71002650., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Postal screening has not previously been validated as a method for identifying fall and fracture risk in community-dwelling populations. We examined prognostic performance of a postal risk screener used in the UK Prevention of Falls Injury Trial (PreFIT; ISRCTN71002650), to predict any fall, recurrent falls, and fractures over 12 months. We tested whether adding variables would improve screener performance., Methods: Nine thousand eight hundred and eight community-dwelling participants, aged 70 years and older, and 63 general practices in the UK National Health Service (NHS) were included in a large, pragmatic cluster randomised trial comparing screen and treat fall prevention interventions. The short postal screener was sent to all participants in the trial intervention arms as an A4 sheet to be completed and returned to the GP (n = 6,580). The postal screener items were embedded in the baseline pre-randomisation postal questionnaire for all arms of the trial (n = 9,808). We assessed discrimination and calibration using area under the curve (AUC). We identified additional predictors using data from the control arm and applied these coefficients to internal validation models in the intervention arm participants. We used logistic regression to identify additional predictor variables., Findings: A total of 10,743 falls and 307 fractures were reported over 12 months. Over one third of participants 3,349/8,136 (41%) fell at least once over 12 month follow up. Response to the postal screener was high (5,779/6,580; 88%). Prediction models showed similar discriminatory ability in both control and intervention arms, with discrimination values for any fall AUC 0.67 (95% CI 0.65 to 0.68), and recurrent falls (AUC 0.71; 95% CI 0.69, 0.72) but poorer discrimination for fractures (AUC 0.60; 95% CI 0.56, 0.64). Additional predictor variables improved prediction of falls but had modest effect on fracture, where AUC rose to 0.71 (95% CI 0.67 to 0.74). Calibration slopes were very close to 1., Conclusion: A short fall risk postal screener was acceptable for use in primary care but fall prediction was limited, although consistent with other tools. Fracture and fall prediction were only partially reliant on fall risk although were improved with the additional variables., (© 2023. The Author(s).)

Background: More than 90% of antibiotics are prescribed in primary care, but 50% may be unnecessary. Reducing unnecessary antibiotic overuse is needed to limit antimicrobial resistance. We conducted a pragmatic trial of a primary care provider-focused antimicrobial stewardship intervention to reduce antibiotic prescriptions in primary care., Methods: Primary care practitioners from six primary care clinics in Toronto, Ontario were assigned to intervention or control groups to evaluate the effectiveness of a multi-faceted intervention for reducing antibiotic prescriptions to adults with respiratory and urinary tract infections. The intervention included provider education, clinical decision aids, and audit and feedback of antibiotic prescribing. The primary outcome was total antibiotic prescriptions for these infections. Secondary outcomes were delayed prescriptions, prescriptions longer than 7 days, recommended antibiotic use, and outcomes for individual infections. Generalized estimating equations were used to estimate treatment effects, adjusting for clustering by clinic and baseline differences., Results: There were 1682 encounters involving 54 primary care providers from January until May 31, 2019. In intervention clinics, the odds of any antibiotic prescription was reduced 22% (adjusted Odds Ratio (OR) = 0.78; 95% Confidence Interval (CI) = 0.64.0.96). The odds that a delay in filling a prescription was recommended was increased (adjusted OR=2.29; 95% CI=1.37, 3.83), while prescription durations greater than 7 days were reduced (adjusted OR=0.24; 95% CI=0.13, 0.43). Recommended antibiotic use was similar in control (85.4%) and intervention clinics (91.8%, p=0.37)., Conclusions: A community-based, primary care provider-focused antimicrobial stewardship intervention was associated with a reduced likelihood of antibiotic prescriptions for respiratory and urinary infections, an increase in delayed prescriptions, and reduced prescription durations., Trial Registration: clinicaltrials.gov ( NCT03517215 )., (© 2021. The Author(s).)

Background: Supervised cardio-pulmonary rehabilitation may be safe and beneficial for people with pulmonary hypertension (PH) in groups 1 (pulmonary arterial hypertension) and 4 (chronic thromboembolic disease), particularly as a hospital in-patient. It has not been tested in the most common PH groups; 2 (left heart disease), 3 (lung disease), or 5 (other disorders). Further it has not been evaluated in the UK National Health Service (NHS) out-patient setting, or with long-term follow-up. The aim of this randomised controlled trial (RCT) is to test the clinical and cost-effectiveness of a supervised exercise rehabilitation intervention with psychosocial support compared to best practice usual care for people with PH in the community/outpatient setting., Methods: This multi-centre, pragmatic, two-arm RCT with embedded process evaluation aims to recruit 352 clinically stable adults with PH (groups 1-5) and WHO functional class II-IV. Participants will be randomised to either the Supervised Pulmonary Hypertension Exercise Rehabilitation (SPHERe) intervention or control. The SPHERe intervention consists of 1) individual assessment and familiarisation sessions; 2) 8-week, twice-weekly, supervised out-patient exercise training; 3) psychosocial/motivational support and education; 4) guided home exercise plan. The control intervention consists of best practice usual care with a single one-to-one practitioner appointment, and general advice on physical activity. Outcomes will be measured at baseline, 4 months (post-intervention) and 12 months by researchers blinded to treatment allocation. The primary outcome is the incremental shuttle walk test at 4 months. Secondary outcomes include health-related quality of life (HRQoL), time to clinical worsening and health and social care use. A purposive sample of participants (n = 20 intervention and n = 20 control) and practitioners (n = 20) will be interviewed to explore experiences of the trial, outcomes and interventions., Discussion: The SPHERe study is the first multi-centre clinical RCT to assess the clinical and cost effectiveness of a supervised exercise rehabilitation intervention compared to usual care, delivered in the UK NHS, for people in all PH groups. Results will inform clinicians and commissioners as to whether or not supervised exercise rehabilitation is effective and should be routinely provided for people with PH., Trial Registration: ISRCTN no. 10608766, prospectively registered on 18th March 2019.

Background: The aim was to estimate the prevalence of frailty and relative contribution of physical/balance, nutritive, cognitive and sensory frailty to important adverse health states (falls, physical activity levels, outdoor mobility, problems in self-care or usual activities, and lack of energy or accomplishment) in an English cohort by age and sex., Methods: Analysis of baseline data from a cohort of 9803 community-dwelling participants in a clinical trial. The sample was drawn from a random selection of all people aged 70 or more registered with 63 general practices across England. Data were collected by postal questionnaire. Frailty was measured with the Strawbridge questionnaire. We used cross sectional, multivariate logistic regression to estimate the association between frailty domains and known correlates and adjusted for age. Some models were stratified by sex., Results: Mean age of participants was 78 years (sd 5.7), range 70 to 101 and 47.5% (4653/9803) were men. The prevalence of overall frailty was 20.7% (2005/9671) and there was no difference in prevalence by sex (Odds Ratio 0.98; 95% Confidence Interval 0.89 to 1.08). Sensory frailty was the most common and this was reported by more men (1823/4586) than women (1469/5056; Odds Ratio for sensory frailty 0.62, 95% Confidence Interval 0.57 to 0.68). Men were less likely than women to have physical or nutritive frailty. Physical frailty had the strongest independent associations with adverse health states. However, sensory frailty was independently associated with falls, less frequent walking, problems in self-care and usual activities, lack of energy and accomplishment., Conclusions: Physical frailty was more strongly associated with adverse health states, but sensory frailty was much more common. The health gain from intervention for sensory frailty in England is likely to be substantial, particularly for older men. Sensory frailty should be explored further as an important target of intervention to improve health outcomes for older people both at clinical and population level., Trial Registration: ISRCTN71002650.

Background: Phase III trials often require large sample sizes, leading to high costs and delays in clinical decision-making. Group sequential designs can improve trial efficiency by allowing for early stopping for efficacy and/or futility and thus may decrease the sample size, trial duration and associated costs. Bayesian approaches may offer additional benefits by incorporating previous information into the analyses and using decision criteria that are more practically relevant than those used in frequentist approaches. Frequentist group sequential designs have often been used for phase III studies, but the use of Bayesian group sequential designs is less common. The aim of this work was to explore how Bayesian group sequential designs could be constructed for phase III trials conducted in emergency medicine., Methods: The PARAMEDIC2 trial was a phase III randomised controlled trial that compared the use of adrenaline to placebo in out-of-hospital cardiac arrest patients on 30-day survival rates. It used a frequentist group sequential design to allow early stopping for efficacy or harm. We constructed several alternative Bayesian group sequential designs and studied their operating characteristics via simulation. We then virtually re-executed the trial by applying the Bayesian designs to the PARAMEDIC2 data to demonstrate what might have happened if these designs had been used in practice., Results: We produced three alternative Bayesian group sequential designs, each of which had greater than 90% power to detect the target treatment effect. A Bayesian design which performed interim analyses every 500 patients recruited produced the lowest average sample size. Using the alternative designs, the PARAMEDIC2 trial could have declared adrenaline superior for 30-day survival with approximately 1500 fewer patients., Conclusions: Using the PARAMEDIC2 trial as a case study, we demonstrated how Bayesian group sequential designs can be constructed for phase III emergency medicine trials. The Bayesian framework enabled us to obtain efficient designs using decision criteria based on the probability of benefit or harm. It also enabled us to incorporate information from previous studies on the treatment effect via the prior distributions. We recommend the wider use of Bayesian approaches in phase III clinical trials., Trial Registration: PARAMEDIC2 Trial registration ISRCTN, ISRCTN73485024. Registered 13 March 2014, http://www.isrctn.com/ISRCTN73485024.

As humans, we cannot regenerate axons within the central nervous system (CNS), therefore, making any damage to it permanent. This leads to the loss of sensory and motor function below the site of injury and can be crippling to a person's health. Spontaneous recovery can occur from plastic changes, but it is minimal. The absence of regeneration is due to the inhibitory environment of the CNS as well as the inherent inability of CNS axons to form growth cones. Amongst many factors, one of the major inhibitory signals of the CNS environment is the myelin-associated Nogo pathway. Nogo-A, Nogo-B and Nogo-C (Nogo), stimulate the Nogo receptor, inhibiting neurite outgrowth by causing growth cones to collapse through activation of Rho Kinase (ROCK). Antibodies can be used to target this signalling pathway by binding to Nogo and thus promote the outgrowth of neuronal axons in the CNS. This use of anti-Nogo antibodies has been shown to upregulate CNS regeneration as well as drastically improve sensory and motor function in both rats and primates when coupled with adequate training. Here, we evaluate whether the experimental success of anti-Nogo at improving CNS regeneration can be carried over into the clinical setting to treat spinal cord injuries (SCI) and their symptoms successfully. Furthermore, we also discuss potential methods to improve the current treatment and any developmental obstacles.

Background: Using data from syndromic surveillance, the New York City Department of Health and Mental Hygiene (DOHMH) identified an increase in the number of emergency department (ED) visits related to synthetic cannabinoids. Syndromic surveillance data were used to target community-level interventions and assess the real-time impact of control measures in reducing synthetic cannabinoid ("K2")-related morbidity., Methods: From April 2015 through September 2015, DOHMH implemented 3 separate interventions to reduce K2-related morbidity by limiting the availability of K2 products. Difference-in-difference analyses compared pre- and post-intervention differences in cannabinoid-related ED visit rates between neighborhoods and controls for Interventions A and B. City-wide count data were used to compare K2-related ED visits before and after Intervention C., Results: Syndromic data showed a reduction in K2-related ED visits following the 3 interventions. Respective decreases in rates of synthetic cannabinoid-related ED visits of 33 and 38% were detected at the neighborhood-level due to Interventions A and B, respectively. A decrease of 29% was calculated at the city level following Intervention C., Conclusions: In addition to identifying emerging public health concerns, syndromic data can provide valuable real-time evidence on the effectiveness of public health interventions., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Background: Mechanical chest compression devices consistently deliver high-quality chest compressions. Small very low-quality studies suggest mechanical devices may be effective as an alternative to manual chest compressions in the treatment of adult in-hospital cardiac arrest patients. The aim of this feasibility trial is to assess the feasibility of conducting an effectiveness trial in this patient population., Methods: COMPRESS-RCT is a multi-centre parallel group feasibility randomised controlled trial, designed to assess the feasibility of undertaking an effectiveness to compare the effect of mechanical chest compressions with manual chest compressions on 30-day survival following in-hospital cardiac arrest. Over approximately two years, 330 adult patients who sustain an in-hospital cardiac arrest and are in a non-shockable rhythm will be randomised in a 3:1 ratio to receive ongoing treatment with a mechanical chest compression device (LUCAS 2/3, Jolife AB/Stryker, Lund, Sweden) or continued manual chest compressions. It is intended that recruitment will occur on a 24/7 basis by the clinical cardiac arrest team. The primary study outcome is the proportion of eligible participants randomised in the study during site operational recruitment hours. Participants will be enrolled using a model of deferred consent, with consent for follow-up sought from patients or their consultee in those that survive the cardiac arrest event. The trial will have an embedded qualitative study, in which we will conduct semi-structured interviews with hospital staff to explore facilitators and barriers to study recruitment., Discussion: The findings of COMPRESS-RCT will provide important information about the deliverability of an effectiveness trial to evaluate the effect on 30-day mortality of routine use of mechanical chest compression devices in adult in-hospital cardiac arrest patients., Trial Registration: ISRCTN38139840 , date of registration 9th January 2017.

Background: The long-term economic and quality-of-life outcomes of patients admitted to intensive care unit (ICU) with acute respiratory distress syndrome are not well understood. In this study, we investigate 1-year costs, survival and quality of life following ICU admission in patients who required mechanical ventilation for acute respiratory distress syndrome., Methods: Economic analysis of data collected alongside a UK-based multi-centre randomised, controlled trial, aimed at comparing high-frequency oscillatory ventilation with conventional mechanical ventilation. The study included 795 critically ill patients admitted to ICU. Hospital costs were assessed using daily data. Post-hospital healthcare costs, patient out-of-pocket expenses, lost earnings of survivors and their carers and health-related quality of life were assessed using follow-up surveys., Results: The mean cost of initial ICU stay was £26,857 (95 % CI £25,222-£28,491), and the average daily cost in ICU was £1738 (CI £1667-£1810). Following hospital discharge, the average 1-year cost among survivors was £7523 (CI £5692-£9354). The mean societal cost at 1 year was £44,077 (£41,168-£46,985), and the total societal cost divided by the number of 1-year survivors was £90,206. Survivors reported significantly lower health-related quality of life than the age- and sex-matched reference population, and this difference was more marked in younger patients., Conclusions: Given the high costs and low health-related quality of life identified, there is significant scope for further research aimed at improving care in this in-need patient group., Trial Registration: ISRCTN10416500.

Background: Dementia is more common in older than in younger people, and as a result of the ageing of the population in developed countries, it is becoming more prevalent. Drug treatments for dementia are limited, and the main support offered to people with dementia and their families is generally services to mitigate against loss of function. Physical exercise is a candidate non-pharmacological treatment for dementia., Methods/design: DAPA is a randomised controlled trial funded by the National Institute for Health Research Health Technology Assessment programme to estimate the effect of a 4-month, moderate- to hard-intensity exercise training programme and subsequent advice to remain active, on cognition (primary outcome) at 12 months in people with mild to moderate dementia. Community-dwelling participants (with their carers where possible), who are able to walk 3 metres without human assistance, able to undertake an exercise programme and do not have any unstable or terminal illness are recruited. Participants are then randomised by an independent statistician using a computerised random number generator to usual care or exercise at a 2:1 ratio in favour of exercise. The exercise intervention comprises 29, 1-hour-long exercise classes, run twice weekly at suitable venues such as leisure centres, which include aerobic exercise (on static bikes) and resistance exercise (using weights). Goals for independent exercise are set while the classes are still running, and supported thereafter with phone calls. The primary outcome is measured using ADAS-cog. Secondary outcome measures include behavioural symptoms, functional ability, quality of life and carer burden. Primary and secondary outcomes will be measured at baseline and at 6 and 12 months after randomisation, by researchers masked to participant randomisation in the participants' own homes. An economic evaluation will be carried out in parallel to the RCT, as will a qualitative study capturing the experiences of participants, carers and staff delivering the intervention., Discussion: The DAPA study will be the first large, randomised trial of the cognitive effects of exercise on people with dementia. The intervention is designed to be capable of being delivered within the constraints of NHS service provision, and the economic evaluation will allow assessment of its cost-effectiveness., Trial Registration: DAPA was registered with the ISRCTN database on 29 July 2011, registration number ISRCTN32612072 .

Background: The role of injections of therapeutic substances into the back as treatment for low back pain is unclear. Facet joint injections are widely used despite the absence of evidence of sustained benefit. We hypothesise that facet joint injections might facilitate engagement with physiotherapist-led, best usual care (a combined physical and psychological programme) and is a clinically and cost-effective treatment for people with suspected low back pain of facet joint origin., Methods/design: We present here the protocol for a randomised controlled feasibility trial for a main trial to test the above hypotheses. Patients referred to secondary care with persistent non-specific low back pain will be screened and invited to take part in the study. Those who meet the eligibility criteria will be invited for a physiotherapy assessment to confirm trial eligibility and for baseline data collection. All participants (n = 150) will be offered the best usual care package with physical and psychological components. Those randomised into the intervention arm (n = 75) will, in addition, receive intra-articular facet joint injections with local anaesthetic and steroids. Primary outcome data will be collected using daily and then weekly text messaging service for a pain score on a 0-10 scale. Questionnaire follow-up will be at 3, 6, and 12 months. Evaluation of trial processes and health economic analyses, including a value of information analysis, will be undertaken. The process evaluation will be mixed methods and will include the views of all stakeholders., Discussion: Whilst this trial is a feasibility study it is currently one of the largest trials in this area. The outcomes will provide some evidence on the use of facet joint injections for patients with clinically diagnosed facet joint pain., Trial Registration: EudraCT identifier 2014-000682-50, (registered on 12 February 14). ISRCTN registry number: ISRCTN93184143 DOI 10.1186/ISRCTN93184143 (registered on 27 February 2014).

Background: The New York City emergency department (ED) syndromic surveillance (SS) system provides near real-time data on the majority of ED visits. The utility of ED SS for injury surveillance has not been thoroughly evaluated. We created injury syndromes based on ED chief complaint information and evaluated their utility compared to administrative billing data., Methods: Six injury syndromes were developed: traffic-related injuries to pedal cyclists, pedestrians, and motor vehicle occupants; fall-related injuries; firearm-related injuries; and assault-related stabbings. Daily injury counts were compared for ED SS and the administrative billing data for years 2008-2010. We examined characteristics of injury trends and patterns between the two systems, calculating descriptive statistics for temporal patterns and Pearson correlation coefficients (r) for temporal trends. We also calculated proportions of demographic and geospatial patterns for both systems., Results: Although daily volume of the injuries varied between the two systems, the temporal patterns were similar (all r values for daily volume exceeded 0.65). Comparisons of injuries by time of day, day of week, and quarter of year demonstrated high agreement between the two systems-the majority had an absolute percentage point difference of 2.0 or less. Distributions of injury by sex and age group also aligned well. Distribution of injury by neighborhood of residence showed mixed results-some neighborhood comparisons showed a high level of agreement between systems, while others were less successful., Conclusions: As evidenced by the strong positive correlation coefficients and the small absolute percentage point differences in our comparisons, we conclude that ED SS captures temporal trends and patterns of injury-related ED visits effectively. The system could be used to identify changes in injury patterns, allowing for situational awareness during emergencies, timely response, and public messaging.

Background: Many types of tree pollen trigger seasonal allergic illness, but their population-level impacts on allergy and asthma morbidity are not well established, likely due to the paucity of long records of daily pollen data that allow analysis of multi-day effects. Our objective in this study was therefore to determine the impacts of individual spring tree pollen types on over-the-counter allergy medication sales and asthma emergency department (ED) visits., Methods: Nine clinically-relevant spring tree pollen genera (elm, poplar, maple, birch, beech, ash, sycamore/London planetree, oak, and hickory) measured in Armonk, NY, were analyzed for their associations with over-the-counter allergy medication sales and daily asthma syndrome ED visits from patients' chief complaints or diagnosis codes in New York City during March 1st through June 10th, 2002-2012. Multi-day impacts of pollen on the outcomes (0-3 days and 0-7 days for the medication sales and ED visits, respectively) were estimated using a distributed lag Poisson time-series model adjusting for temporal trends, day-of-week, weather, and air pollution. For asthma syndrome ED visits, age groups were also analyzed. Year-to-year variation in the average peak dates and the 10th-to-90th percentile duration between pollen and the outcomes were also examined with Spearman's rank correlation., Results: Mid-spring pollen types (maple, birch, beech, ash, oak, and sycamore/London planetree) showed the strongest significant associations with both outcomes, with cumulative rate ratios up to 2.0 per 0-to-98th percentile pollen increase (e.g., 1.9 [95% CI: 1.7, 2.1] and 1.7 [95% CI: 1.5, 1.9] for the medication sales and ED visits, respectively, for ash). Lagged associations were longer for asthma syndrome ED visits than for the medication sales. Associations were strongest in children (ages 5-17; e.g., a cumulative rate ratio of 2.6 [95% CI: 2.1, 3.1] per 0-to-98th percentile increase in ash). The average peak dates and durations of some of these mid-spring pollen types were also associated with those of the outcomes., Conclusions: Tree pollen peaking in mid-spring exhibit substantive impacts on allergy, and asthma exacerbations, particularly in children. Given the narrow time window of these pollen peak occurrences, public health and clinical approaches to anticipate and reduce allergy/asthma exacerbation should be developed.

Background: Ankle fractures account for 9% of all fractures with a quarter of these occurring in adults over 60 years. The short term disability and long-term consequences of this injury can be considerable. Current opinion favours open reduction and internal fixation (ORIF) over non-operative treatment (fracture manipulation and the application of a standard moulded cast) for older people. Both techniques are associated with complications but the limited published research indicates higher complication rates of fracture malunion (poor position at healing) with casting. The aim of this study is to compare ORIF with a modification of existing casting techniques, Close Contact Casting (CCC). We propose that CCC may offer an equivalent functional outcome to ORIF and avoid the risks associated with surgery., Methods/design: This study is a pragmatic multi-centre equivalence randomised controlled trial. 620 participants will be randomised to receive ORIF or CCC after sustaining an isolated displaced unstable ankle fracture. Participants will be recruited from a minimum of 20 National Health Service (NHS) acute hospitals throughout England and Wales. Participants will be aged over 60 years and be ambulatory prior to injury. Follow-up will be at six weeks and six months after randomisation. The primary outcome is the Olerud & Molander Ankle Score, a functional patient reported outcome measure, at 6 months. Follow-up will also include assessments of mobility, ankle range of movement, health related quality of life and complications. The six-month follow-up will be conducted face-to-face by an assessor blinded to the allocated intervention. A parallel economic evaluation will consider both a health service and a broader societal perspective including the individual and their family. In order to explore patient experience of their treatment and recovery, a purposive sample of 40 patients will also be interviewed using a semi-structured interview schedule between 6-10 weeks post treatment., Discussion: This multicentre study was open to recruitment July 2010 and recruitment is due to be completed in December 2013., Trial Registration: Current Controlled Trials ISRCTN04180738.

Background: Group cognitive behavioural intervention (CBI) is effective in reducing low-back pain and disability in comparison to advice in primary care. The aim of this analysis was to investigate the impact of compliance on estimates of treatment effect and to identify factors associated with compliance., Methods: In this multicentre trial, 701 adults with troublesome sub-acute or chronic low-back pain were recruited from 56 general practices. Participants were randomised to advice (control n = 233) or advice plus CBI (n = 468). Compliance was specified a priori as attending a minimum of three group sessions and the individual assessment. We estimated the complier average causal effect (CACE) of treatment., Results: Comparison of the CACE estimate of the mean treatment difference to the intention-to-treat (ITT) estimate at 12 months showed a greater benefit of CBI amongst participants compliant with treatment on the Roland Morris Questionnaire (CACE: 1.6 points, 95% CI 0.51 to 2.74; ITT: 1.3 points, 95% CI 0.55 to 2.07), the Modified Von Korff disability score (CACE: 12.1 points, 95% CI 6.07 to 18.17; ITT: 8.6 points, 95% CI 4.58 to 12.64) and the Modified von Korff pain score (CACE: 10.4 points, 95% CI 4.64 to 16.10; ITT: 7.0 points, 95% CI 3.26 to 10.74). People who were non-compliant were younger and had higher pain scores at randomisation., Conclusions: Treatment compliance is important in the effectiveness of group CBI. Younger people and those with more pain are at greater risk of non-compliance., Trial Registration: Current Controlled Trials ISRCTN54717854.

Background: Survival after out-of-hospital cardiac arrest is closely linked to the quality of CPR, but in real life, resuscitation during prehospital care and ambulance transport is often suboptimal. Mechanical chest compression devices deliver consistent chest compressions, are not prone to fatigue and could potentially overcome some of the limitations of manual chest compression. However, there is no high-quality evidence that they improve clinical outcomes, or that they are cost effective. The Prehospital Randomised Assessment of a Mechanical Compression Device In Cardiac Arrest (PARAMEDIC) trial is a pragmatic cluster randomised study of the LUCAS-2 device in adult patients with non-traumatic out-of-hospital cardiac arrest., Methods/design: The primary objective of this trial is to evaluate the effect of chest compression using LUCAS-2 on mortality at 30 days post out-of-hospital cardiac arrest, compared with manual chest compression. Secondary objectives of the study are to evaluate the effects of LUCAS-2 on survival to 12 months, cognitive and quality of life outcomes and cost-effectiveness., Methods: Ambulance service vehicles will be randomised to either manual compression (control) or LUCAS arms. Adult patients in out-of-hospital cardiac arrest, attended by a trial vehicle will be eligible for inclusion. Patients with traumatic cardiac arrest or who are pregnant will be excluded. The trial will recruit approximately 4000 patients from England, Wales and Scotland. A waiver of initial consent has been approved by the Research Ethics Committees. Consent will be sought from survivors for participation in the follow-up phase., Conclusion: The trial will assess the clinical and cost effectiveness of the LUCAS-2 mechanical chest compression device., Trial Registration: The trial is registered on the International Standard Randomised Controlled Trial Number Registry (ISRCTN08233942).

Background: The aim was to compare effectiveness of group versus individual sessions of physiotherapy in terms of symptoms, quality of life, and costs, and to investigate the effect of patient preference on uptake and outcome of treatment., Methods: A pragmatic, multi-centre randomised controlled trial in five British National Health Service physiotherapy departments. 174 women with stress and/or urge incontinence were randomised to receive treatment from a physiotherapist delivered in a group or individual setting over three weekly sessions. Outcome were measured as Symptom Severity Index; Incontinence-related Quality of Life questionnaire; National Health Service costs, and out of pocket expenses., Results: The majority of women expressed no preference (55%) or preference for individual treatment (36%). Treatment attendance was good, with similar attendance with both service delivery models. Overall, there were no statistically significant differences in symptom severity or quality of life outcomes between the models. Over 85% of women reported a subjective benefit of treatment, with a slightly higher rating in the individual compared with the group setting. When all health care costs were considered, average cost per patient was lower for group sessions (Mean cost difference 52.91 pounds 95%, confidence interval ( 25.82 pounds- 80.00 pounds))., Conclusion: Indications are that whilst some women may have an initial preference for individual treatment, there are no substantial differences in the symptom, quality of life outcomes or non-attendance. Because of the significant difference in mean cost, group treatment is recommended., Trial Registration Number: ISRCTN 16772662.

Background: Reporting numbers needed to treat (NNT) improves interpretability of trial results. It is unusual that continuous outcomes are converted to numbers of individual responders to treatment (i.e., those who reach a particular threshold of change); and deteriorations prevented are only rarely considered. We consider how numbers needed to treat can be derived from continuous outcomes; illustrated with a worked example showing the methods and challenges., Methods: We used data from the UK BEAM trial (n = 1, 334) of physical treatments for back pain; originally reported as showing, at best, small to moderate benefits. Participants were randomised to receive 'best care' in general practice, the comparator treatment, or one of three manual and/or exercise treatments: 'best care' plus manipulation, exercise, or manipulation followed by exercise. We used established consensus thresholds for improvement in Roland-Morris disability questionnaire scores at three and twelve months to derive NNTs for improvements and for benefits (improvements gained+deteriorations prevented)., Results: At three months, NNT estimates ranged from 5.1 (95% CI 3.4 to 10.7) to 9.0 (5.0 to 45.5) for exercise, 5.0 (3.4 to 9.8) to 5.4 (3.8 to 9.9) for manipulation, and 3.3 (2.5 to 4.9) to 4.8 (3.5 to 7.8) for manipulation followed by exercise. Corresponding between-group mean differences in the Roland-Morris disability questionnaire were 1.6 (0.8 to 2.3), 1.4 (0.6 to 2.1), and 1.9 (1.2 to 2.6) points., Conclusion: In contrast to small mean differences originally reported, NNTs were small and could be attractive to clinicians, patients, and purchasers. NNTs can aid the interpretation of results of trials using continuous outcomes. Where possible, these should be reported alongside mean differences. Challenges remain in calculating NNTs for some continuous outcomes., Trial Registration: UK BEAM trial registration: ISRCTN32683578.

Background: Low back pain (LBP) is a major public health problem. Risk factors for the development and persistence of LBP include physical and psychological factors. However, most research activity has focused on physical solutions including manipulation, exercise training and activity promotion., Methods/design: This randomised controlled trial will establish the clinical and cost-effectiveness of a group programme, based on cognitive behavioural principles, for the management of sub-acute and chronic LBP in primary care. Our primary outcomes are disease specific measures of pain and function. Secondary outcomes include back beliefs, generic health related quality of life and resource use. All outcomes are measured over 12 months. Participants randomised to the intervention arm are invited to attend up to six weekly sessions each of 90 minutes; each group has 6-8 participants. A parallel qualitative study will aid the evaluation of the intervention., Discussion: In this paper we describe the rationale and design of a randomised evaluation of a group based cognitive behavioural intervention for low back pain.