Neuronal loss of TRPM8 leads to obesity and glucose intolerance in male mice.

OBJECTIVE: Mice with global deletion of the transient receptor potential channel melastatin family member 8 (TRPM8) are obese, and treatment of diet-induced obese (DIO) mice with TRPM8 agonists decrease body weight. Whether TRPM8 signaling regulates energy metabolism via central or peripheral effects is unknow. Here we assessed the metabolic phenotype of mice with either Nestin Cre-mediated neuronal loss of TRPM8, or with deletion of TRPM8 in Advillin Cre positive sensory neurons of the peripheral nervous system (PNS). METHODS: Nestin Cre- and Advillin Cre-Trpm8 knock-out (KO) mice were metabolically phenotyped under chronic exposure to either chow or high-fat diet (HFD), followed by assessment of energy and glucose metabolism. RESULTS: At room temperature, chow-fed neuronal Trpm8 KO are obese and show decreased energy expenditure when acutely treated with the TRPM8 selective agonist icilin. But body weight of neuronal Trpm8 KO mice is indistinguishable from wildtype controls at thermoneutrality, or when mice are chronically exposed to HFD-feeding. In contrast to previous studies, we show that the TRPM8 agonist icilin has no direct effect on brown adipocytes, but that icilin stimulates energy expenditure, at least in part, via neuronal TRPM8 signaling. We further show that lack of TRPM8 in sensory neurons of the PNS does not lead to a metabolically relevant phenotype. CONCLUSIONS: Our data indicate that obesity in TRPM8-deficient mice is centrally mediated and likely originates from alterations in energy expenditure and/or thermal conductance, but does not depend on TRPM8 signaling in brown adipocytes or sensory neurons of the PVN.

Clustering of comorbidities and associated outcomes in people with osteoarthritis - A UK Clinical Practice Research Datalink study.

OBJECTIVE: To examine the clusters of chronic conditions present in people with osteoarthritis and the associated risk factors and health outcomes. METHODS: Clinical Practice Research Datalink (CPRD) GOLD was used to identify people diagnosed with incident osteoarthritis (n = 221,807) between 1997 and 2017 and age (±2 years), gender, and practice matched controls (no osteoarthritis, n = 221,807) from UK primary care. Clustering of people was examined for 49 conditions using latent class analysis. The associations between cluster membership and covariates were quantified by odds ratios (OR) using multinomial logistic regression. General practice (GP) consultations, hospitalisations, and all-cause mortality rates were compared across the clusters identified at the time of first diagnosis of osteoarthritis (index date). RESULTS: In both groups, conditions largely grouped around five clusters: relatively healthy; cardiovascular (CV), musculoskeletal-mental health (MSK-MH), CV-musculoskeletal (CV-MSK) and metabolic (MB). In the osteoarthritis group, compared to the relatively healthy cluster, strong associations were seen for 1) age with all clusters; 2) women with the MB cluster (OR 5.55: 5.14-5.99); 3) obesity with the CV-MSK (OR 2.11: 2.03-2.20) and CV clusters (OR 2.03: 1.97-2.09). The CV-MSK cluster in the osteoarthritis group had the highest number of GP consultations and hospitalisations, and the mortality risk was 2.45 (2.33-2.58) times higher compared to the relatively healthy cluster. CONCLUSIONS: Of the five identified clusters, CV-MSK, CV, and MSK-MH are more common in OA and CV-MSK cluster had higher health utilisation. Further research is warranted to better understand the mechanistic pathways and clinical implications.

Implementation fidelity of the Falls Management Exercise Programme: a mixed methods analysis using a conceptual framework for implementation fidelity.

OBJECTIVES: Falls in older adults cause significant morbidity and mortality and incur cost to health and care services. The Falls Management Exercise (FaME) programme is a 24-week intervention for older adults that, in clinical trials, improves balance and functional strength and leads to fewer falls. Similar but more modest outcomes have been found when FaME is delivered in routine practice. Understanding the degree to which the programme is delivered with fidelity is important if 'real-world' delivery of FaME is to achieve the same magnitude of outcome as in clinical trials. The objective of this study was to examine the implementation fidelity of FaME when delivered in the community to inform quality improvement strategies that maximise programme effectiveness. STUDY DESIGN: A mixed methods implementation study of FaME programme delivery. METHODS: Data from programme registers, expert observations of FaME classes, and semistructured interviews with FaME instructors were triangulated using a conceptual framework for implementation fidelity. Quantitative data were analysed using descriptive statistics. Interviews were transcribed verbatim and analysed using thematic analysis. RESULTS: In total, 356 participants enrolled on 29 FaME programmes, and 143 (40%) participants completed at least 75% of the classes within a programme. Observations showed that 72%-78% of programme content was delivered, and 80%-84% quality criteria were met. Important content that was most often left out included home exercises, Tai Chi moves, and floor work, whereas quality items most frequently missed out included asking about falls in the previous week, following up attendance absence and explaining the purpose of exercises. Only 24% of class participants made the expected strength training progression. Interviews with FaME instructors helped explain why elements of programme content and quality were not delivered. Strategies for improving FaME delivery were established and helped to maintain quality and fidelity. CONCLUSIONS: FaME programmes delivered in the 'real world' can be implemented with a high degree of fidelity, although important deviations were found. Facilitation strategies could be used to further improve programme fidelity and maximise participant outcomes.

NHS Health Checks for people with mental ill-health 2013-2017: an observational study.

AIMS: People living with serious mental ill-health experience adverse cardiovascular outcomes causing some of the greatest health inequality gaps in England, UK. We describe uptake of the NHS Health Check programme in people with mental ill-health, and rates of new diagnoses and management of cardiovascular risk factors in those who attend NHS Health Checks in comparison to those people without mental ill-health. METHODS: We used a large nationally representative database of people registered with general practitioners in England (QResearch). Between 2013 and 2017, we analysed attendance at NHS Health Checks and outcomes in the succeeding 12 months, in people with serious mental illness (SMI) including psychoses and in people prescribed long-term antidepressant medications (LTAD), with comparison to attendees who did not have these conditions. Hazard ratios (HR) were used to describe the association between outcomes and SMI and LTAD adjusting for sociodemographic variables. RESULTS: In those eligible for the NHS Health Check programme, we found a higher percentage of people with SMI attended an NHS Health Check (65 490, 19.8%) than those without SMI (524 728, 16.6%); adjusted HR 1.05 [95% confidence interval 1.02-1.08]. We also observed a higher percentage of attendance in people on LTAD (46 437, 20.1%) compared to people who were not prescribed LTAD (543 781, 16.7%); adjusted HR 1.10 (1.08-1.13). People with SMI were more likely to be identified with chronic kidney disease (CKD, HR 1.23, 1.12-1.34) and type 2 diabetes (HR 1.14, 1.03-1.25) within the 12 months following their NHS Health Check compared with those without SMI. People on LTAD were more likely to be identified with CKD (HR 1.55, 1.42-1.70) and type 2 diabetes (HR 1.45, 1.31-1.60) and also hypertension, cardiovascular disease, non-diabetic hyperglycaemia, familial hypercholesterolemia and dementia within the 12 months following their NHS Health Check. Statins were more likely to be prescribed to NHS Health Check attendees with SMI and those on LTAD than those without these conditions; HR 1.31 (1.25-1.38) and 1.91 (1.82-2.01), respectively. Antihypertensives were more likely to be prescribed to those on LTAD; HR 1.21 (1.14-1.29). CONCLUSIONS: We found evidence that people with SMI or on LTAD treatment were 5-10% more likely to access NHS Health Checks than people without these conditions. People with SMI or on LTAD treatment who attended NHS Health Checks had higher rates of diagnosis of CKD, type 2 diabetes and some other relevant co-morbidities and increased treatment with statins and also anti-hypertensive medication in people on LTAD. This is likely to contribute to equitable reduction in adverse cardiovascular events for people with mental ill-health.

Trends in incidence and prevalence of osteoarthritis in the United Kingdom: findings from the Clinical Practice Research Datalink (CPRD).

OBJECTIVE: This study aimed to explore the incidence and prevalence of OA in the UK in 2017 and their trends from 1997 to 2017 using a large nationally representative primary care database. DESIGN: The UK Clinical Practice Research Datalink (CPRD) comprising data on nearly 17.5 million patients was used for the study. The incidence and prevalence of general practitioner diagnosed OA over a 20 years period (1997-2017) were estimated and age-sex and length of data contribution standardized using the 2017 CPRD population structure. Cohort effects were examined through Age-period-cohort analysis. RESULTS: During 1997-2017, there were 494,716 incident OA cases aged ≥20 years. The standardised incidence of any OA in 2017 was 6.8 per 1000 person-years (95% CI 6.7 to 6.9) and prevalence was 10.7% (95% CI 10.7-10.8%). Both incidence and prevalence were higher in women than men. The incidence of any-OA decreased gradually in the past 20 years at an annual rate of -1.6% (95%CI -2.0 to -1.1%), and the reduction speeded up for people born after 1960. The prevalence of any-OA increased gradually at an annual rate of 1.4% (95% CI 1.3-1.6%). Although the prevalence was highest in Scotland and Northern Ireland, incidence was highest in the East Midlands. Both incidence and prevalence reported highest in the knee followed by hip, wrist/hand and ankle/foot. CONCLUSION: In the UK approximately one in 10 adults have symptomatic clinically diagnosed OA, the knee being the commonest. While prevalence has increased and become static after 2008, incidence is slowly declining. Further research is required to understand these changes.

Early risk factors for depression, anxiety and post-traumatic distress after hospital admission for unintentional injury: Multicentre cohort study.

OBJECTIVE: To quantify psychological morbidity and identify baseline factors associated with depression, anxiety and post-traumatic distress symptoms up to 12 months post-injury. METHODS: Multicentre cohort study of 668 adults, aged 16 to 70, admitted to 4 UK NHS hospital trusts. Data on injury, socio-demographic characteristics and health status was collected at recruitment. Depression, anxiety and post-traumatic distress were measured at 1, 2, 4 and 12 months post-injury. Multilevel linear regression assessed associations between patient and injury characteristics and psychological outcomes over 12 months follow-up. RESULTS: Depression, anxiety and post-traumatic distress scores were highest 1 month post-injury, and remained above baseline at 2, 4 and 12 months post-injury. Moderate or severe injuries, previous psychiatric diagnoses, higher pre-injury depression and anxiety scores, middle age (45-64 years), greater deprivation and lower pre-injury quality of life (QoL) were associated with higher depression scores post-injury. Previous psychiatric diagnoses, higher pre-injury depression and anxiety scores, middle age, greater deprivation and lower pre-injury QoL were associated with higher anxiety scores post-injury. Traffic injuries or injuries from being struck by objects, multiple injures (≥3), being female, previous psychiatric diagnoses, higher pre-injury anxiety scores and greater deprivation were associated with higher post-traumatic distress scores post-injury. CONCLUSION: A range of risk factors, identifiable shortly after injury, are associated with psychological morbidity occurring up to 12 months post-injury in a general trauma population. Further research is required to explore the utility of these, and other risk factors in predicting psychological morbidity on an individual patient basis.

The impact of psychological factors on recovery from injury: a multicentre cohort study.

PURPOSE: Unintentional injuries have a significant long-term health impact in working age adults. Depression, anxiety and post-traumatic stress disorder are common post-injury, but their impact on self-reported recovery has not been investigated in general injury populations. This study investigated the role of psychological predictors 1 month post-injury in subsequent self-reported recovery from injury in working-aged adults. METHODS: A multicentre cohort study was conducted of 668 unintentionally injured adults admitted to five UK hospitals followed up at 1, 2, 4 and 12 months post-injury. Logistic regression explored relationships between psychological morbidity 1 month post-injury and self-reported recovery 12 months post-injury, adjusting for health, demographic, injury and socio-legal factors. Multiple imputations were used to impute missing values. RESULTS: A total of 668 adults participated at baseline, 77% followed up at 1 month and 63% at 12 months, of whom 383 (57%) were included in the main analysis. Multiple imputation analysis included all 668 participants. Increasing levels of depression scores and increasing levels of pain at 1 month and an increasing number of nights in hospital were associated with significantly reduced odds of recovery at 12 months, adjusting for age, sex, centre, employment and deprivation. The findings were similar in the multiple imputation analysis, except that pain had borderline statistical significance. CONCLUSIONS: Depression 1 month post-injury is an important predictor of recovery, but other factors, especially pain and nights spent in hospital, also predict recovery. Identifying and managing depression and providing adequate pain control are essential in clinical care post-injury.

Psychological morbidity and health-related quality of life after injury: multicentre cohort study.

PURPOSE: To demonstrate the impact of psychological morbidity 1 month post-injury on subsequent post-injury quality of life (HRQoL) in a general injury population in the UK to inform development of trauma care and rehabilitation services. METHODS: Multicentre cohort study of 16-70-year-olds admitted to 4 UK hospitals following injury. Psychological morbidity and HRQoL (EQ-5D-3L) were measured at recruitment and 1, 2, 4 and 12 months post-injury. A reduction in EQ-5D compared to retrospectively assessed pre-injury levels of at least 0.074 was taken as the minimal important difference (MID). Multilevel logistic regression explored relationships between psychological morbidity 1 month post-injury and MID in HRQoL over the 12 months after injury. RESULTS: A total of 668 adults participated. Follow-up rates were 77% (1 month) and 63% (12 months). Substantial reductions in HRQoL were seen; 93% reported a MID at 1 month and 58% at 12 months. Problems with pain, mobility and usual activities were commonly reported at each time point. Depression and anxiety scores 1 month post-injury were independently associated with subsequent MID in HRQoL. The relationship between depression and HRQoL was partly explained by anxiety and to a lesser extent by pain and social functioning. The relationship between anxiety and HRQoL was not explained by factors measured in our study. CONCLUSIONS: Hospitalised injuries result in substantial reductions in HRQoL up to 12 months later. Depression and anxiety early in the recovery period are independently associated with lower HRQoL. Identifying and managing these problems, ensuring adequate pain control and facilitating social functioning are key elements in improving HRQoL post-injury.

Risk and protective factors for falls on stairs in young children: multicentre case-control study.

AIM: To investigate risk and protective factors for stair falls in children aged <5 years. METHODS: Multicentre case-control study at hospitals, minor injury units and general practices in and around four UK study centres. Cases were children with medically attended stair fall injuries. Controls were matched on age, sex, calendar time and study centre. A total of 610 cases and 2658 controls participated. RESULTS: Cases' most common injuries were bangs on the head (66%), cuts/grazes not requiring stitches (14%) and fractures (12%). Parents of cases were significantly more likely not to have stair gates (adjusted OR (AOR) 2.50, 95% CI 1.90 to 3.29; population attributable fraction (PAF) 21%) or to leave stair gates open (AOR 3.09, 95% CI 2.39 to 4.00; PAF 24%) both compared with having closed stair gates. They were more likely not to have carpeted stairs (AOR 1.52, 95% CI 1.09 to 2.10; PAF 5%) and not to have a landing part-way up their stairs (AOR 1.34, 95% CI 1.08 to 1.65; PAF 18%). They were more likely to consider their stairs unsafe to use (AOR 1.46, 95% CI 1.07 to 1.99; PAF 5%) or to be in need of repair (AOR 1.71, 95% CI 1.16 to 2.50; PAF 5%). CONCLUSION: Structural factors including having landings part-way up the stairs and keeping stairs in good repair were associated with reduced stair fall injury risk. Family factors including having stair gates, not leaving gates open and having stair carpets were associated with reduced injury risk. If these associations are causal, addressing these factors in housing policy and routine child health promotion could reduce stair fall injuries.

Risk and protective factors for falls on one level in young children: multicentre case-control study.

BACKGROUND: Childhood falls are an important global public health problem, but there is lack of evidence about their prevention. Falls on one level result in considerable morbidity and they are costly to health services. OBJECTIVE: To estimate ORs for falls on one level in children aged 0-4 years for a range of safety behaviours, safety equipment use and home hazards. DESIGN, SETTING AND PARTICIPANTS: Multicentre case-control study at hospitals, minor injury units and general practices in and around four UK study centres. Participants included 582 children less than 5 years of age with a medically attended fall injury occurring at home and 2460 controls matched on age, sex, calendar time and study centre. MAIN OUTCOME MEASURE: Fall on one level. RESULTS: Cases' most common injuries were bangs on the head (52%), cuts or grazes not needing stitches (29%) or cuts or grazes needing stitches (17%). Comparing cases to community controls in the adjusted analyses, significant findings were observed for only two exposures. Injured children were significantly less likely to live in a household without furniture corner covers (adjusted OR (AOR) 0.72, 95% CI 0.55 to 0.95), or without rugs and carpets firmly fixed to the floor (AOR 0.76, 95% CI 0.59 to 0.98). CONCLUSIONS: We did not find any safety practices, use of safety equipment or home hazards associated with a reduced risk of fall on one level. Our findings do not provide evidence to support changes to current injury prevention practice.

Keeping children safe at home: protocol for a case-control study of modifiable risk factors for scalds.

BACKGROUND: Scalds are one of the most common forms of thermal injury in young children worldwide. Childhood scald injuries, which mostly occur in the home, result in substantial health service use and considerable morbidity and mortality. There is little research on effective interventions to prevent scald injuries in young children. OBJECTIVES: To determine the relationship between a range of modifiable risk factors for medically attended scalds in children under the age of 5 years. DESIGN: A multicentre case-control study in UK hospitals and minor injury units with parallel home observation to validate parental reported exposures. Cases will be 0-4 years old with a medically attended scald injury which occurred in their home or garden, matched on gender and age with community controls. An additional control group will comprise unmatched hospital controls drawn from children aged 0-4 years attending the same hospitals and minor injury units for other types of injury. Conditional logistic regression will be used for the analysis of cases and matched controls, and unconditional logistic regression for the analysis of cases and unmatched controls to estimate ORs and 95% CI, adjusted and unadjusted for confounding variables. MAIN EXPOSURE MEASURES: Use of safety equipment and safety practices for scald prevention and scald hazards. DISCUSSION: This large case-control study will investigate modifiable risk factors for scalds injuries, adjust for potential confounders and validate measures of exposure. Its findings will enhance the evidence base for prevention of scalds injuries in young children.

Exposure to bisphosphonates and risk of common non-gastrointestinal cancers: series of nested case-control studies using two primary-care databases.

BACKGROUND: Bisphosphonates are the most commonly prescribed osteoporosis drugs but long-term effects are unclear, although antitumour properties are known from preclinical studies. METHODS: Nested case-control studies were conducted to investigate bisphosphonate use and risks of common non-gastrointestinal cancers (breast, prostate, lung, bladder, melanoma, ovarian, pancreas, uterus and cervical). Patients 50 years and older, diagnosed with primary cancers between 1997 and 2011, were matched to five controls using the UK practice-based QResearch and Clinical Practice Research Datalink (CPRD) databases. The databases were analysed separately and the results combined. RESULTS: A total of 91 556 and 88 845 cases were identified from QResearch and CPRD, respectively. Bisphosphonate use was associated with reduced risks of breast (odds ratio (OR): 0.92, 95% confidence interval (CI): 0.87-0.97), prostate (OR: 0.87, 95% CI: 0.79-0.96) and pancreatic (OR: 0.79, 95% CI: 0.68-0.93) cancers in the combined analyses, but no significant trends with duration. For alendronate, reduced risk associations were found for prostate cancer in the QResearch (OR: 0.81, 95% CI: 0.70-0.93) and combined (OR: 0.84, 95% CI: 0.75-0.93) analyses (trend with duration P-values 0.009 and 0.001). There were no significant associations from any of the other analyses. CONCLUSION: In this series of large population-based case-control studies, bisphosphonate use was not associated with increased risks for any common non-gastrointestinal cancers.

Estimating the prevalence of medically unexplained symptoms from primary care records.

OBJECTIVES: To develop models to estimate the likely prevalence of medically unexplained symptoms (MUS) and severe MUS in a primary care practice from existing patient electronic records collected in the previous 2 years for secondary prevention and commissioning of psychological treatment. STUDY DESIGN: Cross-sectional survey comparing general practitioners' (GPs) assessment of the presence or absence of MUS and severe MUS with clinical, demographic and service use variables associated with MUS or functional somatic syndromes from previous research in the patient's routine electronic record over the previous 2 years. METHODS: Seventeen GPs from eight practices identified cases of MUS and severe MUS in 828 consecutive consulters in primary care. Models of variables associated with MUS and severe MUS were constructed using multivariate multilevel logistic regression. The predictive validity of the final models was tested, comparing predicted with observed data and expected prevalence rates from the literature. RESULTS: Models to predict MUS and severe MUS had areas under the receiver operating characteristic curve of 0.70 [95% confidence interval (CI) 0.65-0.74] and 0.76 (95% CI 0.70-0.82), respectively. Both models showed adequate goodness of fit with observed data, and had good predictive validity compared with the expected prevalence of MUS, severe MUS, and anxiety or depression. CONCLUSION: Models to predict the prevalence of MUS and severe MUS from routine practice records for commissioning purposes were successfully developed, but they require independent validation before general use. The sensitivity of these models was too low for use in clinical screening.

A study of the safety and harms of antidepressant drugs for older people: a cohort study using a large primary care database.

OBJECTIVES: The aim of this study was to establish the relative safety and balance of risks for antidepressant treatment in older people. The study objectives were to (1) determine relative and absolute risks of predefined adverse events in older people with depression, comparing classes of antidepressant drugs [tricyclic and related antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and other antidepressants] and commonly prescribed individual drugs with non-use of antidepressant drugs; (2) directly compare the risk of adverse events for SSRIs with TCAs; (3) determine associations with dose and duration of antidepressant medication; (4) describe patterns of antidepressant use in older people with depression; and (5) estimate costs of antidepressant medication and primary care visits. DESIGN: A cohort study of patients aged 65 years and over diagnosed with depression. SETTING: The study was based in 570 general practices in the UK supplying data to the QResearch database. PARTICIPANTS: Patients diagnosed with a new episode of depression between the ages of 65 and 100 years, from 1 January 1996 to 31 December 2007. Participants were followed up until 31 December 2008. INTERVENTIONS: The exposure of interest was treatment with antidepressant medication. Antidepressant drugs were grouped into the major classes and commonly prescribed individual drugs were identified. MAIN OUTCOME MEASURES: There were 13 predefined outcome measures: all-cause mortality, sudden cardiac death, suicide, attempted suicide/self-harm, myocardial infarction, stroke/transient ischaemic attack (TIA), falls, fractures, upper gastrointestinal bleeding, epilepsy/seizures, road traffic accidents, adverse drug reactions and hyponatraemia. RESULTS: In total, 60,746 patients were included in the study cohort. Of these, 54,038 (89.0%) received at least one prescription for an antidepressant during follow-up. The associations with the adverse outcomes were significantly different between the classes of antidepressant drugs for seven outcomes. SSRIs were associated with the highest adjusted hazard ratios (HRs) for falls [1.66, 95% confidence interval (CI) 1.58 to 1.73] and hyponatraemia (1.52, 95% CI 1.33 to 1.75), and the group of other antidepressants was associated with the highest HRs for all-cause mortality (1.66, 95% CI 1.56 to 1.77), attempted suicide/self-harm (5.16, 95% CI 3.90 to 6.83), stroke/TIA (1.37, 95% CI 1.22 to 1.55), fracture (1.63, 95% CI 1.45 to 1.83) and epilepsy/seizures (2.24, 95% CI 1.60 to 3.15) compared with when antidepressants were not being used. TCAs did not have the highest HR for any of the outcomes. There were also significantly different associations between the individual drugs for seven outcomes, with trazodone, mirtazapine and venlafaxine associated with the highest rates for several of these outcomes. The mean incremental cost (for all antidepressant prescriptions) ranged between £51.58 (amitriptyline) and £641.18 (venlafaxine) over the 5-year post-diagnosis period. CONCLUSIONS: This study found associations between use of antidepressant drugs and a number of adverse events in older people. There was no evidence that SSRIs or drugs in the group of other antidepressants were associated with a reduced risk of any of the adverse outcomes compared with TCAs; however, they may be associated with an increased risk for certain outcomes. Among individual drugs trazodone, mirtazapine and venlafaxine were associated with the highest rates for some outcomes. Indication bias and residual confounding may explain some of the study findings. The risks of prescribing antidepressants need to be weighed against the potential benefits of these drugs. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Exposure to cyclooxygenase-2 inhibitors and risk of cancer: nested case-control studies.

BACKGROUND: Selective cyclooxygenase-2 (COX2) inhibitors are widely used as analgesics and it is unclear whether its long-term use affects cancer risk. METHODS: A series of nested case-control studies using the QResearch primary care database. Associations of COX2 inhibitor use with risk of all cancers and 10 common site-specific cancers were estimated using conditional logistic regression adjusted for comorbidities, smoking status, socioeconomic status, and use of non-steroidal anti-inflammatory drugs, aspirin and statins. RESULTS: A total of 88,125 cancers, diagnosed between 1998 and 2008, matched with up to five controls, were analysed. Use of COX2 inhibitors for more than a year was associated with a significantly increased risk of breast cancer (odds ratio (OR) 1.24, 95% confidence interval (CI) 1.08-1.42) and haematological malignancies (OR 1.38, 95% CI 1.12-1.69) and a decreased risk of colorectal cancer (OR 0.76, 95% CI 0.63-0.92). There were no other significant associations. CONCLUSION: Prolonged use of COX2 inhibitors was associated with an increased risk of breast and haematological cancers and decreased risk of colorectal cancer. These findings need to be confirmed using other data sources.

Randomised controlled trial of thermostatic mixer valves in reducing bath hot tap water temperature in families with young children in social housing.

OBJECTIVES: To assess the effectiveness of thermostatic mixing valves (TMVs) in reducing bath hot tap water temperature, assess acceptability of TMVs to families and impact on bath time safety practices. DESIGN: Pragmatic parallel arm randomised controlled trial. SETTING: A social housing organisation in Glasgow, Scotland, UK. PARTICIPANTS: 124 families with at least one child under 5 years. INTERVENTION: A TMV fitted by a qualified plumber and educational leaflets before and at the time of TMV fitting. MAIN OUTCOME MEASURES: Bath hot tap water temperature at 3-month and 12-month post-intervention or randomisation, acceptability, problems with TMVs and bath time safety practices. RESULTS: Intervention arm families had a significantly lower bath hot water temperature at 3-month and 12-month follow-up than families in the control arm (3 months: intervention arm median 45.0°C, control arm median 56.0°C, difference between medians, -11.0, 95% CI -14.3 to -7.7); 12 months: intervention arm median 46.0°C, control arm median 55.0°C, difference between medians -9.0, 95% CI -11.8 to -6.2) They were significantly more likely to be happy or very happy with their bath hot water temperature (RR 1.43, 95% CI 1.05 to 1.93), significantly less likely to report the temperature as being too hot (RR 0.33, 95% CI 0.16 to 0.68) and significantly less likely to report checking the temperature of every bath (RR 0.84, 95% CI 0.73 to 0.97). Seven (15%) intervention arm families reported problems with their TMV. CONCLUSIONS: TMVs and accompanying educational leaflets are effective at reducing bath hot tap water temperatures in the short and longer term and are acceptable to families. Housing providers should consider fitting TMVs in their properties and legislators should consider mandating their use in refurbishments as well as in new builds.

Community falls prevention for people who call an emergency ambulance after a fall: randomised controlled trial.

OBJECTIVE: To evaluate whether a service to prevent falls in the community would help reduce the rate of falls in older people who call an emergency ambulance when they fall but are not taken to hospital. DESIGN: Randomised controlled trial. SETTING: Community covered by four primary care trusts, England. PARTICIPANTS: 204 adults aged more than 60 living at home or in residential care who had fallen and called an emergency ambulance but were not taken to hospital. INTERVENTIONS: Referral to community fall prevention services or standard medical and social care. MAIN OUTCOME MEASURES: The primary outcome was the rate of falls over 12 months, ascertained from monthly diaries. Secondary outcomes were scores on the Barthel index, Nottingham extended activities of daily living scale, and falls efficacy scale at baseline and by postal questionnaire at 12 months. Analysis was by intention to treat. RESULTS: 102 people were allocated to each group. 99 (97%) participants in the intervention group received the intervention. Falls diaries were analysed for 88.6 person years in the intervention group and 84.5 person years in the control group. The incidence rates of falls per year were 3.46 in the intervention group and 7.68 in the control group (incidence rate ratio 0.45, 95% confidence interval 0.35 to 0.58, P<0.001). The intervention group achieved higher scores on the Barthel index and Nottingham extended activities of daily living and lower scores on the falls efficacy scale (all P<0.05) at the 12 month follow-up. The number of times an emergency ambulance was called because of a fall was significantly different during follow-up (incidence rate ratio 0.60, 95% confidence interval 0.40 to 0.92, P=0.018). CONCLUSION: A service to prevent falls in the community reduced the fall rate and improved clinical outcome in the high risk group of older people who call an emergency ambulance after a fall but are not taken to hospital. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67535605.

The effect of education and home safety equipment on childhood thermal injury prevention: meta-analysis and meta-regression.

OBJECTIVE: To evaluate whether home safety education and safety equipment provision increases thermal injury prevention practices or reduces thermal injury rates and whether the effect of interventions differs by social group. METHODS: Systematic review and meta-analysis using individual participant data (IPD) evaluating home safety education with or without provision of free or discounted safety equipment provided to children or young people aged 0-19 years. MAIN OUTCOME MEASURES: possession of functional smoke alarm, fitted fireguard and fire extinguisher; keeping hot drinks or food and keeping matches or lighters out of reach; having a safe hot water temperature and rate of medically attended thermal injuries. RESULTS: Home safety interventions were effective in increasing the proportion of families with a functional smoke alarm (odds ratio (OR) 1.83, 95% CI 1.22 to 2.74) and with a safe hot tap water temperature (OR 1.35, 95% CI 1.01 to 1.80). There was some evidence they increased possession of fitted fireguards (OR 1.39, 95% CI 1.00 to 1.94), but there was a lack of evidence that interventions reduced medically attended thermal injury rates (incident rate ratio (IRR) 1.12, 95% CI 0.81 to 1.56). There was no consistent evidence that the effectiveness of interventions varied by social group. CONCLUSIONS: Home safety education, especially with the provision of safety equipment, is effective in increasing some thermal injury prevention practices, but there is insufficient evidence to show whether this also reduces injury rates.

The advocacy in action study a cluster randomized controlled trial to reduce pedestrian injuries in deprived communities.

BACKGROUND: Road traffic-related injury is a major global public health problem. In most countries, pedestrian injuries occur predominantly to the poorest in society. A number of evaluated interventions are effective in reducing these injuries. Very little research has been carried out into the distribution and determinants of the uptake of these interventions. Previous research has shown an association between local political influence and the distribution of traffic calming after adjustment for historical crash patterns. This led to the hypothesis that advocacy could be used to increase local politicians knowledge of pedestrian injury risk and effective interventions, ultimately resulting in improved pedestrian safety. OBJECTIVE: To design an intervention to improve the uptake of pedestrian safety measures in deprived communities. SETTING: Electoral wards in deprived areas of England and Wales with a poor record of pedestrian safety for children and older adults. METHODS: Design mixedmethods study, incorporating a cluster randomized controlled trial. Data mixture of Geographical Information Systems data collision locations, road safety interventions, telephone interviews, and questionnaires. Randomization 239 electoral wards clustered within 57 local authorities. Participants 615 politicians representing intervention and control wards. Intervention a package of tailored information including maps of pedestrian injuries was designed for intervention politicians, and a general information pack for controls. OUTCOME MEASURES: Primary outcome number of road safety interventions 25 months after randomization. Secondary outcomes politicians interest and involvement in injury prevention cost of interventions. Process evaluation use of advocacy pack, facilitators and barriers to involvement, and success.