Pre-existing musculoskeletal pain and its association with mortality in newly diagnosed co-morbid conditions: an electronic health record cohort study.

Objective: Musculoskeletal pain is a common risk factor for co-morbid conditions and might increase the risk of poor outcomes. The objective was to determine whether patients with pre-existing musculoskeletal pain have an increased risk for mortality following a new diagnosis of a co-morbid condition. Methods: Patients aged ≥45 years with a new diagnosis of acute coronary syndrome (ACS), stroke, cancer, dementia or pneumonia recorded in a UK electronic primary care database linked to hospital and mortality records were examined. The association of mortality with musculoskeletal pain (inflammatory conditions, OA and regional pain) was determined. Results: The sample size varied from 128 649 (stroke) to 406 289 (cancer) by cohort, with 22-31% having pre-existing musculoskeletal conditions. In the ACS cohort, there was a higher rate of mortality for all musculoskeletal types. There were also higher unadjusted mortality rates in patients with inflammatory arthritis compared with those without musculoskeletal pain in the stroke, cancer and dementia cohorts and for patients with OA in the stroke and cancer cohorts. After adjustment for the number of prescribed medications and age, the increased risk of mortality remained only for patients with inflammatory arthritis in the ACS cohort (adjusted hazard ratio = 1.07; 95% CI 1.03, 1.10). Conclusion: Older adults with inflammatory arthritis and OA have increased risk of mortality when they develop a new condition, which seems to be related to the prescription of multiple medicines. Pre-existing musculoskeletal pain is an indicator of a complex patient who is at risk of poorer outcomes at the onset of new illnesses.

Musculoskeletal pain and its impact on prognosis following acute coronary syndrome or stroke: A linked electronic health record cohort study.

OBJECTIVE: Musculoskeletal painful conditions are a risk factor for cardiovascular disease (CVD), but less is known about whether musculoskeletal pain also worsens prognosis from CVD. The objective was to determine whether patients with musculoskeletal pain have poorer prognosis following acute coronary syndrome (ACS) or stroke. METHODS: The study utilised UK electronic primary care records (CPRD Aurum) with linkage to hospital and mortality records. Patients aged ≥45 years admitted to hospital with incident ACS/stroke were categorised by healthcare use for musculoskeletal pain (inflammatory conditions, osteoarthritis [OA], and regional pain) based on primary care consultations in the prior 24 months. Outcomes included mortality, length of stay, readmission and management of index condition (ACS/stroke). RESULTS: There were 171,670 patients with incident ACS and 138,512 with stroke; 30% consulted for musculoskeletal pain prior to ACS/stroke and these patients had more comorbidity than those without musculoskeletal pain. Rates of mortality and readmission, and length of stay were higher in those with musculoskeletal pain, particularly OA and inflammatory conditions, in ACS. Readmission was also higher for patients with musculoskeletal pain in stroke. However, increased risks associated with musculoskeletal pain did not remain after adjustment for age and polypharmacy. Inflammatory conditions were associated with increased likelihood of prescriptions for dual anti-platelets (ACS only) and anti-coagulants. CONCLUSIONS: Patients with musculoskeletal pain have higher rates of poor outcome from ACS which relates to being older but also increased polypharmacy. The high rates of comorbidity including polypharmacy highlight the complexity of patients with musculoskeletal pain who have new onset ACS/stroke.

Long-term mortality after acute myocardial infarction among individuals with and without diabetes: A systematic review and meta-analysis of studies in the post-reperfusion era.

AIMS: To conduct a systematic review and meta-analysis with the aim of providing robust estimates of the association between diabetes and long-term (≥1 year) mortality after acute myocardial infarction (AMI). MATERIAL AND METHODS: Medline, Embase and Web of Science databases were searched (January 1985 to July 2016) for terms related to long-term mortality, diabetes and AMI. Two authors independently abstracted the data. Hazard ratios (HRs) comparing mortality in people with and without diabetes were pooled across studies using Bayesian random-effects meta-analysis. RESULTS: A total of 10 randomized controlled trials and 56 cohort studies, including 714 780 patients, reported an estimated total of 202 411 deaths over the median (range) follow-up of 2.0 (1-20) years. The risk of death over time was significantly higher among those with diabetes compared with those without (unadjusted HR 1.82, 95% credible interval [CrI] 1.73-1.91). Mortality remained higher in the analysis restricted to 23/64 cohorts reporting data adjusted for confounders (adjusted HR 1.48, 95% CrI 1.43-1.53). The excess long-term mortality in diabetes was evident irrespective of the phenotype and modern treatment of AMI, and persisted in early survivors (unadjusted HR 1.82, 95% CrI 1.70-1.95). CONCLUSIONS: Despite medical advances, individuals with diabetes have a 50% greater long-term mortality compared with those without. Further research to understand the determinants of this excess risk are important for public health, given the predicted rise in global diabetes prevalence.

The effectiveness of different interventions to promote poison prevention behaviours in households with children: a network meta-analysis.

BACKGROUND: There is evidence from 2 previous meta-analyses that interventions to promote poison prevention behaviours are effective in increasing a range of poison prevention practices in households with children. The published meta-analyses compared any intervention against a "usual care or no intervention" which potentially limits the usefulness of the analysis to decision makers. We aim to use network meta-analysis to simultaneously evaluate the effectiveness of different interventions to increase prevalence of safe storage of i) Medicines only, ii) Other household products only, iii) Poisons (both medicines and non-medicines), iv) Poisonous plants; and v) Possession of poison control centre (PCC) telephone number in households with children. METHODS: Data on the effectiveness of poison prevention interventions was extracted from primary studies identified in 2 newly-undertaken systematic reviews. Effect estimates were pooled across studies using a random effects network meta-analysis model. RESULTS: 28 of the 47 primary studies identified were included in the analysis. Compared to usual care intervention, the intervention with education and low cost/free equipment elements was most effective in promoting safe storage of medicines (odds ratio 2.51, 95% credible interval 1.01 to 6.00) while interventions with education, low cost/free equipment, home safety inspection and fitting components were most effective in promoting safe storage of other household products (2.52, 1.12 to 7.13), safe storage of poisons (11.10, 1.60 to 141.50) and possession of PCC number (38.82, 2.19 to 687.10). No one intervention package was more effective than the others in promoting safe storage of poisonous plants. CONCLUSION: The most effective interventions varied by poison prevention practice, but education alone was not the most effective intervention for any poison prevention practice. Commissioners and providers of poison prevention interventions should tailor the interventions they commission or provide to the poison prevention practices they wish to promote. HIGHLIGHTS: Network meta-analysis is useful for comparing multiple injury-prevention interventions. More intensive poison prevention interventions were more effective than education alone. Education and low cost/free equipment was most effective in promoting safe storage of medicines. Education, low cost/free equipment, home safety inspection and fitting was most effective in promoting safe storage of household products and poisons. Education, low cost/free equipment and home inspection were most effective in promoting possession of a poison control centre number. None of the intervention packages was more effective than the others in promoting safe storage of poisonous plants.

Network meta-analysis of multiple outcome measures accounting for borrowing of information across outcomes.

BACKGROUND: Network meta-analysis (NMA) enables simultaneous comparison of multiple treatments while preserving randomisation. When summarising evidence to inform an economic evaluation, it is important that the analysis accurately reflects the dependency structure within the data, as correlations between outcomes may have implication for estimating the net benefit associated with treatment. A multivariate NMA offers a framework for evaluating multiple treatments across multiple outcome measures while accounting for the correlation structure between outcomes. METHODS: The standard NMA model is extended to multiple outcome settings in two stages. In the first stage, information is borrowed across outcomes as well across studies through modelling the within-study and between-study correlation structure. In the second stage, we make use of the additional assumption that intervention effects are exchangeable between outcomes to predict effect estimates for all outcomes, including effect estimates on outcomes where evidence is either sparse or the treatment had not been considered by any one of the studies included in the analysis. We apply the methods to binary outcome data from a systematic review evaluating the effectiveness of nine home safety interventions on uptake of three poisoning prevention practices (safe storage of medicines, safe storage of other household products, and possession of poison centre control telephone number) in households with children. Analyses are conducted in WinBUGS using Markov Chain Monte Carlo (MCMC) simulations. RESULTS: Univariate and the first stage multivariate models produced broadly similar point estimates of intervention effects but the uncertainty around the multivariate estimates varied depending on the prior distribution specified for the between-study covariance structure. The second stage multivariate analyses produced more precise effect estimates while enabling intervention effects to be predicted for all outcomes, including intervention effects on outcomes not directly considered by the studies included in the analysis. CONCLUSIONS: Accounting for the dependency between outcomes in a multivariate meta-analysis may or may not improve the precision of effect estimates from a network meta-analysis compared to analysing each outcome separately.

Home safety education and provision of safety equipment for injury prevention (Review).

BACKGROUND: In industrialised countries injuries (including burns, poisoning or drowning) are the leading cause of childhood death and steep social gradients exist in child injury mortality and morbidity. The majority of injuries in pre-school children occur at home but there is little meta-analytic evidence that child home safety interventions reduce injury rates or improve a range of safety practices, and little evidence on their effect by social group. OBJECTIVES: We evaluated the effectiveness of home safety education, with or without the provision of low cost, discounted or free equipment (hereafter referred to as home safety interventions), in reducing child injury rates or increasing home safety practices and whether the effect varied by social group. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2009, Issue 2) in The Cochrane Library, MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of Science: Social Sciences Citation Index (SSCI), ISI Web of Science: Conference Proceedings Citation Index- Science (CPCI-S), CINAHL (EBSCO) and DARE (2009, Issue 2) in The Cochrane Library. We also searched websites and conference proceedings and searched the bibliographies of relevant studies and previously published reviews. We contacted authors of included studies as well as relevant organisations. The most recent search for trials was May 2009. SELECTION CRITERIA: Randomised controlled trials (RCTs), non-randomised controlled trials and controlled before and after (CBA) studies where home safety education with or without the provision of safety equipment was provided to those aged 19 years and under, and which reported injury, safety practices or possession of safety equipment. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. We attempted to obtain individual participant level data (IPD) for all included studies and summary data and IPD were simultaneously combined in meta-regressions by social and demographic variables. Pooled incidence rate ratios (IRR) were calculated for injuries which occurred during the studies, and pooled odds ratios were calculated for the uptake of safety equipment or safety practices, with 95% confidence intervals. MAIN RESULTS: Ninety-eight studies, involving 2,605,044 people, are included in this review. Fifty-four studies involving 812,705 people were comparable enough to be included in at least one meta-analysis. Thirty-five (65%) studies were RCTs. Nineteen (35%) of the studies included in the meta-analysis provided IPD. There was a lack of evidence that home safety interventions reduced rates of thermal injuries or poisoning. There was some evidence that interventions may reduce injury rates after adjusting CBA studies for baseline injury rates (IRR 0.89, 95% CI 0.78 to 1.01). Greater reductions in injury rates were found for interventions delivered in the home (IRR 0.75, 95% CI 0.62 to 0.91), and for those interventions not providing safety equipment (IRR 0.78, 95% CI 0.66 to 0.92). Home safety interventions were effective in increasing the proportion of families with safe hot tap water temperatures (OR 1.41, 95% CI 1.07 to 1.86), functional smoke alarms (OR 1.81, 95% CI 1.30 to 2.52), a fire escape plan (OR 2.01, 95% CI 1.45 to 2.77), storing medicines (OR 1.53, 95% CI 1.27 to 1.84) and cleaning products (OR 1.55, 95% CI 1.22 to 1.96) out of reach, having syrup of ipecac (OR 3.34, 95% CI 1.50 to 7.44) or poison control centre numbers accessible (OR 3.30, 95% CI 1.70 to 6.39), having fitted stair gates (OR 1.61, 95% CI 1.19 to 2.17), and having socket covers on unused sockets (OR 2.69, 95% CI 1.46 to 4.96). Interventions providing free, low cost or discounted safety equipment appeared to be more effective in improving some safety practices than those interventions not doing so. There was no consistent evidence that interventions were less effective in families whose children were at greater risk of injury. AUTHORS' CONCLUSIONS: Home safety interventions most commonly provided as one-to-one, face-to-face education, especially with the provision of safety equipment, are effective in increasing a range of safety practices. There is some evidence that such interventions may reduce injury rates, particularly where interventions are provided at home. Conflicting findings regarding interventions providing safety equipment on safety practices and injury outcomes are likely to be explained by two large studies; one clinic-based study provided equipment but did not reduce injury rates and one school-based study did not provide equipment but did demonstrate a significant reduction in injury rates. There was no consistent evidence that home safety education, with or without the provision of safety equipment, was less effective in those participants at greater risk of injury. Further studies are still required to confirm these findings with respect to injury rates.

Extending methods for investigating the relationship between treatment effect and baseline risk from pairwise meta-analysis to network meta-analysis.

Baseline risk is a proxy for unmeasured but important patient-level characteristics, which may be modifiers of treatment effect, and is a potential source of heterogeneity in meta-analysis. Models adjusting for baseline risk have been developed for pairwise meta-analysis using the observed event rate in the placebo arm and taking into account the measurement error in the covariate to ensure that an unbiased estimate of the relationship is obtained. Our objective is to extend these methods to network meta-analysis where it is of interest to adjust for baseline imbalances in the non-intervention group event rate to reduce both heterogeneity and possibly inconsistency. This objective is complicated in network meta-analysis by this covariate being sometimes missing, because of the fact that not all studies in a network may have a non-active intervention arm. A random-effects meta-regression model allowing for inclusion of multi-arm trials and trials without a 'non-intervention' arm is developed. Analyses are conducted within a Bayesian framework using the WinBUGS software. The method is illustrated using two examples: (i) interventions to promote functional smoke alarm ownership by households with children and (ii) analgesics to reduce post-operative morphine consumption following a major surgery. The results showed no evidence of baseline effect in the smoke alarm example, but the analgesics example shows that the adjustment can greatly reduce heterogeneity and improve overall model fit.

Home safety education and provision of safety equipment for injury prevention.

BACKGROUND: In industrialised countries injuries (including burns, poisoning or drowning) are the leading cause of childhood death and steep social gradients exist in child injury mortality and morbidity. The majority of injuries in pre-school children occur at home but there is little meta-analytic evidence that child home safety interventions reduce injury rates or improve a range of safety practices, and little evidence on their effect by social group. OBJECTIVES: We evaluated the effectiveness of home safety education, with or without the provision of low cost, discounted or free equipment (hereafter referred to as home safety interventions), in reducing child injury rates or increasing home safety practices and whether the effect varied by social group. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2009, Issue 2) in The Cochrane Library, MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of Science: Social Sciences Citation Index (SSCI), ISI Web of Science: Conference Proceedings Citation Index- Science (CPCI-S), CINAHL (EBSCO) and DARE (2009, Issue 2) in The Cochrane Library. We also searched websites and conference proceedings and searched the bibliographies of relevant studies and previously published reviews. We contacted authors of included studies as well as relevant organisations. The most recent search for trials was May 2009. SELECTION CRITERIA: Randomised controlled trials (RCTs), non-randomised controlled trials and controlled before and after (CBA) studies where home safety education with or without the provision of safety equipment was provided to those aged 19 years and under, and which reported injury, safety practices or possession of safety equipment. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. We attempted to obtain individual participant level data (IPD) for all included studies and summary data and IPD were simultaneously combined in meta-regressions by social and demographic variables. Pooled incidence rate ratios (IRR) were calculated for injuries which occurred during the studies, and pooled odds ratios were calculated for the uptake of safety equipment or safety practices, with 95% confidence intervals. MAIN RESULTS: Ninety-eight studies, involving 2,605,044 people, are included in this review. Fifty-four studies involving 812,705 people were comparable enough to be included in at least one meta-analysis. Thirty-five (65%) studies were RCTs. Nineteen (35%) of the studies included in the meta-analysis provided IPD.There was a lack of evidence that home safety interventions reduced rates of thermal injuries or poisoning. There was some evidence that interventions may reduce injury rates after adjusting CBA studies for baseline injury rates (IRR 0.89, 95% CI 0.78 to 1.01). Greater reductions in injury rates were found for interventions delivered in the home (IRR 0.75, 95% CI 0.62 to 0.91), and for those interventions not providing safety equipment (IRR 0.78, 95% CI 0.66 to 0.92).Home safety interventions were effective in increasing the proportion of families with safe hot tap water temperatures (OR 1.41, 95% CI 1.07 to 1.86), functional smoke alarms (OR 1.81, 95% CI 1.30 to 2.52), a fire escape plan (OR 2.01, 95% CI 1.45 to 2.77), storing medicines (OR 1.53, 95% CI 1.27 to 1.84) and cleaning products (OR 1.55, 95% CI 1.22 to 1.96) out of reach, having syrup of ipecac (OR 3.34, 95% CI 1.50 to 7.44) or poison control centre numbers accessible (OR 3.30, 95% CI 1.70 to 6.39), having fitted stair gates (OR 1.61, 95% CI 1.19 to 2.17), and having socket covers on unused sockets (OR 2.69, 95% CI 1.46 to 4.96).Interventions providing free, low cost or discounted safety equipment appeared to be more effective in improving some safety practices than those interventions not doing so. There was no consistent evidence that interventions were less effective in families whose children were at greater risk of injury. AUTHORS' CONCLUSIONS: Home safety interventions most commonly provided as one-to-one, face-to-face education, especially with the provision of safety equipment, are effective in increasing a range of safety practices. There is some evidence that such interventions may reduce injury rates, particularly where interventions are provided at home. Conflicting findings regarding interventions providing safety equipment on safety practices and injury outcomes are likely to be explained by two large studies; one clinic-based study provided equipment but did not reduce injury rates and one school-based study did not provide equipment but did demonstrate a significant reduction in injury rates. There was no consistent evidence that home safety education, with or without the provision of safety equipment, was less effective in those participants at greater risk of injury. Further studies are still required to confirm these findings with respect to injury rates.