Search

Alcohol-impaired driving is a formidable public health problem in the United States, claiming the lives of 37 individuals daily in alcohol-related crashes. Alcohol-impaired driving is affected by a multitude of interconnected factors, coupled with long delays between stakeholders’ actions and their impacts, which not only complicate policy-making but also increase the likelihood of unintended consequences. We developed a system dynamics simulation model of drinking and driving behaviors among adolescents and young adults. This was achieved through group model building sessions with a team of multidisciplinary subject matter experts, and a focused literature review. The model was calibrated with data series from multiple sources and replicated the historical trends for male and female individuals aged 15 to 24 from 1982 to 2020. We simulated the model under different scenarios to examine the impact of a wide range of interventions on alcohol-related crash fatalities. We found that interventions vary in terms of their effectiveness in reducing alcohol-related crash fatalities. In addition, although some interventions reduce alcohol-related crash fatalities, some may increase the number of drinkers who drive after drinking. Based on insights from simulation experiments, we combined three interventions and found that the combined strategy may reduce alcohol-related crash fatalities significantly without increasing the number of alcohol-impaired drivers on US roads. Nevertheless, related fatalities plateau over time despite the combined interventions, underscoring the need for new interventions for a sustained decline in alcohol-related crash deaths beyond a few decades. Finally, through model calibration we estimated time delays between actions and their consequences in the system which provide insights for policymakers and activists when designing strategies to reduce alcohol-related crash fatalities.

BackgroundAlthough unhealthy alcohol use is associated with increased morbidity and mortality among people with HIV (PWH), many are ambivalent about engaging in treatment and experience variable responses to treatment. We describe the rationale, aims, and study design for the Financial Incentives, Randomization, with Stepped Treatment (FIRST) Trial, a multi-site randomized controlled efficacy trial.MethodsPWH in care recruited from clinics across the United States who reported unhealthy alcohol use, had a phosphatidylethanol (PEth) >20 ng/mL, and were not engaged in formal alcohol treatment were randomized to integrated contingency management with stepped care versus treatment as usual. The intervention involved two steps; Step 1: Contingency management (n = 5 sessions) with potential rewards based on 1) short-term abstinence; 2) longer-term abstinence; and 3) completion of healthy activities to promote progress in addressing alcohol consumption or conditions potentially impacted by alcohol; Step 2: Addiction physician management (n = 6 sessions) plus motivational enhancement therapy (n = 4 sessions). Participants' treatment was stepped up at week 12 if they lacked evidence of longer-term abstinence. Primary outcome was abstinence at week 24. Secondary outcomes included alcohol consumption (assessed by TLFB and PEth) and the Veterans Aging Cohort Study (VACS) Index 2.0 scores; exploratory outcomes included progress in addressing medical conditions potentially impacted by alcohol. Protocol adaptations due to the COVID-19 pandemic are described.ConclusionsThe FIRST Trial is anticipated to yield insights on the feasibility and preliminary efficacy of integrated contingency management with stepped care to address unhealthy alcohol use among PWH.Clinicaltrialsgov identifier: NCT03089320.

BackgroundFalls are common in older adults and can lead to severe injuries. The Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial cluster-randomized 86 primary care practices across 10 health systems to a multifactorial intervention to prevent fall injuries, delivered by registered nurses trained as falls care managers, or enhanced usual care. STRIDE enrolled 5451 community-dwelling older adults age ≥70 at increased fall injury risk.MethodsWe assessed fall-related outcomes via telephone interviews of participants (or proxies) every 4 months. At baseline, 12 and 24 months, we assessed health-related quality of life (HRQOL) using the EQ-5D-5L and EQ-VAS. We used Poisson models to assess intervention effects on falls, fall-related fractures, fall injuries leading to hospital admission, and fall injuries leading to medical attention. We used hierarchical longitudinal linear models to assess HRQOL.ResultsFor recurrent event models, intervention versus control incidence rate ratios were 0.97 (95% confidence interval [CI], 0.93-1.00; p = 0.048) for falls, 0.93 (95% CI, 0.80-1.08; p = 0.337) for self-reported fractures, 0.89 (95% CI, 0.73-1.07; p = 0.205) for adjudicated fractures, 0.91 (95% CI, 0.77-1.07; p = 0.263) for falls leading to hospital admission, and 0.97 (95% CI, 0.89-1.06; p = 0.477) for falls leading to medical attention. Similar effect sizes (non-significant) were obtained for dichotomous outcomes (e.g., participants with ≥1 events). The difference in least square mean change over time in EQ-5D-5L (intervention minus control) was 0.009 (95% CI, -0.002 to 0.019; p = 0.106) at 12 months and 0.005 (95% CI, -0.006 to 0.015; p = 0.384) at 24 months.ConclusionsAcross a standard set of outcomes typically reported in fall prevention studies, we observed modest improvements, one of which was statistically significant. Future work should focus on patient-, practice-, and organization-level operational strat

BackgroundFalls are common in older adults and can lead to severe injuries. The Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial cluster-randomized 86 primary care practices across 10 health systems to a multifactorial intervention to prevent fall injuries, delivered by registered nurses trained as falls care managers, or enhanced usual care. STRIDE enrolled 5451 community-dwelling older adults age ≥70 at increased fall injury risk.MethodsWe assessed fall-related outcomes via telephone interviews of participants (or proxies) every 4 months. At baseline, 12 and 24 months, we assessed health-related quality of life (HRQOL) using the EQ-5D-5L and EQ-VAS. We used Poisson models to assess intervention effects on falls, fall-related fractures, fall injuries leading to hospital admission, and fall injuries leading to medical attention. We used hierarchical longitudinal linear models to assess HRQOL.ResultsFor recurrent event models, intervention versus control incidence rate ratios were 0.97 (95% confidence interval [CI], 0.93-1.00; p = 0.048) for falls, 0.93 (95% CI, 0.80-1.08; p = 0.337) for self-reported fractures, 0.89 (95% CI, 0.73-1.07; p = 0.205) for adjudicated fractures, 0.91 (95% CI, 0.77-1.07; p = 0.263) for falls leading to hospital admission, and 0.97 (95% CI, 0.89-1.06; p = 0.477) for falls leading to medical attention. Similar effect sizes (non-significant) were obtained for dichotomous outcomes (e.g., participants with ≥1 events). The difference in least square mean change over time in EQ-5D-5L (intervention minus control) was 0.009 (95% CI, -0.002 to 0.019; p = 0.106) at 12 months and 0.005 (95% CI, -0.006 to 0.015; p = 0.384) at 24 months.ConclusionsAcross a standard set of outcomes typically reported in fall prevention studies, we observed modest improvements, one of which was statistically significant. Future work should focus on patient-, practice-, and organization-level operational strat

Background/aimsWhen participants in individually randomized group treatment trials are treated by multiple clinicians or in multiple group treatment sessions throughout the trial, this induces partially nested clusters which can affect the power of a trial. We investigate this issue in the Whole Health Options and Pain Education trial, a three-arm pragmatic, individually randomized clinical trial. We evaluate whether partial clusters due to multiple visits delivered by different clinicians in the Whole Health Team arm and dynamic participant groups due to changing group leaders and/or participants across treatment sessions during treatment delivery in the Primary Care Group Education arm may impact the power of the trial. We also present a Bayesian approach to estimate the intraclass correlation coefficients.MethodsWe present statistical models for each treatment arm of Whole Health Options and Pain Education trial in which power is estimated under different intraclass correlation coefficients and mapping matrices between participants and clinicians or treatment sessions. Power calculations are based on pairwise comparisons. In practice, sample size calculations depend on estimates of the intraclass correlation coefficients at the treatment sessions and clinician levels. To accommodate such complexities, we present a Bayesian framework for the estimation of intraclass correlation coefficients under different participant-to-session and participant-to-clinician mapping scenarios. We simulated continuous outcome data based on various clinical scenarios in Whole Health Options and Pain Education trial using a range of intraclass correlation coefficients and mapping matrices and used Gibbs samplers with conjugate priors to obtain posteriors of the intraclass correlation coefficients under those different scenarios. Posterior means and medians and their biases are calculated for the intraclass correlation coefficients to evaluate the operating characteristics of the Bayes

BackgroundThere is an increasing burden of cardiovascular disease, including coronary artery disease (CAD) and heart failure (HF), among women Veterans. Clinical practice guidelines recommend multiple pharmacotherapies that can reduce risk of mortality and adverse cardiovascular outcomes.ObjectiveTo determine if there are disparities in the use of guideline-directed medical therapy by gender among Veterans with incident CAD and HF.DesignRetrospective.ParticipantsVeterans (934,504; 87.8% men and 129,469; 12.2% women) returning from Operations Enduring Freedom, Iraqi Freedom, and New Dawn.Main measuresDifferences by gender in the prescription of Class 1, Level of Evidence A guideline-directed medical therapy among patients who developed incident CAD and HF at 30 days, 90 days, and 12 months after diagnosis. For CAD, medications included statins and antiplatelet therapy. For HF, medications included beta-blockers and renin-angiotensin-aldosterone system inhibitors.Key resultsOverall, women developed CAD and HF at a younger average age than men (mean 45.8 vs. 47.7 years, p<0.001; and 43.7 vs. 45.4 years, p<0.02, respectively). In the 12 months following a diagnosis of incident CAD, the odds of a woman receiving a prescription for at least one CAD drug was 0.85 (95% confidence interval [CI], 0.68-1.08) compared to men. In the 12 months following a diagnosis of incident HF, the odds of a woman receiving at least one HF medication was 0.54 (95% CI, 0.37-0.79) compared to men.ConclusionsDespite guideline recommendations, young women Veterans have approximately half the odds of being prescribed guideline-directed medical therapy within 1-year after a diagnosis of HF. These results highlight the need to develop targeted strategies to minimize gender disparities in CVD care to prevent adverse outcomes in this young and growing population.

Renalase is a secreted flavoprotein with anti-inflammatory and pro-cell survival properties. COVID-19 is associated with disordered inflammation and apoptosis. We hypothesized that blood renalase levels would correspond to severe COVID-19 and survival. In this retrospective cohort study, clinicopathologic data and blood samples were collected from hospitalized COVID-19 subjects (March-June 2020) at a single institution tertiary hospital. Plasma renalase and cytokine levels were measured and clinical data abstracted from health records. Of 3,450 COVID-19 patients, 458 patients were enrolled. Patients were excluded if <18 years, or opted out of research. The primary composite outcome was intubation or death within 180 days. Secondary outcomes included mortality alone, intensive care unit admission, use of vasopressors, and CPR. Enrolled patients had mean age 64 years (SD±17), were 53% males, and 48% non-whites. Mean renalase levels was 14,108·4 ng/ml (SD±8,137 ng/ml). Compared to patients with high renalase, those with low renalase (< 8,922 ng/ml) were more likely to present with hypoxia, increased ICU admission (54% vs. 33%, p < 0.001), and cardiopulmonary resuscitation (10% vs. 4%, p = 0·023). In Cox proportional hazard model, every 1000 ng/ml increase in renalase decreased the risk of death or intubation by 5% (HR 0·95; 95% CI 0·91-0·98) and increased survival alone by 6% (HR 0·95; CI 0·90-0·98), after adjusting for socio-demographics, initial disease severity, comorbidities and inflammation. Patients with high renalase-low IL-6 levels had the best survival compared to other groups (p = 0·04). Renalase was independently associated with reduced intubation and mortality in hospitalized COVID-19 patients. Future studies should assess the pathophysiological relevance of renalase in COVID-19 disease.

Background/objectivesIn the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) study, a multifactorial intervention was associated with a nonsignificant 8% reduction in time to first serious fall injury but a significant 10% reduction in time to first self-reported fall injury relative to enhanced usual care. The effect of the intervention on other outcomes important to patients has not yet been reported. We aimed to evaluate the effect of the intervention on patient well-being including concern about falling, anxiety, depression, physical function, and disability.DesignPragmatic cluster-randomized trial of 5,451 community-living persons at high risk for serious fall injuries.SettingA total of 86 primary care practices within 10 U.S. healthcare systems.ParticipantsA random subsample of 743 persons aged 75 and older.MeasurementsThe well-being measures, assessed at baseline, 12 months, and 24 months, included a modified version of the Fall Efficacy Scale, Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety and depression scales, and Late-Life Function and Disability Instrument.ResultsParticipants in the intervention (n = 384) and control groups (n = 359) were comparable in age: mean (standard deviation) of 81.9 (4.7) versus 81.8 (5.0) years. Mean scores were similar between groups at 12 and 24 months for concern about falling, physical function, and disability, whereas the intervention group's mean scores on anxiety and depression were .7 points lower (i.e., better) at 12 months and .6 to .8 points lower at 24 months. For each of these outcomes, differences between the groups' adjusted least square mean changes from baseline to 12 and 24 months, respectively, were quantitatively small. The overall difference in means between groups over 2 years was statistically significant only for depression, favoring the intervention: -1.19 (99% confidence interval, -2.36 to -.02), with 3.5 points representing a minimally important differe

Background/objectivesIn the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) study, a multifactorial intervention was associated with a nonsignificant 8% reduction in time to first serious fall injury but a significant 10% reduction in time to first self-reported fall injury relative to enhanced usual care. The effect of the intervention on other outcomes important to patients has not yet been reported. We aimed to evaluate the effect of the intervention on patient well-being including concern about falling, anxiety, depression, physical function, and disability.DesignPragmatic cluster-randomized trial of 5,451 community-living persons at high risk for serious fall injuries.SettingA total of 86 primary care practices within 10 U.S. healthcare systems.ParticipantsA random subsample of 743 persons aged 75 and older.MeasurementsThe well-being measures, assessed at baseline, 12 months, and 24 months, included a modified version of the Fall Efficacy Scale, Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety and depression scales, and Late-Life Function and Disability Instrument.ResultsParticipants in the intervention (n = 384) and control groups (n = 359) were comparable in age: mean (standard deviation) of 81.9 (4.7) versus 81.8 (5.0) years. Mean scores were similar between groups at 12 and 24 months for concern about falling, physical function, and disability, whereas the intervention group's mean scores on anxiety and depression were .7 points lower (i.e., better) at 12 months and .6 to .8 points lower at 24 months. For each of these outcomes, differences between the groups' adjusted least square mean changes from baseline to 12 and 24 months, respectively, were quantitatively small. The overall difference in means between groups over 2 years was statistically significant only for depression, favoring the intervention: -1.19 (99% confidence interval, -2.36 to -.02), with 3.5 points representing a minimally important differe

Background/objectivesAlthough several approaches have been developed to provide comprehensive care for persons living with dementia (PWD) and their family or friend caregivers, the relative effectiveness and cost effectiveness of community-based dementia care (CBDC) versus health system-based dementia care (CBDC) and the effectiveness of both approaches compared with usual care (UC) are unknown.DesignPragmatic randomized three-arm superiority trial. The unit of randomization is the PWD/caregiver dyad.SettingFour clinical trial sites (CTSs) based in academic and clinical health systems.ParticipantsA total of 2,150 English- or Spanish-speaking PWD who are not receiving hospice or residing in a nursing home and their caregivers.InterventionsEighteen months of (1) HSDC provided by a nurse practitioner or physician's assistant dementia care specialist who works within the health system, or (2) CBDC provided by a social worker or nurse care consultant who works at a community-based organization, or (3) UC with as needed referral to the Alzheimer's Association Helpline.MeasurementsPrimary outcomes: PWD behavioral symptoms and caregiver distress as measured by the Neuropsychiatric Inventory Questionnaire (NPI-Q) Severity and Modified Caregiver Strain Index scales.Secondary outcomesNPI-Q Distress, caregiver unmet needs and confidence, and caregiver depressive symptoms. Tertiary outcomes: PWD long-term nursing home placement rates, caregiver-reported PWD functional status, cognition, goal attainment, "time spent at home," Dementia Burden Scale-Caregiver, a composite measure of clinical benefit, Quality of Life of persons with dementia, Positive Aspects of Caregiving, and cost effectiveness using intervention costs and Medicare claims.ResultsThe results will be reported in the spring of 2024.ConclusionD-CARE will address whether emphasis on clinical support and tighter integration with other medical services has greater benefit than emphasis on social support that is tied more

BackgroundInjuries from falls are major contributors to complications and death in older adults. Despite evidence from efficacy trials that many falls can be prevented, rates of falls resulting in injury have not declined.MethodsWe conducted a pragmatic, cluster-randomized trial to evaluate the effectiveness of a multifactorial intervention that included risk assessment and individualized plans, administered by specially trained nurses, to prevent fall injuries. A total of 86 primary care practices across 10 health care systems were randomly assigned to the intervention or to enhanced usual care (the control) (43 practices each). The participants were community-dwelling adults, 70 years of age or older, who were at increased risk for fall injuries. The primary outcome, assessed in a time-to-event analysis, was the first serious fall injury, adjudicated with the use of participant report, electronic health records, and claims data. We hypothesized that the event rate would be lower by 20% in the intervention group than in the control group.ResultsThe demographic and baseline characteristics of the participants were similar in the intervention group (2802 participants) and the control group (2649 participants); the mean age was 80 years, and 62.0% of the participants were women. The rate of a first adjudicated serious fall injury did not differ significantly between the groups, as assessed in a time-to-first-event analysis (events per 100 person-years of follow-up, 4.9 in the intervention group and 5.3 in the control group; hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P = 0.25). The rate of a first participant-reported fall injury was 25.6 events per 100 person-years of follow-up in the intervention group and 28.6 events per 100 person-years of follow-up in the control group (hazard ratio, 0.90; 95% CI, 0.83 to 0.99; P = 0.004). The rates of hospitalization or death were similar in the two groups.ConclusionsA multifactorial intervention, administere

Introduction: Promoting emergency medicine (EM) clinical trials research remains a priority. To characterize the status of clinical EM research, this study assessed trial quality, funding source, and publication of EM clinical trials and compared EM and non-EM trials on these key metrics. We also examined the volume of EM trials and their subspecialty areas.Methods: We abstracted data from ClinicalTrials.gov (February 2000 - September 2013) and used individual study National Clinical Trial numbers to identify published trials (January 2007 - September 2016). We used descriptive statistics and chi-square tests to examine study characteristics by EM and non-EM status, and Kaplan-Meier curves and log-rank tests to compare time to publication of completed EM and non-EM studies.Results: We found 638 interventional EM trials and 59,512 non-EM interventional trials conducted in the United States between February 2000 and September 2013, registered on ClinicalTrials.gov. EM studies were significantly less likely than non-EM studies to be National Institutes of Health-funded or to evaluate a drug or biologic. However, EM studies had significantly larger sample sizes, and were significantly more likely to use randomization and blinding. Overall, 34.3% of EM and 26.0% of non-EM studies were published in peer-reviewed journals. By subspecialty, more EM trials concerned medical/surgical and psychiatric/neurological conditions than trauma.Conclusion: Although EM studies were less likely to have received federal or industry funding, and the EM portfolio consisted of only 638 trials over the 14-year study period, the quality of EM trials surpassed that of non-EM trials, based on indices such as randomization and blinding. This novel finding bodes well for the future of clinical EM research, as does the higher proportion of published EM than non-EM trials. Our study also revealed that trauma studies were under-represented among EM studies. Periodic assessment of EM trials with the m

BackgroundInjuries from falls are major contributors to complications and death in older adults. Despite evidence from efficacy trials that many falls can be prevented, rates of falls resulting in injury have not declined.MethodsWe conducted a pragmatic, cluster-randomized trial to evaluate the effectiveness of a multifactorial intervention that included risk assessment and individualized plans, administered by specially trained nurses, to prevent fall injuries. A total of 86 primary care practices across 10 health care systems were randomly assigned to the intervention or to enhanced usual care (the control) (43 practices each). The participants were community-dwelling adults, 70 years of age or older, who were at increased risk for fall injuries. The primary outcome, assessed in a time-to-event analysis, was the first serious fall injury, adjudicated with the use of participant report, electronic health records, and claims data. We hypothesized that the event rate would be lower by 20% in the intervention group than in the control group.ResultsThe demographic and baseline characteristics of the participants were similar in the intervention group (2802 participants) and the control group (2649 participants); the mean age was 80 years, and 62.0% of the participants were women. The rate of a first adjudicated serious fall injury did not differ significantly between the groups, as assessed in a time-to-first-event analysis (events per 100 person-years of follow-up, 4.9 in the intervention group and 5.3 in the control group; hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P = 0.25). The rate of a first participant-reported fall injury was 25.6 events per 100 person-years of follow-up in the intervention group and 28.6 events per 100 person-years of follow-up in the control group (hazard ratio, 0.90; 95% CI, 0.83 to 0.99; P = 0.004). The rates of hospitalization or death were similar in the two groups.ConclusionsA multifactorial intervention, administere

Introduction: Promoting emergency medicine (EM) clinical trials research remains a priority. To characterize the status of clinical EM research, this study assessed trial quality, funding source, and publication of EM clinical trials and compared EM and non-EM trials on these key metrics. We also examined the volume of EM trials and their subspecialty areas.Methods: We abstracted data from ClinicalTrials.gov (February 2000 - September 2013) and used individual study National Clinical Trial numbers to identify published trials (January 2007 - September 2016). We used descriptive statistics and chi-square tests to examine study characteristics by EM and non-EM status, and Kaplan-Meier curves and log-rank tests to compare time to publication of completed EM and non-EM studies.Results: We found 638 interventional EM trials and 59,512 non-EM interventional trials conducted in the United States between February 2000 and September 2013, registered on ClinicalTrials.gov. EM studies were significantly less likely than non-EM studies to be National Institutes of Health-funded or to evaluate a drug or biologic. However, EM studies had significantly larger sample sizes, and were significantly more likely to use randomization and blinding. Overall, 34.3% of EM and 26.0% of non-EM studies were published in peer-reviewed journals. By subspecialty, more EM trials concerned medical/surgical and psychiatric/neurological conditions than trauma.Conclusion: Although EM studies were less likely to have received federal or industry funding, and the EM portfolio consisted of only 638 trials over the 14-year study period, the quality of EM trials surpassed that of non-EM trials, based on indices such as randomization and blinding. This novel finding bodes well for the future of clinical EM research, as does the higher proportion of published EM than non-EM trials. Our study also revealed that trauma studies were under-represented among EM studies. Periodic assessment of EM trials with the m

Background/objectivesAlthough several approaches have been developed to provide comprehensive care for persons living with dementia (PWD) and their family or friend caregivers, the relative effectiveness and cost effectiveness of community-based dementia care (CBDC) versus health system-based dementia care (CBDC) and the effectiveness of both approaches compared with usual care (UC) are unknown.DesignPragmatic randomized three-arm superiority trial. The unit of randomization is the PWD/caregiver dyad.SettingFour clinical trial sites (CTSs) based in academic and clinical health systems.ParticipantsA total of 2,150 English- or Spanish-speaking PWD who are not receiving hospice or residing in a nursing home and their caregivers.InterventionsEighteen months of (1) HSDC provided by a nurse practitioner or physician's assistant dementia care specialist who works within the health system, or (2) CBDC provided by a social worker or nurse care consultant who works at a community-based organization, or (3) UC with as needed referral to the Alzheimer's Association Helpline.MeasurementsPrimary outcomes: PWD behavioral symptoms and caregiver distress as measured by the Neuropsychiatric Inventory Questionnaire (NPI-Q) Severity and Modified Caregiver Strain Index scales.Secondary outcomesNPI-Q Distress, caregiver unmet needs and confidence, and caregiver depressive symptoms. Tertiary outcomes: PWD long-term nursing home placement rates, caregiver-reported PWD functional status, cognition, goal attainment, "time spent at home," Dementia Burden Scale-Caregiver, a composite measure of clinical benefit, Quality of Life of persons with dementia, Positive Aspects of Caregiving, and cost effectiveness using intervention costs and Medicare claims.ResultsThe results will be reported in the spring of 2024.ConclusionD-CARE will address whether emphasis on clinical support and tighter integration with other medical services has greater benefit than emphasis on social support that is tied more

BackgroundInjuries from falls are major contributors to complications and death in older adults. Despite evidence from efficacy trials that many falls can be prevented, rates of falls resulting in injury have not declined.MethodsWe conducted a pragmatic, cluster-randomized trial to evaluate the effectiveness of a multifactorial intervention that included risk assessment and individualized plans, administered by specially trained nurses, to prevent fall injuries. A total of 86 primary care practices across 10 health care systems were randomly assigned to the intervention or to enhanced usual care (the control) (43 practices each). The participants were community-dwelling adults, 70 years of age or older, who were at increased risk for fall injuries. The primary outcome, assessed in a time-to-event analysis, was the first serious fall injury, adjudicated with the use of participant report, electronic health records, and claims data. We hypothesized that the event rate would be lower by 20% in the intervention group than in the control group.ResultsThe demographic and baseline characteristics of the participants were similar in the intervention group (2802 participants) and the control group (2649 participants); the mean age was 80 years, and 62.0% of the participants were women. The rate of a first adjudicated serious fall injury did not differ significantly between the groups, as assessed in a time-to-first-event analysis (events per 100 person-years of follow-up, 4.9 in the intervention group and 5.3 in the control group; hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P = 0.25). The rate of a first participant-reported fall injury was 25.6 events per 100 person-years of follow-up in the intervention group and 28.6 events per 100 person-years of follow-up in the control group (hazard ratio, 0.90; 95% CI, 0.83 to 0.99; P = 0.004). The rates of hospitalization or death were similar in the two groups.ConclusionsA multifactorial intervention, administere

AimsTo test whether a long-acting GLP-1 receptor agonist would improve glucose control in patients with type 1 diabetes (T1D) and to determine whether the presence of residual beta cell function would affect the response. In addition, we sought to determine whether the drug would affect beta cell function.MethodsWe performed a randomized placebo-controlled trial of exenatide extended release (ER) in participants with T1D with and without detectable levels of C-peptide. Seventy-nine participants were randomized to exenatide ER 2 mcg weekly, or placebo, stratified by the presence or absence of detectable C-peptide levels. The primary outcome was the difference in glycated haemoglobin (HbA1c) levels at 24 weeks. Participants were followed for another 6 months off study drug.ResultsAt week 24, the time of the primary outcome, the least squares (LS) mean HbA1c level was 7.76% (95% confidence interval [CI] 7.42, 8.10) in the exenatide ER group versus 8.0% (95% CI 7.64, 8.35) in the placebo group (P = 0.08). At week 12 the LS mean HbA1c levels were 7.71% (95% CI 7.37, 8.05) in the exenatide ER group versus 8.05% (95% CI 7.7, 8.4) in the placebo group (P = 0.01). The improvement at week 12 was driven mainly by those with detectable levels of C-peptide. Those treated with exenatide ER lost weight at 12 and 24 weeks compared to those treated with placebo (P <0.001 and P = 0.007). The total insulin dose was lower, but not when corrected for body weight, and was not affected by residual insulin production. Adverse events were more frequent with exenatide ER, but hypoglycaemia was not increased.ConclusionTreatment with exenatide ER may have short-term benefits in some individuals with T1D who are overweight or who have detectable levels of C-peptide, but short-term improvements were not sustained.

Background:Fall injuries are a major cause of morbidity and mortality among older adults. We describe the design of a pragmatic trial to compare the effectiveness of an evidence-based, patient-centered multifactorial fall injury prevention strategy to an enhanced usual care. Methods:Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) is a 40-month cluster-randomized, parallel-group, superiority, pragmatic trial being conducted at 86 primary care practices in 10 health care systems across United States. The 86 practices were randomized to intervention or control group using covariate-based constrained randomization, stratified by health care system. Participants are community-living persons, ≥70 years, at increased risk for serious fall injuries. The intervention is a comanagement model in which a nurse Falls Care Manager performs multifactorial risk assessments, develops individualized care plans, which include surveillance, follow-up evaluation, and intervention strategies. Control group receives enhanced usual care, with clinicians and patients receiving evidence-based information on falls prevention. Primary outcome is serious fall injuries, operationalized as those leading to medical attention (nonvertebral fractures, joint dislocation, head injury, lacerations, and other major sequelae). Secondary outcomes include all fall injuries, all falls, and well-being (concern for falling; anxiety and depressive symptoms; physical function and disability). Target sample size was 5,322 participants to provide 90% power to detect 20% reduction in primary outcome rate relative to control. Results:Trial enrolled 5,451 subjects in 20 months. Intervention and follow-up are ongoing. Conclusions:The findings of the STRIDE study will have important clinical and policy implications for the prevention of fall injuries in older adults.

Background:Fall injuries are a major cause of morbidity and mortality among older adults. We describe the design of a pragmatic trial to compare the effectiveness of an evidence-based, patient-centered multifactorial fall injury prevention strategy to an enhanced usual care. Methods:Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) is a 40-month cluster-randomized, parallel-group, superiority, pragmatic trial being conducted at 86 primary care practices in 10 health care systems across United States. The 86 practices were randomized to intervention or control group using covariate-based constrained randomization, stratified by health care system. Participants are community-living persons, ≥70 years, at increased risk for serious fall injuries. The intervention is a comanagement model in which a nurse Falls Care Manager performs multifactorial risk assessments, develops individualized care plans, which include surveillance, follow-up evaluation, and intervention strategies. Control group receives enhanced usual care, with clinicians and patients receiving evidence-based information on falls prevention. Primary outcome is serious fall injuries, operationalized as those leading to medical attention (nonvertebral fractures, joint dislocation, head injury, lacerations, and other major sequelae). Secondary outcomes include all fall injuries, all falls, and well-being (concern for falling; anxiety and depressive symptoms; physical function and disability). Target sample size was 5,322 participants to provide 90% power to detect 20% reduction in primary outcome rate relative to control. Results:Trial enrolled 5,451 subjects in 20 months. Intervention and follow-up are ongoing. Conclusions:The findings of the STRIDE study will have important clinical and policy implications for the prevention of fall injuries in older adults.

This paper examined neurocognitive functioning and its relationship to behavior treatment response among youth with Tourette's Disorder (TD) in a large randomized controlled trial. Participants diagnosed with TD completed a brief neurocognitive battery assessing inhibitory functions, working memory, and habit learning pre- and post-treatment with behavior therapy (CBIT, Comprehensive Behavioral Intervention for Tics) or psychoeducation plus supportive therapy (PST). At baseline, youth with tics and Attention Deficit Hyperactivity Disorder (ADHD) exhibited some evidence of impaired working memory and simple motor inhibition relative to youth with tics without ADHD. Additionally, a small negative association was found between antipsychotic medications and youth's performance speed. Across treatment groups, greater baseline working memory and aspects of inhibitory functioning were associated with a positive treatment response; no between-group differences in neurocognitive functioning at post-treatment were identified. Within the behavior therapy group, pre-treatment neurocognitive status did not predict outcome, nor was behavior therapy associated significant change in neurocognitive functioning post-treatment. Findings suggest that co-occurring ADHD is associated with some impairments in neurocognitive functioning in youth with Tourette's Disorder. While neurocognitive predictors of behavior therapy were not found, participants who received behavior therapy exhibited significantly reduced tic severity without diminished cognitive functioning.

BackgroundPhysicians "purchase" many health care services on behalf of patients yet remain largely unaware of the costs of these services. Electronic health record (EHR) cost displays may facilitate cost-conscious ordering of health services.ObjectiveTo determine whether displaying hospital lab and imaging order costs is associated with changes in the number and costs of orders placed.DesignQuasi-experimental study.ParticipantsAll patients with inpatient or observation encounters across a multi-site health system from April 2013 to October 2015.InterventionDisplay of order costs, based on Medicare fee schedules, in the EHR for 1032 lab tests and 1329 imaging tests.Main measuresOutcomes for both lab and imaging orders were (1) whether an order was placed during a hospital encounter, (2) whether an order was placed on a given patient-day, (3) number of orders placed per patient-day, and (4) cost of orders placed per patient-day.Key resultsDuring the lab and imaging study periods, there were 248,214 and 258,267 encounters, respectively. Cost display implementation was associated with a decreased odds of any lab or imaging being ordered during the encounter (lab adjusted odds ratio [AOR] = 0.97, p = .01; imaging AOR = 0.97, p < .001), a decreased odds of any lab or imaging being ordered on a given patient-day (lab AOR = 0.95, p < .001; imaging AOR = 0.97, p < .001), a decreased number of lab or imaging orders on patient-days with orders (lab adjusted count ratio = 0.93, p < .001; imaging adjusted count ratio = 0.98, p < .001), and a decreased cost of lab orders and increased cost of imaging orders on patient-days with orders (lab adjusted cost ratio = 0.93, p < .001; imaging adjusted cost ratio = 1.02, p = .003). Overall, the intervention was associated with an 8.5 and 1.7% reduction in lab and imaging costs per patient-day, respectively.ConclusionsDisplaying costs within EHR ordering screens was associated with

ObjectiveTo examine moderators and predictors of response to behavior therapy for tics in children and adults with Tourette syndrome and chronic tic disorders.MethodsData from 2 10-week, multisite studies (1 in children and 1 in adults; total n = 248) comparing comprehensive behavioral intervention for tics (CBIT) to psychoeducation and supportive therapy (PST) were combined for moderator analyses. Participants (177 male, 71 female) had a mean age of 21.5 ± 13.9 years (range 9-69). Demographic and clinical characteristics, baseline tic-suppressing medication, and co-occurring psychiatric disorders were tested as potential moderators for CBIT vs PST or predictors of outcome regardless of treatment assignment. Main outcomes measures were the Yale Global Tic Severity Scale Total Tic score and the Clinical Global Impression-Improvement score assessed by masked evaluators.ResultsThe presence of tic medication significantly moderated response to CBIT vs PST (p = 0.01). Participants showed tic reduction after CBIT regardless of tic medication status, but only participants receiving tic medication showed reduction of tics after PST. Co-occurring psychiatric disorders, age, sex, family functioning, tic characteristics, and treatment expectancy did not moderate response. Across both treatments, greater tic severity (p = 0.005) and positive participant expectancy (p = 0.01) predicted greater tic improvement. Anxiety disorders (p = 0.042) and premonitory urge severity (p = 0.005) predicted lower tic reduction.ConclusionsPresence of co-occurring attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, or anxiety disorders did not moderate response to CBIT. Although participants on tic medication showed improvement after CBIT, the difference between CBIT and PST was greater for participants who were not on tic-suppressing medication.Clinicaltrialsgov identifiersThe child and adult CBIT studies are listed on clinical trials.gov (NCT00218777 and NCT00231985, respect

Hyperactivity, impulsiveness, and distractibility are common problems in children with autism spectrum disorder (ASD). Extended-release guanfacine is approved for children with attention deficit hyperactivity disorder but not well studied in ASD.In a multisite, randomized clinical trial, extended-release guanfacine was compared with placebo in children with ASD accompanied by hyperactivity, impulsiveness, and distractibility.Sixty-two subjects (boys, N=53; girls, N=9; mean age=8.5 years [SD=2.25]) were randomly assigned to guanfacine (N=30) or placebo (N=32) for 8 weeks. The guanfacine group showed a 43.6% decline in scores on the Aberrant Behavior Checklist-hyperactivity subscale (least squares mean from 34.2 to 19.3) compared with a 13.2% decrease in the placebo group (least squares mean from 34.2 to 29.7; effect size=1.67). The rate of positive response (much improved or very much improved on the Clinical Global Impression-Improvement scale) was 50% (15 of 30) for guanfacine compared with 9.4% (3 of 32) for placebo. A brief cognitive battery tapping working memory and motor planning showed no group differences before or after 8 weeks of treatment. The modal dose of guanfacine at week 8 was 3 mg/day (range: 1-4 mg/day), and the modal dose was 3 mg/day (range: 2-4 mg/day) for placebo. Four guanfacine-treated subjects (13.3%) and four placebo subjects (12.5%) exited the study before week 8. The most common adverse events included drowsiness, fatigue, and decreased appetite. There were no significant changes on ECG in either group. For subjects in the guanfacine group, blood pressure declined in the first 4 weeks, with return nearly to baseline by endpoint (week 8). Pulse rate showed a similar pattern but remained lower than baseline at endpoint.Extended-release guanfacine appears to be safe and effective for reducing hyperactivity, impulsiveness, and distractibility in children with ASD.

Hyperactivity, impulsiveness, and distractibility are common problems in children with autism spectrum disorder (ASD). Extended-release guanfacine is approved for children with attention deficit hyperactivity disorder but not well studied in ASD.In a multisite, randomized clinical trial, extended-release guanfacine was compared with placebo in children with ASD accompanied by hyperactivity, impulsiveness, and distractibility.Sixty-two subjects (boys, N=53; girls, N=9; mean age=8.5 years [SD=2.25]) were randomly assigned to guanfacine (N=30) or placebo (N=32) for 8 weeks. The guanfacine group showed a 43.6% decline in scores on the Aberrant Behavior Checklist-hyperactivity subscale (least squares mean from 34.2 to 19.3) compared with a 13.2% decrease in the placebo group (least squares mean from 34.2 to 29.7; effect size=1.67). The rate of positive response (much improved or very much improved on the Clinical Global Impression-Improvement scale) was 50% (15 of 30) for guanfacine compared with 9.4% (3 of 32) for placebo. A brief cognitive battery tapping working memory and motor planning showed no group differences before or after 8 weeks of treatment. The modal dose of guanfacine at week 8 was 3 mg/day (range: 1-4 mg/day), and the modal dose was 3 mg/day (range: 2-4 mg/day) for placebo. Four guanfacine-treated subjects (13.3%) and four placebo subjects (12.5%) exited the study before week 8. The most common adverse events included drowsiness, fatigue, and decreased appetite. There were no significant changes on ECG in either group. For subjects in the guanfacine group, blood pressure declined in the first 4 weeks, with return nearly to baseline by endpoint (week 8). Pulse rate showed a similar pattern but remained lower than baseline at endpoint.Extended-release guanfacine appears to be safe and effective for reducing hyperactivity, impulsiveness, and distractibility in children with ASD.

OBJECTIVE: The childhood obesity epidemic has been accompanied by an increasing prevalence of type 2 diabetes (T2D), particularly in minority children. Twenty to thirty percent of obese youth have “prediabetes,” a precursor to diabetes marked by insulin resistance, b-cell dysfunction, and impaired glucose tolerance. The Diabetes Prevention Programdemonstrated that T2D could be prevented/delayed by intensive lifestyle modification in adults with prediabetes, but efficacy of similar interventions in youth has not been established. Therefore, we evaluated the effects of the Bright Bodies (BB) Healthy Lifestyle Program on 2-h oral glucose tolerance test (OGTT) glucose in comparison with adolescents receiving standard of care. RESEARCH DESIGN AND METHODS: A parallel-group randomized controlled trial comparing BB with standard clinical care (CC) in obese adolescents (10–16 years old, Tanner stage >2) with elevated OGTT 2-h blood glucose (130–199 mg/dL) from a racially/ethnically diverse population. OGTTs, including cardiovascular and anthropometric assessments, were conducted at baseline and 6 months. Children attended BB twice per week for exercise and nutrition/behavior modification, and the CC group received CC from their pediatrician. Primary outcome was change in 2-h OGTT glucose and percentage conversion from elevated 2-h blood glucose to nonelevated (,130 mg/dL) 2-h blood glucose. Changes in outcomes were compared between groups using an ANCOVA, with adjustment for baseline outcome and multiple imputation for missing data. RESULTS: Reductions in 2-h glucose weremore favorable in BB compared with CC (227.2 vs. 210.1 mg/dL; difference = 217.1, 95% CI; P = 0.005). Moreover, greater conversion to ,130 mg/dL 2-h glucose occurred in BB than CC (P = 0.003), and other insulin sensitivity indices were significantly improved. CONCLUSIONS: Compared with standard of care, the Yale BB Program is amore effective means of reducing the risk of T2D in obese adolescents with elev

Introduction: To perform a meta-analysis identifying studies instituting protocolized hemodynamic optimization in the emergency department (ED) for patients with severe sepsis and septic shock.Methods: We modeled the structure of this analysis after the QUORUM and MOOSE published recommendations for scientific reviews. A computer search to identify articles was performed from 1980 to present. Studies included for analysis were adult controlled trials implementing protocolizedhemodynamic optimization in the ED for patients with severe sepsis and septic shock. Primary outcome data was extracted and analyzed by 2 reviewers with the primary endpoint being short-term mortality reported either as 28-day or in-hospital mortality.Results: We identified 1,323 articles with 65 retrieved for review. After application of inclusion and exclusion criteria 25 studies (15 manuscripts, 10 abstracts) were included for analysis (n¼9597). The mortality rate for patients receiving protocolized hemodynamic optimization (n¼6031) was 25.8% contrasted to 41.6% in control groups (n¼3566, p,0.0001).Conclusion: Protocolized hemodynamic optimization in the ED for patients with severe sepsis and septic shock appears to reduce mortality. [West J Emerg Med. 2014;15(1):51–59.]

Introduction: To perform a meta-analysis identifying studies instituting protocolized hemodynamic optimization in the emergency department (ED) for patients with severe sepsis and septic shock.Methods: We modeled the structure of this analysis after the QUORUM and MOOSE published recommendations for scientific reviews. A computer search to identify articles was performed from 1980 to present. Studies included for analysis were adult controlled trials implementing protocolizedhemodynamic optimization in the ED for patients with severe sepsis and septic shock. Primary outcome data was extracted and analyzed by 2 reviewers with the primary endpoint being short-term mortality reported either as 28-day or in-hospital mortality.Results: We identified 1,323 articles with 65 retrieved for review. After application of inclusion and exclusion criteria 25 studies (15 manuscripts, 10 abstracts) were included for analysis (n¼9597). The mortality rate for patients receiving protocolized hemodynamic optimization (n¼6031) was 25.8% contrasted to 41.6% in control groups (n¼3566, p,0.0001).Conclusion: Protocolized hemodynamic optimization in the ED for patients with severe sepsis and septic shock appears to reduce mortality. [West J Emerg Med. 2014;15(1):51–59.]

Introduction: To perform a meta-analysis identifying studies instituting protocolized hemodynamic optimization in the emergency department (ED) for patients with severe sepsis and septic shock.Methods: We modeled the structure of this analysis after the QUORUM and MOOSE published recommendations for scientific reviews. A computer search to identify articles was performed from 1980 to present. Studies included for analysis were adult controlled trials implementing protocolizedhemodynamic optimization in the ED for patients with severe sepsis and septic shock. Primary outcome data was extracted and analyzed by 2 reviewers with the primary endpoint being short-term mortality reported either as 28-day or in-hospital mortality.Results: We identified 1,323 articles with 65 retrieved for review. After application of inclusion and exclusion criteria 25 studies (15 manuscripts, 10 abstracts) were included for analysis (n¼9597). The mortality rate for patients receiving protocolized hemodynamic optimization (n¼6031) was 25.8% contrasted to 41.6% in control groups (n¼3566, p,0.0001).Conclusion: Protocolized hemodynamic optimization in the ED for patients with severe sepsis and septic shock appears to reduce mortality. [West J Emerg Med. 2014;15(1):51–59.]

ObjectiveTo compare three statistical strategies for classifying positive treatment response based on a dimensional measure (Yale Global Tic Severity Scale [YGTSS]) and a categorical measure (Clinical Global Impression-Improvement [CGI-I] scale).MethodSubjects (N=232; 69.4% male; ages 9-69years) with Tourette syndrome or chronic tic disorder participated in one of two 10-week, randomized controlled trials comparing behavioral treatment to supportive therapy. The YGTSS and CGI-I were rated by clinicians blind to treatment assignment. We examined the percent reduction in the YGTSS-Total Tic Score (TTS) against Much Improved or Very Much Improved on the CGI-I, computed a signal detection analysis (SDA) and built a mixture model to classify dimensional response based on the change in the YGTSS-TTS.ResultsA 25% decrease on the YGTSS-TTS predicted positive response on the CGI-I during the trial. The SDA showed that a 25% reduction in the YGTSS-TTS provided optimal sensitivity (87%) and specificity (84%) for predicting positive response. Using a mixture model without consideration of the CGI-I, the dimensional response was defined by 23% (or greater) reduction on the YGTSS-TTS. The odds ratio (OR) of positive response (OR=5.68, 95% CI=[2.99, 10.78]) on the CGI-I for behavioral intervention was greater than the dimensional response (OR=2.86, 95% CI=[1.65, 4.99]).ConclusionA 25% reduction on the YGTSS-TTS is highly predictive of positive response by all three analytic methods. For trained raters, however, tic severity alone does not drive the classification of positive response. Clinicaltrials.gov identifiers: NCT00218777; NCT00231985.

OBJECTIVE: To determine if beneficial effects of a weight-management program could be sustained for up to 24 months in a randomized trial in an ethnically diverse obese population. PATIENTS AND METHODS: There were 209 obese children (BMI95th percentile), ages 8 to 16 of mixed ethnic backgrounds randomly assigned to the intensive lifestyle intervention or clinic control group. The control group received counseling every 6 months, and the intervention group received a family-based program, which included exercise, nutrition, and behavior modification. Lifestyle intervention sessions occurred twice weekly for the first 6 months, then twice monthly for the second 6 months; for the last 12 months there was no active intervention. There were 174 children who completed the 12 months of the randomized trial. Follow-up data were available for 76 of these children at 24 months. There were no statistical differences in dropout rates among ethnic groups or in any other aspects. RESULTS: Treatment effect was sustained at 24 months in the intervention versus control group for BMI z score (0.16 [95% confidence interval: 0.23 to 0.09]), BMI (2.8 kg/m2 [95% confidence interval: 4.0 –1.6 kg/m2]), percent body fat (4.2% [95% confidence interval: 6.4% to 2.0%]), total body fat mass (5.8 kg [95% confidence interval: 9.1 kg to 2.6 kg]), total cholesterol (13.0 mg/dL [95% confidence interval:21.7 mg/dL to4.2 mg/dL]), low-density lipoprotein cholesterol (10.4 mg/dL [95% confidence interval: 18.3 mg/dL to 2.4 mg/dL]), and homeostasis model assessment of insulin resistance (2.05 [95% confidence interval: 2.48 to 1.75]). CONCLUSIONS: This study, unprecedented because of the high degree of obesity and ethnically diverse backgrounds of children, reveals that benefits of an intensive lifestyle program can be sustained 12 months after completing the active intervention phase