The Association Between Family Social Network Size and Healthy Lifestyle Factors: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

We examined associations of central family (i.e., children, parents, in-laws) social network size with healthy lifestyle factors (i.e., favorable body mass index, physical activity, diet, alcohol use, smoking). Using data on 15,511 Hispanics/Latinos 18-74 years old from the Hispanic Community Health Study/Study of Latinos, multivariable adjusted survey logistic regression was used to compute associations of social network size with healthy lifestyle factors. A one-unit higher total of central family size was associated with lower odds of healthy body mass index (OR 0.90; 95% CI 0.86-0.93) and having all five healthy lifestyle factors (OR 0.90; 95% CI 0.85-0.96). Findings suggest familial structural social support may contribute to healthy lifestyle factors and differ based on the type of relationship among Hispanics/Latinos.

Negative-pressure wound therapy versus standard dressings for adults with an open lower limb fracture: the WOLLF RCT.

BACKGROUND: Open fractures of the lower limb occur when a broken bone penetrates the skin and is exposed to the outside environment. These are life-changing injuries. The risk of deep infection may be as high as 27%. The type of dressing applied after surgical debridement could potentially reduce the risk of infection in the open-fracture wound. OBJECTIVES: To assess the disability, rate of deep infection, quality of life and resource use in patients with severe open fracture of the lower limb treated with negative-pressure wound therapy (NPWT) versus standard wound management after the first surgical debridement of the wound. DESIGN: A pragmatic, multicentre randomised controlled trial. SETTING: Twenty-four specialist trauma hospitals in the UK Major Trauma Network. PARTICIPANTS: A total of 460 patients aged ≥ 16 years with a severe open fracture of the lower limb were recruited from July 2012 through to December 2015. Patients were excluded if they presented more than 72 hours after their injury or were unable to complete questionnaires. INTERVENTIONS: Negative-pressure wound therapy (n = 226) where an 'open-cell' solid foam or gauze was placed over the surface of the wound and connected to a suction pump which created a partial vacuum over the dressing versus standard dressings not involving negative pressure (n = 234). MAIN OUTCOME MEASURES: Disability Rating Index (DRI) - a score of 0 (no disability) to 100 (completely disabled) at 12 months was the primary outcome measure, with a minimal clinically important difference of 8 points. The secondary outcomes were deep infection, quality of life and resource use collected at 3, 6, 9 and 12 months post randomisaton. RESULTS: There was no evidence of a difference in the patients' DRI at 12 months. The mean DRI in the NPWT group was 45.5 points [standard deviation (SD) 28.0 points] versus 42.4 points (SD 24.2 points) in the standard dressing group, giving a difference of -3.9 points (95% confidence interval -8.9 to 1.2 points) in favour of standard dressings (p = 0.132). There was no difference in HRQoL and no difference in the number of surgical site infections or other complications at any point in the 12 months after surgery. NPWT did not reduce the cost of treatment and it was associated with a low probability of cost-effectiveness. LIMITATIONS: Owing to the emergency nature of the interventions, we anticipated that some patients who were randomised into the trial would subsequently be unable or unwilling to take part. Such post-randomisation withdrawal of patients could have posed a risk to the external validity of the trial. However, the great majority of these patients (85%) were found to be ineligible after randomisation. Therefore, we can be confident that the patients who took part were representative of the population with severe open fractures of the lower limb. CONCLUSIONS: Contrary to the existing literature and current clinical guidelines, NPWT dressings do not provide a clinical or an economic benefit for patients with an open fracture of the lower limb. FUTURE WORK: Future work should investigate alternative strategies to reduce the incidence of infection and improve outcomes for patients with an open fracture of the lower limb. Two specific areas of potentially great benefit are (1) the use of topical antibiotic preparations in the open-fracture wound and (2) the role of orthopaedic implants with antimicrobial coatings when fixing the associated fracture. TRIAL REGISTRATION: Current Controlled Trials ISRCTN33756652 and UKCRN Portfolio ID 11783. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 73. See the NIHR Journals Library website for further project information.

Association of systemic inflammation, adiposity, and metabolic dysregulation with asthma burden among Hispanic adults.

RATIONALE: Obesity-related asthma is associated with higher disease burden than normal-weight asthma among Hispanics. Adiposity, metabolic dysregulation, and inflammation are all implicated in pathogenesis of obesity-related asthma, but their independent contributions are poorly understood. OBJECTIVE: To examine the independent contributions of body fat distribution, metabolic abnormalities and inflammation on asthma symptoms and pulmonary function among Hispanics. METHODS: Participants of the Hispanic Community Health Study/Study of Latinos with doctor-diagnosed asthma who completed an asthma symptom questionnaire and performed a valid spirometry were included in the analysis (n = 1126). Multivariate analysis was used to examine the independent association of general adiposity (assessed using body mass index), truncal adiposity (assessed by waist circumference), metabolic dysregulation (presence of insulin resistance and low HDL) and inflammation (high-sensitivity C-Reactive Protein≥3 mg/L) with reported asthma symptoms or pulmonary function measures (FEV1, and FVC) while adjusting for demographic and clinical covariates. RESULTS: Of the 1126 participants, 334 (29.5%) were overweight, and 648 (57.8%) were obese. FEV1 and FVC were lower in obese compared to normal-weight asthmatics. In analyses controlling for metabolic and adiposity factors, high hs-CRP (>7 mg/L) was associated with more symptoms (prevalence-ratio 1.27 (95%CI 1.05, 1.54), and lower FVC (ß -138 ml (95%CI -27 ml, -249 ml)) and FEV1 (ß -155 ml (95% CI -38 ml, -272 ml). Low HDL was also associated with lower FVC (ß -111 ml (-22 ml, -201 ml) and FEV1 (ß -100 ml (-12 ml, -188 ml)). Results were similar in men and women. CONCLUSIONS: Our findings suggest that hs-CRP and low HDL, rather than general and truncal adiposity, are associated with asthma burden among overweight and obese Hispanic adults.

Cardiovascular health among diverse Hispanics/Latinos: Hispanic Community Health Study/Study of Latinos (HCHS/SOL) results.

BACKGROUND: Seven national 2020 Strategic Impact Goals for cardiovascular health (Life's Simple 7 [LS7]) estimates for major ethnic/racial groups are available, but not for diverse Hispanics/Latinos. Herein, we describe and examine LS7 profiles of diverse Hispanic/Latino groups. METHODS: HCHS/SOL (analytic n = 15,825; ages 18-74 years) data were used to estimate LS7 metrics. LS7 metrics were operationalized as Ideal, Intermediate, or Poor and indexed as an additive score. We calculated Hispanic/Latino group and sex-specific prevalence estimates for LS7 metrics and used survey-based regression models to examine (1) associations between LS7 scores and pertinent sociocultural characteristics and (2) relationships between LS7 scores and coronary heart disease, and stroke and transient ischemic attacks prevalence. RESULTS: Few HCHS/SOL participants met all 7 Ideal LS7 criteria (<1%), and a similarly small proportion did not meet any Ideal LS7 criteria (1.1%). We found significant variability in LS7 distributions between men and women and across HCHS/SOL Hispanic/Latino heritages. We also found a substantial sex-adjusted age gradient in LS7 cardiovascular health (ie, ≥4 Ideal LS7s). Finally, higher Ideal LS7 scores were associated with decreased odds of both coronary heart disease and self-reported stroke/transient ischemic attack; these associations persisted after model covariate adjustments. CONCLUSIONS: Hispanic/Latino LS7s compared favorably with existing national estimates; however, we found areas for improvement. Several Hispanic/Latino LS7 strengths and weaknesses varied by sex and heritage, providing important information to guide targeted health promotion efforts toward achieving 2020 goals.

Impact of second-generation antipsychotics and perphenazine on depressive symptoms in a randomized trial of treatment for chronic schizophrenia.

BACKGROUND: According to the American Psychiatric Association Clinical Practice Guidelines for schizophrenia, second-generation antipsychotics may be specifically indicated for the treatment of depression in schizophrenia. We examined the impact of these medications on symptoms of depression using the data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), conducted between January 2001 and December 2004. METHOD: Patients with DSM-IV-defined schizophrenia (N = 1,460) were assigned to treatment with a first-generation antipsychotic (perphenazine) or one of 4 second-generation drugs (olanzapine, quetiapine, risperidone, or ziprasidone) and followed for up to 18 months (phase 1). Patients with tardive dyskinesia were excluded from the randomization that included perphenazine. Depression was assessed with the Calgary Depression Scale for Schizophrenia (CDSS). Mixed models were used to evaluate group differences during treatment with the initially assigned drug. An interaction analysis evaluated differences in drug response by whether patients had a baseline score on the CDSS of ≥ 6, indicative of a current major depressive episode (MDE). RESULTS: There were no significant differences between treatment groups on phase 1 analysis, although there was a significant improvement in depression across all treatments. A significant interaction was found between treatment and experiencing an MDE at baseline (P = .05), and further paired comparisons suggested that quetiapine was superior to risperidone among patients who were in an MDE at baseline (P = .0056). CONCLUSIONS: We found no differences between any second-generation antipsychotic and the first-generation antipsychotic perphenazine and no support for the clinical practice recommendation, but we did detect a signal indicating a small potential difference favoring quetiapine over risperidone only in patients with an MDE at baseline.

The impact of obesity on health care costs among persons with schizophrenia.

BACKGROUND: Obesity is the second leading cause of preventable death in the United States and is twice as common among individuals with schizophrenia as the general population. METHODS: Data from the Clinical Antipsychotic Trials of Intervention Effectiveness, a multisite trial of antipsychotic pharmacotherapy in 1460 patients with schizophrenia, were used to examine the relationships between body mass index (BMI) and medical costs. RESULTS: ANCOVA analyses found significant increases in both psychiatric and nonpsychiatric medication costs associated with increasing BMI and a significant, but smaller, difference in costs of outpatient medical-surgical service utilization: US$41 per month for morbidly obese patients compared to US$26 per month for patients of normal weight (F=2.4, P=.04). In multivariable logistic regression analyses, morbid obesity was associated with significantly increased odds of any outpatient medical-surgical service costs. When compared to observations of BMI>35, BMI observations within the normal range (18.5-24.9) were half as likely to be associated with any outpatient medical-surgical costs (OR=0.53; 95% CI=0.45, 0.63). CONCLUSIONS: In this large sample of persons with schizophrenia, obesity was associated with increased outpatient general medical service and medication costs even after controlling for demographic characteristics and medical comorbidity, but the absolute dollar amount was small.

Does switching to a new antipsychotic improve outcomes? Data from the CATIE Trial.

PURPOSE: Previous analysis of data from CATIE showed that patients randomly assigned to switch to a new medication were more likely to discontinue study drug than those who stayed on the medication they had been taking prior to randomization. This study addresses additional outcomes measures evaluating symptoms, neurocognition, quality of life, neurological side effects, weight, and health costs. First, considering patients randomized to olanzapine or risperidone, outcomes among patients who had been on the drug to which they were randomized prior to CATIE (N=129 "stayers") were compared to outcomes of those who switched to either of these two drugs (N=269 "switchers"). A second set of analyses considered patients on baseline monotherapy with olanzapine (N=297); risperidone (N=252) or quetiapine (n=87) and compared those randomly assigned to stay on each of these medications with those assigned to switch to any of the other five phase 1 medications in CATIE. In mixed models of each outcome the independent variable of primary interest represented stay vs. switch, with multivariate adjustment for potential confounding factors. RESULTS: With one exception, there were no significant differences between stayers and switchers on any outcome measure in either set of analyses. The exception was that, in the second set of analyses, patients who stayed on olanzapine showed greater weight gain than those who switched from olanzapine to other drugs. CONCLUSION: Switching to a new medication yielded no advantage over staying on the previous medication. Staying on olanzapine was associated with greater weight gain.

What CATIE found: results from the schizophrenia trial.

The authors provide an overview of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) sponsored by the National Institute of Mental Health. CATIE was designed to compare a proxy first-generation antipsychotic, perphenazine, to several newer drugs. In phase 1 of the trial, consenting patients were randomly assigned to receive olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone for up to 18 months on a double-blind basis. Patients with tardive dyskinesia were excluded from being randomly assigned to perphenazine and were assigned to one of the four second-generation antipsychotics in phase 1A. Clozapine was included in phase 2 of the study. Overall, olanzapine had the longest time to discontinuation in phase 1, but it was associated with significant weight and metabolic concerns. Perphenazine was not significantly different in overall effectiveness, compared with quetiapine, risperidone, and ziprasidone. Also, perphenazine was found to be the most cost-effective drug. Clozapine was confirmed as the most effective drug for individuals with a poor symptom response to previous antipsychotic drug trials, although clozapine was also associated with troublesome adverse effects. There were no differences in neurocognitive or psychosocial functioning in response to medications. Subsequent randomizations suggest that a poor response to an initial medication may mean that a different medication will be more effective or better tolerated. Although the CATIE results are controversial, they are broadly consistent with most previous antipsychotic drug trials and meta-analyses; however, the results may not generalize well to patients at high risk of tardive dyskinesia. Patient characteristics and clinical circumstances affected drug effectiveness; these patient factors are important in making treatment choices.

Cost-benefit analysis of second-generation antipsychotics and placebo in a randomized trial of the treatment of psychosis and aggression in Alzheimer disease.

CONTEXT: Second-generation antipsychotics (SGAs) are prescribed for psychosis, aggression, and agitation in Alzheimer disease (AD). OBJECTIVE: To conduct a cost-benefit analysis of SGAs and placebo (taken to represent a "watchful waiting" treatment strategy) for psychosis and aggression in outpatients with AD. DESIGN: Randomized placebo-controlled trial of alternative SGA initiation strategies. SETTING: Forty-two outpatient clinics. PARTICIPANTS: Outpatients with AD and psychosis, aggression, or agitation (N = 421). Intervention Participants were randomly assigned to treatment with olanzapine, quetiapine fumarate, risperidone, or placebo with the option of double-blind rerandomization to another antipsychotic or citalopram hydrobromide or open treatment over 9 months. MAIN OUTCOME MEASURES: Monthly interviews documented health service use and costs. The economic perspective addressed total health care and medication costs. Costs of study drugs were estimated from wholesale prices with adjustment for discounts and rebates. Quality-adjusted life-years (QALYs) were assessed with the Health Utilities Index Mark 3 and were supplemented with measures of functioning, activities of daily living, and quality of life. Primary analyses were conducted using all available data. Secondary analyses excluded observations after the first medication change (ie, phase 1 only). Cost-benefit analysis was conducted using the net health benefits approach in a sensitivity analysis in which QALYs were valued at $50,000 per year and $100,000 per year. RESULTS: Average total health costs, including medications, were significantly lower for placebo than for SGAs, by $50 to $100 per month. There were no differences between treatments in QALYs or other measures of function. Phase 1-only analyses were broadly similar. Net-benefit analysis showed greater net health benefits for placebo as compared with other treatments, with probabilities ranging from 50% to 90%. CONCLUSIONS: There were no differences in measures of effectiveness between initiation of active treatments or placebo (which represented watchful waiting) but the placebo group had significantly lower health care costs. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00015548.

Second-generation antipsychotics: reviewing the cost-effectiveness component of the CATIE trial.

The cost-effectiveness component of the 18-month CATIE trial of schizophrenia pharmacotherapy (n = 1460) showed that the first-generation antipsychotic perphenazine was US$300-600 per month less expensive than each of four second-generation antipsychotics, and no less effective across multiple measures. We consider whether or not each of eight potential methodological limitations could weaken this conclusion: follow-up rates, study duration, sample characteristics, the choice of outcome measures, exclusion of patients with tardive dyskinesia from assignment to perphenazine, choice of study drugs and doses, reliance on intention-to-treat analysis, and differences in prestudy treatment. We conclude that results of CATIE are robust to these limitations. Perphenazine seems to have been a more representative choice for first-generation antipsychotic comparison treatment than haloperidol.

Cost-effectiveness of second-generation antipsychotics and perphenazine in a randomized trial of treatment for chronic schizophrenia.

BACKGROUND: Second-generation antipsychotics have largely replaced first-generation antipsychotics for the treatment of schizophrenia, but a large-scale cost/effectiveness analysis has not been attempted. METHOD: Patients with schizophrenia (N=1,493) were assigned to treatment with a first-generation antipsychotic (perphenazine) or one of four second-generation drugs (olanzapine, quetia-pine, risperidone, or ziprasidone) and followed for up to 18 months. Patients with tardive dyskinesia were prohibited from assignment to perphenazine. Patients could be reassigned at any time to another second-generation drug, including clozapine, but not to perphenazine. The cost analysis included medications plus health services use. Quality-adjusted life year (QALY) ratings were assessed on the basis of Positive and Negative Syndrome Scale (PANSS) subscale scores and side effects. An intention-to-treat analysis included all available observations, classified by initial drug assignment, and costs of reassignment of most patients to another second-generation drug. The analysis was repeated considering only treatment on initially assigned medications. RESULTS: Although QALY ratings, PANSS scores, and other quality of life measures indicated modest improvement over 18 months, there were no significant differences between perphenazine and any second-generation medication. Average total monthly health care costs were 300 dollars-600 dollars (20%-30%) lower for perphenazine than for second-generation antipsychotics because of lower drug cost. Differences in costs remained when maximally discounted drug prices were used for all patients and when only observations during treatment with the first medication were included. CONCLUSIONS: Treatment with perphenazine was less costly than treatment with second-generation antipsychotics with no significant differences in measures of effectiveness. However, the trial was limited by a high dropout rate, and longer-term neurological and metabolic side effects require further study.

Statistical approaches to effectiveness measurement and outcome-driven re-randomizations in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) studies.

The design of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia and Alzheimer's disease studies pose several statistical challenges, including issues related to performing multiple comparisons, defining effectiveness outcomes, and collecting and analyzing data from a design with multiple outcome-driven re-randomizations. We discuss the CATIE strategy for addressing many hypotheses within the context of one clinical trial while controlling the overall type I error rate. We provide motivation for the use of two effectiveness outcomes: time to all-cause discontinuation and composite endpoints that combine outcomes from multiple domains, such as efficacy, safety, cost-effectiveness, and quality of life. Methods for statistical analysis of an outcome-driven re-randomization trial are compared and evaluated. We describe analysis within each phase, analysis based on the first randomization or treatment algorithms, and repeated measures modeling. Finally, strategies are described for designing an electronic data collection system for trials with repeated outcome-driven re-randomizations.