Sarah Leatherman

A Comprehensive Care Management Program to Prevent Chronic Obstructive Pulmonary Disease Hospitalizations: A Randomized, Controlled Trial

BACKGROUNDnImproving a patients ability to self-monitor and manage changes in chronic obstructive pulmonary disease (COPD) symptoms may improve outcomes.nnnOBJECTIVEnTo determine the efficacy of a comprehensive care management program (CCMP) in reducing the risk for COPD hospitalization.nnnDESIGNnA randomized, controlled trial comparing CCMP with guideline-based usual care. (ClinicalTrials.gov registration number: NCT00395083) SETTING: 20 Veterans Affairs hospital-based outpatient clinics.nnnPARTICIPANTSnPatients hospitalized for COPD in the past year.nnnINTERVENTIONnThe CCMP included COPD education during 4 individual sessions and 1 group session, an action plan for identification and treatment of exacerbations, and scheduled proactive telephone calls for case management. Patients in both the intervention and usual care groups received a COPD informational booklet; their primary care providers received a copy of COPD guidelines and were advised to manage their patients according to these guidelines. Patients were randomly assigned, stratifying by site based on random, permuted blocks of variable size.nnnMEASUREMENTSnThe primary outcome was time to first COPD hospitalization. Staff blinded to study group performed telephone-based assessment of COPD exacerbations and hospitalizations, and all hospitalizations were blindly adjudicated. Secondary outcomes included non-COPD health care use, all-cause mortality, health-related quality of life, patient satisfaction, disease knowledge, and self-efficacy.nnnRESULTSnOf the eligible patients, 209 were randomly assigned to the intervention group and 217 to the usual care group. Citing serious safety concerns, the data monitoring committee terminated the intervention before the trials planned completion after 426 (44%) of the planned total of 960 patients were enrolled. Mean follow-up was 250 days. When the study was stopped, the 1-year cumulative incidence of COPD-related hospitalization was 27% in the intervention group and 24% in the usual care group (hazard ratio, 1.13 [95% CI, 0.70 to 1.80]; P= 0.62). There were 28 deaths from all causes in the intervention group versus 10 in the usual care group (hazard ratio, 3.00 [CI, 1.46 to 6.17]; P= 0.003). Cause could be assigned in 27 (71%) deaths. Deaths due to COPD accounted for the largest difference: 10 in the intervention group versus 3 in the usual care group (hazard ratio, 3.60 [CI, 0.99 to 13.08]; P= 0.053).nnnLIMITATIONSnAvailable data could not fully explain the excess mortality in the intervention group. Ability to assess the quality of the educational sessions provided by the case managers was limited.nnnCONCLUSIONnA CCMP in patients with severe COPD had not decreased COPD-related hospitalizations when the trial was stopped prematurely. The CCMP was associated with unanticipated excess mortality, results that differ markedly from similar previous trials. A data monitoring committee should be considered in the design of clinical trials involving behavioral interventions.

Therapies for Active Rheumatoid Arthritis after Methotrexate Failure

BACKGROUNDnFew blinded trials have compared conventional therapy consisting of a combination of disease-modifying antirheumatic drugs with biologic agents in patients with rheumatoid arthritis who have active disease despite treatment with methotrexate--a common scenario in the management of rheumatoid arthritis.nnnMETHODSnWe conducted a 48-week, double-blind, noninferiority trial in which we randomly assigned 353 participants with rheumatoid arthritis who had active disease despite methotrexate therapy to a triple regimen of disease-modifying antirheumatic drugs (methotrexate, sulfasalazine, and hydroxychloroquine) or etanercept plus methotrexate. Patients who did not have an improvement at 24 weeks according to a prespecified threshold were switched in a blinded fashion to the other therapy. The primary outcome was improvement in the Disease Activity Score for 28-joint counts (DAS28, with scores ranging from 2 to 10 and higher scores indicating more disease activity) at week 48.nnnRESULTSnBoth groups had significant improvement over the course of the first 24 weeks (P=0.001 for the comparison with baseline). A total of 27% of participants in each group required a switch in treatment at 24 weeks. Participants in both groups who switched therapies had improvement after switching (P<0.001), and the response after switching did not differ significantly between the two groups (P=0.08). The change between baseline and 48 weeks in the DAS28 was similar in the two groups (-2.1 with triple therapy and -2.3 with etanercept and methotrexate, P=0.26); triple therapy was noninferior to etanercept and methotrexate, since the 95% upper confidence limit of 0.41 for the difference in change in DAS28 was below the margin for noninferiority of 0.6 (P=0.002). There were no significant between-group differences in secondary outcomes, including radiographic progression, pain, and health-related quality of life, or in major adverse events associated with the medications.nnnCONCLUSIONSnWith respect to clinical benefit, triple therapy, with sulfasalazine and hydroxychloroquine added to methotrexate, was noninferior to etanercept plus methotrexate in patients with rheumatoid arthritis who had active disease despite methotrexate therapy. (Funded by the Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, and others; CSP 551 RACAT ClinicalTrials.gov number, NCT00405275.)

Differences in treatment effect among clinical subgroups in a randomized clinical trial of long-acting injectable risperidone and oral antipsychotics in unstable chronic schizophrenia.

Abstract A long-term randomized trial of unstable patients with schizophrenia found no benefit of long-acting injectable (LAI) risperidone over oral treatment in preventing or delaying time to psychiatric hospitalizations or on clinical outcomes. The initial analyses did not examine whether benefits of LAI emerged in selected subgroups. Patients with schizophrenia or schizoaffective disorder who had been hospitalized within the past 2 years or judged to be at risk for hospitalization because of increasing psychiatric service use were randomly assigned to LAI risperidone 12.5 to 50 mg per injection biweekly or to the psychiatrist’s choice of oral antipsychotics and followed for up to 2 years. The primary endpoint was psychiatric rehospitalization. Symptoms, quality of life, and global functioning were assessed through blinded videoconference interviews. Cox’s regression and mixed effects models were used to assess difference in treatment effect within 12 subgroups defined by hospitalization at study entry, substance abuse, race, symptom severity, quality of life, body mass index, age, race or sex, or reported medication compliance. Mixed models and Cox’s regression using up to 24 months of follow-up data showed no significant differences in treatment effect in 10 of 12 subgroups on psychiatric symptoms, quality of life, or time to hospitalization. With adjustment for multiple comparisons, treatment effect differed by race on substance use outcomes, with white participants showing more benefit from LAI than other groups. LAI risperidone showed no superiority to psychiatrist’s choice of oral treatment in most clinically defined subgroups, although the white patients benefited more than the other groups on substance abuse outcomes.

Triple therapy versus biologic therapy for Active Rheumatoid Arthritis a cost-effectiveness analysis

BackgroundnThe RACAT (Rheumatoid Arthritis Comparison of Active Therapies) trial found triple therapy to be noninferior to etanercept-methotrexate in patients with active rheumatoid arthritis (RA).nnnObjectivenTo determine the cost-effectiveness of etanercept-methotrexate versus triple therapy as a first-line strategy.nnnDesignnA within-trial analysis based on the 353 participants in the RACAT trial and a lifetime analysis that extrapolated costs and outcomes by using a decision analytic cohort model.nnnData SourcesnThe RACAT trial and sources from the literature.nnnTarget PopulationnPatients with active RA despite at least 12 weeks of methotrexate therapy.nnnTime Horizonn24 weeks and lifetime.nnnPerspectivenSocietal and Medicare.nnnInterventionnEtanercept-methotrexate first versus triple therapy first.nnnOutcome MeasuresnIncremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs).nnnResults of Base-Case AnalysisnThe within-trial analysis found that etanercept-methotrexate as first-line therapy provided marginally more QALYs but accumulated substantially higher drug costs. Differences in other costs between strategies were negligible. The ICERs for first-line etanercept-methotrexate and triple therapy were

Gender differences in substance abuse, PTSD and intentional self-harm among veterans health administration patients

2.7 million per QALY and

Posttraumatic stress disorder, depression, and non-fatal intentional self-harm in Massachusetts Veterans

0.98 million per QALY over 24 and 48 weeks, respectively. The lifetime analysis suggested that first-line etanercept-methotrexate would result in 0.15 additional lifetime QALY, but this gain would cost an incremental

Veteran subjects willingness to participate in schizophrenia clinical trials.

77xa0290, leading to an ICER of

Identification of Acute Decompensated Heart Failure Hospitalizations Using Administrative Data

521xa0520 per QALY per patient.nnnResults of Sensitivity AnalysisnConsidering a long-term perspective, an initial strategy of etanercept-methotrexate and biologics with similar cost and efficacy is unlikely to be cost-effective compared with using triple therapy first, even under optimistic assumptions.nnnLimitationnData on the long-term benefit of triple therapy are uncertain.nnnConclusionnInitiating biologic therapy without trying triple therapy first increases costs while providing minimal incremental benefit.nnnPrimary Funding SourcenThe Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, Canadian Institutes for Health Research, and an interagency agreement with the National Institutes of Health-American Recovery and Reinvestment Act.

The Rivas Cohort Study: design and baseline characteristics of a Nicaraguan cohort

BACKGROUNDnEpidemiologic studies have reported substance abuse and posttraumatic stress disorder (PTSD) diagnoses as risk factors for suicide among Veterans Health Administration (VHA) patients. Research on risk factors for suicide may not generalize to our understanding of non-fatal intentional self-harm (ISH), given the evidence that these outcomes have unique risk factors. The aims of this study were to examine (1) gender-stratified rates of non-fatal ISH in VHA patients with alcohol abuse/dependence, drug abuse/dependence, and PTSD and (2) gender-stratified interaction between alcohol abuse and dependence and drug abuse and dependence and PTSD in predicting non-fatal ISH.nnnMETHODSnParticipants include all VHA care users who received a PTSD diagnosis in Massachusetts from 2000 to 2008 (n=16,004) and an age- and gender-matched comparison group (n=52,502). Data were obtained from the VHA administrative registries.nnnRESULTSnWe found evidence of stronger interactions between substance abuse diagnoses and PTSD in predicting non-fatal ISH for females than for males. The interaction contrast (IC) for alcohol abuse and dependence and PTSD in predicting non-fatal ISH among female VHA patients was 62.35/100,000 person-years; for male VHA patients the comparable IC was 21.49/100,000 person-years. For female VHA patients the IC for drug abuse and dependence and PTSD predicting ISH was 256.33/100,000 person-years; no interaction was observed for male VHA patients.nnnCONCLUSIONSnThis study contributes to the scant literature on gender differences in substance abuse and PTSD among VHA patients. The findings highlight comorbid diagnoses as particularly important risk factors for non-fatal ISH among female VHA patients.

A novel method to combine assessment of benefit and harm: OMERACT 3x3 methodology applied to two active comparator trials

BackgroundThe literature on the association between Posttraumatic Stress Disorder (PTSD) and fatal and non-fatal intentional self-harm (ISH) among Veterans who receive care within the Veterans Health Administration (VHA) is limited in scope and contradictory. The current study examines the association between PTSD and non-fatal ISH in a gender-stratified sample of patients who received care at a Massachusetts VHA treatment facility between 2000 and 2008.MethodsVHA electronic medical record data were obtained for patients who received a PTSD diagnosis at a Massachusetts treatment facility (nu2009=u200916,004) and a gender/age matched comparison group (nu2009=u200952,502). Rate ratios for the association between PTSD and non-fatal ISH were computed adjusting for marital status, depression, alcohol or drug abuse or dependence, anxiety disorder diagnoses and prior ISH and clustering by hospital using Poisson regression. The interaction between PTSD and depression diagnoses in predicting non-fatal ISH was assessed as the departure from additive effects by calculating the interaction contrast (IC) while adjusting for identified confounders.ResultsOver the eight year study period 146 (0.91%) of those with PTSD experienced non-fatal ISH, while 71 (0.14%) of those without PTSD experienced non-fatal ISH. Strong adjusted associations between PTSD and non-fatal ISH were found for both male (RRu2009=u20093.3, 95% CIu2009=u20092.3, 4.6) and female (RRu2009=u200916, 95% CIu2009=u20094.7, 55) VHA patients. Evidence of an interaction between PTSD and depression diagnoses in predicting non-fatal ISH was found as a departure from additive effects for both sexes, but this association was more marked among women than among men.ConclusionsOur results indicate that non-fatal ISH among women may be more strongly related to PTSD than prior work focusing on suicide has suggested and highlight the importance of gender-stratified examinations of these associations. Further, our results suggest that suicide prevention approaches in the VHA should integrate treatment for PTSD and depression.