Stratification of flare intensity identifies placebo responders in a treatment efficacy trial of patients with osteoarthritis.

OBJECTIVE: Studies evaluating osteoarthritis treatment often use increased arthritis activity ("flare") as a selection criterion, although no standardized assessments are available to quantify flare intensity and little is known about how this criterion affects treatment comparisons. This study evaluated the reliability of a flare assessment and how pretreatment flare intensity impacts conclusions on treatment efficacy. METHODS: Using data from a double-blind, randomized, controlled trial (n = 182), we compared 3 osteoarthritis treatments with placebo in patients who met 3 of 4 flare criteria. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was used to document levels of pain, stiffness, and physical functioning at baseline and at the final visit. Following factor analytic evaluation, the flare items were standardized and summed to create a flare intensity index, which was used to identify patient subgroups. Analysis of covariance was applied to compare change in WOMAC scale scores from baseline to final visit for assessment of treatment differences among the flare intensity subgroups. RESULTS: The flare indicators appeared unidimensional. Analyses were stratified by tertiles of flare intensity. Mean WOMAC scores improved in the patients receiving active treatment who were categorized into the 2 lowest flare intensity subgroups, but mean WOMAC scores improved in patients in all 4 treatment groups (active and placebo) in the most intense flare subgroup. CONCLUSION: Patients with higher intensity flares may be more likely to report substantial improvement in functional status regardless of treatment. Failure to account for flare intensity in analyses of data from pain trials with flare-based designs may inflate the risk of Type I and Type II errors in the interpretation of study results.

Reliability and validity of French, German, Italian, Dutch, and UK English translations of the Medical Outcomes Study HIV Health Survey.

OBJECTIVES: Test the reliability and validity of 5 translations of the 34-item version of the MOS HIV for use in multinational clinical trials. RESEARCH DESIGN: Investigators in five countries followed a standardized protocol and recruited HIV+ patients stratified by disease stage: asymptomatic; symptomatic; and AIDS. During routine clinic visits, patients completed the MOS HIV and a checklist of HIV-related symptoms. Clinicians reported patients' demographics, most recent CD4+ count and disease stage. SUBJECTS: Three hundred and sixty three HIV+ outpatients attending AIDS clinics in The Netherlands, France, Germany, Italy, and England. MEASURES: Dutch, French, German, Italian, and UK English translations of the MOS HIV CD4+ cell count and the SCL-57. RESULTS: All translations recruited roughly equal proportions of each disease stage, although the number of patients recruited differed by translation (n: German = 92, French = 86; Italian = 88; UK English = 72; and Dutch = 25). Internal consistency reliability was similar across translations and adequate (alpha >.70) for all scales except for Mental Health in the French sample. Multi-trait analyses supported structural validity of the MOS HIV scales in each translation. Principal component analysis of scale scores identified 2 dimensions for all translations except German. For all translations, scores were significantly correlated with symptom severity scores but were uncorrelated with CD4+ cell counts. CONCLUSIONS: In general, the 5 translations of the MOS HIV had similar psychometric properties to those reported in the validation study for the original US English version of the MOS HIV. With some revision, these translations promise to provide useful quality of life data from HIV+ subjects in clinical trials.

Impact of zidovudine plus lamivudine or zalcitabine on health-related quality of life.

OBJECTIVE: To assess the impact of treatment with zidovudine plus lamivudine or zalcitabine on health-related quality of life (HRQOL) in patients with HIV. DESIGN: HRQOL assessments were conducted as part of a double-blind, randomized, 24-week (extended to 52 wk) efficacy and safety study. The Medical Outcomes Study HIV Health Survey (MOS-HIV), which assesses 10 physical and psychological domains of HRQOL, was self-administered by patients at baseline and at weeks 16, 32, 52, or at treatment discontinuation. SETTING: Twenty-one outpatient centers in the US, Canada, and Puerto Rico. PATIENTS: The study enrolled 254 HIV-positive patients (CD4+ 100-300 cells/mm3); 206 patients completed the MOS-HIV at baseline and at least once during treatment. Post hoc analyses stratified patients into two subgroups: AIDS (CD4+ < 200 cells/mm3) and non-AIDS (CD4+ > or = 200 cells/mm3). INTERVENTIONS: Patients received zidovudine 200 mg three times daily plus one of the following: lamivudine 150 mg twice daily, lamivudine 300 mg twice daily, or zalcitabine 0.75 mg three times daily. MAIN OUTCOME MEASURE: Change in MOS-HIV scores from baseline to last completed questionnaire. RESULTS: Following an average of 36 weeks of treatment, there were statistically significant differences across treatment groups in mean change scores on the physical functioning, role functioning, and vitality scales, with stable or increased (improved) scores in the zidovudine plus lamivudine 150 mg group and decreased scores in the zidovudine plus zalcitabine and zidovudine plus lamivudine 300 mg groups for most scales. Post hoc analyses found that in the non-AIDS subgroup, only the zidovudine plus lamivudine 150 mg group had increases in mean MOS-HIV scores (on 8 of 10 scales); in the AIDS subgroup, all but two MOS-HIV scores (in the zidovudine plus zalcitabine group) decreased in all three treatment groups. CONCLUSIONS: These results suggest that, of the three combination therapies studied, zidovudine plus lamivudine 150 mg was most likely to maintain or improve HRQOL in HIV-positive patients.

The cost of depression-complicated alcoholism: health-care utilization and treatment effectiveness.

Clinical and epidemiologic evidence suggests that alcoholism complicated by concurrent or a lifetime history of depression is slower to remit and more prone to relapse than uncomplicated alcoholism. Consequently, alcoholics with a history of depressive illness, on average, are likely to use more health care and to have higher treatment costs than those without depression complications. This article contrasts evidence of the suitability of three models for predicting the impact of depression on an alcoholic's health-care use: a null model (assuming no differences), a cumulative-effect model (arguing for a linear increase associated with comorbid depression), and a synergistic model (wherein alcoholism complicated with depression is qualitatively as well as quantitatively different than uncomplicated alcoholism). To test these models, health-care costs and utilization of 491 "pure" alcoholics (those with no history of depression diagnosis) and 199 depression-complicated alcoholics, who received alcohol treatment while enrolled in a self-insured health-care program of a major U.S. manufacturing company, were compared. Results are discussed in terms of the implications for cost containment and the likelihood of relapse among the depression-complicated alcoholism group.

Substance abuse and family illness: evidence from health care utilization and cost-offset research.

Although the substance abuse treatment community recognizes that physical and psychological problems are common among families with a substance-abusing member, third-party funding for comprehensive treatment of the families of substance abusers is limited. Failure to provide treatment for these collateral effects of substance abuse on the family is thought to reduce the efficacy of substance abuse treatment, increase the risk of relapse, and leave untreated secondary pathology among family members. This article presents a review of health care utilization and cost-offset studies of the collateral effects of substance abuse on the family to aid administrators and planners in documenting the economic advantages of comprehensive treatment for the families of substance abusers.