Insurance status and mortality among patients with AIDS.

OBJECTIVES: The aim of the study was to evaluate risk factors for mortality, including health care insurance status, among patients with AIDS in the era of modern combination antiretroviral therapy (cART). METHODS: This study was part of the prospective, multicentre, observational Longitudinal Study of the Ocular Complications of AIDS (LSOCA). Patients were classified as having private health care insurance, Medicare, Medicaid, or no insurance. Hazard ratios (HRs) for death were calculated using proportional hazards regression models and staggered entries, anchored to the AIDS diagnosis date. RESULTS: Among 2363 participants with AIDS, 97% were treated with cART. At enrolment, 31% of participants had private insurance, 29% had Medicare, 24% had Medicaid, and 16% were uninsured. Noninfectious, age-related diseases, such as hypertension, diabetes, and renal disease, were more frequent among persons with Medicare than among those with private insurance. Compared with those who were privately insured, mortality was greater among participants with Medicare [adjusted HR (HRadj ) 1.35; 95% confidence interval (CI) 1.08-1.67; P = 0.008]. Among participants with a suppressed HIV viral load, compared with those who were privately insured, HRadj values for mortality were 1.93 (95% CI 1.08-3.44; P = 0.02) for those with Medicare and 2.09 (95% CI 1.02-4.27; P = 0.04) for those with Medicaid. Mortality among initially uninsured participants was not significantly different from that for privately insured participants, but these participants typically obtained ART and insurance during follow-up. Compared with privately insured participants, time-updated HRadj values for mortality were 1.34 (95% CI 1.05-1.70; P = 0.02) for those with Medicare, 1.34 (95% CI 1.01-1.80; P = 0.05) for those with Medicaid, and 1.35 (95% CI 0.97-1.88; P = 0.05) for those who were uninsured. CONCLUSIONS: In persons with AIDS, compared with those with private insurance, those with public insurance had increased mortality, possibly as a result of a greater burden of noninfectious, age-related diseases.

Clinical review 115: effect of thyroxine therapy on serum lipoproteins in patients with mild thyroid failure: a quantitative review of the literature.

The objective of our study was to estimate the expected change in serum lipoprotein concentrations after treatment with T4 in patients with mild thyroid failure (i.e. subclinical hypothyroidism). Our data sources included MEDLINE, between January 1966 and May 1999, and review of references from relevant articles. There were 1,786 published studies identified, 461 abstracts reviewed, 74 articles retrieved, 24 articles evaluated against predetermined entry criteria, and 13 studies systematically reviewed and abstracted. All studies reported serum total cholesterol concentration changes during T4 treatment, 12 reported triglyceride changes, 10 reported high-density lipoprotein (HDL) cholesterol changes, and 9 reported low-density lipoprotein (LDL) cholesterol changes. There were 247 patients in 13 studies. The mean decrease in the serum total cholesterol concentration was -0.20 mmol/L (-7.9 mg/ dL), with a 95% confidence interval of -0.09 to -0.34. The decline in serum total cholesterol was directly proportional to its baseline concentration. Studies enrolling hypothyroid participants receiving suboptimal T4 doses reported significantly larger decreases in serum total cholesterol after thyroid-stimulating hormone normalization than studies enrolling previously untreated individuals with mild thyroid failure [-0.44 mmol/L (-17 mg/dL) vs. -0.14 mmol/L (-5.6 mg/dL), P = 0.05]. The change in serum LDL cholesterol concentration was -0.26 mmol/L (-10 mg/dL), with a 95% confidence interval of -0.12 to -0.41. Serum HDL and triglyceride concentrations showed no change. These results, although based on fewer than 250 patients, suggest that T4 therapy in individuals with mild thyroid failure lowers mean serum total and LDL cholesterol concentrations. The reduction in serum total cholesterol may be larger in individuals with higher pretreatment cholesterol levels and in hypothyroid individuals taking suboptimal T4 doses. There do not seem to be significant effects of T4 on serum HDL or triglyceride concentrations.

Communications: Should mechanisms be established for sharing among clinical trial investigators experiences in handling problems in design, execution, and analysis? Methodology: the case for improved communications.

Despite their long history, the number that are in operation now, and the current level of expenditures on them, clinical trials have not been the focus of sufficient methodologic research. The paucity of metholologic explorations is further aggravated by the constraints on communications regarding methodology. Those individuals working in the area of clinical trials need to establish some professional identity with the field. Methodology in the areas of design and management of clinical trials needs to be stimulated, perhaps through special requests for applications (RFAs) and requests for proposals (RFPs). Communications could be improved by the establishments of a professional society, the development of an appropriate journal, and establishment of national training and information centers for clinical trials.

Retrospective and prospective identification of unpublished controlled trials: lessons from a survey of obstetricians and pediatricians.

Investigations in which statistically significant differences between treatment groups have not been observed are less likely than others to be reported in scientific journals. In clinical research, this selective suppression of "negative" results may lead to the adoption of ineffective or hazardous treatments. In an attempt to obtain information about unpublished trials in perinatal medicine, letters were sent to 42,000 obstetricians and pediatricians in 18 countries. As a result, we were notified of 395 unpublished randomized trials. Only 18 of the trials had been completed more than 2 years before the survey, a period during which at least 2300 reports of perinatal trials had been published. Of the 395 unpublished trials, 125 had ceased recruitment within the 2 years prior to the survey, 193 were actively recruiting at the time of the survey, and 59 were about to begin recruitment. It was concluded that publication bias will not be addressed successfully by attempts to obtain information about unpublished trials retrospectively. However, since the response rate to our request for details about ongoing and planned trials was good, prospective registration of trials at inception appears to be a feasible approach to reducing publication bias and its adverse consequences. An additional merit of prospective registration of clinical trials is that it should reduce unnecessary duplication (as opposed to necessary replication) in research and promote more effective collaboration.

Infant stimulation curriculum for infants with cerebral palsy: effects on infant temperament, parent-infant interaction, and home environment.

To assess the effects of intervention in cerebral palsy, 48 infants 12 to 19 months of age, with mild to severe spastic diplegia, were randomly assigned to receive either 6 months of infant stimulation followed by 6 months of physical therapy (test group) or 12 months of neurodevelopmental physical therapy (contrast group). The infant stimulation protocol consisted of cognitive, motor, sensory, and language activities. Outcome was assessed after 12 months by using Carey Infant Temperament Questionnaire subscores (activity, rhythmicity, adaptability, approach, threshold, intensity, mood, distractibility, and persistence); Roth Mother-Child Relationship Evaluation subscores (acceptance, overprotection, overindulgence, rejection); and Home Observation for Measurement of the Environment subscores (maternal responsiveness, avoidance of restriction and punishment, organization of environment, play materials, maternal involvement, and variety of daily stimulation). Motor and cognitive outcomes suggesting advantage for the test group have been reported previously. After 12 months of intervention, mothers with infants in the contrast group showed a greater improvement in emotional and verbal responsiveness as measured by the Home Observation for Measurement of the Environment (mean score change in control group = 1.2, test group = 0.3 P less than .04). None of the 19 other measures differed significantly between treatment groups in change from baseline. This study demonstrates no short-term systematic effect on temperament, maternal-infant interaction, or home environment attributable to the inclusion of an infant stimulation curriculum in an intervention program for infants with spastic diplegia. It suggests that motor and cognitive advantages associated with infant stimulation are not mediated by measurable changes in the psychosocial variables studied.

A plea for a discipline of health and medical evaluation.

There is an expanding need for quantitative information to evaluate health and medical care procedures. Existing methods for designing and carrying out evaluation studies need to be improved to provide better techniques for answering questions on efficacy of health and medical procedures, and in providing a more adequate information base on which to set healthy policy. This paper reviews some of the problems in the design and conduct of evaluation research, and makes a plea for creation of a special discipline to support and develop the field of health and medical care evaluation.

Photographic measures of cytomegalovirus retinitis as surrogates for visual outcomes in treated patients.

OBJECTIVE: To evaluate photographic measures of cytomegalovirus (CMV) retinitis as surrogate outcomes for changes in vision in patients with CMV retinitis related to the acquired immunodeficiency syndrome. METHODS: Data from 3 clinical trials of CMV retinitis treatments were analyzed. Two photographic assessments of retinitis in eyes involved at baseline were evaluated: progression (lesion border movement > or = 750 microm or occurrence of a new lesion) and change in area of retina involved with retinitis. Vision measures were decline in best-corrected visual acuity and change in visual field. Photographic measures were evaluated as surrogate outcomes based on 4 criteria: (1) association with vision measure; (2) ability to account for treatment-related differences in vision measure; (3) data completeness; and (4) sample size requirements. RESULTS: Data from 1001 involved eyes (666 patients) were analyzed. Progression and change in area involved were predictive of declines in vision measures, accounted for 50% and 66% of the treatment effect on visual field, and were available from 93% and 64% of involved eyes, respectively. Sample size estimates for a clinical trial were smallest with progression as the design outcome. CONCLUSION: Progression and change in area involved met the first and second criteria for surrogate outcomes for visual field loss; a complete evaluation for visual acuity decline was not possible because treatment-related differences were not observed. Progression met the logistical and sample size criteria better than change in area of retina involved with retinitis.

Factors affecting attrition in a longitudinal study of patients with AIDS.

Anecdotal data have suggested that retention of HIV-infected patients with immune recovery in longitudinal studies may be difficult as they resume normal activities. This study evaluated risk factors for attrition among patients with AIDS in a cohort study in the era of highly active antiretroviral therapy. Patients with AIDS enrolled in the Longitudinal Study of Ocular Complications of AIDS were evaluated every three months with demographic, clinical and laboratory data collected. Lost to follow-up was defined as any patient who missed all study visits and could not be contacted for 12 consecutive months, who had not died and who did not re-enter the study at a later date. Of the 1,052 patients studied, 77 (7.3%) were lost to follow-up (rate = 0.03/person year). In the multivariate analysis, factors associated with attrition were CD4+ T-cell count category (hazard ratio (HR) = 2.03; 95%CI: 1.01, 4.24; P = 0.05 for CD4+ count < or = 50 cells/microL and HR = 1.96; 95%CI: 1.12, 3.40; P = 0.02 for CD4+ count 51-200 cells/microL) and detectable HIV viral load (HR = 1.29; 95%CI: 1.07, 1.53; P < 0.001 for HIV viral load >400 copies/mL). These data suggest that patients with compromised immunologic status are at an increased risk for being lost to follow-up.

Meta-analysis: science or religion?

Meta-analysis of clinical trials has assumed increasing importance in recent years as a means of reaching conclusions regarding the safety and efficacy of treatments evaluated in individual trials. This article discusses impediments to meta-analyses and enumerates needs that should be satisfied to enhance their usefulness. Key among the needs are improved means of identifying trials prior to publication via prospective registration of them and vocabulary and nomenclature for identifying reports of meta-analyses in the published literature.

Toward more definitive clinical trials.

The randomized clinical trial is an essential evaluation tool in the health care field. Unfortunately, the majority of trials performed have too few patients to reach a conclusion regarding the treatments under study. In many instances, the multicenter trial represents the only way to obtain the necessary numbers. Such trials are difficult to organize and costly to carry out, but they have strengths not found in the ordinary single center trial. The multiplicity of disciplines required usually leads to better design and more careful execution than can be achieved with the resources of a single center. The heterogeneity of the population and multiplicity of clinics applying the study treatments provide a more realistic test of the therapies in question than is possible in a single clinic. Sponsors of trials need to stimulate more research into the methodology of multicenter trials, including investigation of the methods of organizing and carrying out such trials in a cost-effective manner. In addition, a communications network should be developed to promote the field of clinical trials as a discipline and to facilitate the identification and dissemination of information on their design and conduct.