Using epidemiological data to model efficiency in reducing the burden of depression*

BACKGROUND: The Global Burden of Disease study has suggested that mental disorders are the leading cause of disability burden in the world. This study takes the leading cause of mental disorder burden, depression, and trials an approach for defining the present and optimal efficiency of treatment in an Australian setting. AIMS OF THE STUDY: To examine epidemiological and service use data for depression to trial an approach for modelling (i) the burden that is currently averted from current care, (ii) the burden that is potentially avertable from a hypothetical regime of optimal care, (iii) the efficiency or cost-effectiveness of both current and optimal services for depression and (iv) the potential of current knowledge for reducing burden due to depression, by applying the WHO five-step method for priorities for investment in health research and development. METHODS: Effectiveness and efficiency were calculated in disability adjusted life years (DALYs) averted by adjusting the disability weight for people who received efficacious treatment. Data on service use and treatment outcome were obtained from a variety of secondary sources, including the Australian National Survey of Mental Health and Wellbeing, and efficacy of individual treatments from published meta-analyses expressed in effect sizes. Direct costs were estimated from published sources. RESULTS: Fifty-five percent of people with depression had had some contact with either primary care or specialist services. Effective coverage of depression was low, with only 32% of cases receiving efficacious treatment that could have lessened their severity (averted disability). In contrast, a proposed model of optimal care for the population management of depression provided increased treatment contacts and a better outcome. In terms of efficiency, optimal care dominated current care, with more health gain for less expenditure (28 632 DALYs were averted at a cost of AUD295 million with optimal care, versus 19 297 DALYs averted at a cost of AUD720 million with current care). However, despite the existence of efficacious technologies for treating depression, only 13% of the burden was averted from present active treatment, primarily because of the low effective coverage. Potentially avertable burden is nearly three times this, if effective treatments can be delivered in appropriate amounts to all those who need it. DISCUSSION: This paper reports a method to calculate the burden currently averted from cross-sectional survey data, and to calculate the burden likely to be averted from an optimal programme estimated from randomized controlled trial data. The approach taken here makes a number of assumptions: that people are accurate in reporting their service use, that effect sizes are a suitable basis for modelling improvements in disability and that the method used to translate effect sizes to disability weight change is valid. The robustness of these assumptions is discussed. Nonetheless it would appear that while optimal care could do more than present services to reduce the burden of depression, current technologies for treating depression are insufficient. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: There is an urgent need to educate both clinicians (primary and specialist) and the general public in the effective treatments that are available for depression. IMPLICATIONS FOR HEALTH POLICIES: Over and above implementing treatments of known efficacy, more powerful technologies are needed for the prevention and treatment of depression. IMPLICATIONS FOR FURTHER RESEARCH: Modelling burden averted from a variety of secondary sources can introduce bias at many levels. Future research should examine the validity of approaches that model reductions in disability burden. A powerful treatment to relieve depression and prevent relapse is needed.     

Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study

OBJECTIVE: Prazosin is a centrally active alpha(1) adrenergic antagonist. The authors' goal was to evaluate prazosin efficacy for nightmares, sleep disturbance, and overall posttraumatic stress disorder (PTSD) in combat veterans. METHOD: Ten Vietnam combat veterans with chronic PTSD and severe trauma-related nightmares each received prazosin and placebo in a 20-week double-blind crossover protocol. RESULTS: Prazosin (mean dose=9.5 mg/day at bedtime, SD=0.5) was superior to placebo for the three primary outcome measures: scores on the 1) recurrent distressing dreams item and the 2) difficulty falling/staying asleep item of the Clinician-Administered PTSD Scale and 3) change in overall PTSD severity and functional status according to the Clinical Global Impression of change. Total score and symptom cluster scores for reexperiencing, avoidance/numbing, and hyperarousal on the Clinician-Administered PTSD Scale also were significantly more improved in the prazosin condition, and prazosin was well tolerated. CONCLUSIONS: These data support the efficacy of prazosin for nightmares, sleep disturbance, and other PTSD symptoms.     

La Crosse encephalitis in Eastern Tennessee: clinical,environmental, and entomological characteristics from a blinded cohort study

A blinded cohort study was conducted in 2000 to better understand the emergence of La Crosse virus infection in eastern Tennessee, with special emphasis on the potential mosquito vector(s). Children with suspected central nervous system infection were enrolled at the time of clinical presentation at a large pediatric referral hospital. Clinical, environmental, and entomological data were collected prior to case confirmation. Sixteen of the 40 children included in the final analysis were confirmed to have La Crosse infection by a fourfold increase in antibody titers between collection of acute- and convalescent-phase sera. Factors significantly associated with La Crosse infection included average number of hours per day spent outdoors (5.9 for La Crosse virus cases vs. 4.0 for noncases, p = 0.049); living in a residence with one or more tree holes within 100 m (relative risk = 3.96 vs. no tree holes within 100 m, p = 0.028); and total burden of Aedes albopictus (number of female and male larvae and adults collected at a site), which was more than three times greater around the residences of La Crosse virus cases versus noncases (p = 0.013). Evidence is accumulating that the newly introduced mosquito species Ae. albopictus may be involved in the emergence of La Crosse virus infection in eastern Tennessee.     

The OptiMARK clinical development program: summary of safety data

PURPOSE: To describe and summarize the safety data from the OptiMARK clinical development program. MATERIALS AND METHODS: In the 18 clinical studies comprising the clinical program, doses ranging from 0.1 to 0.7 mmol/kg were administered to healthy adult volunteers, patients with hepatic or renal impairment, and patients with confirmed or highly suspected central nervous system (CNS), liver, breast, vascular, bone, or soft tissue pathologies. A total of 2038 injections of OptiMARK, Magnevist, or placebo were administered to 1684 subjects. Safety assessments were performed at appropriate intervals during all Phase 1, 2, and 3 studies. RESULTS: Of the 1684 subjects exposed to a study drug or placebo in the clinical development program, 646 subjects experienced 1293 adverse events. Thirty-one percent of the OptiMARK injections were associated with an adverse event. In comparison, 35% of Magnevist injections and 48% of placebo injections were associated with at least one adverse event. CONCLUSIONS: OptiMARK was safe and well-tolerated with a safety profile similar to that of Magnevist.     

Tumoral calcinosis in infants: a report of three cases and review of the literature

Tumoral calcinosis is the deposition of calcium crystals and salts in the periarticular soft tissues. It commonly is seen as a complication of renal dialysis or in patients with a hereditary disposition. Occasionally, it is seen as an isolated condition with no known cause. Tumoral calcinosis usually affects adults and rarely, children. This disorder is extremely uncommon in infants. Only 13 cases have been reported. In this study three additional infants with tumoral calcinosis are reported, bringing the total to 16 cases. These 16 cases provide the opportunity to compare tumoral calcinosis in infants (younger than 18 months) with the disease in older patients. Although histologic and radiologic features in infants and adults are identical, some clinical features differ. In almost all infants, the disease develops without any predisposing factors, such as a family history. Surgical removal of lesions in infants is curative. By contrast, lesions in adults tend to recur after surgery.     

Weight loss favorably modifies anthropometrics and reverses the metabolic syndrome in premenopausal women

OBJECTIVE: To determine the effects of a weight loss program, including dietary modifications, increased physical activity and dietary supplement (L-carnitine or placebo) on anthropometrics, leptin, insulin, the metabolic syndrome (MS) and insulin resistance in overweight /obese premenopausal women. METHODS: Participants consumed a hypocaloric diet; 30% protein, 30% fat and 40% carbohydrate in addition to increasing number of steps/day. Carnitine supplementation followed a randomized double blind protocol. Protocol lasted for 10 weeks. Seventy subjects (35 in the control and 35 in the carnitine group) completed the intervention. Anthropometrics, plasma insulin and leptin concentrations and body composition were measured. The number of subjects with the MetSyn and insulin resistance, were assessed at baseline and post-intervention. RESULTS: Because there were no significant differences between the carnitine and the placebo groups for all measured parameters, participants were grouped together for all analysis. Subjects decreased total energy (-26.6%, p < 0.01) and energy from carbohydrate (-17.3%, p < 0.01) and increased energy from protein by 67% (p < 0.01) and number of steps/day (42.6%, p < 0.01). Body weight (-4.6%, p < 0.001), body mass index (-4.5%, p < 0.01), waist circumference (-6.5%, p < 0.01), total fat mass (-1.7%, p < 0.01), trunk fat mass (-2.0%, p < 0.01), insulin (- 17.9%, p < 0.01) and leptin (-5.9%, p < 0.05) decreased after the intervention. Ten of 19 participants with insulin resistance became insulin sensitive and 7 of 8 participants with the MetSyn no longer had the syndrome after the intervention. CONCLUSION: Moderate increases in physical activity and a hypocaloric/high protein diet resulted in multiple beneficial effects on body anthropometrics and insulin sensitivity. Realistic dietary and physical activity goals must be the focus of intervention strategies for overweight and obese individuals.     

Dietary intake in HIV-positive persons with and without malabsorption.

This review examines the relationship among malabsorption, diarrhea, dietary intake, and body composition in an outpatient cohort of individuals with HIV infection. Twenty-three percent of the participants had malabsorption, which was not associated with the presence of current or chronic diarrhea. In this "outpatient" HIV cohort with a mean body-mass index (BMI) of 25 kg/m2, the presence of malabsorption did not have adverse nutritional outcomes in terms of body weight, lean body mass, hemoglobin, or albumin. The diets of those with or without malabsorption did not meet the goals of the Dietary Guidelines for Americans. Median dietary intake was high in percentage of total fat and saturated fat and low in total fiber intake and some key micronutrients.