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Background: Schizophrenia is a costly and complicated disorder to treat. A variety of schizophrenia treatment guidelines have been developed to provide valuable expert advice to practicing psychiatrists on various treatment options that are presumed to result in the best outcomes. However, examination of antipsychotic medication use patterns has suggested that current prescribing practices do not mirror recommended treatment guidelines and may have adverse economic consequences., Aim of the Study: This study seeks to describe antipsychotic medication treatment patterns and estimate the total costs of care associated with treatment patterns for individuals diagnosed with schizophrenia in usual care settings., Methods: Use of outpatient antipsychotic medications and other health services during 1997 was obtained for 2,082 individuals with a diagnosis of schizophrenia in the IMS Health LifeLink employer claims database. We describe outpatient antipsychotic treatment patterns, estimated the costs of schizophrenia care by treatment pattern, and compared costs by treatment pattern using regression models., Results: During 1997, 26% (n=536) of individuals diagnosed with schizophrenia received no antipsychotic medication in the outpatient setting, while 52% (n=1,088) were treated with only one antipsychotic (Monotherapy). For individuals who received more than one antipsychotic medication during 1997 (n=458), 13% (n=262) switched antipsychotic medications (Switch), 7% (n=154) augmented their original antipsychotic therapy with an additional antipsychotic (Augment), and 2% (n=42) of individuals were on more than one antipsychotic therapy at the start of the year. After adjusting for covariates, Switch and Augment patterns were associated with significant increases in total costs (an increase of 4,706 dollars (p<0.0001) and 4,244 dollars (p=0.0002), respectively) relative to Monotherapy., Discussion: These results indicate that a substantial proportion of individuals with a diagnosis of schizophrenia were not treated with or had low exposure to antipsychotic therapy. Individuals treated with antipsychotic monotherapy experienced nearly half the annual costs as individuals who were treated with antipsychotic polytherapy or who switched antipsychotic medications. These observations should be interpreted in the context of the study limitations., Implications for Health Care Provision and Use: This analysis indicates that there may be considerable room for improvement in the treatment for individuals diagnosed with schizophrenia., Implications for Health Policies: Though schizophrenia affects a very small portion of the population, the individual and societal burden associated with the disorder is quite high. This paper suggests that antipsychotic monotherapy and continuous therapy, commonly recommended by published treatment guidelines, may be associated with economic savings., Implications for Further Research: Future research should evaluate the impact of newer antipsychotic medications on patterns of care and economic outcomes. More information is also needed on which individual patient characteristics are likely to predict success or failure on specific treatments. Finally, more detailed information on the reasons or rationale for switching or augmenting original pharmacotherapy would be valuable in improving medication management in these complex and often difficult to treat patients.

Advances in treatment technologies and development of evidence-based standards of care demand better methods for routine assessment of outcomes for schizophrenia in systems of care. This article describes the development and psychometrics of a new instrument to assess outcomes of routine care for persons with schizophrenia in service systems. Candidate items for the Schizophrenia Care and Assessment Program Health Questionnaire (SCAP-HQ) were drawn from existing measures. Domains covered include disease outcomes (symptoms, subjective medication effects, substance abuse), functional status, health status, quality of life, and public safety. A sample of 1,584 patients with schizophrenia or schizoaffective disorder who were recruited into a large prospective, naturalistic study on the course of treatment for schizophrenia completed the SCAP-HQ at baseline and 1 year later (n = 434), providing data for factor analysis, assessment of internal consistency, convergent validity, and responsiveness to change. A subsample of 121 patients completed a test-retest protocol. Fifteen scales were derived by factor analysis from 55 outcome items on the SCAP-HQ. These factors covered psychiatric symptoms, life satisfaction, instrumental activities of daily living, health-related disability, subjective medication side effects, vitality, legal problems, social relations, mental health-related disability, suicidality, drug and alcohol use, daily activities, victimization, violence, and employment. For most scales, standard psychometric parameters, including internal consistency and test-retest reliability, convergent validity, and responsiveness to change, were acceptable for application to large sample evaluations of care systems. This new measure represents an advance in the development of outcome measures for schizophrenia for use in large-scale studies of routine care.

This study documents the drug therapy patterns and 1-year treatment costs for 18,833 Medicaid patients with schizophrenia treated with conventional antipsychotic medications in Michigan, Kentucky, Alabama, and Georgia. One in four patients used no antipsychotic, but had total costs that were less than for treated patients (-$2,576, p < .0001); 18 percent of treated patients delayed therapy for at least 1 month and had significantly higher total costs of $3,994 (p < .0001); 41 percent of treated patients changed therapy with similar results (+$4,067, p < .0001). Only 20 percent of patients were compliant with drug therapy but this had no significant impact on total treatment costs.

Objective: Human papillomavirus (HPV) infection is a significant risk factor for uterine cervical carcinoma. However, the role of HPV infection in oral squamous cell carcinoma (OSCC) is less well defined. To determine the significance of the relationship of this virus in the progressive development of oral cancer, we estimated the risk of HPV detection in normal oral mucosa, precancerous oral tissue, and oral carcinoma using meta-analysis., Study Design: Case reports and clinical series published in English-language journals were retrieved by searching MEDLINE (January 1980-August 1998). Review articles were also examined to identify additional studies. Studies that used biochemical, immunologic, microscopic, or molecular analyses to detect HPV in tissue or cells derived from normal oral mucosa (n = 25), benign leukoplakia (n = 21), intraepithelial neoplasia (ie, dysplasia and carcinoma in situ; n = 27), and oral cancer (n = 94) were included in the meta-analysis. Information on sample size, age, sex, method of tissue preservation (ie, fresh, frozen, paraffin-embedded), assay, primer amplification region (early, late), high-risk versus low-risk genotype, and use of tobacco or alcohol was abstracted by one author (C.S.M.)., Results: Data from 94 reports that analyzed 4680 samples were included in the meta-analysis. Analyses made by means of a random-effects model with and without adjustments for assay sensitivity showed increased probability of HPV detection in tissue with precancerous and cancerous features compared with normal mucosa. The likelihood of detecting HPV in normal oral mucosa (10.0%; 95% confidence interval [CI], 6.1%-14.6%) was significantly less than of detecting benign leukoplakia (22.2%; 95% CI, 15.7%-29.9%), intraepithelial neoplasia (26.2%; 95% CI, 19.6%-33.6%), verrucous carcinoma (29.5%; 95% CI, 23%-36.8%), and OSCC (46.5%; 95% CI, 37.6%-55.5%). Adjustment of findings for differences in assay sensitivity indicated that these estimates may be conservative. Overall, HPV was between 2 and 3 times more likely to be detected in precancerous oral mucosa and 4.7 times more likely to be detected in oral carcinoma than in normal mucosa. The pooled odds ratio for the subset of studies directly comparing the prevalence of HPV in normal mucosa and OSCC was 5.37, confirming the trend observed in the overall sample. The probability of detecting high-risk HPVs in OSCCs was 2.8 times greater than that of low-risk HPVs., Conclusion: This meta-analysis indicates that HPV is detected with increased frequency in oral dysplastic and carcinomatous epithelium in comparison with normal oral mucosa. The findings provide further quantitative evidence that oral infection with HPV, particularly with high-risk genotypes, is a significant independent risk factor for OSCC.

Objective: To compare the clinical and economic outcomes associated with olanzapine and risperidone treatment for schizophrenia., Design and Setting: An international, multicentre, double-blind, prospective study. To facilitate economic comparisons, our sample was restricted to patients enrolled in US sites. 150 patients with a Diagnostic and Statistical Manual of mental disorders, 4th edition (DSM-IV) diagnosis of schizophrenia, schizoaffective disorder or schizophreniform disorder were randomised to therapy with either olanzapine 10 to 20 mg/day (n = 75) or risperidone 4 to 12 mg/day (n = 75) for a maximum of 28 weeks. In addition to tolerability and efficacy assessments, use of health services was assessed at baseline and prospectively, at 8-week intervals and at study completion. Clinically important response, defined as a 40% improvement in the Positive and Negative Syndrome Scale total score, maintenance of response and rates of treatment-emergent extrapyramidal symptoms were compared between groups. Direct medical costs were estimated by assigning standardised prices to resource units. Median total, inpatient/outpatient service and medication acquisition costs were compared between treatment groups., Main Outcome Measures and Results: The mean modal dosages for the olanzapine and risperidone treatment groups were 17.7 +/- 3.4 mg/day and 7.9 +/- 3.2 mg/day, respectively. Olanzapine-treated patients were more likely to maintain response compared with risperidone-treated patients (p = 0.048). In addition, a smaller proportion of olanzapine-treated patients required anticholinergic therapy compared with risperidone-treated patients (25.3 vs 45.3%; p = 0.016). Total per patient medical costs over the study interval were $US2843 (1997 values) [36%] lower in the olanzapine treatment group than in the risperidone treatment group (p = 0.342). Medication costs were significantly higher for olanzapine-treated patients ($US2513 vs $US1581; p < 0.001), but this difference was offset by a reduction of $US3774 (52%) in inpatient/outpatient service costs for olanzapine-treated patients in comparison with risperidone-treated patients ($US3516 vs $US7291, p = 0.083). Median cost findings were consistent with results observed using other robust measures of central tendency and provide conservative estimates of potential savings that may be obtained from olanzapine therapy., Conclusions: In this study, olanzapine-treated patients experienced clinical improvements that translated into savings in costs of care for both inpatient and outpatient services. These savings offset the difference in medication acquisition cost between olanzapine and risperidone.

The cornerstone of recent pharmacoeconomic work in schizophrenia is the hypothesis that the improved efficacy of novel antipsychotic medications will lead to a reduction in medical services utilization, thereby reducing direct medical costs associated with treatment. Creating the most valid design to prospectively examine the effectiveness and costs of competing pharmacotherapies requires a dialectic of opposing research paradigms. The final protocol must represent a series of decisions that strike a careful balance between being scientifically sound (internal validity) and generalizable to the real world of clinical treatment (external validity). The results must be useful to decision-makers in determining to what extent reductions in healthcare expenditures can offset higher drug acquisition costs within their type of treatment environment. This article is a review of several methodological challenges in the design of medical effectiveness trials, including whether to blind the study, definition of the patient population, degree of physician discretion in treatment, and how to collect and analyze data for patients who discontinue their originally assigned medication. The article also provides a discussion of how clinical practices can inform decisions made to meet these challenges. The issues are illustrated through a prospective study designed to evaluate the cost-effectiveness of the newer antipsychotics in general and olanzapine in particular. Cost-effectiveness studies of novel antipsychotic medications, particularly those with naturalistic designs, will increase in importance as the use of these second-generation agents continues to expand.

Objective: To evaluate the association between drug therapy patterns achieved with conventional antipsychotics and direct healthcare costs over 2 years., Methods: Paid claims data from the California Medicaid (Medi-Cal) program were used to identify 2476 patients with schizophrenia for whom 2 years of data were available. Ordinary least squares (OLS) regression models were used to estimate the association between lack of antipsychotic drug therapy, delayed therapy, changes in medications, and continuous therapy on healthcare costs over a 2-year period., Results: Nearly 99% of Medi-Cal patients with schizophrenia were treated with conventional antipsychotics. Patients with schizophrenia consumed nearly $48,000 in direct costs over 2 years. Over 16% of patients did not use any antipsychotic medication for 2 years. Untreated patients used more healthcare resources than treated patients did ($10,833, P = .0422), especially psychiatric hospital care ($8,027, P = .0004). However, treated patients frequently experienced suboptimal drug use patterns. Nearly 33% of treated patients delayed antipsychotic therapy for up to 2 years. Delayed therapy was associated with increased costs of $12,285 (P = .070). Over 56% of patients experienced changes in therapy that were associated with higher total direct costs ($17,644, P < .0001). Finally, only 3.2% of treated patients used an antipsychotic medication consistently for 2 years. However, continuous drug therapy was not associated with lower costs., Conclusion: Suboptimal drug use patterns are common and costly in Medi-Cal patients with schizophrenia who initiated therapy with conventional antipsychotics.

This study investigated the relationships between antipsychotic drug use patterns and direct costs for 3,321 Medi-Cal patients with schizophrenia. Ordinary least-squares regression models were used to estimate the impact on costs of receiving antipsychotic drug treatment, delays in treatment, changes in therapy, and continuous therapy. Average costs were $25,940 per year per patient. Having used an antipsychotic drug was correlated with lower psychiatric hospital costs ($2,846 less) but higher nursing home costs. Completing one year of uninterrupted drug therapy was correlated with higher nursing home costs. Delayed drug treatment and changes in therapy increased the cost by $9,418 and $9,719, respectively.

Background: Although the results of many clinical studies suggest that breast-fed children score higher on tests of cognitive function than do formula-fed children, some investigators have suggested that these differences are related to confounding covariables such as socioeconomic status or maternal education., Objective: Our objective was to conduct a meta-analysis of observed differences in cognitive development between breast-fed and formula-fed children., Design: In this meta-analysis we defined the effect estimate as the mean difference in cognitive function between breast-fed and formula-fed groups and calculated average effects using fixed-effects and random-effects models., Results: Of 20 studies meeting initial inclusion criteria, 11 studies controlled for >/=5 covariates and presented unadjusted and adjusted results. An unadjusted benefit of 5.32 (95% CI: 4.51, 6.14) points in cognitive function was observed for breast-fed compared with formula-fed children. After adjustment for covariates, the increment in cognitive function was 3.16 (95% CI: 2.35, 3.98) points. This adjusted difference was significant and homogeneous. Significantly higher levels of cognitive function were seen in breast-fed than in formula-fed children at 6-23 mo of age and these differences were stable across successive ages. Low-birth-weight infants showed larger differences (5.18 points; 95% CI: 3.59, 6.77) than did normal-birth-weight infants (2.66 points; 95% CI: 2.15, 3.17) suggesting that premature infants derive more benefits in cognitive development from breast milk than do full-term infants. Finally, the cognitive developmental benefits of breast-feeding increased with duration., Conclusion: This meta-analysis indicated that, after adjustment for appropriate key cofactors, breast-feeding was associated with significantly higher scores for cognitive development than was formula feeding.

Unlabelled: Schizophrenia leads to impairments in mental, social, and physical functioning, which should be included in evaluations of treatment., Objectives: This study was designed to determine the reliability and validity of the Medical Outcomes Study Short Form Health Survey (SF-36) for schizophrenic patients, to characterize perceived functioning and well being and to compare short-term change in SF-36 scores for patients treated with olanzapine or haloperidol., Research Design: Data were obtained from a randomized, double-blind trial comparing these agents for safety, efficacy, and cost effectiveness. A 6-week acute treatment portion preceded a 46-week "responder extension" phase., Subjects: A subsample (n = 1,155) completing a pre-treatment SF-36 provided data for this study., Measures: Psychometric analyses were conducted, and perceived level of functioning was compared with that for the US adult population. Change from baseline to 6 weeks was examined by treatment group., Results: Clear evidence was obtained for the instrument's reliability and validity for these patients. There were marked deficits in General health, Vitality, Mental health, Social functioning, and in Role limitations resulting from both physical and emotional problems. Olanzapine-treated patients improved in 5 of 8 domains to a significantly greater degree than did haloperidol patients., Conclusions: The SF-36 can be a reliable and valid measure of perceived functioning and well being for schizophrenic patients. The perceptions of functioning can be valuable indices of disease burden and can help to demonstrate the effectiveness of newer antipsychotic medications such as olanzapine.

Background: Health plans commonly face the conflicting demands of trying to provide access to novel technologies, including new classes of medications, while trying to contain costs. These demands are particularly acute for California's Medicaid program, known as Medi-Cal, which is responsible for delivery of medical care to an unusually large population of mentally ill individuals in the context of a culturally diverse environment. To meet the challenge, Medi-Cal has instituted a formal process for technology assessment of new and existing pharmaceutical products known as the Therapeutic Class Review (TCR)., Objective: The purpose of this paper is to describe the information produced for Medi-Cal in the TCR process for antidepressant medications and the individual petition review of antipsychotic medications, and to synthesize our experience in a series of policy recommendations designed to improve the quality of coverage decisions., Outcome: A collaborative process between Medi-Cal and Lilly resulted in a substantive body of new evidence regarding the needs of Medi-Cal recipients, the quality of current treatment, and prospects regarding the cost-effectiveness of introducing newer treatments., Conclusion: Medi-Cal has a formal process for evaluating new medicines. This process allows researchers to understand the needs of those who make coverage decisions. We recommend increasing routine epidemiologic surveillance, including service use, and clinical trials that include aspects of usual medical care early in the drug development process.

We utilize data from a large, double-blind, randomized clinical trial of treatment for schizophrenia to compare the effect of therapy with the second generation antipsychotic olanzapine versus therapy with the conventional agent haloperidol on the perceived functioning and well-being of patients over 1 year as measured by the Medical Outcome Study Short Form (SF-36). We also compare the total cost of care between the treatment groups over 1 year and combine cost and functional outcomes information to estimate the incremental cost-effectiveness of both therapies in this sample. Over 1 year of therapy, patients receiving olanzapine experienced a mean of 5.75 units greater improvement than did haloperidol-treated patients on the physical health and functioning factor of the SF-36 and 1.66 units greater improvement on the mental health and functioning factor. The mean annual total cost of care, including the cost of medication therapies, was $9386.87 less for olanzapine-treated patients than for haloperidol-treated patients. The incremental cost-effectiveness ratio for olanzapine versus haloperidol treatment indicated a savings of $1632.50 per unit of improvement in the SF-36 physical health and functioning score and a savings of $5654.74 per unit of improvement in the mental health and functioning composite. Improvements in perceived health and functioning were also associated with reduction in hospital costs in the full sample. These findings suggest that patient-centered measures of functioning such as the SF-36 are an important component of the evaluation of the cost-effectiveness of novel treatments for schizophrenia.

Medications comprise a minor portion of the costs of schizophrenia, but may have a major impact on the likelihood of successful outcome of care. Novel antipsychotic medications which demonstrate superior symptom control, an improved safety profile, and benefits to quality-of-life may also reduce patients' need for medical services and the associated costs of these treatments. This report first considers key experimental design elements involved in integrating pharmacoeconomic and clinical objectives in studies of new drug therapies for schizophrenia. We briefly discuss the choice of therapies for comparison, randomization and blinding, sample size and composition, data collection, selection of the time frame for economic evaluation, and the importance of an intent-to-treat perspective. Second, as an example we present the design and selected results from a new economic clinical trial of the novel antipsychotic olanzapine. This trial utilized a randomized, double-blind design to compare the use of medical services and the cost of treatment for 817 schizophrenic patients from the United States treated with olanzapine or haloperidol. In comprehensive health care cost comparisons that incorporated the expenditures for study medications, the total cost of health care for olanzapine-treated patients was reduced by an average of $431 per month in comparison with haloperidol-treated patients during the initial 6 weeks of treatment. Among treatment responders receiving double-blind therapy for a maximum of 1 year, the total cost of care among olanzapine responders was reduced by an average of $345 per month in comparison with haloperidol responders. The results of this economic evaluation suggest that olanzapine's superior treatment profile may lead to reductions in the overall costs of medical care for patients with schizophrenia.

Objective: This report evaluates the relative contribution of predictors of change in the frequency of alcohol consumption among drinkers, based on the quantitative synthesis of data from 27 longitudinal studies of the general population. The analysis has two objectives: (1) to evaluate the impact of selected demographic characteristics on the magnitude and trajectory of change in drinking across multiple samples, and (2) to assess the influence of methodological characteristics on the consistency of results across studies., Method: Raw data from studies including two serial measures of the frequency of alcohol consumption are analyzed. Fixed, random and mixed effects models for meta-analysis are used to pool measures across observations and model the influence of predictors on variability between results., Results: Gender-based variation in the patterning of change is present across all observations, but concentrated in early periods of the life course. Age displays significant predictive effects across all observations, but statistically uniform results are obtained for subjects aged 30 and over. The national origin of study predicts larger amounts of variation than do other demographic predictors in the models. Significant effects are observed for several methodological characteristics of studies. Variation among effect estimates is associated with differences between samples in the interval between first and final measurements, the date of first measurement (a proxy for the historical context of the sample), the percentage retention of subjects between measurements and the time frame of the original alcohol measure., Conclusions: Based on the synthesis of data from multiple longitudinal samples, this study (1) characterizes normative developmental patterning in the frequency of alcohol consumption and demonstrates the varying effects of demographic factors across the life-course: (2) indicates the key influence of cultural and historical context on the establishment of drinking patterns; and (3) confirms the impact of methodological differences on variation in the results of studies.

Background: This article reports the results of a 5-year, longitudinal evaluation of the effectiveness of Drug Abuse Resistance Education (DARE), a school-based primary drug prevention curriculum designed for introduction during the last year of elementary education. DARE is the most widely disseminated school-based prevention curriculum in the United States., Method: Twenty-three elementary schools were randomly assigned to receive DARE and 8 were designated comparison schools. Students in the DARE schools received 16 weeks of protocol-driven instruction and students in the comparison schools received a drug education unit as part of the health curriculum. All students were pretested during the 6th grade prior to delivery of the programs, posttested shortly after completion, and resurveyed each subsequent year through the 10th grade. Three-stage mixed effects regression models were used to analyze these data., Results: No significant differences were observed between intervention and comparison schools with respect to cigarette, alcohol, or marijuana use during the 7th grade, approximately 1 year after completion of the program, or over the full 5-year measurement interval. Significant intervention effects in the hypothesized direction were observed during the 7th grade for measures of students' general and specific attitudes toward drugs, the capability to resist peer pressure, and estimated level of drug use by peers. Over the full measurement interval, however, average trajectories of change for these outcomes were similar in the intervention and comparison conditions., Conclusions: The findings of this 5-year prospective study are largely consonant with the results obtained from prior short-term evaluations of the DARE curriculum, which have reported limited effects of the program upon drug use, greater efficacy with respect to attitudes, social skills, and knowledge, but a general tendency for curriculum effects to decay over time. The results of this study underscore the need for more robust prevention programming targeted specifically at risk factors, the inclusion of booster sessions to sustain positive effects, and greater attention to interrelationships between developmental processes in adolescent substance use, individual level characteristics, and social context.

Background: In laboratory animals, the consumption of soy protein, rather than animal protein, decreases serum cholesterol concentrations, but studies in humans have been inconclusive. In this meta-analysis of 38 controlled clinical trials, we examined the relation between soy protein consumption and serum lipid concentrations in humans., Methods: We used a random-effects model to quantify the average effects of soy protein intake on serum lipids in the studies we examined and used hierarchical mixed-effects regression models to predict variation as a function of the characteristics of the studies., Results: In most of the studies, the intake of energy, fat, saturated fat, and cholesterol was similar when the subjects ingested control and soy-containing diets; soy protein intake averaged 47 g per day. Ingestion of soy protein was associated with the following net changes in serum lipid concentrations from the concentrations reached with the control diet: total cholesterol, a decrease of 23.2 mg per deciliter (0.60 mmol per liter); 95 percent confidence interval, 13.5 to 32.9 mg per deciliter [0.35 to 0.85 mmol per liter]), or 9.3 percent; low-density lipoprotein (LDL) cholesterol, a decrease of 21.7 mg per deciliter (0.56 mmol per liter); 95 percent confidence interval, 11.2 to 31.7 mg per deciliter [0.30 to 0.82 mmol per liter]), or 12.9 percent; and triglycerides, a decrease of 13.3 mg per deciliter (0.15 mmol per liter; 95 percent confidence interval, 0.3 to 25.7 mg per deciliter [0.003 to 0.29 mmol per liter]), or 10.5 percent. The changes in serum cholesterol and LDL cholesterol concentrations were directly related to the initial serum cholesterol concentration (P < 0.001). The ingestion of soy protein was associated with a nonsignificant 2.4 percent increase in serum concentrations of high-density lipoprotein (HDL) cholesterol., Conclusions: In this meta-analysis we found that the consumption of soy protein rather than animal protein significantly decreased serum concentrations of total cholesterol, LDL cholesterol, and triglycerides without significantly affecting serum HDL cholesterol concentrations.

There is a critical need for the development of effective substance abuse and dependence treatment programs in prisons and jails. One aspect of treatment provision within this population that has received insufficient research attention is the inclusion of health promotion or wellness programs, including exercise and other health-related lifestyle modification training. Little is known about either the physiological or psychological consequences of such lifestyle modification programs among prisoners with substance use disorders. This study reports the effectiveness of an experimental wellness program included as part of a residential treatment unit in a federal correctional institute in the United States. A sample of 43 female offenders with a history of polysubstance abuse or dependence, who had volunteered to be part of a residential drug treatment program, were evaluated. Changes in health status and perceived psychological well-being between entry into the program and exit after maintaining participation for a minimum of 9 months were assessed. Pretest-posttest comparisons on a variety of physiological parameters indicated that significant improvements had occurred in the physical fitness of the group. Thematic analysis of qualitative self-reports by inmates exiting the program suggested that participants had also experienced significant enhancements in a number of areas pertaining to psychological well-being, including self-esteem, health awareness and concerns, healthy lifestyle adoption, and relapse prevention skills. These results suggest that including health promotion training in drug treatment programs for incarcerated offenders may have beneficial results.

The ototoxic action of salicylate was investigated in the guinea pig by perfusion of both salicylate and bromosalicylate through scala tympani. The results qualitatively confirmed experiments using intravenous administration in cats (Stypulkowski, 1990), showing dose-dependent elevations in compound action potential (CAP) thresholds, increases in cochlear microphonics (CM) and level-dependent reductions in 2f1-f2 acoustic distortion products. The endocochlear potential was not significantly affected and iontophoretic injection of salicylate into scala media had no measurable effect on CAP thresholds, consistent with an action on the basolateral walls of the hair cells. Perfusion with indomethacin produced effects similar to those of the salicylates, but at non-physiological doses. Together with the great effectiveness of 5-bromosalicylate, this suggests that salicylate does not act by inhibiting prostaglandin synthesis. The results are qualitatively consistent with the proposition that salicylates act on the basolateral walls of the outer hair cells. However, the magnitude of the CM increases, particularly at high drug concentrations, and the fact that salicylate reduced, but did not eliminate the effects of olivocochlear efferent stimulation on CM amplitude indicate that a simple explanation for salicylate effects based solely on a conductance increase in the outer hair cell membranes may be inadequate.

f2-f1, but not 2f1-f2, was reduced in amplitude during continuous stimulation of the test ear with the primary tones, and with single tones near the primary frequencies. Stimulation of the contralateral ear, either with broad band noise or with single tones near the primary frequencies, also reduced f2-f1. Ipsilateral and contralateral effects were additive and were restricted to the frequency range between about 2 kHz and 7 kHz. Contralateral, but not ipsilateral suppression, was blocked after systemic administration of strychnine. Ipsilateral suppression was eliminated by perfusion of the cochlea with tetrodotoxin. Both contralateral and ipsilateral suppression were abolished after perfusion of the cochlea with bicuculline. The results are evidence for a role for a GABA-ergic efferent system in the modulation of outer hair cell mechanics in the apical cochlea.

In contextual (cross-level) analysis within multiple longitudinal general population studies, individual-level drinking behaviors (quantity per typical occasion, frequency of drinking per month and total volume of drinks per month) at final measurement are assessed by three models that simultaneously enter individual- and group-level measures. Two age groups (15-20 and 21-30) are independently assessed. In each model, the Time 1 individual-level drinking behavior and one of three group-level factors are entered. The group-level factors are (1) the percentage of abstainers at Time 1 for each age/sex cohort, (2) the Time 1 group mean for the drinking measure for the age/sex cohort and (3) the mean difference of the age/sex cohort's change in the drinking measure over time. All variables in the model are controlled by variations to exposure in per capita consumption of alcohol during the age/sex cohort's formative years and at Time 2. Meta-analysis assesses the homogeneity of the findings across studies. Models were proposed with the rationale that (1) understanding of individual drinking behavior can be advanced if individual-level data and group-level data are considered in the same models, and (2) integration of these two levels of analyses are, to date, rare. The rationale for using meta-analysis is that findings from the models can be assessed across social contexts with respect to their generalizability. The mean difference model, controlling for individual drinking at Time 1, is the most influential of the group-level models for the younger age group: the degree to which the group changes its drinking pattern is positively related to individual-level drinking behavior at final measurement, over and above the individual's drinking behavior at Time 1, for individual-level frequency of drinking among males (homogeneous among drinkers only). Younger females show more significant relationships for the mean difference females show more significant relationships for the mean difference model. Findings are significant for all relationships examined for the mean difference of the drinking of the group and the individual drinking among the older males and females. Measures of individual-level drinking for all measures at Time 1, controlling for the group-level effects, are significantly related to individual-level drinking at final measurement. The results are homogeneous for quantity (drinkers only) and volume among the young. Findings indicate that characterizations of the drinking for both the individual and the group to which the individual belongs predict measures of drinking practices on the individual level over time.

The mammalian cochlea responds with exquisite sensitivity to the small fluctuations in air pressure that make up the stimulus of sound. Moreover, it responds to pressure fluctuations that occur extremely rapidly and that vary over a wide range of intensities--in both cases, to an extent outside the capabilities of unaided nerve fibres. Research performed during the past decade has shown that these properties are dependent on a physiological source of mechanical energy that operates probably within the outer hair cells of the organ of Corti. These cells, which are anatomically and functionally similar to the primary receptor cells, the inner hair cells, are believed to function as a source of mechanical power to assist the mechanical sensitivity of the cochlea, by mechanisms that currently are not understood. Several possible mechanisms have been proposed, but each has limitations that may make it an unsuitable candidate. Recent work has also demonstrated the likely role of mechanoelectrical transduction in outer hair cells in controlling the power source and thereby influencing the sensitivity and amplitude range of the cochlea.

The research design and methods utilized by the Collaborative Alcohol-Related Longitudinal Project are described. The project design addresses the critical need to develop procedures to assess the replicability of research results in alcohol studies. Key features of the research plan include: re-analysis of original data from multiple longitudinal studies of drinking behavior in the general population; centralization of all data analyses, developed and implemented by an interdisciplinary core staff; development of the research plan and interpretation of results in co-operation with original investigators of studies included in the project; and use of modeling procedures from meta-analysis to quantify the relative contribution of factors influencing the distribution of effect estimates across studies, including both methodological differences and aggregate level variables. The final section describes statistical methods for meta-analysis used by the project, including procedures for the calculation and combination of estimates of effect magnitude, categorical and continuous modeling procedures for use with effect sizes, and random effects models.

Meta-analysis combines results from multiple longitudinal studies to describe life course variation by age and sex for quantity of drinking per typical occasion (20 studies) and frequency of drinking during one month (27 studies). There is cross-study heterogeneity for the Time 1 means of the drinking variables blocking for age and sex. Age distributions for the Time 1 means are similar by gender within nations; in the aggregate, males exceed females in the magnitude of drinking. Dramatic shifts in the standardized mean difference (M2-M1) occur among the young; greater homogeneity and moderate change (declines) occur later in life. Implicated in improving cross-study homogeneity for M2-M1 among the young are interval between measurements, nation, Time 1 per capita consumption (PCC), difference in PCC and the Time 1 mean. Lower unstandardized regression coefficients are found for quantity among youth, but are not consistently homogeneous within nations; the association for frequency becomes increasingly stable with increasing age. Nation and interval are implicated in improving homogeneity. Decline in quantity occurs among the old. M2-M1 produces homogeneously higher regressions for groups of the young who increase quantity v. those who do not. Linkage of the group-level and individual-level findings is discussed.

This paper introduces the scope and rationale of The Collaborative Alcohol-Related Longitudinal Project and describes the individual longitudinal studies which contribute to this large collaborative project, representing studies from 15 countries. It also serves as an introduction to four reports of the preliminary findings from the project. The project is distinguished by (1) its interdisciplinary research approach which has assembled a multidisciplinary group of scholars to direct and interpret analyses, (2) its use of primary data from multiple longitudinal studies, (3) the parallel analyses of primary data from multiple studies, using comparable measures across studies recorded to a standard format and common analytic model, and (4) its use of meta-analysis to combine results across studies. Its research objectives include determining the cross-study consistency of findings of (1) the incidence and chronicity of drinking patterns and problems, (2) exogeneous factors which initiate and alter drinking careers, (3) socio-behavioral factors measured in childhood and adolescence which predict adult drinking problems, (4) inter-generational biological and social factors which predict adult drinking problems, and (5) aggregate-level factors which account for study differences. The method of sampling of studies from the world's alcohol-related general population longitudinal research is described.

The ototoxic mechanism of cisplatin was investigated. Potentiation of cisplatin ototoxicity by furosemide and amino-oxyacetic acid (AOAA) was observed. Substantial hearing loss in cisplatin-deafened animals was accompanied by normal values of the endocochlear potential and a reduction in the sensitivity of the 2f1-f2 distortion products. The loss in dB of the sensitivity of the distortion products correlated extremely well with the loss of the neural sensitivity in dB. There was also a relationship between the fractional reduction of the low frequency (1000 Hz) microphonic potential and hearing loss in dB. Iontophoresis of cisplatin into scala media resulting in the immediate loss of neural thresholds at the site of iontophoresis. It is concluded that cisplatin caused the hearing loss by blocking OHC transduction channels.