An exploration of secondary sex ratios among women diagnosed with anxiety disorders.

BACKGROUND: Theory suggests that natural selection conserved reactivity in part because highly reactive women spontaneously abort less fit conceptuses, particularly small males. Other literature argues that high reactivity manifests clinically as anxiety disorders. If true, births to women diagnosed with anxiety disorders should exhibit a low secondary sex ratio (i.e. ratio of male to female births). We explored whether births to women diagnosed with anxiety disorders exhibit a lower sex ratio than births to women diagnosed with other psychiatric disorders, or to women without mental health diagnoses. METHODS: We performed a case-control comparison of the secondary sex ratios among groups of women categorized by mental health diagnosis using birth records linked to data from California County Mental Health system records. We compared sex ratios among 5994 deliveries to mothers diagnosed with anxiety disorders, 23 443 deliveries to mothers diagnosed with other psychiatric disorders and 1 099 198 'comparison' births. RESULTS: Although comparison births exhibited a higher sex ratio than births to women diagnosed with anxiety disorders or with other diagnoses, differences were not statistically significant. Births to African American women diagnosed with anxiety disorders, however, exhibited sex ratios significantly lower than comparison births among African Americans (OR = 0.89, P = 0.038) or births to African American women with other mental health diagnoses (OR = 0.88, P = 0.042). CONCLUSIONS: We found that infants born to African American women diagnosed with anxiety disorders exhibited a significantly lower secondary sex ratio than reference groups. We urge confirmatory tests of our findings and discuss implications of the reactivity/anxiety hypothesis for psychiatry, obstetrics and public health.

Effects of the Jamison-Farabee consent decree: due process protection for involuntary psychiatric patients treated with psychoactive medication.

The Jamison-Farabee consent decree in California mandates an outside psychiatrist's review of involuntary medication of state hospital patients. Patients' rights advocates presumably hoped the decree would facilitate more frequent medication refusal, while clinicians predicted the procedure would impair patient care. Outside review led to only a 1.1% rate of medication denial; half of the patients involved deteriorated afterward. Examination of a sample of patients subject to the decree and two comparable samples 1 year and 10 years earlier suggests that patients' successful medication refusal was no more frequent after implementation of the decree and that the procedure had negligible effects on patient care or outcome for patients not denied medication.

Nitrosothiol esters of diclofenac: synthesis and pharmacological characterization as gastrointestinal-sparing prodrugs.

Despite its widespread use, diclofenac has gastrointestinal liabilities common to nonsteroidal antiinflammatory drugs (NSAIDs) that might be reduced by concomitant administration of a gastrointestinal cytoprotectant such as nitric oxide (NO). A series of novel diclofenac esters containing a nitrosothiol (-S-NO) moiety as a NO donor functionality has been synthesized and evaluated in vivo for bioavailability, pharmacological activity, and gastric irritation. All S-NO-diclofenac derivatives acted as orally bioavailable prodrugs, producing significant levels of diclofenac in plasma within 15 min after oral administration to mice. At equimolar oral doses, S-NO-diclofenac derivatives (20a-21b) displayed rat antiinflammatory and analgesic activities comparable to those of diclofenac in the carrageenan-induced paw edema test and the mouse phenylbenzoquinone-induced writhing test, respectively. All tested S-NO-diclofenac derivatives (20a-21b) were gastric-sparing in that they elicited markedly fewer stomach lesions as compared to the stomach lesions caused by a high equimolar dose of diclofenac in the rat. Nitrosothiol esters of diclofenac comprise a novel class of NO-donating compounds having therapeutic potential as nonsteroidal antiinflammatory agents with an enhanced gastric safety profile.

Uric acid content of Drosophila decreases with aging.

Free uric acid concentrations declined with aging in male Oregon R Drosophila melanogaster by 59% or more between 0 and 50 days of adult age. Free xanthine concentrations increased between 0 and 5 days of age and declined by 75% between 5 and 50 days of age. Xanthine oxidase activity was maximal for newly emerged flies and then declined rapidly reaching a minimum at 9 days of age. After 9 days of age xanthine concentrations may be the limiting factor for the production of uric acid by xanthine oxidase in aging fruit flies. Declining uric acid concentrations may represent a loss of antioxidant potential in aging Drosophila.

Calcium, iron, copper, boron, collagen, and density changes in bone with aging in C57BL/6J male mice.

X-rays of old C57BL/6J male mice showed deformed vertebral columns. Bone density was found to increase between 76 and 517 days of age and to decrease after 685 days of age. The boron content of femurs declined by 9% with aging but the decrease was not significant. Calcium increased between 76 and 198 days of age but declined by 36% between 200 and 1000 days of age. Iron increased by 207% by 1000 days of age. Copper declined between 76 and 198 days of age but increased by 61% between 200 and 1000 days of age. Bone collagen as indicated by hydroxyproline and proline content decreased 17.4% by 1000 days of age. The largest single change with aging was, therefore, in the iron content of bone. Several correlations were found to be independent of the age of the animals. Bone density was correlated with bone calcium and collagen. Iron was negatively correlated with calcium and collagen. Calcium and collagen content were unrelated. Bone density and iron were also surprisingly unrelated. A possible explanation for this observation is given. Copper was negatively correlated with bone calcium, bone density, and collagen content. Excess copper was, therefore, the single most important factor associated with decreasing bone size and density.

Ascorbic acid in Drosophila and changes during aging.

The ascorbic acid content of Drosophila melanogaster was found to be high in the absence of a dietary source. The amount of ascorbic acid per fly declined with aging in both the Oregon R and Swedish C strains. The median life span at 25 degrees C was 45 days for Swedish C and 59 days for Oregon R. The amount of ascorbic acid in Swedish C flies (0.078 micrograms/fly) was higher than that for Oregon R (0.058 micrograms/fly) for newly emerged flies but the rate of decline with aging was greater for Swedish C than Oregon R. The decline in ascorbic acid content with aging was 70.4% for Swedish C versus 19.9% for Oregon R. A brief cold shock was found to significantly increase the amount of ascorbic acid in Oregon R flies. Feeding the precursor of ascorbic acid synthesis, L-gulonolactone, did not improve the life span. Life-time feeding of ascorbic acid did not improve the life span of either Swedish C or Oregon R flies.

Pharmacoeconomics of antipsychotic drug therapy.

Treatment cost can have a dramatic effect on treatment availability, and clinicians may find themselves unable to provide expensive treatments they believe their patients should receive. The introduction of new, premium-priced antipsychotic medications has provided visible examples of this problem. Cost considerations must be part of treatment decisions, since resources are often insufficient to provide all potentially helpful treatments. However, the key question regarding expensive drugs is whether other savings can be expected to offset the higher drug price, or if not, whether improved effectiveness justifies the added cost. Pharmacoeconomic research attempts to integrate relevant information on both effectiveness and cost so that clinicians, patients, and other decision-makers can make meaningful treatment choices. This article presents a conceptual framework for cost-effectiveness analysis, illustrates pharmacoeconomic methods with studies of the cost-effectiveness of clozapine treatment, and describes the steps in designing cost-effectiveness research on novel antipsychotic agents.

Patterns of substance use in schizophrenia: a Markov modeling approach.

Markov models were used to examine patterns of substance use and global functioning in a sample of 100 schizophrenic outpatients over an 18 month period. Patterns of changes in substance use and functional status were stable across the evaluation period. Persons remaining in any substance use or functional state for two evaluation periods were highly likely to continue in the same state. Tests of two common causal hypotheses about relationships between substance use and functional status yielded partial support for the hypothesis that substance use leads to functional impairment, but did not support the hypothesis that functional impairment leads to substance use. Furthermore, there was no evidence of any increase in overall substance use or of substance use leading to treatment dropout. These analyses illustrate a promising approach to key questions about substance use in schizophrenia.

Clozapine eligibility: the effect of stringent criteria on ethnic, gender and age subgroups of schizophrenic patients.

1. The purpose of this retrospective chart review study was to determine whether broad and stringent criteria differentially impact clozapine eligibility in ethnic, gender, and age subgroups of schizophrenic patients. 2. 505 patients charts were selected from a random cluster sample of mental health patients known to the city and county of San Francisco. Information related to clozapine eligibility was abstracted by trained non-clinical personnel. The impact of subgroup membership on eligibility was examined using logistic regression procedures. 3. Even under the broadest interpretation of FDA requirements for clozapine use, Asian patients were less likely to be eligible, since fewer Asian patients met clozapine treatment requirements. Under more stringent eligibility criteria, older patients were more likely to be excluded from eligibility when TD does not automatically satisfy treatment criteria, and younger patients were more likely to lose eligibility if the number of required adequate medication trials increases to three. 4. Broad eligibility criteria tend to differentially exclude Asian patients while more stringent criteria differentially exclude younger and older patients.

Does the disbursement of income increase psychiatric emergencies involving drugs and alcohol?

OBJECTIVE: To determine if the incidence of psychiatric emergencies involving drugs or alcohol supports the argument that mentally ill persons contribute to elevated mortality during the days following disbursement of private earnings and public income transfers. STUDY DESIGN: Interrupted time-series using Box-Jenkins methods. DATA COLLECTION/EXTRACTION METHODS: Daily counts of adults admitted to psychiatric emergency services in San Francisco after using drugs or alcohol were derived from medical records for the period January 1 through June 30, 1997. PRINCIPAL FINDINGS: Psychiatric emergencies among males who had used drugs or alcohol were elevated in the early days of the month. Such emergencies among females were not similarly elevated. Emergencies among females who had not used drugs or alcohol were elevated in the early days of the month. CONCLUSION: Elevated mortality in the first week of the month may be attributable, in part, to the "check effect" or use of drugs and alcohol by mentally ill males in the days after they receive income. The contribution of women is more complex and may be induced by drug or alcohol abuse among persons in their social networks. The check effect suggests that persons with a history of substance abuse and mental illness should be offered the opportunity to have their income managed by someone who can monitor and influence how the money is being spent. The fact that drug- or alcohol-related admissions among males exhibit temporal patterns suggests that the provision of preventive as well as treatment services may be strategically scheduled.

Patterns of substance use among patients in an urban psychiatric emergency service.

Data from patients visiting an urban psychiatric emergency service in California were examined to document incidence and patterns of substance use and ethnic differences among users. A total of 392 patients were randomly assigned to receive a drug screen (N = 198) or to receive usual care (N = 194). Forty-four percent of the mandatorily screened patients had positive screens for any substances: 37 percent were positive for any drugs, and 7 percent were positive for alcohol only. Cocaine was present in 62 percent of the drug-positive screens. Blacks were two and a half times more likely than whites to have positive screens for drugs and five times more likely to have positive screens for cocaine.

Utility of routine drug screening in a psychiatric emergency setting.

OBJECTIVE: The study determined whether dispositions from an urban psychiatric emergency service would differ between patients who received a mandatory urine drug test and those who may or may not have had a test based on the attending psychiatrist's clinical judgment. The accuracy of clinicians' suspicion of substance use among mandatorily screened patients was also examined. METHODS: A total of 392 consenting patients presenting to an urban psychiatric emergency service were randomly assigned to a mandatory-screen group (N=198) or a usual-care group (N=194). Physicians ordered screens based on clinical judgment. Additional screens were performed without physicians' knowledge for patients in the mandatory-screen group for whom no screen was ordered. Demographic and clinical information, results of drug screens, and information about dispositions were collected from clinical charts or hospital databases. RESULTS: No difference in dispositions was found between the mandatory-screen group and the usual-care group. Survival analysis did not reveal a difference between the two groups in length of stay in inpatient psychiatric units. As for accuracy of physicians' suspicion of substance use, positive drug screens were recorded for 10.2 percent of the 198 patients in the mandatory-screen group who did not admit drug use or for whom physicians did not expect drug use. A total of 39.3 percent of the patients who were suspected of use and 88.2 percent of those who admitted use had positive drug screens. Only 20.8 percent of patients who denied substance use had positive screens. CONCLUSIONS: Routine urine drug screening in a psychiatric emergency service did not affect disposition or the subsequent length of inpatient stays. The results do not support routine use of drug screens in this setting.

Treatment costs and patient outcomes with use of risperidone in a public mental health setting.

OBJECTIVE: Risperidone's effectiveness in reducing symptoms and its cost were compared with the effectiveness and cost of standard antipsychotic medication among matched groups of outpatients with schizophrenia. METHODS: Data on 56 subjects started on risperidone were compared with data for a matched group of 56 subjects over the 12 months before and after initiation of risperidone. Global Assessment of Functioning (GAF) scores were used to assess effectiveness. Service utilization data were used to calculate the cost of treatment. RESULTS: Total treatment costs for the two groups were not significantly different, although there was a trend toward higher costs in the risperidone group. Monthly GAF scores revealed no group differences in the effectiveness of the medications. CONCLUSIONS: No significant differences in treatment effectiveness or costs were found between the risperidone and comparison groups, despite a trend to higher treatment costs for the risperidone group.

Effects of stringent criteria on eligibility for clozapine among public mental health clients.

OBJECTIVE: This study estimated rates of eligibility for treatment with clozapine among clients in a public mental health system using criteria with various degrees of restrictiveness. METHODS: A stratified, random cluster sample of 293 clients was selected from among all clients with schizophrenic disorders known to the mental health system of the city and county of San Francisco during 1991. Data on variables associated with eligibility for clozapine were abstracted from clinical records, and eligibility was estimated using broad and stringent criteria. RESULTS: An estimated 42.9 percent of the clients were eligible for clozapine using broad eligibility criteria that included a diagnosis of schizophrenia or schizoaffective disorder, two previous neuroleptic trials of at least 600 mg per day chlorpromazine equivalents for at least four weeks or tardive dyskinesia, Global Assessment of Functioning score less than 61, and no contraindications. Eliminating eligibility due to tardive dyskinesia alone, excluding persons with schizoaffective disorder, requiring six-week medication trials, and requiring three adequate medication trials instead of two resulted in substantial reductions in the rate of eligibility. CONCLUSIONS: Varying interpretations of the criteria for clozapine treatment listed in the medication package insert dramatically affect patients' eligibility for clozapine. Mental health agencies should endeavor to maintain a balance between restricting use of clozapine due to cost and providing it to the full spectrum of patients who might benefit from the medication.

Symptom heterogeneity in comorbid alcohol disorder.

The heterogeneity of signs and symptoms of alcohol disorder was examined in a community sample of 1,955 persons with either alcohol disorder alone or alcohol disorder plus one of four categories of major mental disorder (antisocial personality disorder, schizophrenia, affective disorder, anxiety disorder). When all diagnostic categories were combined, persons with comorbid mental and alcohol disorders showed evidence of more severe alcohol-related symptoms than did persons with alcohol disorder alone. Distinct symptom patterns distinguished the four diagnostic groups, reflecting heterogeneity in the manifestation of comorbid alcohol disorder. Most notably, comorbid antisocial personality disorder and schizophrenia were associated with higher levels of alcohol consumption and more severe social consequences of alcohol use. These findings substantiate the need for development of specialized dual diagnosis programs and suggest that additional specialization may be required to address diagnostic group differences in the characteristics of comorbid alcohol disorder.

Dangerous behavior and changes in treatment course.

The association of dangerous behavior with the course of subsequent treatment was examined by comparing treatment courses of 45 severely mentally disabled patients identified as dangerous after an incident of dangerous behavior was noted in their clinical records with treatment courses of 122 severely mentally disabled patients who had no recorded incidents of dangerous behavior. The correlation of dangerousness with subsequent restrictiveness of treatment is clearly present in 6 of the 9 variables examined; the relationship generalizes across two rather different CMHC sites.

Substance use among schizophrenic outpatients: prevalence, course, and relation to functional status.

The prevalence and course of alcohol and drug use were examined in a longitudinal, retrospective study of 100 schizophrenic outpatients. During the 18 month study period, problem substance use (abuse and dependence) was not associated with differential attrition from outpatient treatment. Thirty to forty percent of subjects were using drugs or alcohol during any evaluation period. The overall level of substance use and problem use of alcohol, marijuana, and other drugs remained stable, while problem use of cocaine and multiple substances increased over time. Problem substance use was associated with lower functional status and the detrimental effect of problem substance use appeared to increase with time. These findings underscore the need to address substance use problems in the context of outpatient schizophrenia treatment.

A longitudinal study of substance use and community violence in schizophrenia.

The authors report the findings of a longitudinal study testing the hypothesis that substance use leads to subsequent violence in the community. Subjects were 103 patients with a Structured Clinical Interview for DSM-III-R diagnosis of schizophrenia or schizoaffective disorder who were seen in an outpatient clinic for the treatment of schizophrenia. Data on substance use and violent behavior were collected by review of medical records. Results indicated that use of drugs and alcohol was associated with increased odds of concurrent and future violent behavior when compared with persons with schizophrenia and no substance use. Odds of violence were particularly elevated for individuals having a pattern of polysubstance use involving illicit substances.

Effects of fiscal retrenchment on public mental health services for the chronic mentally ill.

In reviewing the public mental health services of 11 California counties during a period of fiscal retrenchment, we found several common trends: a greater focus on the severely mentally disabled; an increase in utilization of hospital-based care, residential treatment, day treatment, and case management services; and a decrease in the capacity of traditional outpatient services. Although the severely mentally disabled are receiving a higher priority for service, the findings imply that these service systems continue to inadequately address the need for long-term maintenance and supportive services to this population.