Lifetime Cannabis Use Is Not Associated With Negative Beliefs About Medication in Patients With First Treatment Psychosis.

Objective: Cannabis use is common among patients with psychosis, and along with negative beliefs about medication, it has been found to predict poor adherence to antipsychotic drug treatment. Such lack of adherence to antipsychotic drug treatment increases the risk of poor clinical outcomes and relapse in patients with first treatment for psychosis (FTP). However, to date, it is unclear whether cannabis use may be related to negative perceptions about antipsychotic drug treatment. Methods: A cross-sectional sample of 265 FTP patients with schizophrenia spectrum disorder underwent extensive clinical assessments. Three measures of cannabis use were obtained: lifetime, current and meeting diagnostic criteria for abuse or addiction. For the primary analyses we focused on lifetime cannabis use. The Beliefs about Medication Questionnaire (BMQ) was employed to assess the patients' specific concerns and perceptions of antipsychotic medications, as well as general beliefs about pharmacotherapy. The relationship between lifetime cannabis use and BMQ scores was investigated with general linear model (GLM) analyses, controlling for age and sex. Results: Patients with lifetime use of cannabis ≥10 times were more likely to be male, younger at the age of onset of psychosis and with higher levels of alcohol use and daily tobacco smoking, as compared to the non-users (p < 0.05). Neither lifetime use of cannabis, current use nor a cannabis abuse diagnosis was associated with negative beliefs about medicines as measured by the BMQ questionnaire. Conclusion: Use of cannabis is not linked to negative perceptions about antipsychotic medicines in patients with FTP. Other reasons for poor compliance to antipsychotic drug treatment in cannabis users need to be further investigated.

Adiponectin Is Related to Cardiovascular Risk in Severe Mental Illness Independent of Antipsychotic Treatment.

Background: Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) associated with elevated cardiovascular disease (CVD) risk, including obesity. Leptin and adiponectin are secreted by adipose tissue, with pro- and anti-inflammatory properties, respectively. The second generation antipsychotics (AP) olanzapine, clozapine, and quetiapine have been associated with high leptin levels in SMI. However, the link between inflammatory dysregulation of leptin and adiponectin and CVD risk in SMI, and how this risk is influenced by body mass and AP medication, is still not completely understood. We investigated herein if leptin, adiponectin or their ratio (L/A ratio) could predict increased CVD risk in SCZ, BD, and in subgroups according to use of antipsychotic (AP) treatment, independent of other cardio-metabolic risk factors. Methods: We measured fasting plasma levels of leptin and adiponectin, and calculated the L/A ratio in n = 1,092 patients with SCZ and BD, in subgroups according to AP treatment, and in n = 176 healthy controls (HC). Differences in the levels of adipokines and L/A between groups were examined in multivariate analysis of covariance, and the correlations between adipokines and body mass index (BMI) with linear regression. CVD risk was defined by total cholesterol/high-density lipoprotein (TC/HDL) and triglyceride/HDL (TG/HDL) ratios. The adipokines and L/A ratios ability to discriminate individuals with TG/HDL and TC/HDL ratios above threshold levels was explored by ROC analysis, and we investigated the possible influence of other cardio-metabolic risk factors on the association in logistic regression analyses. Results: We observed higher leptin levels and L/A ratios in SMI compared with HC but found no differences in adiponectin. Both adipokines were highly correlated with BMI. The low adiponectin levels showed a fair discrimination in ROC analysis of individuals with CVD risk, with AUC between 0.7 and 0.8 for both TC/HDL and TG/HDL, in all groups examined regardless of diagnosis or AP treatment. Adiponectin remained significantly associated with an elevated TC/HDL and TG/HDL ratio in SMI, also after further adjustment with other cardio-metabolic risk factors. Conclusions: Adiponectin is not dysregulated in SMI but is associated with CVD risk regardless of AP treatment regime.

Atherogenic Lipid Ratios Related to Myeloperoxidase and C-Reactive Protein Levels in Psychotic Disorders.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of premature death in patients with psychotic disorders, where dyslipidemia occurs frequently. In the pathogenesis of these serious mental disorders, a low-grade inflammation seems to be a possible contributor. Concurrently, systemic inflammation and its interplay with dyslipidemia is a central driver in the pathogenesis of CVD. We hypothesize that evaluation of atherogenic lipid ratios together with inflammatory markers reflecting different inflammatory pathways with relevance for atherogenesis, could give novel information on immune-related mechanisms involved in early CVD risk in patients with psychotic disorders. METHODS: As a measure for CVD risk we calculated atherogenic lipid ratios using established sex-specific cut-offs: Total cholesterol/high-density lipoprotein; HDL-c (TC/HDL) and triglyceride/HDL-c (TG/HDL) were evaluated in 571 schizophrenia (SCZ) and 247 bipolar disorder (BD) patients, and in 99 healthy controls (HC). In addition, as a measure of low-grade inflammation, we measured fasting plasma levels of nine stable atherogenic inflammatory markers in patients (SCZ, BD) and in HC. The elevated inflammatory markers and CVD risk in patients, as reflected by TC/HDL and TG/HDL, were further assessed in multivariable analyses adjusting for comorbid cardio-metabolic risk factors. RESULTS: A markedly higher proportion (26%-31%) of patients had increased TC/HDL and TG/HDL ratios compared with HC. Plasma levels of high-sensitivity C-reactive protein (hs-CRP) and myeloperoxidase (MPO) were higher (p<0.05, p<0.001) in patients with psychotic disorders than in HC, and hs-CRP and MPO were independently associated with atherogenic lipid ratios in the multivariable analyses. CONCLUSIONS: Our findings suggest that low-grade inflammation and abnormal neutrophil activation may cause increased CVD risk in patients with psychotic disorders. These mechanisms should be further examined to determine the potential for development of novel risk evaluation strategies.

Metabolic dysfunctions in the kynurenine pathway, noradrenergic and purine metabolism in schizophrenia and bipolar disorders.

BACKGROUND: We aimed at exploring potential pathophysiological processes across psychotic disorders, applying metabolomics in a large and well-characterized sample of patients and healthy controls. METHODS: Patients with schizophrenia and bipolar disorders (N = 212) and healthy controls (N = 68) had blood sampling with subsequent metabolomics analyses using electrochemical coulometric array detection. Concentrations of 52 metabolites including tyrosine, tryptophan and purine pathways were compared between patients and controls while controlling for demographic and clinical characteristics. Significant findings were further tested in medication-free subsamples. RESULTS: Significantly decreased plasma concentrations in patients compared to healthy controls were found for 3-hydroxykynurenine (3OHKY, p = 0.0008), xanthurenic acid (XANU, p = 1.5×10-5), vanillylmandelic acid (VMA, p = 4.5×10-5) and metanephrine (MN, p = 0.0001). Plasma concentration of xanthine (XAN) was increased in the patient group (p = 3.5×10-5). Differences of 3OHKY, XANU, VMA and XAN were replicated across schizophrenia spectrum disorders and bipolar disorders subsamples of medication-free individuals. CONCLUSIONS: Although prone to residual confounding, the present results suggest the kynurenine pathway of tryptophan metabolism, noradrenergic and purinergic system dysfunction as trait factors in schizophrenia spectrum and bipolar disorders. Of special interest is XANU, a metabolite previously not found to be associated with bipolar disorders.

Adipokine levels are associated with insulin resistance in antipsychotics users independently of BMI.

BACKGROUND: The prevalence of obesity, metabolic syndrome and type 2 diabetes mellitus is increased among patients with severe mental disorders, and particularly use of second generation antipsychotic drugs is associated with metabolic side effects. Antipsychotics have been found to alter levels of adipokines which regulate insulin sensitivity, but their role in antipsychotic-associated insulin resistance is not established, and it is unclear whether adipokines affect insulin resistance independently of body mass index (BMI). METHODS: We included 1050 patients with severe mental disorders and 112 healthy controls aged 18-65 years from the Oslo area, Norway. Clinical variables, BMI and use of medication were assessed, fasting blood samples were obtained for calculation of the leptin/adiponectin ratio (L/A ratio) and estimate of insulin resistance using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Case-control analyses were followed by mediation analyses to evaluate the possible direct effect of antipsychotics on HOMA-IR and indirect effect mediated via the L/A ratio. This was performed both with and without adjustment for BMI, in the total sample and in an antipsychotic monotherapy subsample (N = 387). RESULTS: BMI, L/A ratio and HOMA-IR were significantly higher in patients than controls (p < 0.001-p = 0.01). There was a significant direct effect from use of antipsychotics in general on HOMA-IR both without (b = 0.03, p = 0.007) and with adjustment for BMI (b = 0.03, p = 0.013), as well as a significant mediating effect via L/A ratio both without (b = 0.03, p < 0.001) and with adjustment for BMI (b = 0.01, p = 0.041). Use of olanzapine (b = 0.03, p < 0.001) or aripiprazole (b = 0.04, p < 0.001) in monotherapy showed significant effects on HOMA-IR mediated via L/A ratio. CONCLUSIONS: The study suggests that use of antipsychotics may alter adipokine levels, and that increased L/A ratio may play a role in the development of insulin resistance associated with use of antipsychotics also independently of BMI.

Association between serum lipid levels, osteoprotegerin and depressive symptomatology in psychotic disorders.

Although the relationship between positive and negative symptoms of psychosis and dyslipidemia has been thoroughly investigated in recent studies, the potential link between depression and lipid status is still under-investigated. We here examined the association between lipid levels and depressive symptomatology in patients with psychotic disorders, in addition to their possible inflammatory associations. Participants (n = 652) with the following distribution: schizophrenia, schizophreniform and schizoaffective disorder (schizophrenia group, n = 344); bipolar I, II, NOS, and psychosis NOS (non-schizophrenia group, n = 308) were recruited consecutively from the Norwegian Thematically Organized Psychosis (TOP) Study. Clinical data were obtained by Positive and Negative Syndrome Scale (PANSS), and Calgary Depression Scale for Schizophrenia (CDSS). Blood samples were analyzed for total cholesterol (TC), low-density lipoprotein (LDL), triglyceride (TG), C-reactive protein (CRP), soluble tumor necrosis factor receptor 1(sTNF-R1), osteoprotegerin (OPG), and interleukin 1 receptor antagonist (IL-1Ra). After adjusting for age, gender, BMI, smoking, and dyslipidemia-inducing antipsychotics, TC and LDL scores showed significant associations with depression [ß = 0.13, p = 0.007; ß = 0.14, p = 0.007], and with two inflammatory markers: CRP [ß = 0.14, p = 0.007; ß = 0.16, p = 0.007] and OPG [ß = 0.14, p = 0.007; ß = 0.11, p = 0.007]. Total model variance was 17% for both analyses [F(12, 433) = 8.42, p < 0.001; F(12, 433) = 8.64, p < 0.001]. Current findings highlight a potential independent role of depression and inflammatory markers, CRP and OPG in specific, in the pathophysiology of dyslipidemia in psychotic disorders.

Stand-alone health insurance tax credits aren't enough.

Using health insurance tax credits to help reduce the ranks of the nearly 43 million uninsured Americans has attracted broad bipartisan support in Congress. But tax credits alone will not help many sick or older people obtain affordable coverage, according to an expert panel at an April 10, 2001, conference sponsored by the Center for Studying Health System Change (HSC). To make tax credits a viable option for eligible people, the individual insurance market would need significant reforms or a better way to spread risk-similar to large employers-over a large and varied population. This Issue Brief highlights critical issues policy makers should consider when crafting tax credit proposals, including the use of purchasing pools.

Tax credits and purchasing pools: will this marriage work?

Bipartisan interest is growing in Congress for using federal tax credits to help low-income families buy health insurance. Regardless of the approach taken, tax credit policies must address risk selection issues to ensure coverage for the chronically ill. Proposals that link tax credits to purchasing pools would avoid risk selection by grouping risks similar to the way large employers do. Voluntary purchasing pools have had only limited success, however. This Issue Brief discusses linking tax credits to purchasing pools. It uses information from the Center for Studying Health System Change's (HSC) site visits to 12 communities as well as other research to assess the role of purchasing pools nationwide and the key issues and implications of linking tax credits and pools.

Minority physicians' experiences obtaining referrals to specialists and hospital admissions.

CONTEXT: Over the past 15 years, policy makers, healthcare providers, and researchers have focused their attention on understanding and reducing ethnic disparities in access to healthcare. Efforts to understand and reduce these disparities in access are driven by the wealth of studies that document significant differences in the health of ethnic minority groups in the United States. OBJECTIVE: To assess differences in access to medical care from African American, Hispanic, and white physicians' perspectives. DESIGN: Using the Community Tracking Study Physician Survey, a nationally representative survey of US physicians, this study assesses physicians' abilities to obtain medically necessary services for their patients. Physicians were asked how often they could arrange referrals to specialists and inpatient admissions for their patients. RESULTS: Controlling for physician characteristics (eg, providing charity care, participation in managed care, Medicaid, and Medicare) and community characteristics (eg, average managed care participation, supply of hospital beds and specialists per capita) reduces the magnitude of differences between white and ethnic minority physicians. Nevertheless, after controlling for a wide range of practice and environmental characteristics, African American physicians were more likely to report problems obtaining hospital admissions, and Hispanic physicians were more likely to report problems obtaining referrals to specialists, compared with white physicians. CONCLUSIONS: Disparities in ethnic minority physicians' abilities to get medical services for their patients exist. This study corroborates that ethnic disparities are not limited to gaining access to primary health services (eg, having a doctor visit or a usual source of medical care) but extend into the healthcare delivery system itself (eg, getting a referral or hospital admission).

Does managed care enable more low income persons to identify a usual source of care? Implications for access to care.

BACKGROUND: By requiring or encouraging enrollees to obtain a usual source of care, managed care programs hope to improve access to care without incurring higher costs. OBJECTIVES: (1) To examine the effects of managed care on the likelihood of low-income persons having a usual source of care and a usual physician, and; (2) To examine the association between usual source of care and access. RESEARCH DESIGN: Cross-sectional survey of households conducted during 1996 and 1997. SUBJECTS: A nationally representative sample of 14,271 low-income persons. MEASURES: Usual source of care, usual physician, managed care enrollment, managed care penetration. RESULTS: High managed care penetration in the community is associated with a lower likelihood of having a usual source of care for uninsured persons (54.8% vs. 62.2% in low penetration areas) as well as a lower likelihood of having a usual physician (60% vs. 72.8%). Managed care has only marginal effects on the likelihood of having a usual source of care for privately insured and Medicaid beneficiaries. Having a usual physician substantially reduces unmet medical needs for the insured but less so for the uninsured. CONCLUSIONS: Having a usual physician can be an effective tool in improving access to care for low-income populations, although it is most effective when combined with insurance coverage. However, the effectiveness of managed care in linking more low-income persons to a medical home is uncertain, and may have unintended consequences for uninsured persons.

Who has a choice of health plans?

Policy makers are concerned that consumers have no voice in the changing health care system. They debate, however, whether the consumers' voice should be heard through regulation, such as patient protections, or the marketplace. For market forces to work in the consumers' interest, consumers must have a choice of plans and detailed information on which to base their choice. New survey data from the Center for Studying Health System Change (HSC) suggest that more consumers have a choice of plans than is generally believed, and that the proportion of consumers who have plan choice is increasing. According to HSC's 1998-1999 Household Survey, 64 percent of families have a choice of health plans--two percentage points higher than two years ago.

Are defined contributions a new direction for employer-sponsored coverage?

Defined contributions for health benefits are being promoted as the new silver bullet for employers to combat the rising costs of health care, the managed care backlash and the changing climate for employer liability. As interest in this concept grows, so does the number of proposed alternatives for implementing it. Originally called fixed contributions, defined contributions now also refer to cash transfers or vouchers, with reliance on the individual market for health insurance. A more recent angle for defined contributions is using the Internet as an on-line marketplace for purchasing health insurance. This Issue Brief examines defined-contribution strategies and assesses issues relevant to employers, employees and public policy makers.

Monitoring the impact of the Medicare Fee Schedule on access to care for vulnerable populations.

Implementation of the Medicare Fee Schedule (MFS) introduced concerns about the potential for reduced access to care, especially for vulnerable populations. These analyses show differences in access before and after the MFS that cannot be explained by health status. In particular, those without private or public supplementary insurance, those with low incomes, African Americans, and the oldest old had lower utilization before the MFS. The impact after implementation of the MFS on vulnerable populations was similar, for the most part, to that for other beneficiaries: reduced utilization in areas with fee increases and increased utilization in areas with fee decreases. An exception was that African Americans, those without supplemental insurance, and those with low incomes in areas of fee decrease saw reductions in the use of surgical services relative to their counterparts in areas with no fee change.

Insurance aspects of DRG outlier payments.

As part of the prospective payment system, the government pays 'outlier' payments for especially long or expensive cases. These payments can be viewed as insurance for the hospital against excessive losses. They mitigate problems of access and underprovision of care for the sickest patients, and provide additional payments to the hospitals that take care of them, thereby making payments to hospitals more equitable. This paper characterizes the outlier payment formulae that minimize risk for hospitals under any fixed constraints on the sum of outlier payments and minimum hospital coinsurance rate. We then simulate per-case payments for a policy that did not include any outlier payments, the current outlier policy, and several other policies that minimize risk subject to different coinsurance constraints. The current outlier policy achieves each of its goals to at least some extent, but more insurance could be provided without lessening attainment of the other goals. We also discuss some problems with the implementation of the current policy, such as its reliance on day outliers.