Provider imaging practices and outcomes of advanced colorectal cancer.

PURPOSE: To explore the real-world utilization of computerized tomography (CT) in patients with advanced colorectal cancer (CRC) and the associated outcomes. METHODS: Using Optum's de-identified Clinformatics® Data Mart Database (2008-2016), we identified patients with CRC receiving combination of chemotherapies (fluoropyrimidines with either oxaliplatin or irinotecan, or capecitabine with either oxaliplatin or irinotecan) combined with bevacizumab as the initial treatment, and its starting date was registered as the index date. End of treatment was defined by the presence of a gap in therapy > 60 days or treatment switch. We assessed the CT scan utilization during the period between 60 days pre-index and 30 days post-end of treatment. Cox regressions were performed to assess the impact of intensity of follow-up CT scans, measured by time to the first scan from the index date, on likelihood of treatment switch and survival. RESULTS: Among included 4,810 patients, the median (standard deviation) time to the first follow-up scan was 57 (45) days. The mean and median number of CT scans was 4 and 3, respectively. An earlier follow-up scan was associated with significantly greater chance of treatment switch (hazard ratio = 0.99 for each day of delay, P < 0.01), and greater likelihood of death (hazard ratio = 0.99 for each day of delay, P < 0.01). CONCLUSION: More intense follow-up increased the likelihood of treatment switch, yet it was not associated with better survival outcome. Further analysis in populations with longer follow-up period is warranted to elucidate the link between CT scan utilization and outcomes.

A Retrospective Cohort Study of Acute Kidney Injury Risk Associated with Antipsychotics.

BACKGROUND: A recent large database analysis raised concerns of potential acute kidney injury (AKI) risk associated with antipsychotics. However, whether individual atypical and typical antipsychotics are associated with differential AKI risks has not been investigated. OBJECTIVE: The current study compared the risks of AKI and known causes of AKI associated with a broad range of atypical and typical antipsychotics. METHOD: This retrospective cohort analysis used January 2007-June 2013 US nationwide Humana claims data to define episodes of antipsychotic drug therapy for patients with schizophrenia and bipolar disorder. Study drugs were aripiprazole, fluphenazine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone. Study outcomes were hospitalizations with AKI, and known causes of AKI, i.e., hypotension, acute urinary retention, neuroleptic malignant syndrome/rhabdomyolysis, and pneumonia. AKI was the primary outcome of the study. Cox regressions using haloperidol as the baseline comparator were used to estimate the impact of alternative antipsychotics on the risks of study adverse events following the initiation of treatment. The Cox models controlled for treatment history, comorbidities, and concomitant drug use in the prior 6 months. They also controlled for patient demographics and dose of current treatment. RESULTS: The overall incidence of AKI was 25.0 per 1000 person-years. According to our multivariate regression results, the risk of AKI was significantly increased in patients taking olanzapine [hazard ratio (HR) 1.344, 95% confidence interval (CI) 1.057-1.708], quetiapine (HR 1.350, 95% CI 1.082-1.685), and ziprasidone (HR 1.338, 95% CI 1.035-1.729) relative to haloperidol. Aripiprazole (HR 1.152, 95% CI 0.908-1.462) and risperidone (HR 1.147, 95% CI 0.923-1.426) had insignificantly higher risks of AKI compared with haloperidol, whereas fluphenazine (HR 0.729, 95% CI 0.483-1.102) had an insignificantly lower risk of AKI. When compared between drug classes, atypical antipsychotics had a significantly higher risk of AKI (HR 1.313, 95% CI 1.083-1.591) than typical antipsychotics. CONCLUSIONS: Antipsychotics are associated with differential AKI risks, with several atypical antipsychotics having higher risks than haloperidol. However, the overall incidence of AKI was moderate, and AKI risk should only raise concern for clinicians with elderly patients or patients who are vulnerable to kidney disease.

Comparative treatment effectiveness of direct acting antiviral regimens for hepatitis C: Data from the Veterans administration.

BACKGROUND AND AIMS: Data addressing real world effectiveness of direct acting antiviral agents in hepatitis C infected patients are now emerging. This study compared the sustained virologic response rates achieved 12 weeks post-treatment in patients treated with three such agents by the Veterans Health Administration. METHODS: A retrospective cohort study was conducted using patients who terminated treatment by July 1, 2015. Data were retrieved from the Veterans Health Administration electronic medical records system. Patients were included if sufficient viral load laboratory data were available to determine sustained virologic response. Applying an intention to treat approach and logistic regression analysis, the sustained virologic response rates achieved were compared across drug regimens. RESULTS: A total of 11 464 patients met study selection criteria. Without controlling for other risk factors, sustained virologic response at least 12 weeks post treatment was achieved in 92% of ledipasvir/ sofosbuvir, 86% of ombitasvir/paritaprevir/ritonavir/dasabuvir, and 83% of simeprevir/sofosbuvir patients. After adjusting for patient characteristics, simeprevir/sofosbuvir (93.3%) and ledipasvir/sofosbuvir (96.2%) patients were statistically more likely than ombitasvir/paritaprevir/ritonavir/dasabuvir (91.8%) patients to demonstrate sustained virologic response. Human immunodeficiency virus, hepatitis B infection, diabetes, obesity, previous treatment history and augmentation therapy using ribavirin did not impact sustained virologic response rates. Sustained virologic response rates were lower for patients under age 65, with cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, indications of fibrosis, or a non-genotype 1 infection. Women and Caucasian patients were more likely to achieve a sustained virologic response. CONCLUSIONS: All three direct acting antiviral regimens appear highly effective in achieving sustained virologic response.

The Impact of Delayed Hepatitis C Viral Load Suppression on Patient Risk: Historical Evidence from the Veterans Administration.

BACKGROUND: The high cost of new hepatitis C (HCV) treatments has resulted in "watchful waiting" strategies being developed to safely delay treatment, which will in turn delay viral load suppression (VLS). OBJECTIVE: To document if delayed VLS adversely impacted patient risk for adverse events and death. METHODS: 187,860 patients were selected from the Veterans Administration's (VA) clinical registry (CCR), a longitudinal compilation of electronic medical records (EMR) data for 1999-2010. Inclusion criteria required at least 6 months of CCR/EMR data prior to their HCV diagnosis and sufficient data post-diagnosis to calculate one or more FIB-4 scores. Primary outcome measures were time-to-death and time-to-a composite of liver-related clinical events. Cox proportional hazards models were estimated separately using three critical FIB-4 levels to define early and late viral response. RESULTS: Achieving an undetectable viral load before the patient's FIB-4 level exceed pre-specified critical values (1.00, 1.45 and 3.25) effectively reduced the risk of an adverse clinical events by 33-35% and death by 21-26%. However, achieving VLS after FIB-4 exceeds 3.25 significantly reduced the benefit of viral response. CONCLUSIONS: Delaying VLS until FIB-4 >3.25 reduces the benefits of VLS in reducing patient risk.

Clozapine revisited: Impact of clozapine vs olanzapine on health care use by schizophrenia patients on Medicaid.

BACKGROUND: Our purpose was to evaluate health care use and cost patterns for clozapine compared with olanzapine in the treatment of schizophrenia. METHODS: Health care outcomes were measured over a 1-year posttreatment period for episodes of antipsychotic therapy initiated between 1997 and 2002. Four episode categories were defined: restart after lapse in therapy, switch after break, switch without break, and augmentation. We estimated the impact of clozapine or olanzapine using mixed model regression for costs by type of service and days of uninterrupted drug therapy. Time to admission in an acute hospital, psychiatric hospital, or longterm care facility, and time to suicide attempt were compared using Cox proportional hazards models. RESULTS: Clozapine increased duration of therapy and decreased risk of psychiatric hospitalization or suicide attempts compared to olanzapine. However, increased drug costs and use of community mental health centers (CMHC) for complete blood count (CBC) monitoring overwhelmed any offsetting savings. CONCLUSIONS: Clozapine is more expensive than olanzapine over the first year of treatment, primarily due to frequent CMHC visits required for CBC monitoring. However, fewer psychiatric hospitalizations, reduced suicide attempts, and longer duration of treatment should generate more benefits over time, which could eventually outweigh clozapine's higher first-year costs.

Primary nonadherence to medications in an integrated healthcare setting.

OBJECTIVES: To measure primary nonadherence (PNA) rates for 10 therapeutic drug groups and identify factors associated with PNA to chronic and acute medications. STUDY DESIGN: Retrospective cohort study. METHODS: New prescriptions written in an integrated healthcare system for study drugs were identified between December 1, 2009, and February 28, 2010. PNA was defined as the failure to fill a prescription within 14 days of when it was written. PNA rates were calculated by drug group and descriptive statistics were performed. Multivariable logistic regression was used to identify significant patient, provider, and prescription characteristics associated with PNA. Results were stratified by acute versus chronic treatment. RESULTS: A total of 569,095 new prescriptions were written during the 3-month period. Across all drug groups, the PNA rate was 9.8%. PNA rates for individual drug groups varied and were highest for osteoporosis medications (22.4%) and antihyperlipidemics (22.3%). Patients who filled at least 1 prescription in the prior year (odds ratio [OR], 95% confidence interval [CI] for acute = 0.06 [0.06-0.07], for chronic = 0.11 [0.10-0.12]) or had a prescription for a symptomatic disease (OR = 0.51 [0.48-0.53]) were more likely to fill their prescription. Patients were more likely to be primary nonadherent if they were black (OR acute = 1.30 [1.25-1.36], chronic = 1.26 [1.18-1.33]) or treatment-naive to therapy (OR acute = 2.52 [2.36-2.7], chronic=1.07 [1.03-1.12]). CONCLUSIONS: Overall PNA was 9.8% but individual PNA rates varied by therapeutic drug group. Factors of PNA were mostly consistent across drug groups, but some depended on whether the treatment was acute or chronic.

Effect of exenatide, pen insulin, and vial insulin on patient outcomes: a retrospective database analysis of persistence and first-year costs in a commercially insured population.

OBJECTIVE: We compared health care costs and medication persistence for patients with type 2 diabetes initiating treatment using exenatide, pen insulin, or vial insulin. METHODS: Commercial health plan data (2004-2008) were used to identify episodes of antidiabetic drug therapy, which were then classified according to treatment history: first observed treatment, restarting a previous therapy (90-day gap in all treatment), switching therapy, and augmentation therapy. Three time periods were defined for each episode: the month in which the episode was initiated (index month), 6 months before the index month (preindex period), and 12 months after the index month (postindex period). All exenatide and insulin episodes were selected for this analysis of persistence and first-year costs. Multivariate statistical methods were adjusted for demographic characteristics, drug use history, previous medical care use, comorbid medical conditions, and prescription drug profile. Several sensitivity analyses were conducted. RESULTS: A total of 213,701 episodes of antidiabetic drug therapy were identified, of which 7031 patients were initiated using exenatide, 21,011 used vial insulin, and 422 used pen insulin. Time to all-cause discontinuation (TTAD) was measured for the index drug and all diabetic-related drugs. Pen insulin was discontinued 91 days earlier than exenatide, whereas vial insulin was continued 18 days longer than exenatide. Patients using pen insulin discontinued all antidiabetic drugs 34 days earlier than patients on exenatide, whereas patients using exenatide and vial insulin exhibited similar TTAD for all drugs. Exenatide use was estimated to significantly reduce medical costs of the first posttreatment year sufficient to offset higher prescription drug costs. These results were confirmed using propensity score matching estimation and were robust across episode type. CONCLUSIONS: Patients initiating drug therapy using exenatide might incur lower posttreatment costs than similar patients who initiated treatment using insulin.

Economic burden associated with patients diagnosed with hepatitis C.

BACKGROUND: New therapies for Hepatitis C virus (HCV) are under development that will augment pegylated interferon-alpha plus ribavirin to improve patient outcomes. Data documenting the incremental economic and health burden of patients with HCV relative to those who are not infected with HCV will be required to evaluate the comparative effectiveness of these new therapies. OBJECTIVE: The objective of this study was to estimate the incremental impact of HCV infection on health care costs and risk of adverse health events. METHODS: Paid claims data for commercially insured patients in the United States were used to identify 2 matched cohorts of 8861 patients with and without HCV infection. Propensity score matching was used to adjust for patient demographics, diagnostic mix, prior use, and drug profile. Patients with prior cirrhosis, liver cancer, or liver transplantation were excluded. Differences in the first postindex year associated with the diagnosis of an HCV infection were estimated for adverse event risk (logistic regression), costs (ordinary least square regression), and utilization counts (generalized linear models), controlling for patient demographics, prior use, comorbidity profile, and prescription drug profile. RESULTS: The costs of treating patients infected with HCV and a matched sample not infected with HCV were $37,390 and $13,575, respectively. The incremental cost of HCV infection was estimated at +$23,406, primarily because of higher costs for ambulatory care (+$6531), hospital services (+$1827), and prescription drugs (+$6935). The presence of HCV was associated with a significantly higher risk of hospitalization (odds ratio [OR] = 2.5) and number of hospital admissions (+186%); depression (OR = 2.2); cirrhosis (OR = 65.8); hepatic cancer (OR = 28.1), and liver transplantation (OR = 46.1; P < 0.0001 for all estimates). CONCLUSIONS: A diagnosis of HCV infection was correlated significantly with increased adverse event risk and increased health care costs. New alternative treatments are needed that are more efficacious and less burdensome for the patient. Limitations of this study are that only 1 year was used to screen for preexisting conditions and events and that paid claims data do not capture indirect HCV infection costs such as time lost from work.

The impact of the iPLEDGE program on isotretinoin fetal exposure in an integrated health care system.

BACKGROUND: Preventing fetal exposure to isotretinoin is widely acknowledged as an important safety issue. The iPLEDGE program is the latest in a series of Food and Drug Administration-mandated risk management programs designed to prevent pregnancies in female patients of childbearing potential (FCBP) taking isotretinoin. OBJECTIVE: We sought to evaluate the effect of iPLEDGE relative to the prior risk management program (system to manage Accutane-related teratogenicity [SMART]) on the risk of isotretinoin fetal exposure in FCBP in a managed care setting. METHODS: All FCBP at Kaiser Permanente Southern and Northern California who filled at least one prescription for isotretinoin during a 4-year period (March 1, 2004, to February 29, 2008) were included in this retrospective cohort study (n = 8344). Chart review was performed to confirm fetal exposures and outcomes. A Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence intervals. RESULTS: There were a total of 29 fetal exposures and 9912 isotretinoin treatment courses. After iPLEDGE was implemented, the unadjusted rate of fetal exposure decreased from 3.11 to 2.67 per 1000 treatment courses (P = .69). The hazard ratio = 0.76 (95% confidence interval 0.36-1.61) for fetal exposures to isotretinoin during treatment courses filled after iPLEDGE implementation compared with SMART. LIMITATIONS: Limitations include limited generalizability of results, small sample size (n = 29 total documented fetal exposures), and potential uncontrolled confounders. CONCLUSION: Evaluating the impact of iPLEDGE on isotretinoin fetal exposures is important in understanding the full risks and benefits of isotretinoin treatment. We found no evidence that iPLEDGE significantly decreased the risk of fetal exposure in FCBP compared to the SMART program.

A1C and cardiovascular outcomes in type 2 diabetes: a nested case-control study.

OBJECTIVE: Type 2 diabetes is associated with increased cardiovascular risk. The role of aggressive glycemic control in preventing cardiovascular events is unclear. A nested case-control study design was used to evaluate the association between average A1C and cardiovascular outcomes. RESEARCH DESIGN AND METHODS: Adults with type 2 diabetes were identified among members of Kaiser Permanente Southern California. Type 2 diabetes was identified based on ICD-9 diagnosis codes and either A1C >7.5% or prescriptions for hypoglycemic agents. Case subjects were defined based on nonfatal myocardial infarction, nonfatal stroke, or death attributed to cardiovascular events during a 3-year window. Four type 2 diabetes control subjects were matched to each case subject based on age, sex, and index date for the corresponding case. A conditional logistic regression model was used to estimate the odds ratio of cardiovascular events and compare three patient groups based on average A1C measured in the preindex period (≤6, >6-8, >8%). RESULTS: A total of 44,628 control subjects were matched to 11,157 case subjects. Patients with an average A1C ≤6% were 20% more likely to experience a cardiovascular event than the group with an average A1C of >6-8% (P < 0.0001). Patients with an average A1C >8% experienced a 16% increase in the likelihood of a cardiovascular event (P < 0.0001). We found evidence of statistical interaction with A1C category and LDL level (P = 0.0002), use of cardiovascular medications (P = 0.02), and use of antipsychotics (P = 0.001). CONCLUSIONS: High-risk patients with type 2 diabetes who achieved mean A1C levels of ≤6% or failed to decrease their A1C to <8% are at increased risk for cardiovascular events.

Applying comparative effectiveness research methods in bipolar disorders.

BACKGROUND: Randomized clinical trials [RCT] are the Gold Standard of medical evidence. However, observational comparative effectiveness research [CER] based on real-world data is receiving national attention. This paper demonstrates how observational CER can fill important gaps in clinical knowledge left behind by RCT approaches. An example of CER in bipolar disorders is presented. METHODS: Paid claims data from a large commercial insurer were used to identify episodes of drug therapy. Episodes were defined each time a patient initiated or restarted therapy using an antipsychotic, antidepressant or mood stabilizing medication. Episode definitions were based on calculations of continuous days of drug therapy using a 15 day gap definition. 105,440 episodes of drug therapy were included in the analysis. RESULTS: Most episodes were initiated using a mood stabilizing drug (40%) or an antidepressant (40%). Over 59% of all episodes were for augmentation therapy, followed by switching episodes (25%) and restart episodes (16%). Patient outcomes measured by either duration of uninterrupted therapy or one-year post-treatment cost varied significantly with patient treatment history, especially episode type. The comparative effectiveness of alternative therapies was sensitive to the extent to which treatment history is taken into account. CONCLUSIONS: Observational research can evaluate patient outcomes across a wide range of clinical presentations with regard to the patient's treatment history. Treatment history is a major determinant of patient compliance and future treatment costs. Failure to account for treatment history can introduce bias into comparative effectiveness results. Observational CER research can also uncover important questions that require future research.

Duration of antipsychotic drug therapy in real-world practice: a comparison with CATIE trial results.

BACKGROUND: Duration of drug therapy is a key measure of drug effectiveness in schizophrenia. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial found that only olanzapine achieved a longer time to all-cause-discontinuation (TTAD) than a standard therapy comparator. This study compares the TTAD achieved when using alternative antipsychotics to treat patients with schizophrenia in real-world practice settings. METHODS: A total of 219,504 episodes of antipsychotic therapy initiated in the years 2000 to 2002 were identified using data from the California Medicaid (Medi-Cal) program. To capture the full range of treatment scenarios facing clinicians, four episode types were included: restarting therapy using the drug used in the preceding episode; restarting therapy using a different medication (delayed switches); switching therapy without a break in therapy; and augmentation. TTAD and changes in therapy were analyzed using ordinary least squares and logistic regressions and Cox proportional hazards models. RESULTS: Atypical antipsychotics consistently achieved longer TTAD and reduced switching rates relative to conventional antipsychotics. Differences in TTAD favoring atypical antipsychotics were 13 to 15 days in restart episodes; 28 to 36 days for delayed switching episodes; 41 to 52 days in switching episodes; and 59 to 63 days for augmentation (P < 0.0001 for all estimates). Differences between the atypical antipsychotics were smaller than reported in other studies and may not be clinically significant. CONCLUSIONS: This study confirms two results from the CATIE study: Patients with schizophrenia frequently do not achieve stable, long-term drug therapy regardless of the specific drug used, and olanzapine achieved longer TTAD than conventional drugs. However, this study also found that patients treated with risperidone and quetiapine also achieved longer TTAD than patients treated with conventional antipsychotics.

The impact of atypical antipsychotic medications on the use of health care by patients with schizophrenia.

OBJECTIVE: Using data in real-world clinical practice, this study aims to compare the health-care use patterns of patients with schizophrenia who use oral antipsychotics. METHODS: A total of 219,504 episodes of antipsychotic drug therapy initiated during the period from 2000 to 2002 were identified using data from the California Medicaid program. Four types of episodes were analyzed based on the patient's drug use history as far back as 1994: restarting therapy after a break in therapy using the same drug used in the preceding episode; switching therapy after a break in treatment using a different medication; switching therapy without a break in therapy; and augmentation. Health-care use patterns over a 1-year post-treatment period were analyzed using ordinary least squares (OLS) regressions, Cox proportional hazards models, and logistic regression. RESULTS: The impact of atypical antipsychotics on health-care use in the first post-treatment year varies by episode type. Patients switching to atypical medications generally cost significantly more than similar patients switching to a conventional antipsychotic. Olanzapine and risperidone, however, were associated with reductions in total costs relative to conventional antipsychotics when used in restart and augmentation episodes. Differences across all three second-generation antipsychotics were relatively small. CONCLUSIONS: Small differences across the atypical antipsychotics suggest that these drugs are interchangeable, raising the question of whether drug costs could be reduced through selectively contracting for a preferred drug. Potential savings may be limited by several factors. First, most episodes of treatment are restart episodes. Switching these patients to a preferred drug may have clinical risk. Second, patients with schizophrenia switch and augment therapies frequently, thus quickly reducing the population of patients who could be effectively treated with a single preferred drug.

Classifying patients by antipsychotic adherence patterns using latent class analysis: characteristics of nonadherent groups in the California Medicaid (Medi-Cal) program.

OBJECTIVES: This study identifies latent classes defined by varying degrees of adherence to antipsychotic drug therapy and examines the sociodemographic, clinical, and resource utilization correlates associated with membership in each adherence class. DATA AND METHODS: Patient-level data were drawn from the 1994 to 2003, 100%-sample California Medicaid fee-for-service paid claims data for patients with schizophrenia (N = 36,195). The date of the first antipsychotic medication filled after January 1, 1999 was then used to divide each patient's data into a 6-month preindex (baseline) and a 12-month postindex (follow-up) period. Three categorical adherence indicators-a dichotomous variable of medication possession ratio greater than 0.80, the number of antipsychotic treatment attempts, and time to a change in antipsychotic medications-and two covariates-a categorical variable of duration of therapy and a dichotomous variable of polypharmacy-were used in the latent class model. RESULTS: A three-class model returned the lowest values for all the information criteria and was therefore interpreted as follows: The prevalence rates of the latent classes were 1) 14.8% for the adherent; 2) 20.7% for the partially adherent; and 3) 64.5% for the nonadherent. Membership in the nonadherent class was associated with minority ethnicity, being female, eligibility due to welfare status, prior hospitalizations, and a higher number of prior treatment episodes. Membership in the partially adherent class was associated with higher use of outpatient care, higher rates of depot antipsychotic drug use, and polypharmacy. CONCLUSION: Multiple indicators of adherence to antipsychotic medication can be used to define classes of adherence that are associated with patient characteristics and distinct patterns of prior health-care use.

The impact of unrecognized bipolar disorders among patients treated for depression with antidepressants in the fee-for-services California Medicaid (Medi-Cal) program: a 6-year retrospective analysis.

INTRODUCTION: The cost of unrecognized bipolar disorders over time is unknown. METHODS: Ten years of data from the California Medicaid program were used to identify depressed patients initiating new episodes of antidepressant therapy and with 6+ years of post-treatment data. Recognized bipolar (RBP) patients received a BP diagnosis or used mood stabilizers in the pre-index period. Unrecognized bipolar (UBP) patients received an initial BP diagnosis or used a mood stabilizer in the post-index period. Depression-only (MDD) patients had no BP diagnosis or mood stabilizer use. Three analyses were conducted: (1) regression models of cost per year, (2) a regression model of aggregate cost over 6 years and (3) a time trend analysis of the costs for UBP patients. RESULTS: 14,809 patients were identified: RBP 14.5%, UBP 28.2% and MDD 57.3%. The growth in costs per month for UBP patients over 6 years (171%) far exceeds the growth for RBP and MDD patients (82% and 95%, respectively). RBP and MDD patients cost 2316 dollars and 1681 dollars less per year in the 6th year relative to UBP patients (p<0.0001 for both estimates). The cost per month increased by 91 dollars for each month of delayed diagnosis (p=0.011). Costs for UBP patients increased by 10 dollars per month prior to their initial BP diagnosis (p<0.001) and by -1.01 dollars thereafter (p=0.006 for the change in slope). LIMITATIONS: Classification of patients based on diagnosis or mood stabilizer use using paid claims data is inexact. CONCLUSIONS: Early diagnosis of bipolar disorders may significantly reduce health care cost.

Defining and measuring clinical effectiveness in the treatment of schizophrenia.

OBJECTIVES: Expectations in treating schizophrenia are expanding beyond just controlling psychotic symptoms to include functional recovery. This report describes an approach to define and measure the clinical effectiveness of treatment in achieving these objectives. METHODS: A comprehensive literature review established that there is limited information about the meaning of the term "clinical effectiveness." To address this gap a consensus conference of schizophrenia researchers was held to consider the components of clinical effectiveness in real-world community practice and how these components can best be measured. RESULTS: The consensus of the researchers was that effective clinical treatment is characterized by four outcome domains: symptoms of disease, treatment burden, disease burden, and health and wellness. A clinical instrument to measure these four domains was constructed: Global Outcome Assessment of Life in Schizophrenia (GOALS). In using GOALS, clinicians rate each of the four domains on a scale of 1, very much improved, to 7, very much worse. Field-testing of this instrument is planned. CONCLUSIONS: Effective treatment interventions that combine optimal pharmacotherapy and targeted psychosocial treatments are raising expectations about the prospects of functional recovery among patients with schizophrenia. GOALS is proposed as one tool that can provide busy clinicians with a simple, objective measure of the effectiveness and outcomes of the clinical treatment they provide to patients with schizophrenia.

The impact of mirtazapine compared with non-TCA antidepressants on weight change in nursing facility residents.

OBJECTIVE: To examine weight change associated with the use of mirtazapine compared with other antidepressants in elderly, depressed nursing facility residents. DESIGN: Retrospective cohort study. SETTING: Long-term care nursing facilities in the Southern California region. PARTICIPANTS: One hundred eighty-nine elderly patients (>65 years of age) who had a new episode or diagnosis of depression and stayed in the same facility for at least eight months. METHODS: The impact of antidepressant use on weight change and percentage weight change at three months and six months were assessed using Ordinary Least Squares (OLS) regression analysis. Mirtazapine served as the comparator drug. RESULTS: We found no statistically significant differences in weight change at three months and at six months between mirtazapine and all other nontricyclic antidepressants except for fluoxetine, which was associated with a gain of 3.8 pounds relative to mirtazapine at three months (P = 0.05). However, a hypertension diagnosis was associated with significant weight gain at three months (2.2 lbs., P = 0.04 or +1.7%, P = 0.03) and at six months (3.9 lbs., P = 0.005 or +3%, P = 0.006). A diagnosis of diabetes was associated with weight loss at six months (-3.7 lbs., P = 0.03; -3.2%, P = 0.02). Baseline weight was associated with increased weight loss in women at six months (-0.09 lb (per lb. baseline), P = 0.03). CONCLUSIONS: With the exception of fluoxetine, our study showed that the impact on weight using mirtazapine was not statistically different from other nontricyclic antidepressant users after controlling for factors such as baseline weight, gender, dose, and comorbid diagnoses.

The impact of unrecognized bipolar disorders for patients treated for depression with antidepressants in the fee-for-services California Medicaid (Medi-Cal) program.

BACKGROUND: This study compares hospital use, suicide risk and health care costs of antidepressant patients with recognized bipolar disorders (recognized-BP) and unrecognized bipolar disorders (unrecognized-BP) with non-bipolar (non-BP) patients. METHODS: Data from the California Medicaid (Medi-Cal) program were used to identify 25,460 adults with a new episode of antidepressant therapy. Recognized-BP patients received either a bipolar (BP) diagnosis or a mood stabilizer (MS) on or before the initiation of antidepressant therapy. Unrecognized-BP patients received a BP diagnosis or MS therapy after antidepressant initiation. Non-BP patients had no BP diagnosis and no MS use. Multivariate models were used to estimate marginal risks and costs across groups. RESULTS: Recognized-BP and unrecognized-BP represented 14.9% and 6.2% of all antidepressant users, respectively. Less than half of recognized-BP patients used a MS medication in conjunction with their antidepressant. Unrecognized-BP patients were nearly four times more likely to attempt suicide and 50% more likely to be hospitalized than non-BP patients. Recognized-BP patients were at lower risk for attempted suicide and hospitalization relative to unrecognized-BP patients. Unrecognized-BP patients experienced higher 1-year total costs relative to non-BP patients (USD 995, p<0.01) and recognized-BP patients (USD 682, p<0.05). LIMITATIONS: Clinically relevant medical records data were not available making the classification of patients as unrecognized-BP, recognized-BP and non-BP imprecise. CONCLUSIONS: Unrecognized-BP is both common and costly. More than half of all recognized-BP patients do not use an MS at the time they initiated antidepressant therapy. More effort is needed to provide early and correct diagnosis and effectively treat both recognized-BP and unrecognized-BP patients.

Open access to innovative drugs: treatment substitutions or treatment expansion?

Granting open access to new antipsychotic medications by the California Medicaid Program fostered the desired substitution of second-generation medications for conventional antipsychotics. However, open access also generated an immediate but temporary influx of previously treated patients, many with a recent institutionalization, who restarted drug therapy using the new antipsychotics. Persistence with initial therapy declined, but cost outcomes improved due primarily to reduced nursing home use. Racial disparities were also reversed. Program administrators must use caution when evaluating the impact of unrestricted access on drug therapy outcomes and treatment costs given the changes in the characteristics of patients seeking treatment.