Serum potassium as a predictor of adverse clinical outcomes in patients with increasing comorbidity burden.

AIMS: The aim of this study was to establish whether patients with multiple comorbidities may be at elevated risk of hyperkalaemia (HK), a potentially life-threatening electrolyte imbalance, and the associated adverse clinical outcomes. METHODS AND RESULTS: This was a retrospective, observational cohort study using UK primary and secondary care data. Adult patients with at least one of: resistant hypertension, chronic kidney disease stage 3+, dialysis, heart failure (HF), and diabetes, were eligible for inclusion. According to their diagnoses, patients were grouped into overlapping cohorts that were updated as multimorbidity progressed. Outcomes of interest were incident HK, all-cause mortality (ACM), and major adverse cardiovascular events (MACE). A total of 673 686 patients met the eligibility criteria, 36.3% of whom developed multimorbidity during the study period. A consistent U-shaped association was observed between serum K+ level and adjusted incidence of ACM and MACE. Hyperkalaemia was progressively more common with increasing Charlson Comorbidity Index (CCI). Relative to a CCI <3, scores of ≥3 to <6, and ≥6 were associated with 2.9- and 6.2-fold increases, respectively, in crude HK (serum K+ ≥5.0 mmol/L) incidence rate. In all condition-based cohorts except for HF, there was a clear correlation between increasing CCI and the risk of ACM and MACE associated with hypokalaemia and HK. CONCLUSION: Patients with a higher CCI are at an increased risk of developing HK and appear more prone to adverse clinical outcomes associated with abnormal serum K+ levels, warranting additional routine clinical monitoring.

The effect of hyperkalemia and long inter-dialytic interval on morbidity and mortality in patients receiving hemodialysis: a systematic review.

BACKGROUND: Patients with chronic kidney disease, especially those receiving hemodialysis (HD), are at risk of hyperkalemia (HK). This systematic review aimed to evaluate the prevalence of HK in patients with renal disease receiving HD and collate evidence on the effect of HK and differing HD patterns (i.e., long vs. short inter-dialytic intervals [LIDI and SIDI, respectively] in a thrice weekly schedule) on mortality. METHODS: Comprehensive searches were conducted across six databases and selected conference proceedings by two independent reviewers up to September 2020. A hundred and two studies reporting frequency of HK, mortality, or cardiovascular (CV) outcomes in adult patients with acute, chronic or end-stage renal disease in receipt of HD were included. Narrative synthesis of results was undertaken with key findings presented in tables and figures. RESULTS: Median prevalence of HK in patients with renal disease receiving HD was 21.6% and increased in patients receiving concomitant medications - mainly renin-angiotensin-aldosterone system inhibitors and potassium-sparing diuretics. Associations between elevated potassium levels and increased risk of both all-cause and CV mortality in the HD population were consistent across the included studies. In addition, there was a rise in all-cause and CV mortality on the day following LIDI compared with the day after the two SIDIs in patients on HD. CONCLUSIONS: Evidence identified in this systematic review indicates a relationship between HK and LIDI with mortality in patients with renal disease receiving HD, emphasizing the need for effective monitoring and management to control potassium levels both in emergency and chronic HD settings.

Risk factors associated with the incidence and recurrence of hyperkalaemia in patients with cardiorenal conditions.

INTRODUCTION: Hyperkalaemia (HK) is associated with increased mortality risk. Prior studies suggest that the causes of HK are multifactorial. This study aimed to examine risk factors for incident and recurrent HK in six large real-world cohorts of UK patients that could be considered at elevated HK risk because of underlying disease pathology and/or medication use. METHODS: This retrospective, observational cohort study utilised UK primary and secondary care data from Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES), respectively. Patients were included if they were aged ≥18 years and had a record of ≥1 condition of interest (chronic kidney disease [CKD] stage 3+, heart failure, resistant hypertension [RHTN], dialysis, diabetes) and/or renin-angiotensin-aldosterone system inhibitors (RAASi) use between 01 January 2003 and 30 June 2018. Based on their diagnosis/ RAASi prescription record, patients were assigned to overlapping cohorts. The outcomes assessed were HK and recurrent HK, the latter defined as second or subsequent HK episode during follow-up. HK was defined as a serum K+ measurement ≥5.0 mmol/L; thresholds of ≥5.5 and ≥ 6.0 mmol/L were also explored. RESULTS: Of 931 460 meeting the eligibility criteria, 310 535 (33.3%) patients experienced ≥1 HK event and 187 719 (20.2%) experienced HK recurrence. The probability of subsequent HK events increased with event number from 60.5% for the second event to 76.5% for the sixth and the corresponding time to the next HK event decreased from 15.8 months to 6.1 months. Amongst the key risk factors, serum creatinine, serum phosphorus, systolic blood pressure, and white cell count demonstrated direct relationships with incidence and recurrence of HK, while inverse relationships were observed for estimated glomerular filtration rate (eGFR), haemoglobin and diastolic blood pressure. The relationship for Charlson's Comorbidity Index was mixed. The use of RAASi and anti-hyperglycaemic agents was associated with an increased risk of HK, while the use of diuretics (non-K+ -sparing) was protective against HK. CONCLUSION: Several risk factors for HK that are easily measured in routine clinical practice were identified, facilitating the identification of patients who are at the highest risk of experiencing HK, including recurrent HK.

Is the EQ-5D fit for purpose in asthma? Acceptability and content validity from the patient perspective.

BACKGROUND: The increasing emphasis on patient-reported outcomes in health care decision making has prompted greater rigor in the evidence to support the instruments used. Acceptability and content validity are important properties of any measure to ensure it assesses the relevant aspects of the target concept. The purpose of this study was to evaluate the acceptability and content validity of the EQ-5D 5-Level (EQ-5D-5L) to assess the impact of asthma on patients' lives. METHODS: Qualitative interviews were conducted with 40 adults with asthma in the United Kingdom. The first 25 interviews used cognitive-debriefing methods to assess the relevance and acceptability of the EQ-5D-5L and two asthma-specific measures for comparison: an asthma-specific, preference-based measure (the Asthma Quality of Life Utility Index-5 Dimensions) and an Asthma Symptom Diary. The final 15 interviews combined concept elicitation to identify patient-perceived asthma impact, and cognitive debriefing to assess relevance and acceptability of the EQ-5D-5L and the Asthma Symptom Diary. Cognitive-debriefing feedback on the content of the measures was collated and summarized descriptively. The concept-elicitation data were analyzed thematically. RESULTS: Participants were aged 20 to 57 years and 62.5% were female. Although some participants expressed positive opinions on aspects of the EQ-5D-5L, only the usual activities dimension was consistently considered relevant to participants' asthma experiences. The mobility and self-care dimensions prompted strong negative reactions from some participants. Variations in interpretation of the mobility dimension and difficulties with multiple concepts in the pain/discomfort and anxiety/depression dimensions also were noted. Concepts reported by participants as missing included environmental triggers, asthma symptoms, emotions, and sleep. The EQ-5D-5L was the least preferred measure to describe the impact of asthma on participants' lives. Participants reported shortness of breath and impact on activities as especially salient issues. CONCLUSIONS: The content of the EQ-5D-5L was poorly aligned with the patient-perceived impact of asthma, and the measure failed to meet basic standards for acceptability and content validity as a measure to assess the impact of asthma from the patient perspective. The shortcomings identified raise concerns regarding the appropriateness of the EQ-5D in asthma and further evaluation is warranted.

Cost effectiveness of adjunctive quetiapine fumarate extended-release tablets with mood stabilizers in the maintenance treatment of bipolar I disorder.

BACKGROUND: Bipolar I disorder (BPD I) is a recurrent illness that affects 1% of the US population and constitutes a large economic burden. However, few studies have investigated the cost effectiveness of maintenance treatment options for BPD I. OBJECTIVE: To determine the cost effectiveness of maintenance treatment with quetiapine fumarate extended-release (XR) tablets in combination with mood stabilizers (lithium or divalproex) in comparison with the following treatments: placebo in combination with lithium or divalproex; no maintenance treatment; lithium monotherapy; lamotrigine monotherapy; olanzapine monotherapy; and aripiprazole monotherapy. METHODS: The analysis was conducted from the societal and payer perspectives in the US, using a Markov model. The model simulated a cohort of 1000 stabilized BPD I patients and estimated the quarterly risk in three health states: euthymia, mania and depression. Efficacy data were derived from two randomized, double-blind trials comparing quetiapine + lithium/divalproex with placebo + lithium/divalproex for up to 2 years, as well as other published literature. Resource data were extracted from published literature. Drug costs, hospitalizations and physician visits were among the direct costs. Indirect costs included absenteeism, and mortality rates included suicide. Benefits and costs were discounted at 3% and the price reference year was 2009. Endpoints included number of acute mood episodes, hospitalizations due to an acute mood event and costs per QALY. Probabilistic sensitivity analysis (PSA) was conducted to evaluate uncertainty in the model inputs. RESULTS: Treatment with quetiapine XR + lithium/divalproex was associated with reductions in acute mania (46%), acute depression (41%) and related hospitalizations (44%) compared with placebo + lithium/divalproex, and similar reductions in events were observed relative to lithium monotherapy. In the base-case analysis from the payer perspective, the discounted incremental cost per QALY for quetiapine XR + lithium/divalproex compared with placebo + lithium/divalproex was $US22 959, and compared with lithium monotherapy was $US100 235, while all other comparators were dominated. PSA showed these results to be robust to select assumptions. CONCLUSIONS: Quetiapine XR + lithium/divalproex may be a cost-effective maintenance treatment option for patients with BPD I.

Cost-effectiveness of quetiapine with lithium or divalproex for maintenance treatment of bipolar I disorder.

BACKGROUND: Bipolar I disorder is a recurrent illness that affects 1% of the US population and constitutes a large economic burden. Few studies have investigated the cost-effectiveness of maintenance treatment options. The objective of this analysis was to assess the cost-effectiveness of quetiapine (QTP) in combination with lithium (Li) or divalproex (DVP) compared with that of Li or DVP alone for maintenance treatment of bipolar disorder. METHODS: The cost-effectiveness of maintenance treatment with QTP in combination with Li or DVP was compared with placebo (PBO) in combination with Li or DVP from a US direct costs perspective using a Markov model. The model simulated a cohort of 1,000 stabilized patients with bipolar I disorder and estimated the quarterly risk in three health states: euthymia, mania, and depression. Efficacy data were derived from two randomized, double-blind, placebo-controlled trials comparing QTP + Li/DVP with PBO + Li/DVP for up to 2 years. Resource data were obtained from published literature. Direct costs included drug costs, hospitalizations, and physician visits. Outcomes and costs were discounted at 3% and the price reference year was 2007. Endpoints included the number of acute mood episodes, hospitalizations due to an acute mood event, and costs per quality-adjusted life-years. A probabilistic sensitivity analysis (PSA) was conducted to evaluate uncertainty. RESULTS: In the base-case analysis, QTP + Li/DVP dominated PBO + Li/DVP. The PSA showed these results to be robust. In addition, treatment with QTP + Li/DVP was associated with reductions in acute manic episodes (46%), acute depressive episodes (41%), and related hospitalizations (44%) compared with PBO + Li/DVP. CONCLUSIONS: These analyses, based on two randomized clinical trials, suggest that QTP + Li/DVP is a cost-effective maintenance treatment option for patients with bipolar I disorder compared with Li or DVP alone.

A model of the economic impact of a bipolar disorder screening program in primary care.

OBJECTIVE: Unrecognized bipolar disorder in patients presenting with a major depressive episode may lead to delayed diagnosis, inappropriate treatment, and excessive costs. This study models the cost effectiveness of screening for bipolar disorder among adults presenting for the first time with symptoms of major depressive disorder. METHOD: A decision-analysis model was used to evaluate the outcomes and cost over 5 years of screening versus not screening for bipolar disorder. Screening was defined as a 1-time administration of the Mood Disorder Questionnaire at the initial visit followed by referral to a psychiatrist for patients screening positive for bipolar disorder. Health states included correctly diagnosed bipolar disorder, unrecognized bipolar disorder, and correctly diagnosed major depressive episodes. Model outcomes included rates of correct diagnosis of bipolar disorder and discounted costs (2006 US dollars) of screening and treating major depressive episodes. Literature was the primary source of data and was collected from September 2007 through March 2009. RESULTS: According to the model, 1,000 adults in a health plan with 1 million adult members annually present with symptoms of major depressive disorder. An additional 38 patients were correctly diagnosed with depression (unipolar or a major depressive episode) or bipolar disorder (440 with screening vs 402 without screening) through a 1-time screening for bipolar disorder. Estimated 5-year discounted costs per patient were $36,044 without screening and $34,107 with screening (savings of $1,937). Accordingly, total 5-year budgetary savings were estimated at $1.94 million. Results were most sensitive to difference in treatment costs for patients with recognized versus unrecognized bipolar disorder. CONCLUSION: A 1-time screening program for bipolar disorder, when patients first present with a major depressive episode, can reduce health care costs to managed-care plans.

Incidence and costs of treatment-related complications among patients with advanced squamous cell carcinoma of the head and neck.

OBJECTIVE: To evaluate the incidence and costs of complications due to radiotherapy alone vs platinum-based chemoradiotherapy among patients diagnosed as having advanced squamous cell carcinoma of the head and neck (ASCCHN) from a payer perspective. DESIGN: Retrospective cohort study. SETTING: Data from the PharMetrics Patient-Centric Database from June 2000 through June 2006. PATIENTS: The study included patients with ASCCHN and an indication of a secondary malignant neoplasm (both identified based on International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis codes), 124 of whom were treated with radiotherapy alone and 77 of whom were treated with chemoradiotherapy (including 53 with cisplatin plus radiotherapy, 26 with carboplatin plus radiotherapy, and 2 with cisplatin and carboplatin plus radiotherapy). The patients were assigned to 1 of 2 cohorts based on treatment type-radiotherapy only and platinum-based chemoradiotherapy-and were followed up for 6 months. MAIN OUTCOME MEASURES: Incidence and costs of treatment-related complications associated with chemotherapy in ASCCHN. RESULTS: We found significantly (P < .001) higher rates of treatment-related complications among patients receiving chemoradiotherapy (86%) than among patients receiving only radiotherapy (51%). The mean per-patient costs associated with treatment-related complications were approximately $10 000 higher among patients who received chemoradiotherapy than among those treated with radiotherapy alone (P < .001). These costs represented 17% of the total costs during follow-up for patients who received chemoradiotherapy and 11% of costs for those who received radiotherapy. The most expensive complications were dehydration and/or electrolyte imbalance and oral complications. CONCLUSIONS: Our study results suggest that the attributable incidence and costs of treatment-related complications associated with chemotherapy in ASCCHN are substantial. The emergence of safer treatments may have the advantage of alleviating this cost burden.

Association between antipsychotic combination therapy and treatment adherence among individuals with bipolar disorder.

BACKGROUND: This study investigated the effect on antipsychotic treatment adherence of combining quetiapine or risperidone with lithium, anticonvulsants, and/or antidepressants among bipolar individuals with predominantly manic/mixed or depressive symptoms. METHODS: Treatment episodes with quetiapine or risperidone were identified from individuals with medical claims for bipolar/manic disorder. Multiple regression analysis was used to evaluate the impact of antipsychotic combinations on treatment adherence, as measured by intensity (medication possession ratio [MPR]) and treatment duration. RESULTS: Among mixed/manic individuals, combination therapies were associated with lower antipsychotic MPRs than monotherapy (P< .05), with MPR decreasing with number of medications. Quetiapine showed a similar pattern among depressed individuals, whereas risperidone showed a weaker association. For both subgroups, antipsychotic combinations with anticonvulsants were associated with lower MPRs than combinations with lithium. For manic/mixed individuals, combining quetiapine with an anticonvulsant and lithium was associated with shorter treatment durations than quetiapine alone (P

The impact of chronic hepatitis B on quality of life: a multinational study of utilities from infected and uninfected persons.

OBJECTIVES: Chronic hepatitis B (CHB) is a condition that results in substantial morbidity and mortality worldwide because of progressive liver damage. Investigators undertaking economic evaluations of new therapeutic agents require estimates of health-related quality of life (HRQOL). Recently, evidence has begun to accumulate that differences in cultural backgrounds have a quantifiable impact on perceptions of health. The objective was to elicit utilities for six health states that occur after infection with the hepatitis B virus from infected and uninfected respondents living in jurisdictions with low and with high CHB endemicity. METHODS: Standard gamble utilities were elicited from hepatitis patients and uninfected respondents using an interviewer-administered survey in the United States, Canada, United Kingdom, Spain, Hong Kong, and mainland China. Generalized linear models were used to the effect on utilities of current health, age and sex, jurisdiction and, for infected respondents, current disease state. RESULTS: The sample included 534 CHB-infected patients and 600 uninfected respondents. CHB and compensated cirrhosis had a moderate impact on HRQOL with utilities ranging from 0.68 to 0.80. Decompensated cirrhosis and hepatocellular carcinoma had a stronger impact with utilities ranging from 0.35 to 0.41. Significant variation was observed between countries, with both types of respondents in mainland China and Hong Kong reporting systematically lower utilities. CONCLUSIONS: Health states related to CHB infection have substantial reductions in HRQOL and the utilities reported in this study provide valuable information for comparing new treatment options. The observed intercountry differences suggest that economic evaluations may benefit from country-specific utility estimates. The extent that systematic intercountry differences in utilities hold true for other infectious and chronic diseases remains an open question and has considerable implications for the proper conduct and interpretation of economic evaluations.

Cost effectiveness of entecavir versus lamivudine with adefovir salvage in HBeAg-positive chronic hepatitis B.

OBJECTIVE: To evaluate the cost effectiveness of treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) with entecavir compared with lamivudine with adefovir salvage, based primarily on the results of a recent 2-year, randomised, multicentre, clinical trial (n = 709). Previous economic analyses have been limited by the lack of comparative clinical data for entecavir and lamivudine beyond 1-year duration and for salvage therapy. METHODS: We conducted a cost-utility analysis using a Markov model from a US-payer perspective over a lifetime time horizon. The hypothetical cohort was 35-year-old patients with HBeAg-positive CHB. We evaluated 2 years of treatment with entecavir 0.5mg/day versus lamivudine 100mg/day, plus addition of adefovir 10mg/day for patients who developed virologic breakthrough due to resistance to either drug. In a scenario analysis, we considered adefovir plus lamivudine combination therapy for treatment-naive patients. Clinical and economic inputs ($US, year 2006 values) were derived from publicly available data, and probabilistic sensitivity analyses were conducted to evaluate uncertainty in the results. RESULTS: The estimated 10-year cumulative incidence of cirrhosis for patients initiated on entecavir was 2.3% lower than for those on lamivudine (20.5% vs 22.8%). The discounted incremental cost per QALY gained was $US7600 in the base-case analysis, and the 95% central range from probabilistic sensitivity analysis was $US2500-$US19 100. Combination therapy for treatment-naive patients led to an increase in costs without improvement in patient outcomes compared with entecavir monotherapy. CONCLUSIONS: Our analysis suggests entecavir improves health outcomes in a cost-effective manner compared with lamivudine with adefovir salvage or combination therapy, and highlights the importance of using evidence-based effectiveness estimates in economic studies of CHB therapies.

Validation of the breast evaluation questionnaire for use with breast surgery patients.

BACKGROUND: : Reliable and valid assessment instruments in aesthetic surgery are a vital factor in assessing patient satisfaction with physical appearance. Appearance and satisfaction assessments are needed to adequately evaluate quality of life related to changes in the female breast across a variety of surgical interventions. The Breast Evaluation Questionnaire was designed to assess satisfaction with breast attributes. METHODS: : The Breast Evaluation Questionnaire is a 55-item assessment that was validated on 1244 women seeking augmentation mammaplasty. RESULTS: : Subscales of the Breast Evaluation Questionnaire include comfort not fully dressed, comfort fully dressed, and satisfaction with breast attributes. The questionnaire has been demonstrated to be valid and reliable for assessing these factors. CONCLUSIONS: : The assessment is easy to administer and interpret and is recommended for assessing outcomes among breast augmentation patients, breast reconstruction patients, mastectomy patients, lumpectomy/breast-sparing surgery patients, breast reduction patients, and patients who have sustained trauma or injury to their breasts.

Male sexual dysfunction and quality of life in schizophrenia.

OBJECTIVE: To describe the prevalence and clinical correlates of sexual dysfunction in a sample of adult male outpatients with schizophrenia treated with olanzapine, risperidone, quetiapine, or haloperidol, focusing on associations between sexual dysfunction and patient-perceived quality of life. METHOD: Sexual dysfunction was assessed in 139 outpatients with DSM-IV schizophrenia who were receiving olanzapine, risperidone, quetiapine, or haloperidol, but no other medications associated with sexual side effects. Structured assessments were made of psychiatric symptoms, quality of life, and relationships. RESULTS: Sexual dysfunction occurred in 45.3% of patients. Patients with and without sexual dysfunction did not significantly differ with respect to severity of psychiatric symptoms. However, as compared with patients without sexual dysfunction, patients with sexual dysfunction reported significantly lower ratings on global quality of life (t = 2.4, df = 136, p = .02) and the level of enjoyment in their life (t = 2.5, df = 136, p = .01). Patients with sexual dysfunction were significantly less likely than those without sexual dysfunction to report having a romantic partner (17.5% vs. 43.4%; chi(2) = 10.7, df = 1, p = .001), though they were not significantly less likely to report difficulty making friends (27.0% vs. 32.9%; chi(2) = 0.57, df = 1, p = .45). Among patients with romantic partners, those with sexual dysfunction reported significantly poorer quality of their relationships (t = 2.3, df = 42, p = .02) and were less likely to talk to their partner about their illness (t = 2.0, df = 42, p = .047). CONCLUSIONS: Sexual dysfunction is common in men with schizophrenia who are treated with olanzapine, risperidone, quetiapine, or haloperidol and is associated with diminished quality of life, decreased occurrence of romantic relationships, and reduced intimacy when relationships are established. High prevalence and substantial interference with quality of life combine to make sexual dysfunction an important area for clinical assessment and appropriate intervention in the community management of schizophrenia.

Antipsychotic exposure and type 2 diabetes among patients with schizophrenia: a matched case-control study of California Medicaid claims.

PURPOSE: To examine the risk of developing type 2 diabetes mellitus among people with schizophrenia exposed to atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone) compared to those exposed to conventional antipsychotics. METHODS: A matched case-control design was used to examine California Medicaid beneficiaries. Cases developed diabetes subsequent to being diagnosed with schizophrenia (ICD-9295), were 18 years or older, and were exposed to at least one antipsychotic medication at some point during the 12 weeks preceding diabetes diagnosis. Diabetes was defined by diagnostic claim (ICD-9250) or prescription for antidiabetic agents. A total of 3663 cases were matched to 14 523 non-diabetic controls (people with schizophrenia matched on gender and age +/-5 years). All had to be continuously eligible for benefits during the 12-week period preceding diabetes onset in the case. Conditional logistic regression modeled the risk of exposure, controlling for age, ethnicity, and exposure to selected concomitant medications. Analyses were repeated with 24- and 52-week exposure windows. RESULTS: Using a 12-week exposure window, olanzapine (OR = 1.36, 95%CI 1.20-1.53), clozapine (OR = 1.34, 95%CI 1.16-1.55), and combination atypical therapy (OR = 1.58, 95%CI 1.33-1.88), but not risperidone or quetiapine, were associated with increased odds of developing diabetes compared to conventional antipsychotics. Changing to a 24-week exposure window, the risks were: olanzapine (OR = 1.38, 95%CI 1.22-1.56), clozapine (OR = 1.32, 95%CI 1.14-1.53), or combinations (OR = 1.54, 95%CI 1.29-1.84). With a 52-week exposure window, the risks were: olanzapine (OR = 1.41, 95%CI 1.24-1.60), clozapine (OR = 1.41, 95%CI 1.21-1.65), combinations (OR = 1.58, 95%CI 1.31-1.90). Risk for olanzapine increased with dose. Hispanic, African American, and unknown ethnicity were significant risks for development of type 2 diabetes as was exposure to selected concomitant medications. CONCLUSIONS: Exposure to olanzapine or clozapine is associated with a 34-41% increase in the developing of type 2 diabetes among California Medicaid recipients with schizophrenia. Prospective, randomized trials are needed to confirm these retrospective, observational findings.

Association between antipsychotic treatment and hyperlipidemia among California Medicaid patients with schizophrenia.

OBJECTIVE: To examine the risk of hyperlipidemia among people with schizophrenia exposed to new antipsychotics (clozapine, olanzapine, quetiapine, risperidone) compared with those exposed to older generation antipsychotics. METHODS: A case-control study of Medi-Cal claims. Cases developed hyperlipidemia after being diagnosed with schizophrenia (ICD-9: 295) and were exposed to only one antipsychotic drug at some point within 12 weeks prior to the hyperlipidemia diagnosis. Hyperlipidemia was defined by diagnostic claim (ICD-9: 272.1-272.4) or prescription claim for antilipemic agents. Cases were matched on gender and age +/- 3 years to patients with schizophrenia who did not develop hyperlipidemia. Conditional logistic regression assessed the risk of antipsychotic exposure, controlling for age, ethnicity, prior type 2 diabetes or hypothyroidism, and exposure to other medications that may cause hyperlipidemia. Analyses were repeated using a 24- and 52-week retrospective exposure windows. RESULTS: For the 12-week exposure window, olanzapine (OR = 1.20, 95% CI 1.08-1.33) was associated with increased risk of developing hyperlipidemia compared with older antipsychotic medications. Exposure to clozapine (OR = 1.16, 95% CI 0.99-1.37), risperidone (OR = 1.00, 95% CI 0.90-1.12), and quetiapine (OR = 1.01, 95% CI 0.78-1.32) was not. Hypothesis tests comparing the 4 atypicals to one another revealed that the odds ratio for olanzapine was greater than that for risperidone (P = 0.002). Other than clozapine's odds ratio being significant at 24 weeks (OR = 1.22, 95% CI 1.03-1.45), increasing the exposure window to 24 or 52 weeks did not substantially alter the results. CONCLUSIONS: Compared with older generation antipsychotics, exposure to olanzapine and, somewhat less consistently, to clozapine is associated with an increased risk of hyperlipidemia among people with schizophrenia.

Weight gain and new onset diabetes associated with olanzapine and risperidone.

OBJECTIVE: To assess whether newer antipsychotic medications are associated with weight gain and development of diabetes. DESIGN: Retrospective cohort study. SETTING: Data from a comprehensive electronic medical record serving an urban public hospital and a citywide network of mental health clinics. PATIENTS/PARTICIPANTS: Three thousand one hundred fifteen patients at least 18 years old who were prescribed a single antipsychotic drug for at least 1 year. METHODS: We identified independent predictors of significant weight gain (> or =7%) and new onset of diabetes mellitus in the first year of antipsychotic drug treatment, using logistic regression adjusted for demographic characteristics, obesity, preexisting psychiatric diagnoses, alcohol and drug abuse, number of primary care, psychiatric clinic, and emergency department visits, and pretreatment weight. MEASUREMENTS AND MAIN RESULTS: Twenty-five percent of patients taking older phenothiazines developed significant weight gain in the first year of treatment compared to 40% of the patients taking olanzapine (adjusted odds ratio [OR], 2.8; 95% confidence interval [CI], 1.7 to 4.6; P <.0001) and 37% of patients taking risperidone (adjusted OR, 2.3; 95% CI, 1.5 to 3.4; P <.0001). New diabetes developed in 3% of patients taking older phenothiazines was new onset diabetes compared to 8.0% of patients taking olanzapine (adjusted OR, 1.9; 95% CI, 1.1 to 3.3; P=.03) and 3.5% of patients taking risperidone (adjusted OR, 0.7; 95% CI, 0.4 to 1.4; P=.3). No association was found between significant weight gain and developing diabetes (adjusted OR, 0.7; 95% CI, 0.4 to 1.4; P=.4). CONCLUSIONS: Olanzapine and risperidone use was associated with gaining weight in the first year, but only olanzapine was associated with developing diabetes mellitus.

Costs of lower-extremity ulcers among patients with diabetes.

OBJECTIVE: The objective of this study was to characterize health care costs associated with diabetic lower-extremity ulcers. RESEARCH DESIGN AND METHODS: Adult patients with diabetes who had a lower-extremity ulcer episode during 2000 and 2001 were identified using claims data. Ulcer-related direct health care costs were computed for each episode. Episodes were stratified according to severity level based on the Wagner classification. RESULTS: A total of 2,253 patients were identified. The mean age was 68.9 years, and 59% of the patients were male. The average episode duration was 87.3 +/- 82.8 days. Total ulcer-related costs averaged 13,179 dollars per episode and increased with severity level, ranging from 1,892 dollars (level 1) to 27,721 dollars (level 4/5). Inpatient hospital charges accounted for 77% (10,188 dollars) of the overall cost, indicating that hospitalization was a major cost driver. Total ulcer-related costs were significantly higher for patients <65 years of age compared with those of older patients (16,390 dollars vs. 11,925 dollars, P = 0.02) and for patients with inadequate vascular status compared with patients with adequate vascular status (23,372 dollars vs. 5,218 dollars, P < 0.0001). Patients who progressed to a higher severity level also had significantly higher ulcer-related costs compared with patients who did not progress (20,136 dollars vs. 3,063 dollars, P < 0.0001). CONCLUSIONS: The high costs of treating diabetic lower-extremity ulcers emphasize the value of intensive outpatient interventions designed to prevent ulcer progression.

Systems factors in the reporting of serious medication errors in hospitals.

Underreporting of medication errors poses a threat to quality improvement initiatives. Hospital risk management programs encourage medication error reporting for effective management of systems failures. This study involved a survey of 156 medical-surgical hospitals in the United States to evaluate systems factors associated with the reporting of serious medication errors. Prior to controlling for bed size, a multivariate logistic regression model showed increased reporting of medication errors in hospitals with 24-h pharmacy services, presumably because of better error reporting systems. When number of occupied beds was included, the final model demonstrated bed size to be the only statistically significant factor. Increased reporting rates for serious medication errors warrant further evaluation, but higher error reporting may paradoxically indicate improved error surveillance. Results suggest that increased availability of pharmacist services results in opportunities for more diligent systematic efforts in detecting and reporting medication errors, which should lead to improved patient safety.