A cohort study of acute pancreatitis in relation to exenatide use.

AIM: Reports of acute pancreatitis associated with exenatide treatment prompted this study to estimate the association between acute pancreatitis and exenatide use relative to other antihyperglycaemic drugs. METHODS: This cohort study included patients without claims for prior pancreatic disease who initiated exenatide or other antihyperglycaemic drugs between June 2005 and December 2007. Acute pancreatitis was identified with diagnosis codes and confirmed through review of blinded medical records. Poisson regression models provided estimates of rate ratios (RRs) and 95% confidence intervals (CIs) comparing the rate of acute pancreatitis during periods of current (days supplied + 31 days), recent (current definition + 31 days) and past use (≥32 days beyond current definition) of exenatide relative to other antihyperglycaemic drugs, adjusted for propensity scores. A prespecified nested case-control analysis provided RR estimates adjusted for patient characteristics abstracted from medical records. RESULTS: Initiators of exenatide (N = 25719) had more baseline claims for obesity and concomitant diabetes drugs than comparators (N = 234536). There were 40 confirmed cases of acute pancreatitis in the exenatide cohort and 254 among other antihyperglycaemic drug initiators. Compared to other antihyperglycaemic drugs, the propensity score-adjusted RR for exenatide was 0.5 (95% CI 0.2-0.9) for current use, 1.1 (95% CI 0.4-3.2) for recent use and 2.8 (95% CI 1.6-4.7) for past use. The case-control analysis resulted in a RR of 0.2 for current use (95% CI 0.0-1.4) and 0.1 for recent use (95% CI 0.0-1.3), but an attenuated RR in the past use association (RR 1.1; 95% CI 0.1-11.0). CONCLUSIONS: Exenatide use was not associated with an increased risk of acute pancreatitis.

U.S. prevalence of endocrine therapy-naïve locally advanced or metastatic breast cancer.

Background: Variations in treatment choice, or late stage at first diagnosis, mean that, despite guideline recommendations, not all patients with hormone receptor (hr)-positive locally advanced or metastatic breast cancer (la/mbca) will have received endocrine therapy before disease progression. In the present study, we aimed to estimate the proportion of women with postmenopausal hr-positive la/mbca in the United States who are endocrine therapy-naïve. Methods: Women in the Optum Electronic Health Record (ehr) database with a breast cancer (bca) diagnosis (January 2008-March 2015) were included. Patient and malignancy characteristics were identified using structured data fields and natural-language processing of free-text clinical notes. The proportion of women with postmenopausal hr-positive, human epidermal growth factor 2 (her2)-negative (or unknown) la/mbca who had not received prior endocrine therapy was determined. Results were extrapolated to the entire U.S. population using the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results database. Results are presented descriptively. Results: In the ehr database, 11,831 women with bca had discernible information on postmenopausal status, hr status, and disease stage. Of those women, 1923 (16.3%) had postmenopausal hr-positive, her2-negative (or unknown) la/mbca, and 70.7% of those 1923 patients (n = 1360) had not received prior endocrine therapy, accounting for 11.5% of the overall population. Extrapolating those estimates nationally suggests an annual incidence of 14,784 cases, and a 5-year limited duration prevalence of 50,638 cases. Conclusions: A substantial proportion of women with postmenopausal hr-positive la/mbca in the United States could be endocrine therapy-naïve.

Are risk evaluation and mitigation strategies associated with less off-label use of medications? The case of immune thrombocytopenia.

Using data from a large commercial health insurer, we studied prescribing of romiplostim (Nplate) and eltrombopag (Promacta), two drugs for primary immune thrombocytopenia (ITP) for which risk evaluation and mitigation strategies (REMS) with elements to assure safe use were initially imposed and then removed. We identified 103 and 117 new users of romiplostim and eltrombopag, respectively. Use was almost exclusively for FDA-approved indications ("on-label") while the REMS with elements to assure safe use were in place. After these elements were lifted, off-label use of eltrombopag among patients with hepatitis C virus (HCV), a subsequently approved indication, increased. The ratio of incidence rate ratios of off-label/HCV to on-label initiation of eltrombopag between the two time periods was significant (13.41; P < 0.001). Our finding of an association with reduced off-label prescribing suggests that REMS with elements to assure safe use can help promote patient safety but may also prevent promising off-label drug uses.

Clinically relevant differences between the statins: implications for therapeutic selection.

Although the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, share a common lipid-lowering effect, there are differences within this class of drugs. The low-density lipoprotein (LDL) cholesterol-lowering efficacy, pharmacokinetic properties, drug-food interactions, and cost can vary widely, thus influencing the selection of a particular statin as a treatment option. The statins that produce the greatest percentage change in LDL cholesterol levels are atorvastatin and simvastatin. Atorvastatin and fluvastatin are least affected by alterations in renal function. Fewer pharmacokinetic drug interactions are likely to occur with pravastatin and fluvastatin, because they are not metabolized through the cytochrome P450 (3A4) system. The most cost-effective statins, based on cost per percentage change in LDL cholesterol levels, are fluvastatin, cerivastatin, and atorvastatin. Awareness of these differences may assist in the selection or substitution of an appropriate statin for a particular patient.

Efficacy of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors in the treatment of patients with hypercholesterolemia: a meta-analysis of clinical trials.

Recent studies have documented the long-term impact of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on mortality and morbidity related to coronary heart disease, establishing the link between lowering cholesterol levels and reducing cardiac events. Our study was a comparative literature review and meta-analysis of the efficacy of four HMG-CoA reductase inhibitors-fluvastatin, lovastatin, pravastatin, and simvastatin-used in the treatment of patients with hypercholesterolemia. The data sources for our meta-analysis of the efficacy of these cholesterol-lowering agents were 52 randomized, double-masked clinical trials with at least 25 patients per treatment arm. The results showed all four agents to be effective in reducing blood cholesterol levels. We computed summary efficacy estimates for all published dose strengths for the four agents. Fluvastatin 20 mg/d reduced low-density lipoprotein cholesterol (LDL-C) levels by 21.0% and total cholesterol (total-C) levels by 16.4%; fluvastatin 40 mg/d reduced these levels by 23.1% and 17.7%, respectively. Lovastatin 20 mg/d reduced LDL-C levels by 24.9% and total-C levels by 17.7%; lovastatin 80 mg/d reduced these levels by 39.8% and 29.2%, respectively. Pravastatin 10 mg/d reduced LDL-C levels by 19.3% and total-C levels by 14.0%; pravastatin 80 mg/d reduced these levels by 37.7% and 28.7%, respectively. Simvastatin 2.5 mg/d reduced LDL-C levels by 22.9% and total-C levels by 15.7%; simvastatin 40 mg/d reduced these levels by 40.7% and 29.7%, respectively. The results of our meta-analysis can be used in conjunction with treatment objectives and comparative cost-effectiveness data for these agents to decide appropriate therapeutic alternatives for individual patients.

Atorvastatin calcium: an addition to HMG-CoA reductase inhibitors.

Atorvastatin calcium is an HMG-coenzyme A (CoA) reductase inhibitor that was approved by the Food and Drug Administration on December 17, 1996. Like other such agents, it inhibits the action of HMG-CoA reductase and thereby decreases endogenous cholesterol synthesis, leading to a decrease in circulating low-density lipoprotein cholesterol. In addition to its effect on lipoprotein profile, atorvastatin reduces triglycerides to a greater extent than other HMG-CoA reductase inhibitors. These actions occur in a dose-dependent fashion. The adverse effect profile is similar to that of other agents in this class. Indications for atorvastatin include primary hypercholesterolemia as well as other lipid disorders.

Characteristics associated with ability to prevent adverse drug reactions in hospitalized patients.

We conducted a retrospective analysis to identify characteristics of preventable adverse drug reactions (ADRs). We reviewed reports on 612 ADRs occurring in hospitalized patients over 4 years, identified by the hospital's spontaneous ADR reporting program, and classified the events as potentially preventable or not preventable. Characteristics related to ADR preventability in the univariate analysis were the patient's clinical service, organ system involved in the ADR, class of drug causing the ADR, relationship to dosage, type of ADR, and probability that the reaction was due to the drug. Among these, relationship to dosage (p<0.001) and type of ADR (p<0.001) appeared to be most strongly related to preventability. In a multivariate analysis, preventable ADRs were associated with dosing (OR 3.82, 95% CI 2.42-6.03) and previous allergy to the drug (OR 3.46, 95% CI 1.01-11.88). An ADR that was classified as an allergic (OR 0.50, 95% CI 0.27-0.94) or idiosyncratic reaction (OR 0.44, 95% CI 0.28-0.71) was unlikely to be considered preventable. Preventable ADRs in hospitalized patients are likely to be dosage related or to occur among patients allergic to the specific agent.

The low-density lipoprotein cholesterol-lowering effect of pravastatin and factors associated with achieving targeted low-density lipoprotein levels in an African-American population.

STUDY OBJECTIVES: To describe the low-density lipoprotein cholesterol (LDL)-lowering effect of pravastatin in African-American patients and to identify factors associated with achieving National Cholesterol Education Program (NCEP)-defined target levels. DESIGN: Retrospectively defined cohort study. SETTING: Large, government-owned, teaching hospital. PATIENTS: Eighty-four African-American patients starting therapy with pravastatin in October-November 1997. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Whether or not target LDL concentrations were achieved was used to measure efficacy. Stepwise logistic regression identified the target LDL, baseline LDL, and baseline high-density lipoprotein cholesterol (HDL) as significant predictors of achieving the target. The proportion of patients achieving their target LDL when that target was below 160, below 130, and 100 mg/dl or below was 64%, 32%, and 13% (p=0.004), respectively. Medical record review identified the reasons for not achieving target as incorrect drug regimen, inadequate lipid monitoring, and noncompliance. CONCLUSION: These results indicate that substantial numbers of patients receiving lipid-lowering therapy are not meeting NCEP-defined targets and that with increased drug monitoring and compliance, improvements in achieving NCEP target LDL levels could be realized.

Estimating the rate of adverse drug reactions with capture-recapture analysis.

The capture-recapture technique used to estimate the number of ADRs at UICMC may offer institutions and health systems a way to better identify and address the occurrence of ADRs.

Control charts to monitor rates of adverse drug reactions.

We describe the use of control charts in monitoring rates of adverse drug reactions. Adverse drug reactions are recognized as important outcomes of patient care and are specifically associated with the process of medication use. The systematic monitoring of adverse drug reactions may allow one to identify opportunities to improve this process. Reported adverse drug reactions from 36 consecutive months at a university hospital were analyzed. The mean rate of adverse drug reaction reporting was 1.65% (denominator of patient admissions) and the 3 sigma upper and lower control limits were 3.22% and 0.08%, respectively. The mean rate of preventable adverse drug reactions was 21.25% (denominator of total reported adverse drug reactions) and the 3 sigma upper and lower control limits were 73.54% and < 0%, respectively. The experience described in this report suggests that monitoring adverse drug reactions using control charts, facilitates identification of trends in reporting and the actual incidence of adverse drug reactions, and allows identification of opportunities to improve the systems and processes of medication use.

Characteristics and antecedents of progressive multifocal leukoencephalopathy in an insured population.

Based on health insurance claims from a large U.S. health insurer, the authors identified 44 progressive multifocal leukoencephalopathy (PML) cases from 2002 through 2004 and described their characteristics, including antecedent diagnoses and treatments as well as survival. Immunosuppressive conditions such as HIV/AIDS, rather than potentially immunosuppressive treatments, were the main antecedents of PML. A lower mortality was observed among PML patients whose antecedent diagnosis was HIV/AIDS, the majority of whom received highly active antiretroviral therapy.

Analysis of a survey of UHC hospitals--College of Pharmacy relationships.

The University HealthSystem Consortium (UHC) Pharmacy Advisory Council commissioned a survey of the methods and resources used to support pharmacy practice education. This article presents the results of the two-part survey, and presents a brief description and analysis of the results. Fifty-two of the UHC's member hospitals' pharmacies replied to the survey. An unblinded study sought to characterize the types and numbers of students and staff involved. A second blinded portion of the survey requested the opinions and comments of pharmacy managers.

A cost-effectiveness analysis of treatment options for patients with methotrexate-resistant rheumatoid arthritis.

OBJECTIVE: Recently, new treatment options for rheumatoid arthritis (RA) patients with an inadequate response to methotrexate (MTX) have become available. Given the wide variability in efficacy and costs among these different treatment options, we sought to determine their cost-effectiveness (CE) in order to guide policy in different cost-constrained settings. METHODS: We performed a CE analysis comparing 6 treatment options for patients with MTX-resistant RA: 1) etanercept + MTX, 2) etanercept monotherapy, 3) cyclosporine + MTX, 4) triple therapy (hydroxychloroquine, sulfasalazine, and MTX), 5) continuation of MTX monotherapy, and 6) no second-line agent. A decision model was used with a time horizon of 6 months. We used 2 measures of effectiveness based on published clinical trial data: the American College of Rheumatology 20% response criteria (ACR 20); and a weighted average of proportions of patients achieving responses of ACR 70, ACR 50, and ACR 20 (ACR 70 weighted response [ACR 70WR]). Incremental CE ratios were calculated as the additional cost per patient achieving either outcome, compared with the next least expensive option. To help interpret CE relative to these RA-specific outcomes, we conducted a separate, "reference" CE analysis of MTX use in MTX-naive RA patients, using the same outcomes. RESULTS: In our reference analysis, MTX therapy for MTX-naive RA cost $1,100 per ACR 20 outcome and $1,500 per ACR 70WR, compared with no second-line agent. In our base-case analysis with either outcome, MTX continuation, cyclosporine + MTX, and etanercept monotherapy cost more, but either were not more efficacious or had a higher incremental CE ratio than the next most expensive option (i.e., they were dominated). Therefore, these options were not cost-effective. The least expensive option, triple therapy, cost 1.3 times more per patient with ACR 20 outcome ($1,500/ACR 20) and 2.1 times more per ACR 70WR ($3,100/ACR 70WR) than MTX therapy for MTX-naive RA. The most efficacious option, the combination of etanercept and MTX, cost 38 times more per patient with ACR 20 outcome ($4,600/ACR 20) and 23 times more per ACR 70WR ($34,800/ACR 70WR) than MTX therapy for MTX-naive RA. Overall, the results of extensive sensitivity analyses did not substantially affect these results. CONCLUSION: Our analysis indicates that if 15 mg/week MTX is cost-effective for achieving ACR 20 or ACR 70WR in MTX-naive RA over a 6-month period, then most likely so is triple therapy in MTX-resistant RA. Whether etanercept + MTX is cost-effective depends on whether $34,800/ACR 70WR (or $42,600/ACR 20) over a 6-month period is considered acceptable.

Rapid estimation of creatinine clearances in patients with liver dysfunction.

Different methods are available for rapid assessment of renal function using the patient's serum creatinine concentration and body weight without obtaining urine collection over 24 hr. However, the reliability of these methods in patients with liver diseases has not been established. The purpose of this study was to determine the accuracy and precision of the estimated creatinine clearances obtained by the methods of Cockcroft-Gault, Jelliffe, Mawer, and Siersbaek-Nielsen in patients with liver diseases who have different degrees of renal function. Creatinine clearances obtained from 24-hr urine collection were used as the standard. The different methods for rapid renal function estimation had limited accuracy and reliability in patients with severe liver dysfunction (Child-Pugh class C) and also in those with creatinine clearances of less than 60 ml/min. Creatinine clearances were overestimated by about 40-100%. Using lean body weights, instead of total body weights, reduced the prediction errors. In patients with mild liver dysfunction (Child-Pugh class A), all four estimation methods provided reasonable estimation of the creatinine clearances.

Botulinum toxin A versus fixed cast stretching for dynamic calf tightness in cerebral palsy.

OBJECTIVE: To compare botulinum toxin A injections with fixed plaster cast stretching in the management of cerebral palsied children with dynamic (i.e. non-fixed) calf tightness. METHODS: The settings were the Women's and Children's Hospital (WCH) and the Crippled Children's Association of South Australia (CCA), Adelaide, South Australia. Twenty children were selected by two paediatric rehabilitation specialists. A prospective, randomized, single-blind controlled study, was carried out, with 10 children in each arm. The clinicians were blinded as to the allocated interventions. The outcome measures for 6 months post intervention were clinical assessment, modified Ashworth Scale, Gross Motor Function Measure, 2 D-video ratings using a modified Physical Rating Scale and a global scoring scale and a parent satisfaction questionnaire. RESULTS AND CONCLUSION: Botulinum toxin A injections were of similar efficacy to serial fixed plaster casting in improving dynamic calf tightness in ambulant or partially ambulant children with cerebral palsy. The ease of outpatient administration, reduction of muscle tone and safety with botulinum toxin A was confirmed. Parents consistently favoured botulinum toxin A and highlighted the inconvenience of serial casting.

Performance of comorbidity scores to control for confounding in epidemiologic studies using claims data.

Comorbidity is an important confounder in epidemiologic studies. The authors compared the predictive performance of comorbidity scores for use in epidemiologic research with administrative databases. Study participants were British Columbia, Canada, residents aged >or=65 years who received angiotensin-converting enzyme inhibitors or calcium channel blockers at least once during the observation period. Six scores were computed for all 141,161 participants during the baseline year (1995-1996). Endpoints were death and health care utilization during a 12-month follow-up (1996-1997). Performance was measured by using the c statistic ranging from 0.5 for chance prediction of outcome to 1.0 for perfect prediction. In logistic regression models controlling for age and gender, four scores based on the International Classification of Diseases, Ninth Revision (ICD-9) generally performed better at predicting 1-year mortality (c = 0.771, c = 0.768, c = 0.745, c = 0.745) than medication-based Chronic Disease Score (CDS)-1 and CDS-2 (c = 0.738, c = 0.718). Number of distinct medications used was the best predictor of future physician visits (R(2) = 0.121) and expenditures (R(2) = 0.128) and a good predictor of mortality (c = 0.745). Combining ICD-9 and medication-based scores improved the c statistics (1.7% and 6.2%, respectively) for predicting mortality. Generalizability of results may be limited to an elderly, predominantly White population with equal access to state-funded health care.

Self-directed work teams: application to a drug information center.

OBJECTIVE: To describe the transition of a drug information center from a traditionally managed center to a self-directed work team responsible for service, education, research, and drug use policy development. SUMMARY: To adapt to economic, educational, and technologic changes, traditional management structures in healthcare organizations are being reassessed. In some instances, a team approach (using self-directed work teams [SDWTs]) is being implemented. SDWTs have the potential to provide a number of benefits to an organization, including reduced costs and greater employee motivation. The University of Illinois at Chicago Drug Information Center had functioned under a traditional management structure. For economic and professional reasons, the management structure of the center was changed to an SDWT, prompting a reevaluation of the mission and activities of the center. DISCUSSION: Although still in transition, the center's change to a team structure has proven to be positive. The nature of the SDWT requires greater involvement by team members in all aspects of the center's operation, adding to the experience of team members. The team structure also allows for greater freedom to pursue projects of personal interest to individual team members. A number of issues still need to be resolved, such as performance-based compensation and peer- and self-evaluations. CONCLUSIONS: SDWTs can provide many benefits. The successful implementation of an SDWT, however, has a number of requirements, the most important of which are a commitment from management and effective communication among team members and with management.