Clinical, humanistic, and economic burden of chronic obstructive pulmonary disease (COPD) in Canada: a systematic review.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic, irreversible disease and a leading cause of worldwide morbidity and mortality. In Canada, COPD is the fourth leading cause of death. This systematic review was undertaken to update healthcare professionals and decision makers regarding the recent clinical, humanistic and economic burden evidence in Canada. METHODS: A systematic literature search was conducted in PubMed, EMBASE, and Cochrane databases to identify original research published January 2000 through December 2012 on the burden of COPD in Canada. Each search was conducted using controlled vocabulary and key words, with "COPD" as the main search concept and limited to Canadian studies, written in English and involving human subjects. Selected studies included randomized controlled trials, observational studies and systematic reviews/meta-analyses that reported healthcare resource utilization, quality of life and/or healthcare costs. RESULTS: Of the 972 articles identified through the literature searches, 70 studies were included in this review. These studies were determined to have an overall good quality based on the quality assessment. COPD patients were found to average 0-4 annual emergency department visits, 0.3-1.5 annual hospital visits, and 0.7-5 annual physician visits. Self-care management was found to lessen the overall risk of emergency department (ED) visits, hospitalization and unscheduled physician visits. Additionally, integrated care decreased the mean number of hospitalizations and telephone support reduced the number of annual physician visits. Overall, 60-68 % of COPD patients were found to be inactive and 60-72 % reported activity restriction. Pain was found to negatively correlate with physical activity while breathing difficulties resulted in an inability to leave home and reduced the ability to handle activities of daily living. Evidence indicated that treating COPD improved patients' overall quality of life. The average total cost per patient ranged between CAN $2444-4391 from a patient perspective to CAN $3910-6693 from a societal perspective. Furthermore, evidence indicated that COPD exacerbations lead to higher costs. CONCLUSIONS: The clinical, humanistic and economic burden of COPD in Canada is substantial. Use of self-care management programs, telephone support, and integrated care may reduce the overall burden to Canadian patients and society.

Meta-analysis of studies examining medication adherence, persistence, and discontinuation of oral antihyperglycemic agents in type 2 diabetes.

OBJECTIVE: To estimate overall rates of adherence, persistence, and discontinuation for patients with type 2 diabetes mellitus (T2DM) prescribed oral antihyperglycemic agents (OAHAs) by combining results of published studies. RESEARCH DESIGN AND METHODS: A systematic literature review was conducted to identify articles published in English over the last 10 years evaluating the use of OAHAs for the treatment of T2DM. Databases searched included PubMed/MEDLINE, EMBASE, and the Cochrane Library. Seventy studies reporting adherence, persistence or discontinuation were identified by two independent reviewers and 40 reported relevant endpoints for the analysis. Outcomes included: (1) mean adherence defined as the average medication possession ratio (MPR); (2) proportion of adherent patients (MPR ≥ 80%); (3) discontinuation; and (4) persistence. Adherence and persistence were reported in observational studies only. Discontinuation was examined separately in randomized controlled trials (RCTs) and observational studies. Meta-analyses were conducted using both fixed and random effects models. When meta-analysis was not appropriate for a given outcome, descriptive statistics were provided. RESULTS: The pooled mean MPR (95% confidence interval [CI]) was 75.3% (68.8%-81.7%; n = 13) and the proportion of adherent patients (95% CI) was 67.9% (59.6%-76.3%; n = 12). The discontinuation rate (95% CI) in RCTs was 31.8% (17.0%-46.7%; n = 7). Persistence and discontinuation were not assessed via meta-analysis for observational studies due to the limited number of available studies and differences in outcome definitions. In these studies, persistence estimates ranged from 41.0% to 81.1%, with a mean (95% CI) of 56.2% (46.1%-66.3%; n = 6), while discontinuation estimates ranged from 9.9% to 60.1%, with a mean (95% CI) of 31.4% (17.6%-45.3%; n = 6). LIMITATIONS: Limitations include (1) the use of MPR as a proxy for adherence, (2) limited number of studies available, and (3) observed heterogeneity. CONCLUSION: The results of the analysis demonstrate that medication adherence, persistence, and discontinuation rates are suboptimal in patients with T2DM prescribed OAHAs.

Relationship between treatment effects on progression-free survival and overall survival in multiple myeloma: a systematic review and meta-analysis of published clinical trial data.

BACKGROUND: Demonstrating improved overall survival (OS) with new multiple myeloma (MM) treatments is becoming difficult because of extended survival, so progression-free survival (PFS) is commonly used as a surrogate endpoint for OS. We evaluated PFS as a potential surrogate for OS by examining whether observed treatment effects on PFS are positively associated with treatment effects on OS in MM. METHODS: A systematic literature review identified 21 randomized control trials reporting hazard ratios (HRs) for treatment effects on PFS and OS. Pearson's r estimated the relationship between HRs (HRPFS and HROS), and between log-transformed HRs (log(HRPFS) and log(HROS)). R(2) values were estimated from linear regression models of the HR and the log(HR) relationships. Sensitivity and subgroup analyses examined the robustness of the HR findings. RESULTS: Positive correlations were found between HRPFS and HROS (r = 0.82; p < 0.0001) and between log(HRPFS) and log(HROS) (r = 0.80; p < 0.0001). Linear regression models produced R(2) values of 0.67 and 0.63 when regressing HROS on HRPFS, and log(HROS) on log(HRPFS), respectively. Sensitivity analyses supported the HR findings. CONCLUSION: This analysis provides evidence for a positive association between treatment effects on PFS and OS. Studies involving patient level data are necessary to confirm whether PFS is a valid surrogate for OS in MM.

Heterogeneity of response to biologic treatment: perspective for psoriasis.

Psoriasis treatment responses are affected by patient characteristics. However, the literature does not contain reviews of factors that affect the response to biologic therapies. We therefore performed a comprehensive literature search to identify papers describing demographic, lifestyle, and clinical factors associated with response to biologic drug therapy in psoriatic patients. We found that age, gender, ethnicity, alcohol consumption, smoking, geographic location, age at diagnosis, duration and severity of psoriasis, and baseline C-reactive protein levels did not consistently affect response to biologic psoriasis therapy. However, increased body mass index (BMI) appears to adversely affect responses. It might therefore be valuable to include BMI as a stratification variable in future studies of psoriasis therapies and to consider a patient's weight or BMI when selecting a systemic psoriasis treatment.

Chronic kidney disease in gout in a managed care setting.

BACKGROUND: To study the prevalence of chronic kidney disease (CKD) and its impact on allopurinol dosing and uric acid control among patients with gout. METHODS: This was a retrospective study using data from a large US health plan. Claims and laboratory data were analyzed for enrollees from the health plan database from January 2002 through December 2005. Patients with gout were identified from pharmacy and medical claims data based on the presence of codes for gout medication or gout diagnosis. Severity of CKD was determined using the estimated glomerular filtration rate (eGFR). Allopurinol titration was defined as a change in average daily dose from first prescription to last prescription of ≥ 50 mg. RESULTS: A total of 3,929 patients were identified for inclusion in this study, 39% of whom had CKD (based on having an eGFR < 90 mL/min/1.73 m2). Subjects with CKD were older (p < 0.01) and more likely to be women (p < 0.01), had a greater number of comorbid conditions (p < 0.01), and were more likely to be prescribed allopurinol (p < 0.01) compared to those with no CKD. The average starting dose of allopurinol was lower among those with CKD, and it decreased with worsening kidney function. Among the 3,122 gout patients who used allopurinol, only 25.6% without CKD and 22.2% with CKD achieved a serum uric acid concentration of < 6.0 mg/dL (p = 0.0409). Also, only 15% of allopurinol users had an upward dose titration (by ≥50 mg), but the average increase in dose did not differ significantly between those with and without CKD. CONCLUSIONS: About two out of every five patients with gout in this population had CKD. Allopurinol doses were not adjusted in the majority of CKD patients. Serum uric acid control in gout was poor among patients without CKD and even worse among those with CKD.

Review of treatment response in rheumatoid arthritis: assessment of heterogeneity.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic, systemic, progressive, inflammatory disorder. The primary goals of treatment in RA are to reduce the signs and symptoms of disease, prevent progression of joint damage and improve patients' physical function. Patients with different sociodemographic characteristics, varying degrees of severity of illness, and comorbidities tend to exhibit differential response to treatment. The purpose of this review was to identify a broad set of factors that are associated with and/or predictive of RA treatment response and determine those that warrant further research. RESEARCH DESIGN AND METHODS: A comprehensive review of the literature from the last 10 years was performed using three key databases (PubMed, EMBASE, and Cochrane). All relevant articles that met the inclusion/exclusion criteria were selected and scored for their levels of evidence using the National Institute of Clinical Excellence (NICE) scoring method. Data on study design, interventions and treatment outcomes were abstracted using a structured abstraction table. RESULTS: A total of 30 articles were included in the review and data abstraction. Besides gender, baseline clinical variables such as C-reactive protein level, erythrocyte sedimentation rate, measures of disease activity, and Health Assessment Questionnaire scores (based on five patient-centered dimensions) were consistently associated with treatment response over time. CONCLUSIONS: This comprehensive literature review identified several factors associated with treatment response which might be valuable to include as relevant measures in future studies of RA treatment. Inclusion of these factors, particularly those in the clinical and sociodemographic domains, in the design of future trials will further the understanding that ultimately may help clinicians deliver targeted treatment to community practice RA patients, thus resulting in improved patient outcomes.

Burden of illness among patients at high risk versus low risk for major cardiovascular events.

OBJECTIVE: This study was designed to compare the burden of illness (BOI) in patients at high risk versus low risk of developing a major cardiovascular (CV) event. METHODS: This retrospective claims data analysis included commercial health plan members identified with a primary diagnosis on a medical claim for cardiovascular disease (CVD) from January 1, 2001 through December 31, 2002. Patients were categorized as: low risk (LR), high risk (HR), or high risk aged≥55 (HR55), based on the ONTARGET clinical trial. RESULTS: Most patients (85%) were in the LR category (8% in HR55, 7% in HR). A significantly greater proportion of patients in the HR55 group were hospitalized and experienced a greater number of ambulatory visits compared with LR and HR patients. Controlling for covariates, HR55 patients averaged $22,502 in paid healthcare services over 2 years versus $15,645 for HR patients and $11,423 for LR patients (p<0.001). CV-related costs represented about 46% of costs for the HR55 group, versus 41% for the HR group and 31% for the LR group. LIMITATIONS: Claims data are collected for the purpose of payment and not research and the presence of a diagnosis code is not proof of disease, due to possible coding errors or the use of a rule-out criterion. Also, patients who died in the follow-up were not included in the analyses, resulting in lower BOI estimates. Finally, the results of this study reflect treatment of CVD in managed-care settings, and may not be applicable to a different type of population. CONCLUSION: This study demonstrates the high BOI associated with CVD, especially for patients within the high-risk group aged≥55 years. Opportunities exist for reducing costs in this population.

Predictors of adherence among Alzheimer's disease patients receiving oral therapy.

OBJECTIVES: Treatment effectiveness depends upon administering medications as prescribed, and adherence is critical for Alzheimer's disease (AD) patients to receive optimal benefit from therapy. The objective of this study was to investigate factors associated with adherence to AD oral medications. METHODS: This retrospective claims analysis identified AD patients who initiated oral AD therapy (rivastigmine, donepezil, galantamine, or memantine) between January 1, 2006 and December 31, 2007 from a large US health plan. Patient baseline characteristics were assessed during the 6-month pre-index period; outcomes were assessed during the 1-year post-index period. Pill burden was measured as a count of unique units of medication/day. Adherence was measured by medication possession ratio (MPR), with MPR >or=80% defined as adherent. Multivariate logistic regression was used to assess how potential covariates affect adherence probability. RESULTS: A total of 3091 AD patients (36% male; mean age 80 [8.25 SD]) were identified. Only 58% of patients were adherent to oral AD medications. Compared to patients <75 years, patients >or=86 years were likely to be more adherent (OR = 1.401, p < 0.001). Other factors found to be positively associated with the probability of adherence to AD medications were male gender (OR = 1.175, p < 0.05), overall pill burden (OR = 1.192, p < 0.001), and a lower formulary tier status of the AD medication (OR = 1.332, p < 0.001). CONCLUSION: Among the several variables assessed, being male, >or=86 years of age, having a greater overall daily pill burden, or using a lower formulary tier AD medication was associated with better adherence to oral AD medication in patients diagnosed with AD. The database had no information on caregiver support, medication management interventions, or use of adherence aids that may have affected adherence in this cohort, yet, a substantial proportion of patients (42%) remained non-adherent. A better understanding of the causes of non-adherence is necessary, and methods to improve adherence, such as transdermal medications and educational programs, should be considered.

Impact of persistence with antiplatelet therapy on recurrent ischemic stroke and predictors of nonpersistence among ischemic stroke survivors.

OBJECTIVE: Medication adherence is an important component of effective secondary stroke prevention. The objectives of this study were to examine the impact of persistence with two prescription antiplatelet therapies on the outcome of recurrent hospitalized stroke, and to identify the predictors of nonpersistence with these antiplatelet therapies. RESEARCH DESIGN AND METHODS: Administrative claims from a large, geographically diverse US health plan were used to evaluate acetylsalicylic acid / extended-release dipyridamole (ASA/ERDP) treated and clopidogrel treated patients from November 1, 2002 - December 31, 2005 who had an ischemic stroke requiring hospitalization. Nonpersistence was defined as failure to refill index medication within 30 days from the run-out date of the prior prescription. A Cox proportional hazards model was used to identify key factors associated with time to nonpersistence. MAIN OUTCOME MEASURES: Patient demographic variables, clinical characteristics, comorbidities hypothesized to affect the risk of current stroke, stroke outcomes, treatment patterns, and compliance were assessed. RESULTS: A total of 1413 patients hospitalized for ischemic stroke were identified. Mean age was 63.4 years and 44.2% were female. The proportion of patients persistent per person-year was 45.1%. Persistence with medication was significantly associated with a longer time to recurrent hospitalized stroke (HR 0.275; 95% CI 0.134-0.564; p < 0.0004). A medication copayment of >$40 (relative to a copayment of < or =$20) was the only significant factor predicting time to nonpersistence (HR 1.320; 95% CI 1.091-1.596; p < 0.0042). CONCLUSIONS: Persistence with antiplatelet medication within a cohort of hospitalized ischemic stroke patients was associated with a 72.5% lower likelihood of recurrent hospitalized stroke. Higher medication copayment was found to negatively impact patient persistence with antiplatelet therapy. The findings of this study must be considered within the limitations of database analysis, as claims data are collected for the purpose of payment and not research.

GERD-related health care utilization, therapy, and reasons for transfer of GERD patients between primary care providers and gastroenterologists in a US managed care setting.

PURPOSE: Patient flow between primary care physicians and gastroenterologists in the continuum of gastroesophageal reflux disease (GERD) care is poorly understood. Using administrative claims data from a large US health plan linked with data abstracted from medical records, we examined: health care resource utilization for GERD subjects treated by primary care physicians (PCPs) and gastroenterologists (GEs), determinants of GERD subject transfer between these physician types, and reasons for GERD therapy change. RESULTS: Within a sample of 169,884 patients, 211,043 PCP-based episodes of care and 40,304 GE-based episodes of care were developed. In unadjusted comparisons, GE episodes were characterized by more endoscopic procedures, on average (50.5/100 episodes), compared with PCP episodes (6.3/100, P < 0.001). Multivariate analysis showed that patients with esophagitis had 57.3% higher odds (P < 0.01) of transfer from PCP to GE compared with patients without esophagitis; patients with esophageal stricture had 98.6% higher odds (P < 0.01) of PCP-GE transfer. Patients with endoscopy during a first GE episode had 32.2% higher odds of transfer to a PCP (P < 0.01). The principal reasons for change in GERD therapy were no change or worsening of symptoms (51.7% of PCP charts; 9.5% of GE charts) and lack of response to therapy (51.7% of PCP charts, 26.2% of GE charts). CONCLUSION: Resource utilization varies greatly based on the physician's specialty. We infer that timely transfer of GERD patients to gastroenterologists when empiric treatment is insufficient may lead to more efficient clinical management.

Appropriate use of inhaled corticosteroid and long-acting beta(2)-adrenergic agonist combination therapy among asthma patients in a US commercially insured population.

OBJECTIVE: To examine health care utilization measures indicating which asthma patients are appropriate for inhaled corticosteroid and long-acting beta(2)-adrenergic agonist (ICS/LABA) therapy and determine whether two ICS/LABA therapies were initiated in accordance with guidelines. RESEARCH DESIGN AND METHODS: A retrospective cohort study of commercially insured asthma patients aged > or =12 years that initiated fluticasone propionate/salmeterol (FSC) or budesonide/formoterol fumarate dihydrate (BFC) combination therapy in 2007 was conducted. Use was considered appropriate if patients met any of the following during a 1-year period before ICS/LABA initiation: ICS or leukotriene receptor antagonist (LTRA) use; an asthma-related emergency department (ED) visit or hospitalization; > or =2 oral corticosteroids (OCS) courses; or > or =6 short-acting beta(2)-adrenergic agonist (SABA) canisters. Multivariate logistic regression was used to assess factors associated with appropriate ICS/LABA use. Certain limitations inherent to the use of claims data for research apply to this study. RESULTS: Of 24,231 patients who initiated ICS/LABA therapy, 993 received BFC and 23,238 received FSC. Among all patients, 37.6% met > or =1 criteria for appropriate use. However, compared with FSC users, BFC users had a significantly higher likelihood of meeting > or =1 of these criteria (odds ratio, 2.01; 95% CI, 1.76-2.30; p < 0.001), and a higher proportion of BFC than FSC patients met 4 of the 5 appropriate use criteria. In total, 58.4% of BFC patients versus 36.7% of FSC patients met > or =1 criteria for appropriate use. Other factors associated with appropriate use included age, region, Charlson comorbidity score, number of medications, and prescriber specialty. CONCLUSION: Fewer than half of all patients fulfilled the specified criteria for being appropriate for ICS/LABA therapy. However, a significantly higher proportion of BFC than FSC users met the criteria for appropriate use of ICS/LABA therapy. These results may suggest a need for improved physician awareness of consensus guidelines for the initiation of ICS/LABA therapy.

Niacin and fibrate use among patients with high triglycerides and low high-density lipoprotein cholesterol.

BACKGROUND: National guidelines recommend treating low HDL and/or high triglycerides (TG) with adjunctive therapy that supplements statin monotherapy in patients with multiple cardiovascular disease (CVD) risk factors. Niacin and fibrates have been shown in clinical trials to be effective as adjunctive therapy for these lipid abnormalities. OBJECTIVE: To evaluate the pharmacologic treatment of low HDL and high TG in real-world practice by assessing a large managed-care population with CVD risk factors enrolled in a commercial health plan. RESEARCH DESIGN AND METHODS: Complete lipid panel results (LDL, HDL, TG) obtained between 1/1/2006 and 12/31/2006 (index lab) were available for all participants. Subjects were observed 180 days pre-index to determine which CVD risk factors were present (male aged 45+, female 55+, coronary heart disease, hypertension, diabetes mellitus). Patients whose LDL was at goal but who had low HDL and high TG were assessed for lipid treatment status by evaluating outpatient pharmacy claims 6 months pre- and post-index. RESULTS: Treatment with any lipid therapy increased for all risk groups, and by total risk factors, from pre-index to post-index. Use of fibrates and niacin, alone or in combination with a statin, also increased for all risk groups, and by total risk factors as well, but was below expectations based on guideline recommendations. For example, among patients with 4 risk factors, <20% of patients with low HDL/high TG received niacin and/or a fibrate post-index date. CONCLUSIONS: Our results indicate that in actual clinical practice, niacin and fibrates are underutilized in the treatment of low HDL and high TG. The findings of this study must be considered within the limitations of database analysis as claims data are collected for the purpose of payment and not research.

Trends in RA patients' adherence to subcutaneous anti-TNF therapies and costs.

OBJECTIVE: To examine adherence to adalimumab (ADA) and etanercept (ETA) and health care costs in rheumatoid arthritis (RA) patients, and to explore the association between adherence, utilization and costs. RESEARCH DESIGN AND METHODS: Using administrative claims data from a large managed health care plan, RA patients treated with etanercept or adalimumab during the period from 01/01/2005 through 12/31/2005 were identified. The first dispensing date was defined as the index date. Patient adherence and costs were assessed during the 1 year post-index period. MAIN OUTCOME MEASURES: Nonadherence (medication possession ratio <80%) was modeled using logistic regression. Hazard ratios (HR) comparing time to discontinuation were estimated using Cox proportional hazard (PH) models. Propensity score matching with multivariate generalized linear modeling adjustment was done to assess cost difference between ADA and ETA. RESULTS: Of 3829 eligible RA patients, 1292 (765 existing, 527 naïve) and 2537 (1834 existing, 703 naïve) patients used ADA and ETA, respectively. Compared with ADA users, ETA users had longer average treatment duration (316 vs. 291 days; p < 0.0001). Unadjusted adherence rates for naïve and existing users were 63% and 70% (ADA), and 65% and 73% (ETA). Logistic regression analysis indicated that compared with ETA users, ADA users were more likely to be nonadherent (OR, naïve 1.24; existing; 1.25). Cox PH models indicated that existing ADA users were more likely to discontinue (HR = 1.11; p = 0.06) their medication than existing ETA users. Compared with ADA users, ETA users had significantly lower RA-related pharmacy costs (naïve: $10,892 vs. $12,534, p < 0.01; existing: $12,192 vs. $13,752, p < 0.01) and RA-related total costs (naïve: $11,976.42 vs. $13,511.99, p < 0.05; existing: $14,031 vs. $15,454, p < 0.05). CONCLUSIONS: ETA users had longer treatment duration, were more likely to adhere to their medication regimen and had lower RA-related pharmacy and RA-related total costs compared with ADA users. These findings must be considered within the limitations of this database analysis.

Dyslipidemia treatment of patients with diabetes mellitus in a US managed care plan: a retrospective database analysis.

BACKGROUND: To evaluate real-world pharmacologic treatment of mixed dyslipidemia in patients with diabetes mellitus (DM). METHODS: All commercial health plan members in a large US managed care database with complete lipid panel results (HDL-C, LDL-C, TG) between 1/1/2006 and 12/31/2006 were identified (N = 529,236). DM patients (N = 53,679) with mixed dyslipidemia were defined as having any 2 suboptimal lipid parameters (N = 28,728). Lipid treatment status 6 months pre- and post-index date was determined using pharmacy claims for any lipid therapy. RESULTS: Post-index, 41.1% of DM patients with 2 abnormal lipid parameters and 45.1% with 3 abnormal lipid parameters did not receive lipid-modifying treatment. Post-index treatment rates were 57.4%, 63.6%, and 66.4% for patients with LDL-C, HDL-C, and TG in the most severe quartiles, respectively. Statin monotherapy was the primary lipid-modifying regimen prescribed (54.8% and 47.8% of patients with any 2 and all 3 lipids not at goal, respectively). Less than 30% of treated patients received combination therapy. CONCLUSION: Over 40% of DM patients with mixed dyslipidemia received no lipid-modifying therapy during the follow-up period. Those who were treated were primarily prescribed statin monotherapy. This study suggests that DM patients are not being treated to ADA-suggested targets.

Mortality associated with gastrointestinal bleeding events: Comparing short-term clinical outcomes of patients hospitalized for upper GI bleeding and acute myocardial infarction in a US managed care setting.

OBJECTIVES: To compare the short-term mortality rates of gastrointestinal (GI) bleeding to those of acute myocardial infarction (AMI) by estimating the 30-, 60-, and 90-day mortality among hospitalized patients. METHODS: United States national health plan claims data (1999-2003) were used to identify patients hospitalized with a GI bleeding event. Patients were propensity-matched to AMI patients with no evidence of GI bleed from the same US health plan. RESULTS: 12,437 upper GI-bleed patients and 22,847 AMI patients were identified. Propensity score matching yielded 6,923 matched pairs. Matched cohorts were found to have a similar Charlson Comorbidity Index score and to be similar on nearly all utilization and cost measures (excepting emergency room costs). A comparison of outcomes among the matched cohorts found that AMI patients had higher rates of 30-day mortality (4.35% vs 2.54%; p < 0.0001) and rehospitalization (2.56% vs 1.79%; p = 0.002), while GI bleed patients were more likely to have a repeat procedure (72.38% vs 44.95%; p < 0.001) following their initial hospitalization. The majority of the difference in overall 30-day mortality between GI bleed and AMI patients was accounted for by mortality during the initial hospitalization (1.91% vs 3.58%). CONCLUSIONS: GI bleeding events result in significant mortality similar to that of an AMI after adjusting for the initial hospitalization.

Treatment failure rates and health care utilization and costs among patients with community-acquired pneumonia treated with levofloxacin or macrolides in an outpatient setting: a retrospective claims database analysis.

BACKGROUND: Macrolide antibiotics and fluoroquinolones are extensively used in the treatment of community-acquired pneumonia (CAP). OBJECTIVE: This analysis was conducted to compare treatment failure rates and health care utilization and cost outcomes among patients with CAP treated with levo-floxacin (500 or 750 mg) or macrolides (azithromycin, clarithromycin, or erythromycin) in an outpatient setting. METHODS: This was a retrospective analysis of claims data from a large US health plan. Patients were aged > or =18 years and had a primary diagnosis of CAP that was treated with oral levofloxacin or a macrolide in an outpatient setting (including physicians' offices, outpatient clinics, urgent care centers, and large ambulatory health centers). Patients were followed for 30 days after the index drug date to measure study outcomes. Multivariate regression analysis and a propensity score technique were used to compare rates of treatment failure and CAP-related health care utilization and costs. Two post hoc subgroup analyses were conducted in patients aged > or =50 and > or =65 years. RESULTS: Of the 7526 patients meeting the inclusion criteria, 2968 (39.4%) were treated with levofloxacin and 4558 (60.6%) with a macrolide. Unadjusted rates of treatment failure were 21.1% and 22.7% in the levofloxacin and macrolide cohorts, respectively. After adjustment for demographic characteristics, baseline comorbidities, and severity of illness, levofloxacin recipients were significantly less likely to experience treatment failure than macrolide recipients (odds ratio [OR] = 0.84; 95% CI, 0.75-0.94, P = 0.003). The likelihood of treatment failure was significantly lower in levofloxacin recipients aged > or =50 years (OR = 0.79; 95% CI, 0.66-0.94; P = 0.007) and > or =65 years (OR = 0.65; 95% CI, 0.43-1.00; P = 0.049) compared with the corresponding subgroups of macrolide recipients. The magnitude of this difference was greatest in the subgroup aged > or =65 years, which had a 35% reduced risk of treatment failure compared with the corresponding group of macrolide-treated patients. The rate of CAP-related emergency department visits was significantly lower among patients receiving levofloxa-cin (OR = 0.68; 95% CI, 0.51-0.91; P = 0.009); there were no differences in CAP-related hospitalizations or total CAP-related health care costs between levofloxa-cin and macrolide recipients. CONCLUSIONS: Multivariate-adjusted rates of treatment failure in outpatients with CAP were significantly lower in those treated with levofloxacin relative to those treated with a macrolide. The lower rates of treatment failure with levofloxacin were consistently observed across all patients and in the subgroups aged > or =50 and > or =65 years. Rates of emergency department visits were also significantly lower among levofloxacin-treated patients, whereas overall CAP-related hospitali-zations and costs did not differ significantly between the 2 treatment groups.

Lipid therapy utilization rates in a managed-care mixed dyslipidemia population.

BACKGROUND: National clinical treatment guidelines recommend pharmacologic treatment in addition to therapeutic lifestyle modifications in patients with mixed dyslipidemia and multiple risk factors for coronary heart disease (CHD). OBJECTIVES: To evaluate real-world pharmacologic treatment of mixed dyslipidemia patients with cardiovascular disease (CVD) risk factors. METHODS: Commercial health plan members in a large, United States managed-care database with complete lipid panel results (ie, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC], triglycerides [TG]) between January 1, 2006 and December 31, 2006 were included. Mixed dyslipidemia was defined as any two nonoptimal lipid parameters (LDL-C, HDL-C, TG) according to National Cholesterol Education Program/Adult Treatment Panel III guidelines. Subjects were observed for 182 days pre-index to determine CVD risk factors (ie, male aged 45+ years, female 55+ years, CHD history, hypertension, diabetes mellitus). Lipid treatment status 6 months pre- and post-index dates was determined using pharmacy claims for any lipid monotherapy (statin, fibrate, niacin, "other"), or combination therapy (statin + fenofibrate; statin + niacin; statin + other). RESULTS: Lipid treatment increased post-index for all mixed dyslipidemia groups and by total number of risk factors. The increased LDL-C and low HDL-C group had the lowest treatment rates; the group with low HDL-C and elevated TG had the highest. In the latter group, when treated, primarily statin monotherapy (51%) was used post-index; only 26% received niacin or fibrate therapy targeting HDL-C or TG abnormalities. Across all mixed dyslipidemia patients, >30% with three to four CVD risk factors were not treated ≥6 months post-index. CONCLUSIONS: In real-world clinical practice, pharmacologic treatment rates increased upon assessment of multiple lipid abnormalities and by total risk factors for CHD. However, mixed dyslipidemia remained undertreated with low rates of niacin and fibrate usage.

Similarity of insulin detemir pharmacokinetics, safety, and tolerability profiles in healthy caucasian and Japanese american subjects.

The objective of this study was to compare the pharmacokinetics of insulin detemir in three ascending doses in healthy Japanese and Caucasian subjects. This was an open-label, single-center, parallel-group design evaluating 30 subjects (15 Japanese and 15 Caucasians). Subjects received a total of three subcutaneous injections (one injection per visit) of insulin detemir (0.19, 0.38, 0.75 U/kg [1 U = 24 nmol]) in ascending order. Following drug administration, subjects received intravenous glucose in 0.5-mg/kg/min increments every 30 minutes, followed by a constant rate of 2.0 mg/kg/min for up to 12 hours. For pharmacokinetic evaluations, serial blood sampling was performed over a period of 30 hours after dosing. Of the subjects, 36 were enrolled, and 30 completed the study. There was a linear dose-response relationship between the three ascending insulin detemir doses and serum insulin detemir AUC values for both the Japanese and Caucasian subjects. The two dose-response regression lines had equivalent slopes but slightly different intercepts (although not statistically significant). This difference may be due to variation in AUC, body weight differences, or chance. Six subjects discontinued the study, 2 as a result of adverse events (blood draw-related ecchymosis and hypoglycemia). The most frequent treatment-emergent adverse events (TEAE) were headache, dizziness, and reactions related to blood draws/infusion sites. All TEAEs were mild to moderate in severity. The results show that an increase in insulin detemir dose will result in a similar increase in insulin detemir concentration in the two ethnic groups. Therefore, therapeutic dosing of insulin detemir is expected to be similar in both ethnic groups, with no special dose adjustment or algorithm based on race. Insulin detemir at 0.19, 0.38, and 0.75 U/kg was generally well tolerated in both Japanese and Caucasian subjects.

Delayed onset of oculogyric crisis and torticollis with intramuscular haloperidol.

OBJECTIVE: To report a case of delayed-onset dystonic reactions, oculogyric crisis (OGC), and torticollis after treatment with intramuscular haloperidol lactate injection. CASE SUMMARY: A 22-year-old Mexican American woman received intramuscular haloperidol lactate 7.5 mg followed 4 hours later by 10 mg. Twenty-six hours after the first injection, the patient reported that she was unable to lower her gaze and that her neck was stiff. She was immediately given intramuscular benztropine 2 mg; there was a nearly complete remission of symptoms within 15 minutes of treatment. An objective causality assessment revealed a probable relationship between the OGC/torticollis and haloperidol therapy. DISCUSSION: Dystonic reactions have been reported in 10-60% of patients treated with neuroleptic medication, most commonly when patients just start or increase the dose of the drug. The highest frequency of dystonic reactions has occurred in patients receiving high-potency neuroleptics. It has also been suggested that haloperidol-induced dystonic reactions are a result of the toxic metabolites of that agent. CONCLUSIONS: OGC and torticollis reactions may occur 12-24 hours after treatment with a high-potency neuroleptic, even in the absence of symptoms of extrapyramidal side effects (EPSEs). The delayed dystonic reaction may begin suddenly (no early EPSE symptomatology).

Galantamine hydrobromide: an agent for Alzheimer's disease.

The pharmacology, dosage, adverse effects, efficacy, and economics of galantamine hydrobromide are discussed. Galantamine hydrobromide is a tertiary alkaloid that has been extracted from plant sources and is now synthesized for use in the treatment of mild to moderate Alzheimer's disease (AD). Galantamine acts both as a reversible competitive inhibitor of acetylcholinesterase (AChE) and as an allosteric modulator of nicotinic acetylcholine receptors. The recommended starting dosage is 4 mg (as the hydrobromide) twice daily. The dosage should be increased in increments of 8 mg/day in two divided doses after four weeks at a given dosage until a maintenance dosage of 16-24 mg/day in two divided doses is reached. Adverse effects are primarily mild and cholinergic and include nausea, vomiting, diarrhea, and dizziness. Five large clinical trials demonstrated that galantamine is more effective than placebo in controlling the symptoms of mild to moderate AD. Optimal therapy appears to require early initiation of the drug and a dosage-adjustment period of eight weeks. In one study, galantamine delayed full-time care by 10% and reduced the overall cost of care by $528. Because galantamine has not yet been compared directly with other AChE inhibitors, cost should be the principal factor weighed during formulary evaluations. Galantamine provides the clinician with another choice of an AChE inhibitor for use in treating AD.