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This study summarizes the literature on the prevalence, incidence, and proportion of patients receiving treatment for male hypogonadism and a systematic literature search was performed for articles published in the last 20 years. Of the 97 studies identified, 96 examined the prevalence, 2 examined the incidence, and 4 examined the proportion of males with hypogonadism patients receiving treatment. Based on studies conducted in Europe and USA, the prevalence of hypogonadism in the general population ranged from 2.1% to 12.8% of middle-aged to older men, with an estimated incidence of 12 new cases per 1,000 person-years. Prevalence was higher among patients with comorbid conditions, such as type 2 diabetes mellitus and obesity. Approximately 10–12% of men with hypogonadism were receiving testosterone treatment. This literature review suggests that there is potentially a significant burden of hypogonadism in the general population. Burden seems to increase with age and in the presence of certain disease conditions. Data suggests that many hypogonadal men who may benefit from testosterone replacement are not receiving treatment. This may be the result of underdiagnosis of the disease, lack of awareness by patients or physicians, irregularities surrounding the diagnostic criteria, and deficiency of long-term safety studies.

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.

Background Heterogeneity in overall response and outcomes to pharmacological treatment has been reported in several depression studies but with few sources that integrate these results. The goal of this study was to review the literature and attempt to identify nongenetic factors potentially predictive of overall response to depression treatments. Methods A comprehensive review of the literature from the last 10 years was performed using three key databases (PubMed, EMBASE, and Cochrane). All relevant studies that met the inclusion criteria were selected and scored for their levels of evidence using the NICE scoring method. A subjective assessment of the strength of evidence for each factor was performed using predefined criteria. Results Our broad search yielded 76 articles relevant to treatment heterogeneity. Sociodemographic factors, disease characteristics, and comorbidities were the most heavily researched areas. Some of the factors associated with more favorable overall response include being married, other social support, and low levels of baseline depressive symptoms. Evidence relating to baseline disease severity as a factor predictive of antidepressant response was particularly convincing among the factors reviewed. The presence of comorbid anxiety and pain contributed to worse antidepressant treatment outcomes. Conclusions Several factors either predictive of or associated with overall response to antidepressant treatment have been identified. Inclusion of factors predictive of response in the design of future trials may help tailor treatments to depression patients presenting to the average clinical practice, resulting in improved outcomes.

Summary Aim: To assess and present the current body of evidence regarding composite measures associated with differential treatment response or outcome as a result of patient heterogeneity and to evaluate their consistency across disease areas. Methods: A comprehensive review of the literature from the last 10 years was performed using three databases (PubMed, Embase and Cochrane). All articles that met the inclusion/exclusion criteria were selected, abstracted and assessed using the NICE level-of-evidence criteria. Results: Forty-nine studies were identified in the data abstraction. Approximately one-third focused on existing composite measures, and the rest investigated emerging composite factors. The majority of studies targeted patients with cancer, cardiovascular disease or psychological disorders. As a whole, the composite measures were found to be disease-specific, but some composite elements, including age, gender, comorbidities and health status, showed consistency across disease areas. To complement these findings, common individual factors found in five previous independent disease-specific literature assessments were also summarised, including age, gender, treatment adherence and satisfaction, healthcare resource utilisation and health status. Conclusions: Composite measures can play an important role in characterising heterogeneity of treatment response and outcome in patients suffering from various medical conditions. These measures can help clinicians to better distinguish between patients with high likelihood to respond well to treatment and patients with minimal chances of positive therapeutic outcomes. Herein, the individual factors identified can be used to develop novel predictive or prognostic composite measures that can be applicable across disease areas. Reflecting these cross-disease measures in clinical and public health decisions has the distinctive appeal to enable targeted treatment for patients suffering from multiple medical conditions, which may ultimately yield significant gains in individual outcomes, population health and cost-effective resource allocation.

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.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.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.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.

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.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.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 (p0.001). CV-related costs represented about 46% of costs for the HR55 group, versus 41% for the HR group and 31% for the LR group.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.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.

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.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 MPRor=80% defined as adherent. Multivariate logistic regression was used to assess how potential covariates affect adherence probability.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 patients75 years, patientsor=86 years were likely to be more adherent (OR = 1.401, p0.001). Other factors found to be positively associated with the probability of adherence to AD medications were male gender (OR = 1.175, p0.05), overall pill burden (OR = 1.192, p0.001), and a lower formulary tier status of the AD medication (OR = 1.332, p0.001).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.

To assess 12-month healthcare resource utilization and costs associated with upper gastrointestinal (UGI) bleeding events.Patients hospitalized with a UGI bleeding event were identified in US national health-plan claims data (1999-2003) and propensity matched to control patients without UGI bleeding in the same health plan. Matching criteria included age, gender, index date, Charlson Comorbidity Index score, geographic region, and prior medical utilization.A total of 9,033 UGI-bleed patients and 579,018 control patients met the inclusion criteria, yielding 4,651 matched pairs. After matching, differences between the UGI bleed and general population cohorts remained for office visits, ER visits, and ER costs during the 6-month baseline period prior to the index date. During the 12 months following the index date, both UGI-related healthcare utilization and total healthcare, medical, and pharmacy costs incurred by the UGI-bleed cohort were significantly greater (p0.0001) than those incurred by the general population cohort (mean of $20,405 vs. 3,652), even after excluding the initial hospitalization costs (mean of $11,228 vs. 3,652). Costs were primarily due to inpatient hospitalizations (mean of $13,059 for the UGI-bleed cohort vs. $729 for the general population cohort) and ambulatory services (mean of $4,037 for the UGI-bleed cohort vs. $1,537 for the general population cohort). Sixteen percent of the UGI-bleed cohort had a GI-related hospitalization, and about 40% of total costs occurred after the initial hospitalization.Patients with UGI bleeds experienced significantly higher (p0.0001) 12-month health-resource utilization and costs than patients without UGI bleeds. This study provides empirical evidence of the long-term economic burden associated with UGI bleeding. Interpretation of the results should take into account the lack of available information in claims data that could have an effect on study outcomes, such as particular clinical and disease-specific parameters that are not mitigated by propensity score and comorbidity index matching. In addition, this study is limited by the intensive demographic matching that was done between the two cohorts, which may have eliminated the sickest UGI patients and the healthiest general health-plan population patients.

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.A retrospective cohort study of commercially insured asthma patients agedor =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; oror =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.Of 24,231 patients who initiated ICS/LABA therapy, 993 received BFC and 23,238 received FSC. Among all patients, 37.6% metor =1 criteria for appropriate use. However, compared with FSC users, BFC users had a significantly higher likelihood of meetingor =1 of these criteria (odds ratio, 2.01; 95% CI, 1.76-2.30; p0.001), 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 metor =1 criteria for appropriate use. Other factors associated with appropriate use included age, region, Charlson comorbidity score, number of medications, and prescriber specialty.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.

C Mel Wilcox1, Byron L Cryer2, Henry J Henk3, Victoria Zarotsky3, Gergana Zlateva41University of Alabama, Birmingham, AL, USA; 2University of Texas Southwestern Medical School, Dallas, TX; 3i3 Innovus, Eden Prairie, MN, USA; 4Pfizer, Inc., New York, NY, USA 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.Keywords: gastrointestinal, bleeding, mortality, acute myocardial infarction, claims 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 ≥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 ≥50 and ≥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 ≥50 years (OR = 0.79; 95% CI, 0.66–0.94; P = 0.007) and ≥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 ≥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 ≥50 and ≥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.

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.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.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 include (1) the use of MPR as a proxy for adherence, (2) limited number of studies available, and (3) observed heterogeneity.The results of the analysis demonstrate that medication adherence, persistence, and discontinuation rates are suboptimal in patients with T2DM prescribed OAHAs.

Endometriosis is a chronic and progressive disease that affects approximately 10% of women of reproductive age. Its aetiology remains unknown, however, factors such as retrograde menstruation, heredity, impaired immune function and environmental toxins have been implicated. Laparoscopy is still considered the mainstay for diagnosis, however non-invasive diagnostic methods such as transvaginal ultrasound and MRI may also be complementary. Treatment should be individualised and current treatment options include medical treatment and surgery, however, disease recurrence is common following treatment. Hormonal therapy induces atrophy of endometriotic lesions. Conservative surgery may be successful in removing visible lesions, however in cases of severe or incapacitating illness, removal of the uterus and ovaries may be necessary. In such cases, extreme care must be taken to remove all traces of disease. Experimental treatments for endometriosis show promising preliminary results and include GnRH antagonists, aromatase inhibitors, selective oestrogen receptor modulators and mifepristone.

Researchers have for some time appreciated the role of the neurotransmitter acetylcholine in Alzheimer's disease, and have realized the development of a number of acetylcholinesterase inhibitors. Bridging and dynabridging studies have played an important role in the development of these agents. Several acetylcholinesterase inhibitors have demonstrated tolerability and efficacy in a number of clinical trials. The most common adverse events associated with acetylcholinesterase inhibitors are cholinergic in nature, namely nausea and vomiting. The various properties of the three acetylcholinesterase inhibitors in clinical use today provide the clinician with the only meaningful treatment choices for Alzheimer's disease (AD) at the present time. Drug Dev. Res. 56:347–353, 2002. Copyright © 2002 John Wiley & Sons, Ltd.

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)). R2 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 R2 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.

The decreasing cost and rapid growth of technological advances has dramatically impacted the way students are taught and learn in college. Faculty augment their lectures with computer-generated slides, videos and Digital Video Disks (DVD). Computer programs are available to help organize lecture material, provide students with computer assisted learning, provide “real” life cases and simulations, and test the students’ knowledge with computer based exams. New ideas can be accessed and transmitted instantly anywhere in the world with a click of a mouse through the World Wide Web. Guest speakers can be “brought into the classroom” through telephone or video conferencing. Students can obtain degrees, or professionals can get continuing education courses at any time from any place through distance learning. All of these exciting changes have changed the face of what education is like as we proceed into the new millennium. Despite these advances, tests of intelligence have not improved to a significant degree. Nevertheless, most students continue to prefer human-to-human interaction to a technology driven environment. Further training and development of technology in pharmacy education is needed and will continue to be explored.

Heterogeneity in overall response and outcomes to pharmacological treatment has been reported in several depression studies but with few sources that integrate these results. The goal of this study was to review the literature and attempt to identify nongenetic factors potentially predictive of overall response to depression treatments.A comprehensive review of the literature from the last 10 years was performed using three key databases (PubMed, EMBASE, and Cochrane). All relevant studies that met the inclusion criteria were selected and scored for their levels of evidence using the NICE scoring method. A subjective assessment of the strength of evidence for each factor was performed using predefined criteria.Our broad search yielded 76 articles relevant to treatment heterogeneity. Sociodemographic factors, disease characteristics, and comorbidities were the most heavily researched areas. Some of the factors associated with more favorable overall response include being married, other social support, and low levels of baseline depressive symptoms. Evidence relating to baseline disease severity as a factor predictive of antidepressant response was particularly convincing among the factors reviewed. The presence of comorbid anxiety and pain contributed to worse antidepressant treatment outcomes.Several factors either predictive of or associated with overall response to antidepressant treatment have been identified. Inclusion of factors predictive of response in the design of future trials may help tailor treatments to depression patients presenting to the average clinical practice, resulting in improved outcomes.

The response to treatment for type 2 diabetes typically varies among individuals within a study population. This variation is known as heterogeneity of treatment response. We conducted a comprehensive literature review to identify factors that account for heterogeneity of treatment response in patients treated for type 2 diabetes. Three databases (PubMed, EMBASE and Cochrane Library) were searched for articles published in the last 10 years describing investigations of factors associated with treatment response and outcomes among people with type 2 diabetes receiving pharmacological treatment. Of the 43 articles extracted and summarized, 35 (81%) discussed clinical factors, 31 (72%) described sociodemographic factors and 17 (40%) reported on comorbidity or behavioural factors. Clinical factors identified included baseline glycated hemoglobin A1c or fasting plasma glucose (FPG) levels, insulin response or sensitivity, C-peptide, body composition, adipose tissue proteins, lipid profile, plasma albumin levels and duration of disease or insulin treatment. Other factors identified included age, sex, race, socioeconomic status and comorbidities. This review identified the following research gaps: use of multiple definitions for response, few patient-reported measures and lack of evidence regarding whether factors were associated with treatment response for only specific medications or across pharmacological therapies. Furthermore, identification of factors associated with type 2 diabetes treatment response was generally a secondary objective in the research reviewed. Understanding which patient subgroups are more likely to respond to treatment and identifying factors associated with response may result in targeted treatment decisions and alter the interpretation of efficacy or effectiveness of results. In conclusion, accounting for these factors in clinical trials and when making clinical treatment decisions may improve therapy selection and individual patient outcomes.

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.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.Patient demographic variables, clinical characteristics, comorbidities hypothesized to affect the risk of current stroke, stroke outcomes, treatment patterns, and compliance were assessed.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; p0.0004). A medication copayment of$40 (relative to a copayment ofor =$20) was the only significant factor predicting time to nonpersistence (HR 1.320; 95% CI 1.091-1.596; p0.0042).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.

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.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.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.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.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.

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.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.Nonadherence (medication possession ratio80%) 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.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; p0.0001). 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, p0.01; existing: $12,192 vs. $13,752, p0.01) and RA-related total costs (naïve: $11,976.42 vs. $13,511.99, p0.05; existing: $14,031 vs. $15,454, p0.05).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.

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

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.

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.

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.

In recent years generalised anxiety disorder (GAD) has become a much better defined disorder, with specific criteria distinguishing it from the other anxiety disorders; however, it still lacks the same public and scientific interests as some of the other anxiety disorders such as panic and social phobia. Nevertheless, refinement in the treatment of GAD is becoming more evident through the conduct of clinical trials. Up until the mid-1980's, treatment consisted primarily of benzodiazepines. However, as a result of growing characterisation of their abuse potential, other therapeutic options were explored. Benzodiazepines became seen as an effective short-term therapy, and buspirone and some of the newer antidepressants have become the treatment of choice for patients with GAD requiring long-term treatment. Buspirone was the first available alternative to the benzodiazepines in the US; however, the initial excitement over this agent was somewhat dampened because of its mild efficacy combined with a slow onset of action. The antidepressants were seen as beneficial for the treatment of GAD because of the high comorbidity with depression, thus allowing a better outcome for these patients. The antidepressants that offer both a good adverse effect profile and efficacy are the selective serotonin reuptake inhibitors including paroxetine, and the serotonin-norepinephrine reuptake inhibitors such as venlafaxine. Clinicians should also consider the potential benefits of psychotherapy as an adjunct to medication. There are a number of potentially new pharmacotherapies being investigated, including newer serotonin 5-HT1A receptor agonists, cholecystokinin receptor antagonists, neurokinin receptor antagonists, gabapentin and its analogues, and gamma-aminobutyric acid (GABA)A receptor modulators. However, these compounds are all in the early stages of investigation, and there are no new therapies expected to be released in the near future. Nonetheless, in the search for the ideal anxiolytic, a more positive outlook is allowed by imminent future research for new treatment options in patients with GAD.

e17017 Background: Multiple tests are often needed to ensure accurate differential diagnosis (DDX) of hematologic malignancies, particularly for rare/complex conditions. Integration of morphology, immunophenotype, cytogenetic, and molecular results present challenges but is critical to determine prognostic parameters and treatment (tx) decisions. Methods: Systematic literature search was performed (PubMed/MedLine, EMBASE, Cochrane Library) for US-based articles in last 10 yrs regarding DDX of myelodysplastic syndrome, myeloproliferative neoplasm, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and multiple myeloma. Results: 35 articles were identified that addressed methods (n=27) and/or accuracy/timing (n=15) of establishing a diagnosis. Diagnostic (dx) ability improved with use of systematic processes/algorithms (ALG), comparative techniques, and harmonization/central review; few ALG were comprehensive. Updates/revisions of disease-specific dx criteria could result in dx change. Accuracy improved with experienced clinicians (disease-specific knowledge), specialized pathologists (vs. generalists), tissue sample type/quality, and ancillary test availability. A pathologist’s dx ability was related to experience with rare/complex histological subtypes. Dx accuracy was often complicated by inconsistent/overlapping clinical presentation and lack of standardized terminology or reproducible results across facilities. Delays were attributed to lack of dx experience and patient’s health insurance type. Impact of dx delay on clinical outcomes was largely not addressed. Conclusions: With shift from morphologic- to genetic/molecular-based approaches, determination of tests done in parallel/reflexively often requires expert input. Impact of delayed dx on clinical outcomes is lacking. Standardized dx processes/ALG, along with access to expert hematopathologist review and interpretation of test results, may lead to earlier and improved dx accuracy and appropriate/timely tx initiation, thereby avoiding consequences of erroneous dx, especially of benign conditions initially dx as malignant.

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.

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.