Characterizing female patients with haemophilia A: Administrative claims analysis and medical chart review.

AIM: Haemophilia A (HA) is a male-predominant disorder, yet women and girls can have factor VIII (FVIII) deficiency with bleeding events requiring treatment. This study aimed to identify and characterize female patients with HA. METHODS: Administrative claims dated 01 January 2012-31 July 2016 were accessed for patients with 18 months' coverage by commercial or Medicare Advantage with Part D insurance. Patients were included by HA diagnoses or treatments and/or bleeding-related diagnoses or procedures, and excluded by haemophilia B or qualitative platelet disorder diagnoses. A sample of charts was examined for bleeding history, HA therapies and bleeding treatments. All-cause healthcare utilization and costs were also described. RESULTS: Among 353 patients meeting initial inclusion criteria, 86 charts were procured, with 8 patients identified as having HA. Their mean age was 60 ± 17 years and most were Medicare-insured. The mean Charlson Comorbidity Index score was 2.50 ± 2.56; the most prevalent comorbid conditions involved coagulation/haemorrhage, fluid/electrolyte balance and non-traumatic joint disorders. Over 18 months, a mean of 54 ambulatory visits and 120 pharmacy fills were observed; mean medical costs were $86 694 and pharmacy costs were $25 396. CONCLUSIONS: Identifying females with HA is challenging using healthcare claims, because diagnostic nomenclature is unclear for female patients treated for bleeding events. Although chart abstraction enhanced claims data, very few female patients were identified with HA. Nevertheless, even in a small sample, sizeable burden in comorbidity and healthcare use was observed. Improved nomenclature and coding for HA diagnoses for women and girls is key to improving research and treatment.

Reducing the Population Burden of Coronary Heart Disease by Modifying Adiposity: Estimates From the ARIC Study.

Background Excess adiposity, which affects 69% of US adults, increases coronary heart disease (CHD) risk in an association that manifests below conventional obesity cut points. The population-level impact on CHD risk that is attainable through modest adiposity reductions in populations is not well characterized. We estimated the effect of hypothetical reductions in both body mass index (BMI) and waist circumference (WC) on CHD incidence. Methods and Results The study population included 13 610 ARIC (Atherosclerosis Risk in Communities) participants. Our hypothetical reduction in BMI or WC was applied relative to the temporal trend, with no hypothetical reduction among those with BMI >24 or WC >88 cm, respectively. This threshold for hypothetical reduction is near the clinical guidelines for excess adiposity. CHD risk differences compared the hypothetical reduction with no reduction. Sensitivity analysis was conducted to estimate the effect of applying the hypothetical BMI reduction at the established overweight cut point of 25. Cumulative 12-year CHD incidence with no intervention was 6.3% (95% CI, 5.9-6.8%). Risk differences following the hypothetical BMI and WC reductions were -0.6% (95% CI, -1.0% to -0.1%) and -1.0% (95% CI, -1.4% to -0.5%), respectively. These results were robust for the sensitivity analyses. Consequently, we estimated that this hypothetical reduction of 5% in BMI and WC, respectively, could have prevented 9% and 16%, respectively, of the CHD events occurring in this study population over 12 years, after adjustment for established CHD risk factors. Conclusions Meaningful CHD risk reductions could derive from modest reductions in adiposity attainable through lifestyle modification.

European and Russian physician awareness of best management approaches for infections due to antibiotic-resistant Gram-negative bacteria.

OBJECTIVES: The rapid spread of infections due to antibiotic-resistant, Gram-negative bacteria in Europe and surrounding regions requires a heightened level of awareness among physicians within their practice settings. METHODS: We surveyed 800 physicians who treat these infections across France, Germany, Spain, Italy, and Russia to assess their awareness of best management approaches. RESULTS: We found that more than two-thirds do not consider themselves highly aware of best management practices. The respondents are facing these resistant infections as evidenced by the antibiotics they report using and their stated interest in newer agents. Respondents indicated that precious time is lost waiting for culture results, but also said they will need more information about accuracy, use, and costs for adopting rapid molecular testing. CONCLUSIONS: The survey further identified the need for treatment guidelines and clinical decision support tools that can be applied at the bedside.

Pharmacoepidemiology of Clinically Relevant Hypothyroidism and Hypertension from Sunitinib and Sorafenib.

BACKGROUND: Thyroid dysfunction and hypertension (HTN) have been sporadically reported with sunitinib (SUN) and sorafenib (SOR). Determination of the side effect incidence will enhance monitoring and management recommendations. METHODS: An observational cohort study was performed using deidentified pharmacy claims data from a 3-year period to evaluate patients prescribed SUN, SOR, or capecitabine (CAP; comparison group). The primary outcome was time to first prescription for thyroid replacement or HTN treatment. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox proportional hazards models. RESULTS: A total of 20,061 patients were eligible for evaluation of thyroid replacement therapy, which was initiated in 11.6% of those receiving SUN (HR, 16.77; 95% CI, 13.54-20.76), 2.6% of those receiving SOR (HR, 3.47; 95% CI, 2.46-4.98), and 1% of those receiving CAP, with median time to initiation of 4 months (range, 1-35 months). A total of 14,468 patients were eligible for evaluation of HTN therapy, which was initiated in 21% of SUN recipients (HR, 4.91; 95% CI, 4.19-5.74), 14% of SOR recipients (HR, 3.25; 95% CI, 2.69-3.91), and 5% of CAP recipients, with median time to initiation of 1 month (range, 1-18 months) for SOR and 2 months (range, 1-25 months) for SUN. CONCLUSION: SUN and SOR significantly increased the risk for clinically relevant hypothyroidism; the risk was at least 4 times greater with SUN than with SOR. Patients receiving SUN and SOR had a similar elevated risk for clinically relevant HTN. These data provide robust measures of the incidence and time to onset of these clinically actionable adverse events. The Oncologist 2017;22:208-212Implications for Practice: The side effect profiles for novel therapies are typically used to create monitoring and management recommendations using clinical trial data from patient populations that may not represent those seen in standard clinical practice. This analysis using a large pharmacy claims database better reflects typical patients treated with sorafenib or sunitinib outside of a clinical trial. The findings of increased need for thyroid replacement in patients receiving sunitinib compared with sorafenib and a similar increase in need for hypertension therapy with both agents can be used to form clinically relevant monitoring recommendations for these agents.

Determinants of adherence to diabetes medications: findings from a large pharmacy claims database.

OBJECTIVE: Adults with diabetes typically take multiple medications for hyperglycemia, diabetes-associated conditions, and other comorbidities. Medication adherence is associated with improved outcomes, including reduced health care costs, hospitalization, and mortality. We conducted a retrospective analysis of a large pharmacy claims database to examine patient, medication, and prescriber factors associated with adherence to antidiabetic medications. RESEARCH DESIGN AND METHODS: We extracted data on a cohort of >200,000 patients who were treated for diabetes with noninsulin medications in the second half of 2010 and had continuous prescription benefits eligibility through 2011. Adherence was defined as a medication possession ratio ≥ 0.8. We used a modified adherence measure that accounted for switching therapies. Logistic regression analysis was performed to determine factors independently associated with adherence. RESULTS: Sixty-nine percent of patients were adherent. Adherence was independently associated with older age, male sex, higher education, higher income, use of mail order versus retail pharmacies, primary care versus nonendocrinology specialist prescribers, higher daily total pill burden, and lower out-of-pocket costs. Patients who were new to diabetes therapy were significantly less likely to be adherent. CONCLUSIONS: Several demographic, clinical, and potentially modifiable system-level factors were associated with adherence to antidiabetic medications. Patients typically perceived to be healthy (those who are younger, new to diabetes, and on few other medications) may be at risk for nonadherence. For all patients, efforts to reduce out-of-pocket costs and encourage use of mail order pharmacies may result in higher adherence.

Patient preferences for change in symptoms associated with opioid-induced constipation.

INTRODUCTION: While opioids have become a standard treatment option for those experiencing moderate to severe chronic pain, side effects of constipation and related symptoms have interfered with their usage in as many as 40-50% of treated patients. Prior research has elucidated the range of these symptoms, but no study has determined which of these symptoms patients most desire improving or whether improving constipation itself by as little as one more bowel movement per week is deemed an important change. METHODS: We conducted an online patient survey of 513 participants residing in one of six countries who reported having chronic pain, were taking opioids, and experiencing opioid-induced constipation (OIC) to address these questions. RESULTS: Respondents rank ordered their preferences and the following eight symptoms generated >80% endorsement as important to improve: improvement in having bowel movements without rectal pain, soft stools that are not loose or watery, regular bowel movements, a reduction in rectal straining, relief from feeling bloated, feeling less fear about having OIC when following their opioid medication regime, a desire to worry less overall about having a bowel movement, and with less 'stomach' area pain. When asked 'how important is it you to have 1 more bowel movement per week", over 90% endorsed it was 'somewhat', 'very', or 'extremely important' with nearly 70% (n = 354) endorsing the 'extremely' or 'very important' response options. In multivariate models, being in more overall pain or reporting fewer than 3 bowel movements per week were found to be independent predictors of the importance. CONCLUSIONS: These results highlight the notable range of OIC symptoms most desired by patients to improve and demonstrate that bowel movements of only one more per week were important to register a meaningful improvement. The latter is particularly helpful for those assessing the minimal clinically important difference in treating this condition.

Greater adherence to diabetes drugs is linked to less hospital use and could save nearly $5 billion annually.

Improving adherence to medication offers the possibility of both reducing costs and improving care for patients with chronic illness. We examined a national sample of diabetes patients from 2005 to 2008 and found that improved adherence to diabetes medications was associated with 13 percent lower odds of subsequent hospitalizations or emergency department visits. Similarly, losing adherence was associated with 15 percent higher odds of these outcomes. Based on these and other effects, we project that improved adherence to diabetes medication could avert 699,000 emergency department visits and 341,000 hospitalizations annually, for a saving of $4.7 billion. Eliminating the loss of adherence (which occurred in one out of every four patients in our sample) would lead to another $3.6 billion in savings, for a combined potential savings of $8.3 billion. These benefits were particularly pronounced among poor and minority patients. Our analysis suggests that improved adherence among patients with diabetes should be a key goal for the health care system and policy makers. Strategies might include reducing copayments for certain medications or providing feedback about adherence to patients and providers through electronic health records.

Impact of proton pump inhibitors on the effectiveness of clopidogrel after coronary stent placement: the clopidogrel Medco outcomes study.

STUDY OBJECTIVE: To investigate the potential impact of proton pump inhibitors (PPIs) on the effectiveness of clopidogrel in preventing recurrent ischemic events after percutaneous coronary intervention (PCI) with stent placement. DESIGN: Population-based, retrospective cohort study. DATA SOURCE: National medical and pharmacy benefit claims database comprising approximately 19 million members. PATIENTS: A total of 16,690 patients who had undergone PCI with stent placement and who were highly adherent to clopidogrel therapy alone (9862 patients) or to clopidogrel with a PPI (6828 patients) between October 1, 2005, and September 30, 2006. MEASUREMENTS AND MAIN RESULTS: The primary end point was the occurrence of a major adverse cardiovascular event during the 12 months after stent placement. These events were defined as hospitalization for a cerebrovascular event (stroke or transient ischemic attack), an acute coronary syndrome (myocardial infarction or unstable angina), coronary revascularization (PCI or coronary artery bypass graft), or cardiovascular death. A composite event rate was compared between patients who received clopidogrel alone and those who received concomitant clopidogrel-PPI therapy. Baseline differences in covariates were adjusted by using Cox proportional hazards models. In the 9862 patients receiving clopidogrel alone, 1766 (17.9%) experienced a major adverse cardiovascular event compared with 1710 patients (25.0%) who received concomitant clopidogrel-PPI therapy (adjusted hazard ratio 1.51, 95% confidence interval 1.39-1.64, p<0.0001). Similar associations of increased risk were observed for each PPI studied (omeprazole, esomeprazole, pantoprazole, and lansoprazole). CONCLUSION: Concomitant use of a PPI and clopidogrel compared with clopidogrel alone was associated with a higher rate of major adverse cardiovascular events within 1 year after coronary stent placement.

Is there a relationship between early statin compliance and a reduction in healthcare utilization?

OBJECTIVE: To investigate whether compliance during the first 2 years of statin therapy is associated with reduced hospitalization rates and direct medical costs during year 3. STUDY DESIGN: An integrated pharmacy and medical claims database was used to identify adult patients with a new statin prescription between July 1, 2001, and June 30, 2002. The study tracked statin prescription refills during the first 2 years after the initial statin claim and tracked hospitalizations and direct medical costs during the first 3 years. METHODS: Patients were stratified according to compliance in the first 2 years using the medication possession ratio, where 80% or higher is compliant and less than 80% is noncompliant. The relationship between compliance rates and direct medical costs was evaluated using a generalized linear model. Adjusting for covariates that may affect cardiovascular risk, the relationship between compliance and the likelihood of hospitalization was assessed using logistic regression models. RESULTS: The 2-year medication possession ratio was 80% or higher in 3512 patients (compliant) and was less than 80% in 6715 patients (noncompliant). Compared with the noncompliant patients, the compliant patients during year 3 had significantly fewer hospitalizations (16% vs 19%) and lower total direct medical costs (excluding the cost of statin therapy) ($4040 vs $4908 per patient) (P <.01 for both). CONCLUSION: Compliance with statin therapy in the first 2 years of use may reduce hospitalization rates and direct medical costs in the subsequent year.

Warfarin genotyping reduces hospitalization rates results from the MM-WES (Medco-Mayo Warfarin Effectiveness study).

OBJECTIVES: This study was designed to determine whether genotype testing for patients initiating warfarin treatment will reduce the incidence of hospitalizations, including those due to bleeding or thromboembolism. BACKGROUND: Genotypic variations in CYP2C9 and VKORC1 have been shown to predict warfarin dosing, but no large-scale studies have prospectively evaluated the clinical effectiveness of genotyping in naturalistic settings across the U.S. METHODS: This national, prospective, comparative effectiveness study compared the 6-month incidence of hospitalization in patients receiving warfarin genotyping (n = 896) versus a matched historical control group (n = 2,688). To evaluate for temporal changes in the outcomes of warfarin treatment, a secondary analysis compared outcomes for 2 external control groups drawn from the same 2 time periods. RESULTS: Compared with the historical control group, the genotyped cohort had 31% fewer hospitalizations overall (adjusted hazard ratio [HR]: 0.69, 95% confidence interval [CI]: 0.58 to 0.82, p < 0.001) and 28% fewer hospitalizations for bleeding or thromboembolism (HR: 0.72, 95% CI: 0.53 to 0.97, p = 0.029) during the 6-month follow-up period. Findings from a per-protocol analysis were even stronger: 33% lower risk of all-cause hospitalization (HR: 0.67, 95% CI: 0.55 to 0.81, p < 0.001) and 43% lower risk of hospitalization for bleeding or thromboembolism (HR: 0.57, 95% CI: 0.39 to 0.83, p = 0.003) in patients who were genotyped. During the same period, there was no difference in outcomes between the 2 external control groups. CONCLUSIONS: Warfarin genotyping reduced the risk of hospitalization in outpatients initiating warfarin. (The Clinical and Economic Impact of Pharmacogenomic Testing of Warfarin Therapy in Typical Community Practice Settings [MHSMayoWarf1]; NCT00830570).

Ke 'Ano Ola: Moloka'i's community-based healthy lifestyle modification program.

We evaluated a community-based 12-week healthy lifestyle program in Moloka'i, HI, called Ke 'Ano Ola, which was developed to decrease chronic disease risk through health education emphasizing weight loss, exercise, and risk factor reduction. Program leaders' strong commitment and positive role modeling, along with social and group support and community involvement, were key elements. A pre-post evaluation of weight, blood pressure, total cholesterol, and blood sugar showed significant improvements for weight (mean change [Delta] = -7.4 lbs; P < .001), systolic blood pressure (Delta = -3.8 mm Hg; P = .027), diastolic blood pressure (Delta = -4.6 mm Hg; P < .001), and total cholesterol (Delta = -9.7 mg/dL; P < .001). Attrition was low, with 89% of participants attending all 12 sessions. Our findings show that lifestyle improvements in a predominantly Native Hawaiian community are achievable in a support group setting.

Oseltamivir prescribing in pharmacy-benefits database, United States, 2004-2005.

We reviewed information from a US pharmacy benefits manager database from 2004 through 2005 during periods with little influenza activity. We calculated rates of oseltamivir prescriptions to enrollees. Prescription rates increased significantly from 27.3/100,000 in 2004 to 134/100,000 in 2005 (p<0.05), which suggested that personal stockpiling of oseltamivir occurred.

Pharmacogenomic biomarker information in drug labels approved by the United States food and drug administration: prevalence of related drug use.

STUDY OBJECTIVES: To review the labels of United States Food and Drug Administration (FDA)-approved drugs to identify those that contain pharmacogenomic biomarker information, and to collect prevalence information on the use of those drugs for which pharmacogenomic information is included in the drug labeling. DESIGN: Retrospective analysis. DATA SOURCES: The Physicians' Desk Reference Web site, Drugs@FDA Web site, and manufacturers' Web sites were used to identify drug labels containing pharmacogenomic information, and the prescription claims database of a large pharmacy benefits manager (insuring > 55 million individuals in the United States) was used to obtain drug utilization data. MEASUREMENTS AND MAIN RESULTS: Pharmacogenomic biomarkers were defined, FDA-approved drug labels containing this information were identified, and utilization of these drugs was determined. Of 1200 drug labels reviewed for the years 1945-2005, 121 drug labels contained pharmacogenomic information based on a key word search and follow-up screening. Of those, 69 labels referred to human genomic biomarkers, and 52 referred to microbial genomic biomarkers. Of the labels referring to human biomarkers, 43 (62%) pertained to polymorphisms in cytochrome P450 (CYP) enzyme metabolism, with CYP2D6 being most common. Of 36.1 million patients whose prescriptions were processed by a large pharmacy benefits manager in 2006, about 8.8 million (24.3%) received one or more drugs with human genomic biomarker information in the drug label. CONCLUSION: Nearly one fourth of all outpatients received one or more drugs that have pharmacogenomic information in the label for that drug. The incorporation and appropriate use of pharmacogenomic information in drug labels should be tested for its ability to improve drug use and safety in the United States.

Trends in medication treatment for ADHD.

OBJECTIVE: This study examines demographic trends in the use of medications to treat ADHD in adult and pediatric populations. METHOD: Using pharmacy claims data for a large population of commercially insured Americans, the study measures ADHD treatment prevalence and drug use from 2000 to 2005. RESULTS: In 2005, 4.4% of children (ages 0 to 19) and 0.8% of adults (ages 20 and older) used ADHD medications. Treatment rates were higher in boys (6.1%) than in girls (2.6%), but the rates for men and women were approximately equal (0.8%). During the period of the study, treatment prevalence increased rapidly (11.8% per year) for the population as a whole. Treatment rates grew more rapidly for adults than for children, more rapidly for women than for men, and more rapidly for girls than for boys. CONCLUSION: Improved identification of ADHD in adult and female patients has contributed to rapid growth in ADHD medication use.

Dispensing error rate in a highly automated mail-service pharmacy practice.

STUDY OBJECTIVE: To measure the rate of dispensing errors and to identify the types and sources of dispensing errors in a highly automated mail-service pharmacy practice. DESIGN: Descriptive analysis of a random sample of completed prescriptions. SETTING: A high-volume mail-service pharmacy practice comprising a network of prescription processing and dispensing pharmacies in the United States. MEASUREMENTS AND MAIN RESULTS: During September and October 2003, new and refill prescriptions were retrieved before shipping and evaluated for dispensing accuracy. Container contents were compared against the container label, and the label record was compared against the original prescription order. The overall dispensing error rate was 0.075% (16 dispensing errors among 21,252 prescriptions, 95% confidence interval 0.043-0.122). Fourteen errors involved incomplete or incorrect directions on the final label. All dispensing errors were associated with the initial stages of prescription processing (including order entry); no errors were associated with the mechanical stages of product dispensing. CONCLUSION: A highly automated mail-service pharmacy can achieve a dispensing error rate of less than 1 error/1000 prescriptions, which is substantially lower than the rates reported for retail pharmacies. A high degree of automation in the mechanical aspects of dispensing appears to be a key factor in achieving this high dispensing accuracy.

Estimating medication persistency using administrative claims data.

OBJECTIVES: To review the definitions and methods for measuring medication persistency, and to propose a uniform definition of and calculation for persistency using pharmacy claims data. STUDY DESIGN: Literature review. METHODS: A MEDLINE search (1966 to present) was performed to identify articles detailing a definition or method of persistency measurement based on automated pharmacy data. Articles were screened for relevance by title and abstract. References from identified articles were used to expand the search results. RESULTS: The concept behind medication persistency measurement is to capture the amount of time that an individual remains on chronic drug therapy. The methods to calculate medication persistency can be classified into 1 of 3 categories: (1) Persistency as a function of the medication possession ratio; (2) persistency as a function of medication availability at a fixed point in time; and (3) persistency as a function of the gaps between refills. CONCLUSIONS: The common goal of all persistency measures should be to reflect the continuity of medication usage and to capture the timeliness and the frequency of refilling. The measurement of persistency as a function of the gaps between refills provides the best assessment of refill compliance across a variety of medication and disease states and lends itself to the well-established measurements of survival analysis.

Evaluation of a depression health management program to improve outcomes in first or recurrent episode depression.

OBJECTIVES: To evaluate the impact of telephone counseling and educational materials on medication adherence and persistency among members with newly diagnosed depression enrolled in a pharmacy benefit management-sponsored disease management program. STUDY DESIGN: Longitudinal cohort observation. METHODS: The study population comprised 505 members with a new or recurrent episode of depression who consented and enrolled in a depression disease management program. After written consent was obtained, program participants received up to 4 telephone-counseling calls and 5 educational mailings focused on the importance of medication compliance, barriers to medication compliance, quality of life, symptoms, and satisfaction with the program. A control group of 3744 members was selected from client companies that opted not to offer the depression program. Measures of medication adherence, persistency with prescription drug therapy, and patient refill timeliness were computed for both groups and compared. RESULTS: Patients enrolled in the depression disease management program were significantly more likely to adhere to their medication regimen during acute (89.0% vs 67.7%, P < .001) and continuation treatment phases (81.1% vs 57.6%, P < .001). In addition, members enrolled in the program were significantly more likely to continue their therapy after 7 months (77.8% vs 49.5%, P < .001) and refilled their prescriptions on a more timely basis (0 vs 18 days, P < .001). CONCLUSIONS: A pharmacy benefit management-sponsored health management depression program succeeded in encouraging patients with new or recurrent depression to stay on antidepressant medication and to reach treatment goals outlined by best practice guidelines.

Comparative analysis of two quality-of-life instruments for patients with chronic obstructive pulmonary disease.

OBJECTIVE: The St. George's Respiratory Questionnaire (SGRQ) has been validated and widely used in assessing quality of life among patients with chronic obstructive pulmonary disease (COPD), but it is time-consuming and complicated to score. A more concise instrument, the Airways Questionnaire (AQ), was developed to measure quality of life (QoL) among patients with asthma and COPD. The shorter version of this instrument has 20 items (AQ20) and the longer version has 30 items (AQ30). The purpose of this study was to determine the relationship between QoL scores measured by the AQ20/30 or the SGRQ scale and utilization of health-care services by COPD patients and to evaluate the comparative advantage of any one of these instruments in measuring the QoL of COPD patients. METHODS: Results from a survey of 1000 patients participating in a pilot COPD health management program were used for this analysis. A total of 303 patients completed both the AQ20/30 and the SGRQ questionnaires. Logistic regression models were used to analyze the relationship between utilization of health care services and QoL scores while controlling for a set of covariates. Spearman's rank correlation was used to determine whether the AQ30 and the SGRQ scores for symptoms, activity, and impact, and the overall scores were correlated. RESULTS: The regression results demonstrate that there is a strong relationship between quality-of-life scores and health-care utilization variables. Moreover, the degree of association between the AQ20/30 scores and utilization variables and the SGRQ and utilization variables are comparable. Both the AQ20 and the AQ30 were highly correlated with the overall SGRQ score and with symptoms, activity, and impact component scores. CONCLUSION: The AQ20/30 and the SGRQ scores are comparable in terms of measuring QoL in COPD patients and are equally useful in determining the association between utilization of health-care services and QoL.