Depression and anxiety in persons with Von Willebrand disease.

OBJECTIVE: We assessed sociodemographic and clinical characteristics associated with depression and anxiety in individuals with Von Willebrand disease (VWD) aged ≥12 years. METHODS: The study collected data on patients' sociodemographic, joint problems and health-related quality of life (HRQoL) using EQ-5D-3L, 8-item patient health questionnaire for depression and 7-item Generalized Anxiety Disorder Questionnaire from participants in seven geographically diverse US haemophilia treatment centres. RESULTS: Analyses included 77 participants. The rates of depression and anxiety were 63.6% and 58.3%, respectively. Persons with low VWF displayed higher rates of depression (86.7%) or anxiety (69.2%) compared to those with VWD (58.1%, p = .04 for depression, and 55.9%, p = .38 for anxiety). Logistic regression analyses demonstrated that having joint problems (odds ratio [OR] = 6.3, confidence interval [CI] = 2.0-20.1) was the most important variable associated with depression, followed by being single, divorced, widowed, or separated in adult participants or parents of participants age < 18 years (OR = 7.0, CI = 1.7-29.0. The most important variable associated with anxiety was being single or lacking a partner (OR = 10.8, CI = 2.5-47.5), followed by age 12-17 years old (OR = 6.7, CI = 1.6-26.9), or having worse health compared to 3-months ago (OR = 12.3, CI = 1.3-116.2). Mean covariates adjusted EQ visual analogue scale score was significantly lower among persons with depression (68.77 ± 3.15 vs. 77.58 ± 4.24, p = .03) than those without depression. CONCLUSIONS: Our study revealed concerning levels of depression and anxiety in this VWD sample. Lack of social support was determined an important factor associated with depression and anxiety in this sample. Mental health screening is critical in VWD clinical evaluation and care.

Trends in prescribing practices for management of haemophilia: 1999-2021.

INTRODUCTION: People with haemophilia rely on specialists for their care, yet the specific dosing regimens of treatments prescribed by these specialists have not been widely studied. AIM: The objective of this study is to describe trends in clinician prescribing practices for the management of haemophilia in the United States (US). METHODS: We administered surveys to members of the Hemostasis and Thrombosis Research Society via paper surveys at its in-person annual symposia in 1999 and 2015, and an online survey in 2021. The surveys collected information on haemophilia treatments including factor dosing, inhibitor therapy and gene therapy. RESULTS: Clinicians treating haemophilia for more than 50% of their practice time have increased from 37.5% of respondents in 1999 to 46.3% in 2021. Clinicians prescribing factor concentrates at >40 units/kg for routine bleeding events increased from 0% in 1999 to 29.3% in 2021 in haemophilia A (HA) and from 22.5% to 87.8% in haemophilia B (HB). In 2021, the clinicians reported prescribing emicizumab to treat HA patients (>89.5% paediatric, >85.7% adult) with or without inhibitors at least some of the time. Approximately 78.0% of respondents reported that they expected to recommend gene therapy at least some of time. CONCLUSION: These data indicate changing trends in prescribing practices among US haemophilia specialists during the past 22 years. Preference for high doses of factor (>40 units/kg) has increased during this period. Emicizumab prophylaxis has been prescribed for patients with and without HA inhibitors. Clinicians expect gene therapy to have value for some haemophilia patients.

Non-severe haemophilia: Is it benign? - Insights from the PROBE study.

INTRODUCTION: There are limited data on the impact of haemophilia on health status and health-related quality of life (HRQL) in people with non-severe (mild and moderate) haemophilia. AIM: To evaluate the health status of people living with mild or moderate haemophilia. METHODS: Data on respondents with no bleeding disorder (NoBD), mild and moderate haemophilia patients were drawn from the PROBE study. Respondents were enrolled using network patient organizations. This analysis was performed as a cross-sectional study. Primary outcomes were reported bleeding, acute and chronic pain, activities of daily living and HRQL. RESULTS: A total of 862 respondents with NoBD (n = 173), mild (n = 102) and moderate (n = 134) haemophilia were eligible, with a median age of 33, 42 and 43, respectively. In relation to haemophilia-related sequalae, 53% of male and 29% of female patients with mild and 83% of males with moderate haemophilia had more than 2-3 bleeds in the last 12 months. Reporting of acute and chronic pain is less in those with NoBD compared to the mild and moderate cohorts for both genders. Multivariate analysis demonstrates significant reductions in quality of life using VAS, EQ-5D-5L and PROBE for males with mild and moderate haemophilia (P ≤ .001) with only PROBE indicating a significant reduction for females with mild (P = .002). CONCLUSION: People affected by mild or moderate haemophilia report a significant HRQL impact due to haemophilia-related bleeding. Future research is needed to identify the optimal care management of patients with mild and moderate haemophilia.

Evaluation of the sexual health in people living with hemophilia.

BACKGROUND: Knowledge about sexual health, difficulty with sexual activity and intimacy (sexual difficulty), in people with hemophilia is little understood. OBJECTIVES: The objectives were to determine the prevalence of sexual difficulty in people living with hemophilia (PWH) compared to people with no bleeding disorders (PWNoBD), and to determine factors associated with it. METHODS: This was an analysis of the PROBE study. We recruited individuals who had hemophilia A or B (PWH) and PWNoBD who were 18 years old or older. We calculated proportions of participants with sexual difficulty and odds ratios (ORs) adjusted for sex and age with 95% confidence intervals. RESULTS: There were 2007 PWH and 1972 PWNoBD. Mean (standard deviation) age was 41 (15) years in PWH and 42 (13) years in PWNoBD. Sexual difficulty was reported in 302 (15.1%) PWH and 79 (4.0%) PWNoBD. The odds of sexual difficulty were significantly higher in PWH (OR 3.82, 95% CI 2.85, 5.11). Among PWH, older age, experiencing acute or chronic pain in the past 12 months, bleeds within the past two weeks, ≥3 spontaneous joint bleeds (past six months), limitation of range of motion of any joints, and any life- or limb-threatening bleeds in the past 12 months were associated with sexual difficulty. CONCLUSIONS: Sexual difficulty is more prevalent in people living with hemophilia and associated with markers of disease severity. Sexual health issues should be incorporated in comprehensive hemophilia care, future research, and hemophilia related health policy.

Exploring regional variations in the cross-cultural, international implementation of the Patient Reported Outcomes Burdens and Experience (PROBE) study.

BACKGROUND: The Patient Reported Outcomes Burdens and Experience (PROBE) study has developed and validated the PROBE questionnaire for assessing patient-reported outcomes in people with haemophilia and participants without bleeding disorders. OBJECTIVE: To explore the regional variations in the international implementation of the PROBE questionnaire. METHODS: Data were collected from participants in four regions (Western Pacific, South America, North America and Europe). Participants were able to choose English or translated versions of the PROBE questionnaire into their first language. We used analysis of variance methods and multivariable regression to determine the relative contribution of the variance explained by region controlling for haemophilia diagnosis, age group and levels of educations. We also explored interactions between region and the other components. RESULTS: We used 862 questionnaires from 14 countries. Mean age of participants was 40.03 years (standard deviation 13.89), and 73.67% were male. After adjusting, region contributed 0.44%-7.98% of the variance component in subitem scores and 0.26% in the PROBE score. Years of education contributed 0.34% in the PROBE score. Age and haemophilia diagnosis contributed 3.42% and 22.42% of the PROBE score. CONCLUSIONS: The results demonstrate that the PROBE questionnaire is valid to implement for assessing health status among patients with haemophilia and participants without bleeding disorders across regions.

Test-retest properties of the Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire and its constituent domains.

BACKGROUND: The Patient Reported Outcomes, Burdens and Experiences (PROBE) study aims to develop and validate questionnaire for assessing health status in patients with haemophilia and participants without bleeding disorders. OBJECTIVE: To investigate the test-retest properties of the PROBE questionnaire. METHODS: The PROBE questionnaire covers four domains and is comprised of 29 questions. People with haemophilia (PWH) and participants without bleeding disorder were invited to participate in this study. All participants were asked to complete the PROBE questionnaire three times (paper-based survey on two consecutive days: T1 and T2 and then a web-based version: T3). Test-retest properties and percentage agreement were analysed. RESULTS: A total of 63 participants were enrolled in this study with a median age of 50 (range: 17-76) years. Of these, 30 (47.6%) were PWH. On the questions common to PWH and participants without bleeding disorder, Kappa coefficients ranged from 0.69 to 1.00, indicating substantial to almost perfect agreement (T1 vs T2). For haemophilia-related questions (T1 vs T2), Kappa coefficients ranged from 0.5 to 1.0. Of these, 5 of 11 items were in perfect agreement (Kappa = 1.0). The web-based questionnaire (T3) showed substantial to almost perfect agreement with the paper version (T1 test-retest properties were comparable between PWH and individuals without a bleeding disorder). CONCLUSIONS: The results suggest that PROBE is a reliable tool to assess patient-reported outcomes for PWH and benchmark data in participants without bleeding disorder. The web-based questionnaire and the standard paper-based version can be used interchangeably.

Economic Burden of Illness among Persons with Hemophilia B from HUGS Vb: Examining the Association of Severity and Treatment Regimens with Costs and Annual Bleed Rates.

OBJECTIVES: To determine US societal burden of illness, including direct and indirect costs and annual bleed rate (ABR), for persons with hemophilia B (HB), a rare and debilitating genetic disorder, and to examine associations of hemophilia severity and treatment regimens with costs and ABR. METHODS: From 2009 to 2014, the Hemophilia Utilization Group Studies Part Vb collected prospective data from 10 US hemophilia treatment centers. Participants with HB completed initial surveys on sociodemographic characteristics, clinical characteristics, and treatment patterns. During the 2-year follow-up, participants reported bleeding episodes, work absenteeism, and caregiver time quarterly. These data were used to calculate ABR and indirect costs. Direct costs were calculated using 1-year clinical chart records and 2-year dispensing records. RESULTS: Of the 148 participants, 112 with complete medical records and one or more follow-up survey were included. Total mean annual per-person costs were $85,852 (median $20,160) for mild/moderate HB, $198,733 (median $147,891) for severe HB, and $140,240 (median $63,617) for all participants without inhibitors (P < 0.0001). Mean ABR for participants with severe HB on prophylaxis (5.5 ± 7.9 bleeds/y) was almost half that of those treated episodically. Clotting factor and indirect costs accounted for 85% and 9% of total costs, respectively. Compared with episodic treatment, prophylaxis use was associated with 2.5-fold higher clotting factor costs (P < 0.01), low but significantly more missed parental workdays (P < 0.0001) and clinician (P < 0.001) or nursing visits (P < 0.0001), less part-time employment and unemployment, and lower hospitalizations costs (P = 0.17) and ABR (P < 0.0001). CONCLUSIONS: HB is associated with high economic burden, primarily because of clotting factor costs. Nevertheless, prophylaxis treatment leads to clinical benefits and may reduce other nonfactor costs.

Young adults with hemophilia in the U.S.: demographics, comorbidities, and health status.

Improvements in hemophilia care over the last several decades might lead to expectations of a near-normal quality of life for young adults with hemophilia. However, few published reports specifically examine health status indicators in this population. To remedy this knowledge gap, we examined the impact of hemophilia on physical and social functioning and quality of life among a national US cohort of 141 young men with hemophilia aged 18-34 years of age who received care at 10 geographically diverse, federally funded hemophilia treatment centers in 11 states between 2005 and 2013 and enrolled in the Hemophilia Utilization Group Studies. Indicators studied included educational achievement, employment status, insurance, health-related quality of life, and prevalence of the following comorbidities: pain, range of motion limitation, overweight/obesity, and viral status. The cohort was analyzed to compare those aged 18-24 to those aged 25-34 years. When compared to the general US adult population, this nationally representative cohort of young US adults with hemophilia experienced significant health and social burdens: more liver disease, joint damage, joint pain, and unemployment as well as lower high-school graduation rates. Nearly half were overweight or obese. Conversely, this cohort had higher levels of health insurance and equivalent mental health scores. While attention has typically focused on newborns, children, adolescents, and increasingly, on older persons with hemophilia, our findings suggest that a specific focus on young adults is warranted to determine the most effective interventions to improve health and functioning for this apparently vulnerable age group.

Longitudinal changes in health-related quality of life for chronic diseases: an example in hemophilia A.

BACKGROUND: Patients with well-managed rare chronic diseases such as hemophilia maintain a stable health state and health-related quality of life (HrQoL) that may be affected by acute events. Longitudinal HrQoL assessments analyzed using multivariate multilevel (MVML) modelling can determine the impact of such events on individuals (within-person effect) and identify factors influencing within-population differences (between-person effect). OBJECTIVES: To demonstrate the application of MVML modelling in a longitudinal study of HrQoL in hemophilia A. METHODS/DESIGN/PARTICIPANTS: Using data on 136 adults and 125 children from a two-year observational cohort study of burden of illness in US hemophilia A patients, MVML modelling determined the effect of time-invariant (sociodemographic and clinical characteristics) and time-varying factors (bleeding frequency, emergency room visits, and missed work/school days) on within-person and between-person HrQoL changes. HrQoL was assessed using the SF-12 health survey (adults) and PedsQL inventory (children) at baseline, then every 6 months. RESULTS: In children, within-person (p < 0.0001) and between-person (p < 0.0001) psychosocial functioning was reduced by each additional bleed and missed day (within-person: p = 0.0089; between-person: p = 0.0060). Within-person physical functioning was reduced by each additional bleed (p < 0.0001), emergency room (ER) visit (p = 0.0284), and missed day (p = 0.0473). Between-persons, additional missed days (p < 0.0001) significantly decreased physical functioning. In adults, each additional missed day reduced SF-12 Health Survey mental (p = 0.0025) and physical (p = 0.0093) component summary scores. Each additional bleed also decreased physical component summary (PCS) significantly (p = 0.0093). CONCLUSIONS: This study demonstrated the applicability of MVML modelling in identifying time-invariant and time-varying factors influencing HrQoL in a rare chronic disease population. Small but significant within-person and between-person changes in HrQoL with each additional acute event experienced were identified, which if frequent, could have a large cumulative impact. The results suggest that MVML modelling may be applied to future studies of longitudinal change in HrQoL in other rare chronic disease populations.

Impact of mental health comorbidities on health care utilization and expenditure in a large US managed care adult population with ADHD.

OBJECTIVE: To estimate the health resource use (HRU) and expenditure of adult patients with attention deficit/hyperactivity disorder (ADHD) subsequently diagnosed with one or more mental health (MH) comorbidities. METHODS: Using Kaiser Permanente Southern California electronic medical records (January 1, 2006, to December 31, 2009), we identified adults with at least one ADHD diagnosis and at least two subsequent prescriptions fills for ADHD medication. The date of first MH comorbidity diagnosis after the index ADHD diagnosis was defined as the index transition date. Continuous eligibility 12 months before and after the index transition date was required. For patients with multiple transitions (≥2), the post-transition period reflected the 12 months after the second transition. HRU for all-cause inpatient, outpatient, emergency department, behavioral therapy, overall prescription fill counts, and ADHD-specific prescription fill counts and mean patient expenditure (2010 US $) were estimated. Generalized estimating equations were used to evaluate differences in HRU and expenditure between the pre- and post-transition periods, respectively. RESULTS: Of the 3809 patients with ADHD identified, 989 (26%) had at least one transition (n = 357 single and n = 632 multiple). From the pre- to the post-transition period, for single transition cohort, all HRU increased significantly except for behavioral therapy. In the multiple transition cohort, all HRU increased significantly. Total expenditure increased by mean ± SE of $1822 ± $306 and $4432 ± $301 (both P < 0.0001) in the single and multiple transition cohorts, respectively. CONCLUSIONS: Twenty-six percent of patients with ADHD transitioned to MH comorbid diagnoses. Increased HRU and expenditure were associated with MH transitions. Identifying of patients with ADHD at risk for MH comorbidities may help to improve their outcomes.

Multiple medication adherence and its effect on clinical outcomes among patients with comorbid type 2 diabetes and hypertension.

OBJECTIVE: To investigate multiple medication adherence (MMA) and its impact on microvascular and macrovascular complications using instrumental variables (IVs). RESEARCH DESIGN: A retrospective observational study was conducted using administrative claims and electronic medical records from a large physician group in Southern California (N=2334). SUBJECTS: We identified individuals between January 2006 and June 2009 newly starting oral diabetes (DM) or hypertension (HTN) medications with preexisting comorbid HTN or DM prescription history. MEASURES: MMA was defined as a proportion of days covered where both DM and HTN medications were simultaneously available over a 33-month follow-up period. Microvascular or macrovascular complications included myocardial infarction, stroke, renal failure, and diabetic retinopathy. Multivariable logistic regressions and an IV estimation using physician-related variables were implemented. RESULTS: MMA was supoptimal as the mean (SD) proportion of days covered was 0.53 (0.32). Patients were more adherent to medications for a preexisting condition in comparison with those for the newer disease. Older age, number of index medications [OR (95% CI)=1.36 (1.22-1.52)], receiving care from a physician who prescribed statin more frequently [OR (95% CI)=2.63 (1.67-4.14)], and receiving care from the same physician for both DM and HTN [OR (95% CI)=1.57 (1.08-2.27)] were significant factors of being adherent. Using physician-related IVs, MMA reduced microvascular and macrovascular complications. The increase in MMA from 50% to 80% reduced the average predicted probability of microvascular or macrovascular complication rate by 29.5%. CONCLUSIONS: Adherence to medications for DM and HTN were differed and higher MMA reduced microvascular or macrovascular complications when controlling for endogeneity bias.

Changes in serum prostate-specific antigen levels and the identification of prostate cancer in a large managed care population.

OBJECTIVE: To determine whether the rate of change in total serum prostate-specific antigen (PSA) levels accurately detects prostate cancer and to evaluate whether it adds any predictive value to a single measurement of serum PSA alone, in general practice settings. MATERIALS AND METHODS: A retrospective cohort of 219,388 community-dwelling men, aged ≥45 years, enrolled in the Kaiser Permanente Southern California health plan, with no history of prostate cancer and at least three PSA measurements, were followed from 1 January 1998 to 31 December 2007, for the development of biopsy-confirmed prostate cancer. Annual percent changes in total serum PSA levels were estimated using linear mixed models. The accuracy of prostate cancer prediction was assessed for prostate cancer overall and for aggressive disease (Gleason score ≥7) and compared with that of a single measure of PSA level using area under the receiver-operating characteristic curves (AUCs). RESULTS: The men in this cohort experienced a mean change of 2.9% in PSA levels per year and the rate of change in PSA increased modestly with age (P ≤ 0.001). Annual percent changes in PSA accurately predicted the presence of prostate cancer (AUC = 0.963) and aggressive disease (AUC = 0.955) and had more predictive accuracy for aggressive disease than did a single measurement of PSA alone (AUC = 0.727). CONCLUSIONS: Longitudinal measures of PSA improve the accuracy of aggressive prostate cancer detection when compared with a single measurement of PSA alone. Findings from this study provide insight into the usefulness of PSA velocity as a detection marker for aggressive prostate cancer.

Incremental expenditure of biologic disease modifying antirheumatic treatment using instrumental variables in panel data.

In health care, decision makers are generally interested in simultaneous comparisons among multiple treatments or interventions available as treatment choices in real-world clinical setting. The lack of random assignment to treatment in real-world clinical settings leads to selection-bias issues when evaluating the marginal benefits of treatment. The application of instrumental variables (IV) estimation to mitigate selection bias has traditionally been limited to comparing only two treatments/interventions concurrently. Using the case of biologic treatment in rheumatoid arthritis, we describe a generalized method of moments (GMM)-based panel data IV (IV-GMM) framework, to simultaneously estimate multiple treatment effects in the presence of time-varying selection bias and time-invariant heterogeneity. To satisfy the order and rank conditions for identification with multiple endogeneity, we propose lagged values of each treatment as excluded instruments. We evaluate the validity of the IV estimation assumptions on instrument relevance and exogeneity. Results indicate that the IV-GMM model offers enhanced control over selection bias and heterogeneity, and more importantly the panel data framework can provide valid excluded instruments that satisfy the order and rank conditions for identification when dealing with multiple endogenous variables. The approach outlined in this article has broad application for comparative effectiveness and health technology assessment involving multiple treatments/interventions using real-world nonexperimental data.

What quantifies good primary care in the United States? A review of algorithms and metrics using real-world data.

Primary care physicians (PCPs) play an indispensable role in providing comprehensive care and referring patients for specialty care and other medical services. As the COVID-19 outbreak disrupts patient access to care, understanding the quality of primary care is critical at this unprecedented moment to support patients with complex medical needs in the primary care setting and inform policymakers to redesign our primary care system. The traditional way of collecting information from patient surveys is time-consuming and costly, and novel data collection and analysis methods are needed. In this review paper, we describe the existing algorithms and metrics that use the real-world data to qualify and quantify primary care, including the identification of an individual's likely PCP (identification of plurality provider and major provider), assessment of process quality (for example, appropriate-care-model composite measures), and continuity and regularity of care index (including the interval index, variance index and relative variance index), and highlight the strength and limitation of real world data from electronic health records (EHRs) and claims data in determining the quality of PCP care. The EHR audits facilitate assessing the quality of the workflow process and clinical appropriateness of primary care practices. With extensive and diverse records, administrative claims data can provide reliable information as it assesses primary care quality through coded information from different providers or networks. The use of EHRs and administrative claims data may be a cost-effective analytic strategy for evaluating the quality of primary care.

Cost-effectiveness of Prostate Health Index for prostate cancer detection.

OBJECTIVE: • To evaluate the cost-effectiveness of early prostate cancer detection with the Beckman Coulter Prostate Health Index (phi) (not currently available in the USA) adding to the serum prostate-specific antigen (PSA) test compared with the PSA test alone from the US societal perspective. PATIENTS AND METHODS: • Phi was developed as a combination of PSA, free PSA, and a PSA precursor form [-2]proPSA to calculate the probability of prostate cancer and was used as an aid in distinguishing prostate cancer from benign prostatic conditions for men with a borderline PSA test (e.g. PSA 2-10 ng/mL or 4-10 ng/mL) and non-suspicious digital rectal examination. • We constructed a Markov model with probabilistic sensitivity analysis to estimate expected costs and utilities of prostate cancer detection and consequent treatment for the annual prostate cancer screening in the male population aged 50-75 years old. • The transition probabilities, health state utilities and prostate cancer treatment costs were derived from the published literature. The diagnostic performance of phi was obtained from a multi-centre study. Diagnostic related costs were obtained from the 2009 Medicare Fee Schedule. • Cost-effectiveness was compared between the strategies of PSA test alone and PSA plus phi under two PSA thresholds (≥2 ng/mL and ≥4 ng/mL) to recommend a prostate biopsy. RESULTS: • Over 25 annual screening cycles, the strategy of PSA plus phi dominated the PSA-only strategy using both thresholds of PSA ≥2 ng/mL and PSA ≥4 ng/mL, and was estimated to save $1199 or $443, with an expected gain of 0.08 or 0.03 quality adjusted life years, respectively. • The probabilities of PSA plus phi being cost effective were approximately 77-70% or 78-71% at a range of $0-$200,000 willingness to pay using PSA thresholds ≥2 ng/mL and ≥4 ng/mL, respectively. CONCLUSION: • The strategy PSA plus phi may be an important strategy for prostate cancer detection at both thresholds of PSA ≥2 ng/mL and PSA ≥4 ng/mL to recommend a prostate biopsy compared with using PSA alone.

Temporal trend of opioid and nonopioid pain medications: results from a national in-home survey, 2001 to 2018.

Introduction: The opioid epidemic persists in the United States. The use of opioid medications is often assessed by claims data but potentially underestimated. Objectives: We evaluated the temporal trend in the use of opioid and nonopioid pain medications from a national survey. Methods: Using data from the 2001 to 2018 National Health and Nutrition Examination Survey (NHANES), we examined the current use of prescription analgesics in the past 30 days among 50,201 respondents aged 20 years or older. Joinpoint regressions were used to test statistically meaningful trends of opioid vs nonopioid analgesics. Results: The mean percentage of people who had pain medications in the past 30 days was 6.4% (5.3%-7.1%) for opioid and 11.3% (9.0%-14.8%) for nonopioid analgesics. The availability of opioid and nonopioid prescriptions at home has remained stable, except for the slight decline of opioids among cancer-free patients in 2005 to 2018. The most frequently used opioid analgesic medications included hydrocodone/acetaminophen, tramadol, and hydrocodone. Conclusion: We uniquely measured the proportion of people who had opioid and nonopioid pain medications at home in the United States and supplemented the previous knowledge of prescription rates mainly obtained from claims data.

Comorbidities, Health-Related Quality of Life, Health-care Utilization in Older Persons with Hemophilia-Hematology Utilization Group Study Part VII (HUGS VII).

Purpose: We compare the impact of hemophilia on comorbidities, joint problems, health-related quality of life (HRQoL) and health-care utilization between two age groups: 40-49 years and ≥50 years. Patients and Methods: The HUGS VII study recruited persons with hemophilia A or B age ≥40 years. Participants completed surveys to collect data on sociodemographic and clinical characteristics, hemophilia treatment regimen, pain, joint problems, comorbidities, HRQoL, depression and anxiety, at baseline and 6-months later. Clinical chart reviews documented hemophilic severity and treatment. Results: The sample includes 69 males, 65.2% aged ≥50 years, 75.4% with hemophilia A. Individuals ≥50 years were more likely to have mild or moderate hemophilia (68.9% vs 41.7%, P = 0.03) than those 40-49 years old. Among persons with mild/moderate hemophilia, those ≥50 years old reported a higher rate of joint pain (83.9% vs 70.0%, P = 0.34 at baseline, 91.3% vs 57.1%, P = 0.06 at follow up) or range of motion limitation (73.3% vs 60.0%, P = 0.43 at baseline, 73.9% vs 28.6%, P = 0.04 at follow up) than the younger group. Compared to the younger group, the older group reported fewer emergency room visits (4.5% vs 21.7%, P = 0.03), and physical therapy visits (15.9% vs 43.5%, P = 0.01) at baseline. The sample depression rate was 85.7%, but the differences among the age groups were not significant. The mean covariate-adjusted EQ-5D index score was lower in older persons (0.77 vs 0.89, P = 0.02). Conclusion: Older persons with hemophilia in this sample are over-represented by individuals with mild/moderate disease, potentially due to premature death among those with severe disease. Although this group included a larger proportion of individuals with mild disease than the younger group, they experienced lower quality of life, more comorbidities both of aging and of hemophilic arthropathy, and lower rates of health-care utilization.

The impact of change in visual field on health-related quality of life the los angeles latino eye study.

PURPOSE: To assess the impact of change in visual field (VF) on change in health-related quality of life (HRQoL) at the population level. DESIGN: Prospective cohort study. PARTICIPANTS: Three thousand one hundred seventy-five Los Angles Latino Eye Study participants. METHODS: Objective measures of VF and visual acuity and self-reported HRQoL were collected at baseline and at the 4-year follow-up. Analysis of covariance was used to evaluate mean differences in change of HRQoL across severity levels of change in VF and to test for effect modification by covariates. MAIN OUTCOME MEASURES: General and vision-specific HRQoL. RESULTS: Of 3175 participants, 1430 (45%) showed a change in VF (≥1 decibel [dB]) and 1715 (54%) reported a clinically important change (≥5 points) in vision-specific HRQoL. Progressive worsening and improvement in the VF were associated with increasing losses and gains in vision-specific HRQoL for the composite score and 10 of its 11 subscales (all P(trend)<0.05). Losses in VF of more than 5 dB and gains of more than 3 dB were associated with clinically meaningful losses and gains in vision-specific HRQoL, respectively. Areas of vision-specific HRQoL most affected by greater losses in VF were driving, dependency, role-functioning, and mental health. The effect of change in VF (loss or gain) on mean change in vision-specific HRQoL varied by level of baseline vision loss (in VF, visual acuity, or both) and by change in visual acuity (all P(interaction)<0.05). Those with moderate or severe VF loss at baseline and with a more than 5 dB loss in VF during the study period had a mean loss of vision-specific HRQoL of 11.3 points, whereas those with no VF loss at baseline had a mean loss of 0.97 points. Similarly, with a more than 5 dB loss in VF and baseline visual acuity impairment (mild or severe), there was a loss in vision-specific HRQoL of 10.5 points, whereas with no visual acuity impairment at baseline, there was a loss of vision-specific HRQoL of 3.7 points. CONCLUSIONS: Both losses and gains in VF produce clinically meaningful changes in vision-specific HRQoL. In the presence of pre-existing vision loss (VF and visual acuity), similar levels of VF change produce greater losses in QOL.

Patient-reported reasons for discontinuing overactive bladder medication.

OBJECTIVE: To evaluate patient-reported reasons for discontinuing antimuscarinic prescription medications for overactive bladder (OAB). PATIENTS AND METHODS: A phase 1 screening survey was sent to a representative sample of 260 000 households in the USA to identify patients using antimuscarinic agents for OAB. A detailed phase-2 follow-up survey was sent to 6577 respondents with one or more antimuscarinic prescriptions for OAB in the 12 months before the phase 1 survey. The follow-up survey included questions about demographics, clinical characteristics, antimuscarinic use, beliefs about OAB, treatment expectations, OAB symptom bother, and pre-coded reasons for discontinuation. Patients who reported discontinuing one or more OAB medication during the 12 months before phase 2 were grouped by reason, using latent class analysis (LCA); the Lo-Mendell-Rubin likelihood statistical test was used to determine the number of classes. Conditional probabilities of reasons for discontinuation were calculated for each class. Multivariable logistic regression was used to assess the influence of demographic and clinical characteristics on class assignment. RESULTS: In all, 162 906 (63%) and 5392 (82%) useable responses were returned in phases 1 and 2, respectively; the demographics were similar in respondents and nonrespondents in both phases. In all, 1322 phase 2 respondents (24.5%) reported discontinuing one or more antimuscarinic drugs during the 12 months before phase 2. LCA identified two classes (Lo-Mendell-Rubin statistic, P = 0.01) based on reasons for discontinuation. Most respondents (89%) reported discontinuing OAB medication primarily due to unmet treatment expectations and/or tolerability; many respondents in this class switched to a new antimuscarinic agent. A smaller group (11%) indicated a general aversion to taking medication. Age, sex, race, income, and history of incontinence were not predictive of class assignment. CONCLUSIONS: Expectations about treatment efficacy and side-effects are the most important considerations in discontinuing OAB medications for most patients. Interventions to promote realistic expectations about treatment efficacy and side-effects might enhance adherence.

Estimating the effect of medication adherence on health outcomes among patients with type 2 diabetes--an application of marginal structural models.

OBJECTIVE: We applied marginal structural models (MSMs) to estimate the effects of medication adherence with hypoglycemics on reducing the risk of microvascular complications in type 2 diabetic patients. METHODS: A retrospective longitudinal cohort study for type 2 diabetes patients was conducted using the California Medicaid claims database (1995-2002). Medication adherence and multiple time-varying confounders were measured quarterly over a maximum of 7.5 years follow-up. Cox regression models and MSMs results on the effect of compliance were compared. RESULTS: Of 4708 eligible patients, 2644 (56.2%) experienced microvascular complications during the follow-up period. After controlling for baseline covariates, standard Cox models estimated that adherence was associated with increased risk of complication with hazard ratio (HR) of 1.09 (95% confidence interval (CI): 1.00, 1.18). With adjustment of time-varying confounders as exogenous variables, the HR was 0.96 (0.88, 1.04). Using the MSM technique, the HR was 0.76 (95% bootstrap CI: 0.60, 0.92), indicating a significant benefit of medication adherence with hypoglycemics on the reduction of microvascular complications. This result contrasts with the negative results obtained in the hazard model, and is more consistent with prior clinical trial results CONCLUSION: Unlike conventional models, MSMs estimated that higher medication adherence may result in reduced risk of microvascular complications among patients with type 2 diabetes.