The challenges and opportunities in using real-world data to drive advances in healthcare in East Asia: expert panel recommendations.

OBJECTIVE: To provide recommendations for overcoming the challenges associated with the generation and use of real-world evidence (RWE) in regulatory approvals, health technology assessments (HTAs), and reimbursement decision-making in East Asia. METHODS: A panel of experts convened at the International Society for Pharmacoeconomics and Outcomes Research Asia Pacific 2020 congress to discuss the challenges limiting the use of RWE in healthcare decision-making and to provide insights into the perspectives of regulators, HTA agencies, the pharmaceutical industry, and physicians in China, Japan, and Taiwan. A nonsystematic literature review was conducted to expand on the themes addressed. RESULTS: The use of RWE in regulatory approvals, HTAs, and reimbursement decision-making remains limited by legal/regulatory, technical, and attitudinal challenges in East Asia. CONCLUSIONS: We recommend approaches and initiatives that aim to drive improvements in the utilization of RWE in healthcare decision-making in East Asia and other regions. We encourage large-scale collaborations that leverage the full range of skills offered by different stakeholders. Government agencies, hospitals, research organizations, patient groups, and the pharmaceutical industry must collaborate to ensure appropriate access to robust and reliable real-world data and seek alignment on how to address prioritized evidence needs. Increasingly, we believe that this work will be conducted by multidisciplinary teams with expertise in healthcare research and delivery, data science, and information technology. We hope this work will encourage further discussion among all stakeholders seeking to shape the RWE landscape in East Asia and other regions and drive next-generation healthcare.

Relationship between lymphopenia and disease activity in persons with multiple sclerosis treated with dimethyl fumarate.

BACKGROUND: Dimethyl fumarate (DMF) is a disease-modifying therapy (DMT) used to treat relapsing multiple sclerosis (MS). Its precise mechanism in treating MS involves nuclear factor erythroid-derived 2-related factor-dependent and -independent pathways. Lymphopenia, defined according to NIH Common Terminology for Adverse Events v5.0, is one potential adverse effect. It is unclear whether lymphopenia correlates with disease activity; existing studies have yielded conflicting results. OBJECTIVE: To determine whether lymphopenia in DMF-treated persons with MS (PwMS) correlates with disease activity. METHODS: A retrospective chart review of 66 PwMS treated with DMF between January 1, 2013 and September 30, 2020. RESULTS: Participants who experienced lymphopenia were older (p < 0.001), and had a longer disease duration (p = 0.012) and lower baseline absolute lymphocyte count (ALC) (p < 0.001). Breakthrough disease activity was the most common reason for DMF discontinuation (53.0%). Lymphopenia occurred in 36.4%, with ALCs decreasing over the first 12 months of therapy before plateauing. Lymphopenia was associated with a trend towards reduced relapses (p = 0.059) and significantly improved MRI activity (p = 0.001) and no evidence of disease activity (NEDA-3) (p = 0.022), but not disability progression (p = 0.549). Persons with lymphopenia were significantly less likely to be treated with another DMT after DMF (p = 0.036). CONCLUSION: Risk factors for and rates of lymphopenia resembled existing data. Lymphopenia was associated with significantly improved MRI activity and achievement of NEDA-3, and whether PwMS were treated with another DMT after DMF. Further studies are required to clarify the mechanism of DMF, lymphocyte subsets and their relationship with disease activity, and which characteristics predict response to DMF.

Is there a multiple sclerosis personality? Personality characteristics in newly diagnosed multiple sclerosis and association with mood and cognition.

BACKGROUND: Neuropsychiatric changes are common in multiple sclerosis (MS). Personality in persons with MS (pwMS) is understudied despite its implications for health behaviours, symptoms, and quality of life (QOL). OBJECTIVE: To assess baseline personality characteristics and their relationship to information processing speed (IPS) and mood in persons with early MS. METHODS: A retrospective chart review of 384 pwMS who had psychometric testing within 2 years of diagnosis between February 2012 and May 2021. Testing included the NEO-Five Factor Inventory, Symbol Digit Modalities Test, and Hospital Anxiety and Depression Scale (HADS). RESULTS: Participants were highly agreeable (53.7%). Most had impaired IPS (60.5%). Anxiety and depression were present in 194 (50.5%) and 87 (22.6%) participants, respectively. Females were more agreeable and conscientious. Neuroticism, conscientiousness, and extraversion had moderate-high correlations with anxiety and depression. Despite weak correlations with conscientiousness, extraversion, and openness, pwMS with impaired versus normal IPS had no significant personality differences. CONCLUSIONS: Individuals with recently diagnosed MS are agreeable, typically have impaired IPS, and often have anxiety or depression. Significant personality differences exist between sexes and between pwMS with or without anxiety or depression. Early identification of these neuropsychiatric traits in pwMS may improve treatment adherence, symptoms, and QOL.

Real-world assessment and treatment of locally advanced basal cell carcinoma: Findings from the RegiSONIC disease registry.

BACKGROUND: Limited information is available regarding real-world treatment patterns and their effectiveness and safety in patients with locally advanced basal cell carcinoma, including patients not typically represented in clinical trials. The purpose of the current study was to describe how clinicians diagnose and treat locally advanced basal cell carcinoma in the United States. METHODS: This prospective, multicenter, observational registry study included patients with newly diagnosed, Hedgehog pathway inhibitor-naive locally advanced basal cell carcinoma without basal cell carcinoma nevus syndrome (n = 433) treated at 75 US academic and community practices, including dermatology, Mohs surgery, and medical oncology sites. The main outcomes of this study were treatment patterns and associated effectiveness and safety for patients with locally advanced basal cell carcinoma in real-world settings. RESULTS: Determination of locally advanced basal cell carcinoma was mainly based on lesion size (79.6% of patients), histopathology (54.3%), extent of involvement (49.0%), and location (46.2%). Within 90 days of determination of locally advanced disease, 115 patients (26.6%) received vismodegib, 251 (58.0%) received surgery/other (non-vismodegib) treatment, and 67 (15.5%) had not yet received treatment (observation). Vismodegib-treated patients had a higher prevalence of high-risk clinical features predictive for locoregional recurrence than those with non-vismodegib treatment or observation. Clinical response rate was 85.1% with vismodegib and 94.9% with non-vismodegib treatment (primarily surgery). The most common adverse events with vismodegib were ageusia/dysgeusia, muscle spasms, alopecia, and weight loss. Rates of cutaneous squamous cell cancers were comparable between vismodegib and non-vismodegib treatment. CONCLUSIONS: This prospective observational study offers insight on real-world practice, treatment selection, and outcomes for a nationally representative sample of US patients with locally advanced basal cell carcinoma. For patients with lesions that were not amenable to surgery, vismodegib treatment was associated with effectiveness and safety that was consistent with that observed in clinical trials.

Harmonized Outcome Measures for Use in Non-Small Cell Lung Cancer Patient Registries and Clinical Practice.

BACKGROUND: Lung cancer is the leading cause of cancer-related death in the United States and globally, and many questions exist about treatment options. Harmonizing data across registries and other data collection efforts would yield a robust data infrastructure to help address many research questions. The purpose of this project was to develop a minimum set of patient and clinician relevant harmonized outcome measures that can be collected in non-small cell lung cancer (NSCLC) patient registries and clinical practice. METHODS: Seventeen lung cancer registries and related efforts were identified and invited to submit outcome measures. Representatives from medical specialty societies, government agencies, health systems, health information technology groups, patient advocacy organizations, and industry formed a stakeholder panel to categorize the measures and harmonize definitions using the Agency for Healthcare Research and Quality's supported Outcome Measures Framework (OMF). RESULTS: The panel reviewed 66 outcome measures and identified a minimum set of 8 broadly relevant measures in the OMF categories of patient survival, clinical response, events of interest, and resource utilization. The panel harmonized definitions for the 8 measures through in-person and virtual meetings. The panel did not reach consensus on 1 specific validated instrument for capturing patient-reported outcomes. The minimum set of harmonized outcome measures is broadly relevant to clinicians and patients and feasible to capture across NSCLC disease stages and treatment pathways. A pilot test of these measures would be useful to document the burden and value of the measures for research and in clinical practice. CONCLUSIONS: By collecting the harmonized measures consistently, registries and other data collection systems could contribute to the development research infrastructure and learning health systems to support new research and improve patient outcomes.

Anti-CV2/CRMP5 antibody-associated hemorrhagic leukoencephalomyelitis treated with steroids, intravenous immunoglobulin, plasmapheresis, and cyclophosphamide.

Anti-CV2 or anti-collapsing response-mediator protein-5 (CRMP5) autoantibodies (anti-CV2/CRMP5-Ab) are associated with various paraneoplastic neurological disorders. The best therapy is typically removal of the underlying cancer. We describe a previously healthy elderly male who had no known malignancy. He presented with a demyelinating encephalomyelitis and later developed hemorrhagic changes on neuroimaging. He was treated with intravenous immunoglobulin (IVIG), intravenous steroids, and plasmapheresis; however, sustained clinical and radiographic stabilization and improvement only occurred following cyclophosphamide. He unexpectedly died of a cardiac arrest. postmortem, his serum paraneoplastic screen was found to be weakly positive for anti-CV2/CRMP5-Ab.

De Novo Versus Recurrent HER2-Positive Metastatic Breast Cancer: Patient Characteristics, Treatment, and Survival from the SystHERs Registry.

BACKGROUND: Limited data exist describing real-world treatment of de novo and recurrent HER2-positive metastatic breast cancer (MBC). MATERIALS AND METHODS: The Systemic Therapies for HER2-Positive Metastatic Breast Cancer Study (SystHERs) was a fully enrolled (2012-2016), observational, prospective registry of patients with HER2-positive MBC. Patients aged ≥18 years and ≤6 months from HER2-positive MBC diagnosis were treated and assessed per their physician's standard practice. The primary endpoint was to characterize treatment patterns by de novo versus recurrent MBC status, compared descriptively. Secondary endpoints included patient characteristics, progression-free and overall survival (PFS and OS, by Kaplan-Meier method; hazard ratio [HR] and 95% confidence interval [CI] by Cox regression), and patient-reported outcomes. RESULTS: Among 977 eligible patients, 49.8% (n = 487) had de novo and 50.2% (n = 490) had recurrent disease. A higher proportion of de novo patients had hormone receptor-negative disease (34.9% vs. 24.9%), bone metastasis (57.1% vs. 45.9%), and/or liver metastasis (41.9% vs. 33.1%), and a lower proportion had central nervous system metastasis (4.3% vs. 13.5%). De novo patients received first-line regimens containing chemotherapy (89.7%), trastuzumab (95.7%), and pertuzumab (77.8%) more commonly than recurrent patients (80.0%, 85.9%, and 68.6%, respectively). De novo patients had longer median PFS (17.7 vs. 11.9 months; HR, 0.69; 95% CI, 0.59-0.80; p < .0001) and OS (not estimable vs. 44.5 months; HR, 0.55; 95% CI, 0.44-0.69; p < .0001). CONCLUSION: Patients with de novo versus recurrent HER2-positive MBC exhibit different disease characteristics and survival durations, suggesting these groups have distinct outcomes. These differences may affect future clinical trial design. Clinical trial identification number. NCT01615068 (clinicaltrials.gov). IMPLICATIONS FOR PRACTICE: SystHERs was an observational registry of patients with HER2-positive metastatic breast cancer (MBC), which is a large, modern, real-world data set for this population and, thereby, provides a unique opportunity to study patients with de novo and recurrent HER2-positive MBC. In SystHERs, patients with de novo disease had different baseline demographics and disease characteristics, had superior clinical outcomes, and more commonly received first-line chemotherapy and/or trastuzumab versus those with recurrent disease. Data from this and other studies suggest that de novo and recurrent MBC have distinct outcomes, which may have implications for disease management strategies and future clinical study design.

Baseline Characteristics, Treatment Patterns, and Outcomes in Patients with HER2-Positive Metastatic Breast Cancer by Hormone Receptor Status from SystHERs.

PURPOSE: We report treatments and outcomes in a contemporary patient population with HER2-positive metastatic breast cancer (MBC) by hormone receptor (HR) status from the Systemic Therapies for HER2-positive Metastatic Breast Cancer Study (SystHERs). EXPERIMENTAL DESIGN: SystHERs (NCT01615068) was an observational, prospective registry study of U.S.-based patients with newly diagnosed HER2-positive MBC. Endpoints included treatment patterns and clinical outcomes. RESULTS: Of 977 eligible patients (enrolled from 2012 to 2016), 70.1% (n = 685) had HR-positive and 29.9% (n = 292) had HR-negative disease. Overall, 59.1% (405/685) of patients with HR-positive disease received any first-line endocrine therapy (with or without HER2-targeted therapy or chemotherapy); 34.9% (239/685) received HER2-targeted therapy + chemotherapy + sequential endocrine therapy. Patients with HR-positive versus HR-negative disease had longer median overall survival (OS; 53.0 vs 43.4 months; hazard ratio, 0.70; 95% confidence interval, 0.56-0.87). Compared with patients with high HR-positive staining (10%-100%, n = 550), those with low HR-positive staining (1%-9%, n = 60) received endocrine therapy less commonly (64.2% vs 33.3%) and had shorter median OS (53.8 vs 40.1 months). Similar median OS (43.4 vs 40.1 months) was observed in patients with HR-negative versus low HR-positive tumors (1%-9%). CONCLUSIONS: Despite evidence that first-line HER2-targeted therapy, chemotherapy, and sequential endocrine therapy improves survival in patients with HR-positive, HER2-positive disease, only 34.9% of patients in this real-world setting received such treatment. Patients with low tumor HR positivity (1%-9%) had lower endocrine therapy use and worse survival than those with high tumor HR positivity (10%-100%).

Central Nervous System Metastasis in Patients with HER2-Positive Metastatic Breast Cancer: Patient Characteristics, Treatment, and Survival from SystHERs.

PURPOSE: Patients with HER2-positive metastatic breast cancer (MBC) with central nervous system (CNS) metastasis have a poor prognosis. We report treatments and outcomes in patients with HER2-positive MBC and CNS metastasis from the Systemic Therapies for HER2-positive Metastatic Breast Cancer Study (SystHERs). EXPERIMENTAL DESIGN: SystHERs (NCT01615068) was a prospective, U.S.-based, observational registry of patients with newly diagnosed HER2-positive MBC. Study endpoints included treatment patterns, clinical outcomes, and patient-reported outcomes (PRO). RESULTS: Among 977 eligible patients enrolled (2012-2016), CNS metastasis was observed in 87 (8.9%) at initial MBC diagnosis and 212 (21.7%) after diagnosis, and was not observed in 678 (69.4%) patients. White and younger patients, and those with recurrent MBC and hormone receptor-negative disease, had higher risk of CNS metastasis. Patients with CNS metastasis at diagnosis received first-line lapatinib more commonly (23.0% vs. 2.5%), and trastuzumab less commonly (70.1% vs. 92.8%), than patients without CNS metastasis at diagnosis. Risk of death was higher with CNS metastasis observed at or after diagnosis [median overall survival (OS) 30.2 and 38.3 months from MBC diagnosis, respectively] versus no CNS metastasis [median OS not estimable: HR 2.86; 95% confidence interval (CI), 2.05-4.00 and HR 1.94; 95% CI, 1.52-2.49]. Patients with versus without CNS metastasis at diagnosis had lower quality of life at enrollment. CONCLUSIONS: Despite advances in HER2-targeted treatments, patients with CNS metastasis continue to have a poor prognosis and impaired quality of life. Observation of CNS metastasis appears to influence HER2-targeted treatment choice.

ALK Testing Trends and Patterns Among Community Practices in the United States.

PURPOSE: Targeted therapy of ALK in patients with metastatic nonsquamous non-small-cell lung cancer (NSCLC) and ALK rearrangements improves outcomes compared with chemotherapy. This study assessed real-world ALK testing patterns among community practices in the United States in patients with advanced (stage IIIB or IV) NSCLC. METHODS: Patients age ≥ 18 years with two or more visits within the Flatiron Health electronic health record-derived database after January 2011 and diagnosed with stage IIIB or IV NSCLC through May 2017 were included in this analysis. Logistic regression was used to examine the association between demographic and clinical characteristics and testing for ALK rearrangements. RESULTS: Of 31,483 patients analyzed from the database, 16,726 patients (53.1%) were tested for ALK rearrangements. ALK testing rates were 66.9% and 18.5% in patients with nonsquamous and squamous histology, respectively. Average ALK testing rates increased over time from 32.4% in 2011 to 62.1% in 2016. Fluorescent in situ hybridization was the most common ALK testing method. Agreement between fluorescent in situ hybridization and other assays ranged from 94.1% to 97.9%. Median (interquartile range) time from laboratory receipt of sample to first ALK test result was 7 (7) days; median time from advanced diagnosis to first ALK test result was 25 (29) days. Patients who were older, male, had a history of smoking, lived in non-Western US regions, and who had recurrent disease or squamous histology were less likely to be tested for ALK. Patients with Medicaid and Medicare insurance were less likely to be tested than patients with commercial insurance. Overall, 21.5% of patients initiated therapy (20.4% chemotherapy) before receiving test results. CONCLUSION: ALK testing rates have increased over time. However, certain subgroups of patients are less likely to be tested, suggesting that additional education on molecular testing is warranted.

Occurrence and outcome of de novo metastatic breast cancer by subtype in a large, diverse population.

PURPOSE: To examine the occurrence and outcomes of de novo metastatic (Stage IV) breast cancer, particularly with respect to tumor HER2 expression. METHODS: We studied all 6,268 de novo metastatic breast cancer cases diagnosed from 1 January 2005 to 31 December 2011 and reported to the California Cancer Registry. Molecular subtypes were classified according to HER2 and hormone receptor (HR, including estrogen and/or progesterone receptor) expression. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) of Stage IV versus Stage I-III breast cancer; Cox proportional hazards regression was used to assess relative hazard (RH) of mortality. RESULTS: Five percent of invasive breast cancer was metastatic at diagnosis. Compared to patients with earlier stage disease, patients with de novo metastatic disease were significantly more likely to have HER2+ tumors (HR+/HER2+: OR 1.29, 95 % CI 1.17-1.42; HR-/HER2+: OR 1.40, 95 %CI 1.25-1.57, vs. HR+/HER2-). Median survival improved over time, but varied substantially across race/ethnicity (Asians: 34 months; African Americans: 6 months), neighborhood socioeconomic status (SES) (highest: 34 months, lowest: 20 months), and molecular subtype (HR+/HER2+: 45 months; triple negative: 12 months). In a multivariable model, triple negative (RH 2.85, 95 % CI 2.50-3.24) and HR-/HER2+ (RH 1.60, 95 % CI 1.37-1.87) had worse, while HR+/HER2+ had similar, risk of all-cause death compared to HR+/HER2- breast cancer. CONCLUSIONS: De novo metastatic breast cancer was more likely to be HER2+. Among metastatic tumors, those that were HER2+ had better survival than other subtypes.

Incidence and relevance of proteinuria in bevacizumab-treated patients: pooled analysis from randomized controlled trials.

BACKGROUND: This analysis evaluated the incidence of and risk factors for bevacizumab-related proteinuria and assessed for any associated clinical sequelae, including renal function changes. METHODS: Patient-level adverse event and laboratory data from a pooled safety database were used to characterize alterations in urine protein excretion following interventional therapy ± bevacizumab in 17 randomized trials across multiple tumor types. Severity of renal function change was assessed using changes in serum creatinine concentration from baseline values. Potential predictors of proteinuria and the association between proteinuria and other adverse events were also investigated. RESULTS: Among 14,548 patients, the incidence of any-grade proteinuria was 8.2% (733/8,917) and 4.6% (257/5,631) in the bevacizumab and control groups, respectively; rates of grade ≥3 proteinuria were 1.4 and 0.2%. Post-baseline proteinuria grade and bevacizumab were associated with increased rates of renal dysfunction. Patients developing proteinuria had an increased rate of any-grade infection but not thromboembolic events. History of diabetes was the only examined risk factor that appeared to have a significant association with proteinuria development. CONCLUSIONS: This analysis confirmed a significant increase in the development of proteinuria during bevacizumab treatment. We also observed an increased rate of renal dysfunction associated with bevacizumab treatment and among subjects with proteinuria, although the dysfunction was generally mild. The development of proteinuria was also associated with a modest increase in risk of infection.

Incidence of catheter-related complications in patients with central venous or hemodialysis catheters: a health care claims database analysis.

BACKGROUND: Central venous catheter (CVC) and hemodialysis (HD) catheter usage are associated with complications that occur during catheter insertion, dwell period, and removal. This study aims to identify and describe the incidence rates of catheter-related complications in a large patient population in a United States-based health care claims database after CVC or HD catheter placement. METHODS: Patients in the i3 InVision DataMart® health care claims database with at least 1 CVC or HD catheter insertion claim were categorized into CVC or HD cohorts using diagnostic and procedural codes from the US Renal Data System, American College of Surgeons, and American Medical Association's Physician Performance Measures. Catheter-related complications were identified using published diagnostic and procedural codes. Incidence rates (IRs)/1000 catheter-days were calculated for complications including catheter-related bloodstream infections (CRBSIs), thrombosis, embolism, intracranial hemorrhage (ICH), major bleeding (MB), and mechanical catheter-related complications (MCRCs). RESULTS: Thirty percent of the CVC cohort and 54% of the HD cohort had catheter placements lasting <90 days. Catheter-related complications occurred most often during the first 90 days of catheter placement. IRs were highest for CRBSIs in both cohorts (4.0 [95% CI, 3.7-4.3] and 5.1 [95% CI, 4.7-5.6], respectively). Other IRs in CVC and HD cohorts, respectively, were thrombosis, 1.3 and 0.8; MCRCs, 0.6 and 0.7; embolism, 0.4 and 0.5; MB, 0.1 and 0.3; and ICH, 0.1 in both cohorts. Patients with cancer at baseline had significantly higher IRs for CRBSIs and thrombosis than non-cancer patients. CVC or HD catheter-related complications were most frequently seen in patients 16 years or younger. CONCLUSIONS: The risk of catheter-related complications is highest during the first 90 days of catheter placement in patients with CVCs and HD catheters and in younger patients (≤16 years of age) with HD catheters. Data provided in this study can be applied toward improving patient care.

Prevalence of acid-reducing agents (ARA) in cancer populations and ARA drug-drug interaction potential for molecular targeted agents in clinical development.

Acid-reducing agents (ARAs) are the most commonly prescribed medications in North America and Western Europe. There are currently no data describing the prevalence of their use among cancer patients. However, this is a paramount question due to the potential for significant drug-drug interactions (DDIs) between ARAs, most commonly proton pump inhibitors (PPIs), and orally administered cancer therapeutics that display pH-dependent solubility, which may lead to decreased drug absorption and decreased therapeutic benefit. Of recently approved orally administered cancer therapeutics, >50% are characterized as having pH-dependent solubility, but there are currently no data describing the potential for this ARA-DDI liability among targeted agents currently in clinical development. The objectives of this study were to (1) determine the prevalence of ARA use among different cancer populations and (2) investigate the prevalence of orally administered cancer therapeutics currently in development that may be liable for an ARA-DDI. To address the question of ARA use among cancer patients, a retrospective cross-sectional analysis was performed using two large healthcare databases: Thomson Reuters MarketScan (N = 1,776,443) and the U.S. Department of Veterans Affairs (VA, N = 1,171,833). Among all cancer patients, the total prevalence proportion of ARA use (no. of cancer patients receiving an ARA/total no. of cancer patients) was 20% and 33% for the MarketScan and VA databases, respectively. PPIs were the most commonly prescribed agent, comprising 79% and 65% of all cancer patients receiving a prescription for an ARA (no. of cancer patients receiving a PPI /no. of cancer patients receiving an ARA) for the MarketScan and VA databases, respectively. To estimate the ARA-DDI liability of orally administered molecular targeted cancer therapeutics currently in development, two publicly available databases, (1) Kinase SARfari and (2) canSAR, were examined. For those orally administered clinical candidates that had available structures, the pKa's and corresponding relative solubilities were calculated for a normal fasting pH of 1.2 and an "ARA-hypochlorhydric" pH of 4. Taking calculated pKa's and relative solubilities into consideration, clinical candidates were classified based on their risk for an ARA-DDI. More than one-quarter (28%) of the molecules investigated are at high risk for an ARA-DDI, and of those high risk molecules, nearly three-quarters (73%) are being clinically evaluated for at least one of five cancer types with the highest prevalence of ARA use (gastrointestinal, pancreatic, lung, glioblastoma multiforme, gastrointestinal stromal tumor (GIST)). These data strongly suggest that with the clinical development of ARA-DDI-susceptible cancer therapeutics will come continued challenges for drug-development scientists, oncologists, and regulatory agencies in ensuring that patients achieve safe and efficacious exposures of their cancer therapeutics and thus optimal patient outcomes.

Myocardial infarction and cerebrovascular accident in patients with retinal vein occlusion.

OBJECTIVE: To compare the incidence rates of myocardial infarction (MI) and cerebrovascular accident (CVA) in hospitalized patients with and without branch or central retinal vein occlusion (RVO). METHODS: In this retrospective cohort study, a US population-based health care claims database was used to identify patients with RVO and control patients, matched for age and sex. Events of MI, CVA, and covariates were identified for patients with and without RVO. Incidences of MI or CVA events prompting hospitalization and adjusted rate ratios (RRs) were calculated; RRs were adjusted for covariates consistent with risk factors for outcomes. RESULTS: Of 4500 patients with RVO and 13,500 controls, the event rates for MI were 0.87 per 100 person-years and 0.67 per 100 person-years, respectively. The adjusted RR for MI was 1.03 (95% confidence interval [CI], 0.75-1.42; P = .85 for RVO vs controls). Event rates for CVA were 1.16 and 0.52 per 100 person-years for RVO and controls, respectively. The adjusted RR for CVA was 1.72 (95% CI, 1.27-2.34; P = .001) for RVO vs controls. CONCLUSIONS: This study provides quantitative data on the incidence of cardiovascular and cerebrovascular outcomes in patients with RVO in a large US population-based health care claims database. Event rates for MI were similar in patients with RVO and controls; however, the event rate for CVA in patients with RVO was almost 2-fold that observed in controls.

Racial differences in prostate cancer risk remain among US servicemen with equal access to care.

BACKGROUND: Prostate cancer is the most common cancer among US men, however, the etiology remains unclear. Yet, one consistency is that black non-Hispanic men are at increased risk for prostate cancer compared to white, non-Hispanic men. The goal of this study was to assess relations between demographic and other potential prostate cancer risk factors in the context of the US military healthcare system, which provides equal access to all US servicemen. METHODS: Military healthcare and demographic data were used to describe risk factors for prostate cancer in the US military from September 1993 to September 2003. Cox's proportional hazards regression was employed to model the time to prostate cancer hospitalization. RESULTS: Four hundred eight first prostate cancer hospitalizations were identified among 2,761,559 servicemen. The adjusted rate per 100,000 persons rose from 1.41 to 3.62 for white non-Hispanic men and 1.43 to 6.08 for black non-Hispanic men by the end of the study. The increasing incidence over time for combined race/ethnic groups was similar to trends reported in the Surveillance, Epidemiology, and End Results Program for the US civilian population. No association was observed between occupation and prostate cancer hospitalization. However, black non-Hispanic men were at increased risk compared with white non-Hispanic men (hazard ratio = 2.72, 95% confidence interval: 2.12, 3.49). CONCLUSIONS: No association was observed between occupation and prostate cancer hospitalization. In this relatively young cohort, black non-Hispanic race/ethnicity was found to be predictive of prostate cancer, and this association existed regardless of access to care and socioeconomic status.

Challenges of self-reported medical conditions and electronic medical records among members of a large military cohort.

BACKGROUND: Self-reported medical history data are frequently used in epidemiological studies. Self-reported diagnoses may differ from medical record diagnoses due to poor patient-clinician communication, self-diagnosis in the absence of a satisfactory explanation for symptoms, or the "health literacy" of the patient. METHODS: The US Department of Defense military health system offers a unique opportunity to evaluate electronic medical records with near complete ascertainment while on active duty. This study compared 38 self-reported medical conditions to electronic medical record data in a large population-based US military cohort. The objective of this study was to better understand challenges and strengths in self-reporting of medical conditions. RESULTS: Using positive and negative agreement statistics for less-prevalent conditions, near-perfect negative agreement and moderate positive agreement were found for the 38 diagnoses. CONCLUSION: This report highlights the challenges of using self-reported medical data and electronic medical records data, but illustrates that agreement between the two data sources increases with increased surveillance period of medical records. Self-reported medical data may be sufficient for ruling out history of a particular condition whereas prevalence studies may be best served by using an objective measure of medical conditions found in electronic healthcare records. Defining medical conditions from multiple sources in large, long-term prospective cohorts will reinforce the value of the study, particularly during the initial years when prevalence for many conditions may still be low.