Association between SARS-CoV-2 infection and select symptoms and conditions 31 to 150 days after testing among children and adults.

BACKGROUND: An increasing number of studies have described new and persistent symptoms and conditions as potential post-acute sequelae of SARS-CoV-2 infection (PASC). However, it remains unclear whether certain symptoms or conditions occur more frequently among persons with SARS-CoV-2 infection compared with those never infected with SARS-CoV-2. We compared the occurrence of specific COVID-associated symptoms and conditions as potential PASC 31- to 150-day following a SARS-CoV-2 test among adults and children with positive and negative test results. METHODS: We conducted a retrospective cohort study using electronic health record (EHR) data from 43 PCORnet sites participating in a national COVID-19 surveillance program. This study included 3,091,580 adults (316,249 SARS-CoV-2 positive; 2,775,331 negative) and 675,643 children (62,131 positive; 613,512 negative) who had a SARS-CoV-2 laboratory test during March 1, 2020-May 31, 2021 documented in their EHR. We used logistic regression to calculate the odds of having a symptom and Cox models to calculate the risk of having a newly diagnosed condition associated with a SARS-CoV-2 positive test. RESULTS: After adjustment for baseline covariates, hospitalized adults and children with a positive test had increased odds of being diagnosed with ≥ 1 symptom (adults: adjusted odds ratio[aOR], 1.17[95% CI, 1.11-1.23]; children: aOR, 1.18[95% CI, 1.08-1.28]) or shortness of breath (adults: aOR, 1.50[95% CI, 1.38-1.63]; children: aOR, 1.40[95% CI, 1.15-1.70]) 31-150 days following a SARS-CoV-2 test compared with hospitalized individuals with a negative test. Hospitalized adults with a positive test also had increased odds of being diagnosed with ≥ 3 symptoms or fatigue compared with those testing negative. The risks of being newly diagnosed with type 1 or type 2 diabetes (adjusted hazard ratio[aHR], 1.25[95% CI, 1.17-1.33]), hematologic disorders (aHR, 1.19[95% CI, 1.11-1.28]), or respiratory disease (aHR, 1.44[95% CI, 1.30-1.60]) were higher among hospitalized adults with a positive test compared with those with a negative test. Non-hospitalized adults with a positive test also had higher odds or increased risk of being diagnosed with certain symptoms or conditions. CONCLUSIONS: Patients with SARS-CoV-2 infection, especially those who were hospitalized, were at higher risk of being diagnosed with certain symptoms and conditions after acute infection.

Association between SARS-CoV-2 Infection and Select Symptoms and Conditions 31 to 150 Days After Testing among Children and Adults.

Background: An increasing number of studies have described new and persistent symptoms and conditions as potential post-acute sequelae of SARS-CoV-2 infection (PASC). However, it remains unclear whether certain symptoms or conditions occur more frequently among persons with SARS-CoV-2 infection compared with those never infected with SARS-CoV-2. We compared the occurrence of specific COVID-associated symptoms and conditions as potential PASC 31 to 150 days following a SARS-CoV-2 test among adults (≥20 years) and children (<20 years) with positive and negative test results documented in the electronic health records (EHRs) of institutions participating in PCORnet, the National Patient-Centered Clinical Research Network. Methods and Findings: This study included 3,091,580 adults (316,249 SARS-CoV-2 positive; 2,775,331 negative) and 675,643 children (62,131 positive; 613,512 negative) who had a SARS-CoV-2 laboratory test (nucleic acid amplification or rapid antigen) during March 1, 2020-May 31, 2021 documented in their EHR. We identified hospitalization status in the day prior through the 16 days following the SARS-CoV-2 test as a proxy for the severity of COVID-19. We used logistic regression to calculate the odds of receiving a diagnostic code for each symptom outcome and Cox proportional hazard models to calculate the risk of being newly diagnosed with each condition outcome, comparing those with a SARS-CoV-2 positive test to those with a negative test. After adjustment for baseline covariates, hospitalized adults and children with a positive test had increased odds of being diagnosed with ≥1 symptom (adults: adjusted odds ratio[aOR], 1.17[95% CI, 1.11-1.23]; children: aOR, 1.18[95% CI, 1.08-1.28]) and shortness of breath (adults: aOR, 1.50[95% CI, 1.38-1.63]; children: aOR, 1.40[95% CI, 1.15-1.70]) 31-150 days following a SARS-CoV-2 test compared with hospitalized individuals with a negative test. Hospitalized adults with a positive test also had increased odds of being diagnosed with ≥3 symptoms (aOR, 1.16[95% CI, 1.08 - 1.26]) and fatigue (aOR, 1.12[95% CI, 1.05 - 1.18]) compared with those testing negative. The risks of being newly diagnosed with type 1 or type 2 diabetes (aHR, 1.25[95% CI, 1.17-1.33]), hematologic disorders (aHR, 1.19[95% CI, 1.11-1.28]), and respiratory disease (aHR, 1.44[95% CI, 1.30-1.60]) were higher among hospitalized adults with a positive test compared with those with a negative test. Non-hospitalized adults with a positive SARS-CoV-2 test had higher odds of being diagnosed with fatigue (aOR, 1.11[95% CI, 1.05-1.16]) and shortness of breath (aOR, 1.22[95% CI, 1.15-1.29]), and had an increased risk (aHR, 1.12[95% CI, 1.02-1.23]) of being newly diagnosed with hematologic disorders (i.e., venous thromboembolism and pulmonary embolism) 31-150 days following SARS-CoV-2 test compared with those testing negative. The risk of being newly diagnosed with certain conditions, such as mental health conditions and neurological disorders, was lower among patients with a positive viral test relative to those with a negative viral test. Conclusions: Patients with SARS-CoV-2 infection were at higher risk of being diagnosed with certain symptoms and conditions, particularly fatigue, respiratory symptoms, and hematological abnormalities, after acute infection. The risk was highest among adults hospitalized after SARS-CoV-2 infection.

Cost Effectiveness of Mirabegron Compared with Antimuscarinic Agents for the Treatment of Adults with Overactive Bladder in Colombia.

OBJECTIVES: The aim of this study was to evaluate the cost effectiveness of mirabegron relative to two antimuscarinics, oxybutynin extended release (ER) and tolterodine ER, in patients with overactive bladder (OAB) from the perspective of a third-party payer in Colombia. METHODS: A Markov model simulated the therapeutic management, disease course, and complications in hypothetical cohorts of OAB patients over a 5-year period. The model predicted costs and three outcomes: quality-adjusted life-years (QALYs), micturition state improvement (MSI), and incontinence state improvement (ISI). In each 1-month cycle, patients could transition between different health states reflecting symptom severity. Transition probabilities were estimated from a published mirabegron trial and mixed treatment comparison. Other inputs such as treatment discontinuation based on treatment-specific rates of persistence, resource use and costs, anticholinergic burden, comorbidity treatment, and drug acquisition were obtained from Società Italiana Scienze Mediche, Instituto de Seguros Sociales Tariff Manual, published literature, and expert opinion. Deterministic and probabilistic sensitivity analyses were conducted. Costs are presented in 2017 Colombia Pesos (COP). RESULTS: Mirabegron was cost effective for all outcome measures at a willingness-to-pay threshold of 124,919,725 COP, which is three times the per capita gross domestic product (GDP). Using QALYs as the measure of effect, mirabegron had an incremental cost-effectiveness ratio (ICER) of 85,802,036 COP/QALY (26,365 USD/QALY) and 66,360,134 COP/QALY (20,384 USD/QALY) versus oxybutynin and tolterodine, respectively. Probabilistic sensitivity analyses showed that mirabegron was cost effective in 99.5% and 100% of simulations compared with oxybutynin and tolterodine, respectively. Using MSI and ISI as the measure of effects yielded ICERs below one GDP. CONCLUSIONS: Mirabegron is a cost effective alternative to oxybutynin and tolterodine from the perspective of a third-party payer in Colombia.

Prevalence of depression and anxiety in women newly diagnosed with vulvovaginal atrophy and dyspareunia.

OBJECTIVE: To quantify the association between vulvovaginal atrophy and depression, major depressive disorder, and anxiety. METHODS: Women with vulvovaginal atrophy from the Truven Health MarketScan Commercial and Medicare Supplemental Databases (01/2010-09/2016) with ≥365 days of continuous insurance coverage before and after the first vulvovaginal atrophy/dyspareunia diagnosis (index date) were selected. Women with vulvovaginal atrophy were matched 1:3 to women without (controls) according to age, calendar year, health plan, and region. The study period spanned from 12 months before to 12 months after index date. The ratios of diagnosed depression, major depressive disorder, and anxiety among women with vulvovaginal atrophy and the controls were calculated. Logistic regressions adjusting for proxies of menopause were used to compare prevalence. RESULTS: In all, 125,889 women with vulvovaginal atrophy and 376,057 controls were included (mean age 60.7 [45-101]). The prevalence of depression, major depressive disorder, and anxiety was higher among women with vulvovaginal atrophy compared with controls (23.9% vs 18.9%, 6.3% vs 4.7%, 16.6% vs 11.3%), with prevalence ratios of 1.26, 1.33, and 1.47, respectively (all P < 0.0001). Highest prevalences and differences were observed in younger women. Findings were consistent when analyzing newly diagnosed conditions. When adjusting for proxies of menopause (insomnia, vasomotor symptoms, dysuria, and estrogen therapy), vulvovaginal atrophy remained significant (prevalence odds ratios; depression 1.23, major depressive disorder 1.22, anxiety 1.39; all P < 0.0001). CONCLUSIONS: Vulvovaginal atrophy is associated with a significantly higher prevalence/incidence of depression, major depressive disorder, and anxiety. The higher prevalence/incidence and greater differences in younger women highlight the need for a multidisciplinary approach and early diagnosis/management of vulvovaginal atrophy.

Does the route of administration for estrogen hormone therapy impact the risk of venous thromboembolism? Estradiol transdermal system versus oral estrogen-only hormone therapy.

OBJECTIVE: The aim of this study was to quantify the magnitude of risk reduction for venous thromboembolism events associated with an estradiol transdermal system relative to oral estrogen-only hormone therapy agents. METHODS: A claims analysis was conducted using the Thomson Reuters MarketScan database from January 2002 to October 2009. Participants 35 years or older who were newly using an estradiol transdermal system or an oral estrogen-only hormone therapy with two or more dispensings were analyzed. Venous thromboembolism was defined as one or more diagnosis codes for deep vein thrombosis or pulmonary embolism. Cohorts of estradiol transdermal system and oral estrogen-only hormone therapy were matched 1:1 based on both exact factor and propensity score matching, and an incidence rate ratio was used to compare the rates of venous thromboembolism between the matched cohorts. Remaining baseline imbalances from matching were included as covariates in multivariate adjustments. RESULTS: Among the matched estradiol transdermal system and oral estrogen-only hormone therapy users (27,018 women in each group), the mean age of the cohorts was 48.9 years; in each cohort, 6,044 (22.4%) and 1,788 (6.6%) participants had a hysterectomy and an oophorectomy at baseline, respectively. A total of 115 estradiol transdermal system users developed venous thromboembolism, compared with 164 women in the estrogen-only hormone therapy cohort (unadjusted incidence rate ratio, 0.72; 95% CI, 0.57-0.91; P = 0.006). After adjustment for confounding factors, the incidence of venous thromboembolism remained significantly lower for estradiol transdermal system users than for estrogen-only hormone therapy users. CONCLUSIONS: This large population-based study suggests that participants receiving an estradiol transdermal system have a significantly lower incidence of venous thromboembolism than do participants receiving oral estrogen-only hormone therapy.

Health Care Resource Utilization and Costs in Patients with Chronic Myeloid Leukemia with Better Adherence to Tyrosine Kinase Inhibitors and Increased Molecular Monitoring Frequency.

BACKGROUND: Frequent molecular monitoring (qPCR tests), as recommended by evidence-based monitoring guidelines, is associated with higher adherence to tyrosine kinase inhibitors (TKIs) in the management of chronic myeloid leukemia (CML); both factors have been associated with better clinical and economic outcomes. OBJECTIVES: To (a) estimate the effect of more frequent qPCR tests on health care resource utilization (HRU) and associated costs, including direct (effect of qPCR test frequency on HRU) and indirect (through TKI adherence) effects, and (b) develop an economic model applicable to multiple clinical practice scenarios. METHODS: Adult patients newly diagnosed with CML who started TKI firstline therapy were identified from U.S. administrative claims data (2010-2015). TKI adherence (medication possession ratio [MPR]), number of inpatient days, emergency room (ER) visits, outpatient service days, and mean costs per HRU event were measured during the first year of CML treatment. Direct and indirect effects of qPCR test frequency were estimated using multivariate regression models. Subsequently, an economic model was developed to assess the overall effect of varying qPCR test frequency on HRU and associated costs during the first year of CML treatment under different clinical practice scenarios; the scenario reported is the increase from 1 to 2 qPCR tests. RESULTS: Of the 1,431 patients included, 36% had no qPCR tests, the average qPCR test frequency was 1.6, and the average MPR was 0.86 during the first year of CML treatment. The direct effect of increasing qPCR test frequency by 1 was associated with 13.0% fewer inpatient days (adjusted incidence rate ratio [adjusted IRR] = 0.87; P = 0.010); 8.3% fewer ER visits (adjusted IRR = 0.92; P = 0.043); and 3.0% more outpatient service days (adjusted IRR = 1.03; P = 0.002). Each increase of 1 test was associated with an increase in TKI adherence by 2.2 percentage points (adjusted MPR difference = 0.022; P < 0.001). When considering the indirect effect of qPCR test frequency through TKI adherence, an increase of 1 qPCR test combined with an increase in TKI adherence by 2.2 percentage points was associated with a greater reduction of inpatient days from 13.0% to 15.2%, ER visits from 8.3% to 8.6%, and a smaller increase of outpatient service days from 3.0% to 2.6%. Based on the economic model, an increase from 1 to 2 qPCR tests, considering the increase in TKI adherence, was associated with a reduction of 0.87 (95% CI = -1.49, -0.18) inpatient days and 0.06 (95% CI = -0.12, 0.05) ER visits, an increase of 0.98 (95% CI = 0.25, 1.60) outpatient service days and a cost savings of $2,918 (95% CI = -5,213, -349) per patient per year. CONCLUSIONS: Closer alignment with the monitoring guidelines' recommended qPCR test frequency and better adherence to TKIs were associated with lower HRU and medical service costs. Managed care initiatives to increase qPCR test frequency and TKI adherence might benefit from an enhanced reduction because of the interaction between both factors. DISCLOSURES: This study was funded by Novartis Pharmaceuticals, which was involved in all stages of the study and in the decision to submit the report for publication. Latremouille-Viau, Guerin, Gagnon-Sanschagrin, and Dea are employees of Analysis Group, which received consulting fees from Novartis Pharmaceuticals for work on this study. Joseph is an employee of Novartis Pharmaceuticals and owns stock in Amgen and Pfizer. Cohen was an employee of Novartis Pharmaceuticals at the time of this study. Portions of this study were presented online (beginning May 20, 2016) as part of the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, on June 3-7, 2016, and as a poster at the American Society of Hematology (ASH) Annual Meeting in San Diego, California, on December 3-6, 2016. Study concept and design were contributed by Latremouille-Viau and Guerin, along with the other authors. Gagnon-Sanschagrin and Dea took the lead in data collection, assisted by the other authors, and data interpretation was performed by Cohen and Joseph, along with the other authors. The manuscript was written by Latremouille-Viau, along with the other authors, and revised by Joseph, along with the other authors.

Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-α inhibitors versus methotrexate.

BACKGROUND: Psoriasis is associated with increased risk for cardiovascular disease. OBJECTIVE: To compare major cardiovascular event risk in psoriasis patients receiving methotrexate or tumor necrosis factor-α inhibitor (TNFi) and to assess TNFi treatment duration impact on major cardiovascular event risk. METHODS: Adult psoriasis patients with ≥2 TNFi or methotrexate prescriptions in the Truven MarketScan Databases (Q1 2000-Q3 2011) were classified as TNFi or methotrexate users. The index date for each of these drugs was the TNFi initiation date or a randomly selected methotrexate dispensing date, respectively. Cardiovascular event risks and cumulative TNFi effect were analyzed by using multivariate Cox proportional-hazards models. RESULTS: By 12 months, TNFi users (N = 9148) had fewer cardiovascular events than methotrexate users (N = 8581) (Kaplan-Meier rates: 1.45% vs 4.09%: P < .01). TNFi users had overall lower cardiovascular event hazards than methotrexate users (hazard ratio = 0.55; P < .01). Over 24 months' median follow-up, every 6 months of cumulative exposure to TNFis were associated with an 11% cardiovascular event risk reduction (P = .02). LIMITATIONS: Lack of clinical assessment measures. CONCLUSIONS: Psoriasis patients receiving TNFis had a lower major cardiovascular event risk compared to those receiving methotrexate. Cumulative exposure to TNFis was associated with a reduced risk for major cardiovascular events.

Variation in Care for Patients with Irritable Bowel Syndrome in the United States.

OBJECTIVES: Irritable bowel syndrome (IBS) affects nearly one in seven Americans. Significant national variations in care may exist, due to a current lack of standardized diagnosis and treatment algorithms; this can translate into a substantial additional economic burden. The study examines healthcare resource utilization in patients with IBS and in the subset of IBS patients with constipation (IBS-C) and analyzes the variation of IBS care for these patients across the United States (US). METHODS: Healthcare resource use (HRU), including gastrointestinal (GI) procedures and tests, all-cause and intestinal-related medical visits, GI specialist visits, and constipation or diarrhea pharmacy prescriptions for IBS patients enrolled in a large US administrative claims database (2001-2012) were analyzed for the 24-month period surrounding first diagnosis. Multivariate regression models, adjusting for age, gender, year of first diagnosis, insurance type, and Charlson comorbidity index, compared HRU across states (each state vs. the average of all other states). RESULTS: Of 201,322 IBS patients included, 77.2% were female. Mean age was 49.4 years. One in three patients had ≥3 distinct GI medical procedures or diagnostic tests; 50.1% visited a GI specialist. Significant HRU differences were observed in individual states compared to the national average. IBS-C patients had more medical visits, procedures, and pharmacy prescriptions for constipation/diarrhea than IBS patients without constipation. CONCLUSIONS: This study is the first to identify considerable regional variations in IBS healthcare across the US and to note a markedly higher HRU by IBS-C patients than by IBS patients without constipation. Identifying the reasons for these variations may improve quality of care and reduce the economic burden of IBS.

Economic outcomes with prasugrel versus clopidogrel in acute coronary syndrome patients: observations from prasugrel users and matched clopidogrel users.

OBJECTIVE: To compare healthcare costs between clopidogrel and prasugrel over 30-day and 365-day periods after discharge from the hospital or emergency room (ER) in patients treated with prasugrel who were hospitalized or had an ER visit for an acute coronary syndrome (ACS) event. METHODS: This retrospective observational study was based on claims from January 2009-July 2012 in the Truven Health Analytics MarketScan database. Clopidogrel patients were propensity-score matched 1:1 to prasugrel-treated patients. Lin's frequentist cost history method for censored data and Bayesian zero-inflated gamma regression models were used to analyze healthcare costs. RESULTS: The clopidogrel/prasugrel matched-cohort included 10,963 well-matched pairs of patients. Lin's frequentist analysis showed that outpatient visit costs were significantly lower for clopidogrel than prasugrel after 30 days of follow-up. At 30 days, Bayesian data analysis showed strong evidence that clopidogrel was superior to prasugrel for all-cause and ACS-related hospitalization costs and showed very strong evidence that clopidogrel was superior to prasugrel for all-cause and ACS-related outpatient visit costs. At 365 days, Bayesian data analysis showed strong evidence that clopidogrel was superior to prasugrel for all-cause outpatient visit costs and very strong evidence that clopidogrel was superior to prasugrel for ACS-related outpatient visit costs. Point estimates of the all-cause and ACS-related ER visit costs at 30 days and 365 days were similar, but statistical results were inconclusive because of the large variability in this outcome variable. CONCLUSION: Based on retrospective observational data in a real-world setting, all-cause and ACS-related hospitalization and outpatient visit costs were lower for clopidogrel than prasugrel over 30 days after discharge from a hospitalization or ER visit associated with ACS in patients treated with prasugrel. At 365 days the difference in all-cause and ACS-related outpatient costs remained, but there was little evidence of a difference in either all-cause or ACS-related hospitalization costs.

Brain metastases in patients with ALK+ non-small cell lung cancer: clinical symptoms, treatment patterns and economic burden.

OBJECTIVE: Brain metastases (BM) are highly prevalent among anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) patients; yet little is known about their real-world treatment patterns and clinical and economic burdens. This study aimed to describe these patients' treatment patterns, symptoms, and costs. RESEARCH DESIGN AND METHODS: Retrospective study pooling data from three large administrative databases in the US (08/2011-06/2013). ALK+ NSCLC patients with BM and continuous enrollment for ≥ 60 days before and ≥ 30 days after the first observed BM diagnosis were identified by pharmacy records for crizotinib among patients with lung cancer and BM diagnostic codes. MAIN OUTCOME MEASURES: Treatment patterns, symptoms, healthcare resource utilization, and costs, before and after BM diagnosis. RESULTS: Of the 213 crizotinib patients with BM diagnoses meeting the selection criteria, 23.0% had BM prior to NSCLC diagnosis; 47.4% had BM prior to crizotinib initiation; 19.2% during crizotinib treatment; and 10.3% post-crizotinib treatment. For those diagnosed with BM after NSCLC diagnosis, the median time between the NSCLC and BM diagnoses was 88 days. Following the first observed BM diagnosis, 88.7% used chemotherapy, 63.4% had radiotherapy, and 31.9% had stereotactic radiosurgery. The prevalence of BM-related symptoms substantially increased post-BM-diagnosis: fatigue (from 15% to 39%), headaches (from 5% to 24%), and depression (from 5% to 15%). Monthly costs per patient averaged $5983 before the BM diagnosis and $22,645 after diagnosis. Patients' resource utilization increased significantly post-BM-diagnosis, with a 3-fold increase in OP visits and a 6-fold increase in IP stays. Post-BM-diagnosis costs were driven by pharmacy (42.0%), inpatient (29.6%), and outpatient costs (26.0%). LIMITATIONS: The study sample was limited to crizotinib-treated patients. CONCLUSIONS: Post-BM-diagnosis, patients experience high symptom burden. Post-BM-diagnosis, treatment is highly variable and costly: average monthly costs per patient almost quadrupled post-BM-diagnosis.

Gastrointestinal comorbidities associated with atrial fibrillation.

This observational study was conducted to describe the risk of gastrointestinal (GI) events among patients with atrial fibrillation (AF). We analyzed Thomson Reuters MarketScan® data from 2005 to 2009. Subjects aged ≥18 years with ≥ 1 AF diagnosis were selected. GI events were identified from claims with a primary or secondary diagnosis code for any GI condition. The risk of GI events was assessed using cumulative incidence (new GI events/patients with AF without GI condition at baseline) and incidence rates (IRs), calculated as the number of patients with new GI events divided by patient-years of observation. In addition, the CHADS2 score was evaluated at baseline to determine the patient's risk of stroke. A total of 557,123 AF patients were identified. The mean (median) AF patient age was 68.2 years (70); 45% were female. The cumulative incidences of any GI event and dyspepsia were 40% and 19%, respectively. The corresponding IRs were 38.8 and 14.7 events per 100 patient-years. IRs of any GI events for female and male patients were 43.6 and 35.5; for patients in the age groups <65, 65-74, 75-84, and ≥85 years, IRs were 32.3, 38.9, 44.6, and 52.7; for patients with a CHADS2 score of 0, 1-2, 3-4, and 5-6, IRs were 30.3, 41.6, 56.9, and 74.5, respectively. In this large claims database, 40% of AF patients experienced a GI event, predominantly dyspepsia. Physicians should take age and comorbidities into consideration when managing AF patients.

Association between regular molecular monitoring and tyrosine kinase inhibitor therapy adherence in chronic myelogenous leukemia in the chronic phase.

OBJECTIVE: Adherence with oral tyrosine kinase inhibitor (TKI) therapy over prolonged timeframes is required for successful outcomes among patients with chronic phase chronic myelogenous leukemia (CP-CML). Since quantitative polymerase chain reaction (qPCR) monitoring may identify early suboptimal responses, and thereby permit detection of non-adherence to therapy, we sought to assess the association between frequency of molecular monitoring and medication adherence. RESEARCH DESIGN AND METHODS: This is a retrospective cohort study design of diagnosed CP-CML obtained from two large US administrative claims databases. Patients were grouped into cohorts based on the number of qPCR tests they had. Adherence was assessed both by medication possession ratio (MPR) and proportion of days covered (PDC) and was compared between qPCR cohorts. A sensitivity analysis was performed by adjusting for the number of oncology outpatient visits not due to routine molecular monitoring. RESULTS: Over the 12 month study period, 1205 CML patients met the selection criteria; 41.0% had no qPCR tests, 31.9% had 1-2 tests, and 27.1% had 3-4 tests; 88.9% of patients were initiated on imatinib. Patients in the 3-4 qPCR tests cohort had an average MPR that was 10.22 (p < 0.001) and 9.54 (p < 0.001) percentage points higher compared to patients in the 0 tests cohort and the 1-2 tests cohort. When using PDC as a measure of adherence, similar results were obtained. The results of the sensitivity analysis were consistent with core analysis findings, excluding number of physician visits as a potential driver of adherence. LIMITATIONS: These findings demonstrate an association, not causation, between molecular monitoring frequency and adherence. CONCLUSIONS: Frequent molecular monitoring (3-4 times per year as recommended in current guidelines) is associated with greater TKI treatment adherence for patients diagnosed with CML. Since TKI adherence >80% has been associated with better clinical outcomes, this study underscores the importance of molecular monitoring.

Economic benefits of adequate molecular monitoring in patients with chronic myelogenous leukemia.

OBJECTIVE: Molecular monitoring of chronic myeloid leukemia (CML) has been associated with improved clinical outcomes during tyrosine kinase inhibitor therapy (TKI), yet recent studies have demonstrated its use is far below published guidelines. This study sought to determine frequencies of molecular monitoring and its impact on resource utilization and medical costs. METHODS: A retrospective US claims administrative database (IMS LifeLink Health Plan Claims and Truven Health Analytics MarketScan databases, 11/2007-06/2012) was used to analyze the economic impact of qPCR testing in CML patients on first-line TKIs during the initial 12-months of treatment. RESULTS: One thousand two hundred and five adult CML patients met the sample selection criteria. Among these, 41.0% had no qPCR tests, 31.9% had 1-2 tests, and 27.1% had 3-4 tests; 88.9% were initiated on imatinib; 47.7% were female. Patients in the 3-4 tests cohort incurred 44% (p < 0.001) fewer in-patient (IP) admissions than patients in the 0-tests cohort. Adjusted all-cause IP cost was $5663 (p = 0.005) lower for the 3-4 tests cohort than the 0-tests cohort. Adjusted progression-related IP cost was $4132 (p = 0.013) lower for the 3-4 tests cohort than the 0-tests cohort. Adjusted medical service cost was $5997 (p = 0.049) lower for the 3-4 tests cohort than the 0-tests cohort. LIMITATIONS: Claims databases did not include information on the primary cause of hospitalizations. CONCLUSIONS: Among CML patients in two large claims databases, nearly three-quarters did not receive adequate molecular monitoring per published guidelines. Those who were more frequently monitored incurred lower medical service costs, with the majority of the difference in costs being related to disease progression. These findings underscore the clinical and economic values of molecular monitoring in CML.

All-cause and disease-related health care costs associated with recurrent venous thromboembolism.

It was the objective of this study to quantify the risk of complications and the incremental health care costs associated with recurrent VTE events. Health care insurance claims from the Ingenix IMPACT database from 01/2004-09/2008 were analysed. Subjects aged ≥18 years on the date of first recurrent VTE diagnosis with ≥12 months of baseline observation prior to the index recurrent VTE were matched 1:1 with no-recurrent VTE patients based on propensity scores. The risk of developing post-thrombotic syndrome (PTS) and other disease-related diagnoses (thrombocytopenia, superficial venous thrombosis, venous ulcer, pulmonary hypertension, stasis dermatitis, and venous insufficiency) was compared between the recurrent and no-recurrent VTE groups for up to one year. All-cause and disease-related costs per patient per year (PPPY) were calculated. The recurrent VTE and no-recurrent VTE cohorts (8,001 subjects in each group) were matched with respect to age, gender, and comorbidities. The risk ratios (RRs) indicated that the risk of developing post-event complications was significantly higher for the recurrent VTE group compared to the no-recurrent VTE group (RR [95% CI]: PTS: 2.7 [2.4 - 2.9], p-value <0.01). Patients with recurrent VTE had significantly higher average PPPY all-cause costs compared to no-recurrent VTE patients ($86,744 versus $37,525, cost difference: $49,219 [€33,617]; 95% CI= 46,253-51,989). Corresponding disease-related health care costs PPPY were also significantly higher for the recurrent VTE group ($11,120 vs $1,262, cost difference: $9,858 [€6,733]; 95% CI= $9,081-$10,476). In conclusion, in this large matched-cohort study, recurrent VTE patients had significantly higher risk of complications and health care costs compared to no-recurrent VTE patients.

All-cause and potentially disease-related health care costs associated with venous thromboembolism in commercial, Medicare, and Medicaid beneficiaries.

BACKGROUND: Patients with venous thromboembolism (VTE) are at increased risk of developing recurrent VTE and post-thrombotic syndrome (PTS), a complication of deep vein thrombosis (DVT) characterized by venous reflux and residual venous obstruction that may manifest as chronic pain and swelling. Therefore, formulary/policy decision makers should understand the clinical and economic consequences associated with VTE. OBJECTIVES: To describe the real-world clinical complications, such as recurrent VTE and PTS, associated with VTE and quantify the incremental direct all-cause and potentially disease-related health care costs associated with VTE. METHODS: Health insurance claims between January 2004 and December 2008 from the Ingenix Impact database were used. Adult patients with an initial VTE diagnosis (index DVT, pulmonary embolism [PE], or both) with at least 12 months of enrollment prior to the index VTE were matched 1:1 with comparison patients without VTE. Matching criteria included demographic factors, baseline health care costs, and diagnoses of VTE risk factors such as multiple traumas, malignant cancer, or major surgery. Each patient's observation period began on the date of the index VTE, or corresponding study index date for comparison cases, and ended on the earliest of 1 year after the study index date, the health plan disenrollment date, or December 31, 2008. The proportions of patients with (a) recurrent hospital-documented VTE, defined as an inpatient episode with a diagnosis of VTE in any claim field; (b) PTS; and (c) other potentially disease-related diagnoses (thrombocytopenia, superficial venous thrombosis, venous ulcer, pulmonary hypertension, stasis dermatitis, and venous insufficiency) were calculated. Health care costs were defined as standardized net provider payments after subtraction of member cost-sharing amounts. All-cause incremental health care costs and disease-related costs, defined as provider payments for hospitalization or outpatient claims with a primary or secondary diagnosis of VTE, PTS, or any of the potentially disease-related diagnoses, were computed. Costs were calculated per patient per year (PPPY) by weighting each patient's total cost for up to 1 year post-index by the length of follow-up. RESULTS: The matched VTE and no-VTE cohorts included 16,969 subjects in each group. The index VTE event was DVT, PE, or both in 12,711, 2,473, and 1,785 patients, respectively. In the VTE cohort, the risks of recurrent VTE and PTS during the follow-up period (mean [SD] observation of 271.7 [121.6] days) were 3.6% and 7.1%, respectively. Patients with VTE had significantly higher average PPPY all-cause costs compared with the no-VTE patients (mean [SD] $33,531 [$70,393] vs. $17,590 [$42,011]; cost difference = $15,941, 95% CI = $14,819-$17,012). Corresponding potentially disease-related health care costs PPPY were also significantly higher for the VTE group (mean [SD] $3,141 [$17,055] vs. $228 [$3,221]; cost difference = $2,913, 95% CI = $2,693-$3,157) and represented 18.3% (i.e., $2,913 of $15,941) of the all-cause cost difference between the 2 groups. CONCLUSIONS: In this large matched-cohort study, VTE was associated with a 3.6% risk of hospital-documented recurrence and a 7.1% risk of PTS up to 1 year after index VTE. Potentially disease-related costs represented approximately one-fifth of the incremental all-cause costs associated with VTE.

Does the route of administration for estrogen hormone therapy impact the risk of venous thromboembolism? Estradiol transdermal system versus oral estrogen-only hormone therapy.

OBJECTIVE: The aim of this study was to quantify the magnitude of risk reduction for venous thromboembolism events associated with an estradiol transdermal system relative to oral estrogen-only hormone therapy agents. METHODS: A claims analysis was conducted using the Thomson Reuters MarketScan database from January 2002 to October 2009. Participants 35 years or older who were newly using an estradiol transdermal system or an oral estrogen-only hormone therapy with two or more dispensings were analyzed. Venous thromboembolism was defined as one or more diagnosis codes for deep vein thrombosis or pulmonary embolism. Cohorts of estradiol transdermal system and oral estrogen-only hormone therapy were matched 1:1 based on both exact factor and propensity score matching, and an incidence rate ratio was used to compare the rates of venous thromboembolism between the matched cohorts. Remaining baseline imbalances from matching were included as covariates in multivariate adjustments. RESULTS: Among the matched estradiol transdermal system and oral estrogen-only hormone therapy users (27,018 women in each group), the mean age of the cohorts was 48.9 years; in each cohort, 6,044 (22.4%) and 1,788 (6.6%) participants had a hysterectomy and an oophorectomy at baseline, respectively. A total of 115 estradiol transdermal system users developed venous thromboembolism, compared with 164 women in the estrogen-only hormone therapy cohort (unadjusted incidence rate ratio, 0.72; 95% CI, 0.57-0.91; P = 0.006). After adjustment for confounding factors, the incidence of venous thromboembolism remained significantly lower for estradiol transdermal system users than for estrogen-only hormone therapy users. CONCLUSIONS: This large population-based study suggests that participants receiving an estradiol transdermal system have a significantly lower incidence of venous thromboembolism than do participants receiving oral estrogen-only hormone therapy.

Risks and cost burden of venous thromboembolism and bleeding for patients undergoing total hip or knee replacement in a managed-care population.

BACKGROUND: Total hip and total knee replacement (THR/TKR) patients are at increased risk of developing venous thromboembolism (VTE). VTE prevention using anticoagulation therapy increases the risk of bleeding. Therefore, any assessment of the cost of VTE and its prevention should also take into consideration risks and costs of bleeding. OBJECTIVE: To assess the risks of developing VTE and bleeding in patients after THR or TKR given real-world use of thromboprophylaxis, and to quantify the incremental cost associated with each. METHODS: Analyses of insurance healthcare claims from the Ingenix IMPACT National Managed Care Database(TM) from January 2004 to December 2008 were conducted. Subjects were ≥18 years and had ≥1 procedure code for THR or TKR. Patients had to have ≥180 days of observation prior to surgery and were observed for ≤3 months after THR or TKR. VTE was defined as ≥1 diagnosis code for deep vein thrombosis or pulmonary embolism. Bleeding events were classified as major or non-major. Risks of VTE or bleeding events were calculated as number of patients with an event divided by number of patients with the procedure. Incremental all-cause healthcare costs associated with VTE or bleeding were calculated as the difference between cohorts of patients without VTE or bleeding matched 1:1 to patients with VTE or bleeding. RESULTS: Of 119,729 patients (43,670 THR and 76,059 TKR), 7974 had a VTE event and 4849 had a bleeding event (2216 major bleeding [a subset of 'any bleeding']). The risks of VTE, any bleeding, and major bleeding were 6.7, 4.0, and 1.9 events, respectively, per 100 patients. Up to 3 months after THR/TKR, mean incremental all-cause healthcare costs per patient per month associated with VTE, bleeding, and major bleeding were $2729, $2696, and $4304, respectively. Total monthly costs versus matched controls over 3 months were: VTE: $12,333 vs. $9604; any bleeding: $12,481 vs. $9785; major bleeding: $14,015 vs. $9710; p < 0.001 for all. LIMITATIONS: Key limitations included potential inaccuracies or omissions in procedures, diagnoses, or costs of claims data; lack of information on the amount of blood transfused or decreases in the hemoglobin level to evaluate the severity of a bleeding event; and potential biases due to the observational design of the study. CONCLUSION: From the managed-care population perspective, in THR/TKR patients the greater incidence of VTE compared to any bleeding and major bleeding translated into a higher cumulative cost burden.