Montelukast as a repurposable additive drug for standard-efficacy multiple sclerosis treatment: Emulating clinical trials with retrospective administrative health claims data.

BACKGROUND: Effective and safe treatment options for multiple sclerosis (MS) are still needed. Montelukast, a leukotriene receptor antagonist (LTRA) currently indicated for asthma or allergic rhinitis, may provide an additional therapeutic approach. OBJECTIVE: The study aimed to evaluate the effects of montelukast on the relapses of people with MS (pwMS). METHODS: In this retrospective case-control study, two independent longitudinal claims datasets were used to emulate randomized clinical trials (RCTs). We identified pwMS aged 18-65 years, on MS disease-modifying therapies concomitantly, in de-identified claims from Optum's Clinformatics® Data Mart (CDM) and IQVIA PharMetrics® Plus for Academics. Cases included 483 pwMS on montelukast and with medication adherence in CDM and 208 in PharMetrics Plus for Academics. We randomly sampled controls from 35,330 pwMS without montelukast prescriptions in CDM and 10,128 in PharMetrics Plus for Academics. Relapses were measured over a 2-year period through inpatient hospitalization and corticosteroid claims. A doubly robust causal inference model estimated the effects of montelukast, adjusting for confounders and censored patients. RESULTS: pwMS treated with montelukast demonstrated a statistically significant 23.6% reduction in relapses compared to non-users in 67.3% of emulated RCTs. CONCLUSION: Real-world evidence suggested that montelukast reduces MS relapses, warranting future clinical trials and further research on LTRAs' potential mechanism in MS.

Validating methods used to identify non-adherence adverse drug events in Canadian administrative health data.

AIMS: Medication non-adherence is a type of adverse drug event that can lead to untreated and exacerbated chronic illness, and that drives healthcare utilization. Research using medication claims data has attempted to identify instances of medication non-adherence using the proportion of days covered or by examining gaps between medication refills. We sought to validate these measures compared to a gold standard diagnosis of non-adherence made in hospital. METHODS: This was a retrospective analysis of adverse drug events diagnosed during three prospective cohorts in British Columbia between 2008 and 2015 (n = 976). We linked prospectively identified adverse drug events to medication claims data to examine the sensitivity and specificity of typical non-adherence measures. RESULTS: The sensitivity of the non-adherence measures ranged from 22.4% to 37.5%, with a proportion of days covered threshold of 95% performing the best; the non-persistence measures had sensitivities ranging from 10.4% to 58.3%. While a 7-day gap was most sensitive, it classified 61.2% of the sample as non-adherent, whereas only 19.6% were diagnosed as such in hospital. CONCLUSIONS: The methods used to identify non-adherence in administrative databases are not accurate when compared to a gold standard diagnosis by healthcare providers. Research that has relied on administrative data to identify non-adherent patients both underestimates the magnitude of the problem and may label patients as non-adherent who were in fact adherent.

Monitoring Pregnancies Exposed to Galcanezumab for Migraine in a United States Administrative Claims Database.

PURPOSE: Galcanezumab is a calcitonin gene-related peptide monoclonal antibody indicated for migraine prevention in adults. Due to the long half-life of galcanezumab and the prevalence of migraine in women of childbearing age, galcanezumab exposure may occur during pregnancy. However, real-world use and safety of galcanezumab during pregnancy has not been fully described. To help fill this gap, galcanezumab has two ongoing pregnancy safety studies, one of which is an insurance claims database study. METHODS: This database study is actively identifying and following pregnancies exposed to galcanezumab using commercial claims from the Healthcare Integrated Research Database (HIRD). Patient accrual is planned from September 2018 to June 2026, with a final study report planned for December 2027. This study requires 430 galcanezumab-exposed pregnancies with linked infants to reach power for comparative analysis of major congenital malformations. RESULTS: Recent monitoring of patient accrual, including data from 28 September 2018 to 31 January 2023, identified 207 galcanezumab-exposed pregnancies in women with migraine in the HIRD, of which 110 were live births and 73 of which were linked to an infant. This represents an annual accrual rate of approximately 17 pregnancies linked to infants, which is substantially lower than the 55 required annually to reach target size within current regulatory-committed study timelines. CONCLUSIONS: The accrual of a sufficient number of galcanezumab-exposed pregnancies represents a substantial, but not uncommon, barrier to conducting comparative analyses in pregnancy studies. Potential solutions that would allow for timely dissemination of important safety information to patients and providers may be available.

The Impact of Direct-Acting Antiviral Therapy on End-Stage Liver Disease Among Individuals with Chronic Hepatitis C and Substance Use Disorders.

BACKGROUND AND AIMS: Our aim was to evaluate the impact of direct-acting antivirals (DAAs) on decompensated cirrhosis (DCC) and HCC in patients with chronic HCV and substance use disorder (SUD) compared with those without an SUD. APPROACH AND RESULTS: This retrospective cohort study used the MarketScan database (2013-2018) to identify 29,228 patients with chronic HCV, where 22% (n = 6,385) had ≥1 SUD diagnosis. The inverse probability of treatment weighted multivariable Cox proportional hazard models were used to compare the risk of developing DCC and HCC. Among the those who were noncirrhotic, treatment reduced the DCC risk among SUD (adjusted hazard ratio [aHR] 0.13; 95% CI, 0.06-0.30) and non-SUD (aHR 0.11; 95% CI, 0.07-0.18), whereas the risk for HCC was not reduced for the SUD group (aHR 0.91; 95% CI, 0.33-2.48). For those with cirrhosis, compared with patients who were untreated, treatment reduced the HCC risk among SUD (aHR, 0.33; 95% CI, 0.13-0.88) and non-SUD (aHR, 0.40; 95% CI, 0.25-0.65), whereas the risk for DCC was not reduced for the SUD group (aHR, 0.64; 95% CI, 0.37-1.13). Among patients with cirrhosis who were untreated, the SUD group had a higher risk of DCC (aHR, 1.52; 95% CI, 1.03-2.24) and HCC (aHR, 1.69; 95% CI, 1.05-2.72) compared with non-SUD group. CONCLUSIONS: Among the HCV SUD group, DAA treatment reduced the risk of DCC but not HCC for those who were noncirrhotic, whereas DAA treatment reduced the risk of HCC but not DCC for those with cirrhosis. Among the nontreated, patients with an SUD had a significantly higher risk of DCC and HCC compared with those without an SUD. Thus, DAA treatment should be considered for all patients with HCV and an SUD while also addressing the SUD.

Healthcare utilization and costs among patients with chronic migraine, episodic migraine, and tension-type headache enrolled in commercial insurance plans.

OBJECTIVE: To quantify and compare healthcare utilization and costs for patients with chronic migraine (CM), episodic migraine (EM), and tension-type headache (TTH) enrolled in US commercial health plans. METHODS: This retrospective cohort study used the Optum Clinformatics® Data Mart database from January 2015 to December 2018. Adult patients with a diagnosis of EM, CM or TTH and at least 12 months of continuous enrollment before and after diagnosis were included. Inverse probability of treatment weighting was used to adjust for baseline differences among the three groups. Patient demographic and clinical characteristics at baseline, and healthcare utilization and costs during follow-up, were described and compared between the three groups. RESULTS: A total of 45,849 patients were included: 8955 with CM, 31,961 with EM, and 4933 with TTH. The total all-cause annual direct medical costs of patients with CM ($17,878) were 1.38 times higher (95% CI: 1.31-1.44) than those with EM ($12,986), and 2.26 times higher (95% CI: 2.08-2.47) than those with TTH ($7902). The annual migraine/TTH-related costs of patients with CM ($1869) were 4.19 times higher (95% CI: 3.92-4.48) than those with EM ($446), and 11.90 times (95% CI: 10.59-13.52) higher than those with TTH ($157). In the adjusted analyses, for all service categories (emergency department, inpatient, outpatient, and prescriptions), the expected costs in the migraine groups were higher than in the TTH group (all p < 0.001), while controlling for covariates. Main findings were consistent in both weighted and unweighted samples, and with both unadjusted and adjusted analyses. CONCLUSION: This study provides an updated assessment of healthcare utilization and expenditures for adult patients with primary headache disorders. Compared to TTH, migraine is associated with higher resource use and direct medical costs, especially for those with a chronic condition. Future studies are needed to understand the indirect medical costs (productivity loss) and humanistic burden (quality of life) between migraine and TTH.

Decrease in hospital admissions for respiratory diseases during the COVID-19 pandemic: a nationwide claims study.

Non-pharmaceutical interventions (NPIs) have been widely implemented to mitigate the spread of COVID-19. We assessed the effect of NPIs on hospitalisations for pneumonia, influenza, COPD and asthma. This retrospective, ecological study compared the weekly incidence of hospitalisation for four respiratory conditions before (January 2016-January 2020) and during (February-July 2020) the implementation of NPI against COVID-19. Hospitalisations for all four respiratory conditions decreased substantially during the intervention period. The cumulative incidence of admissions for COPD and asthma was 58% and 48% of the mean incidence during the 4 preceding years, respectively.

Comparative Outcomes for Pelvic Organ Prolapse Surgery among Nursing Home Residents and Matched Community Dwelling Older Adults.

PURPOSE: We compared short and long-term outcomes between nursing home residents and matched community dwelling older adults undergoing surgery for pelvic organ prolapse. MATERIALS AND METHODS: This retrospective cohort study evaluates women 65 years old or older undergoing different types of pelvic organ prolapse repairs (anterior/posterior, apical and colpocleisis) between 2007 and 2012 using Medicare claims and the Minimum Data Set for Nursing Home Residents. Long-stay nursing home residents were identified and propensity score matched (1:2) to community dwelling older individuals based on procedure type, age, race and Charlson score. Generalized estimating equation models were created to determine the relative risk of hospital length of stay 3 or more days, 30-day complications and 1-year mortality between the 2 groups. Kaplan-Meier curves were created comparing 1-year mortality between groups. RESULTS: There were 799 nursing home residents and 1,598 matched community dwelling older adults who underwent pelvic organ prolapse surgery and were included in our analyses. Nursing home residents demonstrated statistically significant increased risk for hospital length of stay 3 or more days (38.9% vs 18.6%, adjusted RR 2.1, 95% CI 1.8-2.4), 30-day complications (15.1% vs 3.8%, aRR 3.9, 95% CI 2.9-5.3) and 1-year mortality (11.1% vs 3.2%, aRR 3.5, 95% CI 2.5-4.8) compared to community dwelling older adults. Kaplan-Meier curves illustrated similar survival findings at 1 year (11.1%, 95% CI 9.0-13.3 vs 3.2%, 95% CI 2.3-4.1, p <0.0001). CONCLUSIONS: Despite matching on several characteristics, nursing home residents demonstrated worse short and long-term outcomes compared to community dwelling older adults, suggesting other key vulnerabilities exist that contribute additional surgical risk in this population.

Comorbidity in lung cancer patients and its association with hospital readmission and fatality in China.

BACKGROUND: Comorbidity has been established as one of the important predictors of poor prognosis in lung cancer. In this study, we analyzed the prevalence of main comorbidities and its association with hospital readmission and fatality for lung cancer patients in China. METHODS: The analyses are based on China Urban Employees' Basic Medical insurance (UEBMI) and Urban Residents' Basic Medical Insurance (URBMI) claims database and Hospital Information System (HIS) Database in the Beijing University Cancer Hospital in 2013-2016. We use Elixhauser Comorbidity Index to identify main types of comorbidities. RESULTS: Among 10,175 lung cancer patients, 32.2% had at least one comorbid condition, and the proportion of patients with one, two, and three or more comorbidities was 21.7, 8.3 and 2.2%, respectively. The most prevalent comorbidities identified were other malignancy (7.5%), hypertension (5.4%), pulmonary disease (3.7%), diabetes mellitus (2.5%), cardiovascular disease (2.4%) and liver disease (2.3%). The predicted probability of having comorbidity and the predicted number of comorbidities was higher for middle elderly age groups, and then decreased among patients older than 85 years. Comorbidity was positively associated with increased risk of 31-days readmission and in-hospital death. CONCLUSION: Our study is the first to provide an overview of comorbidity among lung cancer patients in China, underlines the necessity of incorporating comorbidity in the design of screening, treatment and management of lung cancer patients in China.

Cardiovascular medications and survival in people with ovarian cancer: A population-based cohort study from British Columbia, Canada.

OBJECTIVES: Research examining survival among people with ovarian cancer following use of statins or ß-blockers has been conflicting. Many studies to date have suffered from immortal time bias and/or had limited power. To address these limitations, we used time-dependent analyses to study the association between statin or ß-blocker use among all people diagnosed with an epithelial ovarian cancer in British Columbia, Canada between 1997 and 2015. METHODS: Population-based administrative data were linked for 4207 people with ovarian cancer. Statin or ß-blocker use was examined using time-dependent variables for any use, cumulative duration of use and by user-group according to whether use was initiated before or after their ovarian cancer diagnosis. Cox proportional hazards models were run to estimate the association between statin or ß-blocker use and survival. RESULTS: Any postdiagnosis use of statins was associated with better ovarian cancer survival in the full cohort (adjusted hazard ratio (aHR) = 0.76, 95% CI 0.64, 0.89) and among women with serous cancers (aHR = 0.80, 95%CI 0.67-0.96). This was primarily driven by new use post-diagnosis (aHR = 0.67, 95%CI, 0.51-0.89), but there was a trend towards better survival among those who continued use from before diagnosis (aHR 0.83, 95%CI, 0.68-1.00). There was no statistically significant association between ß-blocker use and survival. CONCLUSION: Postdiagnosis statin use was associated with improved survival among people with ovarian cancer. Given the consistency of this finding in the literature, we recommend a randomized clinical trial of statin use in people with ovarian cancer.

Eligibility for cervical cancer screening exit: Comparison of a national and safety net cohort.

OBJECTIVE: To determine eligibility for discontinuation of cervical cancer screening. METHODS: Women aged 64 with employer-sponsored insurance enrolled in a national database between 2016 and 2018, and those aged 64-66 receiving primary care at a safety net health center in 2019 were included. Patients were evaluated for screening exit eligibility by current guidelines: no evidence of cervical cancer or HIV-positive status and no evidence of cervical precancer in the past 25 years, and had evidence of either hysterectomy with removal of the cervix or evidence of fulfilling screening exit criteria, defined as two HPV screening tests or HPV plus Pap co-tests or three Pap tests within the past 10 years without evidence of an abnormal result. RESULTS: Of the 590,901 women in the national claims database, 131,059 (22.2%) were eligible to exit due to hysterectomy (1.6%) or negative screening (20.6%). Of the 1544 women from the safety net health center, 528 (34.2%) were eligible to exit due to hysterectomy (9.3%) or negative screening (24.9%). Most women did not have sufficient data available to fulfill exit criteria: 382,509 (64.7%) in the national database and 875 (56.7%) in the safety net hospital system. Even among women with 10 years of insurance claims data, only 41.5% qualified to discontinue screening. CONCLUSIONS: Examining insurance claims in a national database and electronic medical records at a safety net institution led to remarkably similar findings: two thirds of women fail to qualify for screening exit. Additional steps to ensure eligibility prior to screening exit may be necessary to decrease preventable cervical cancers among women aged >65. CLINICAL TRIAL REGISTRATION: N/A.

Trends in the use of cervical cancer screening tests in a large medical claims database, United States, 2013-2019.

OBJECTIVE: To examine trends in the use of cervical cancer screening tests during 2013-2019 among commercially insured women. METHODS: The study population included women of all ages with continuous enrollment each year in the IBM MarketScan commercial or Medicare supplemental databases and without known history of cervical cancer or precancer (range = 6.9-9.8 million women per year). Annual cervical cancer screening test use was examined by three modalities: cytology alone, cytology plus HPV testing (cotesting), and HPV testing alone. Trends were assessed using 2-sided Poisson regression. RESULTS: Use of cytology alone decreased from 34.2% in 2013 to 26.4% in 2019 among women aged 21-29 years (P < .0001). Among women aged 30-64 years, use of cytology alone decreased from 18.9% in 2013 to 8.6% in 2019 (P < .0001), whereas cotesting use increased from 14.9% in 2013 to 19.3% in 2019 (P < .0001). Annual test use for HPV testing alone was below 0.5% in all age groups throughout the study period. Annually, 8.7%-13.6% of women aged 18-20 years received cervical cancer screening. There were persistent differences in screening test use by metropolitan residence and census regions despite similar temporal trends. CONCLUSIONS: Temporal changes in the use of cervical cancer screening tests among commercially insured women track changes in clinical guidelines. Screening test use among individuals younger than 21 years shows that many young women are inappropriately screened for cervical cancer.

Decreasing Surgical Management of Secondary Hyperparathyroidism in the United States.

BACKGROUND: Secondary hyperparathyroidism (SHPT) commonly occurs in end-stage renal disease (ESRD), leading to vascular calcification and increased mortality. For SHPT refractory to medical management, parathyroidectomy improves symptoms and decreases mortality. Medical management has changed with the release of new guidelines and advent of novel medications. We investigate recent national trends in parathyroidectomy for SHPT. MATERIALS AND METHODS: We used the National/Nationwide Inpatient Sample from 2004 to 2016 to identify hospitalizations including parathyroidectomy for SHPT and calculated parathyroidectomy rates utilizing data from the United States Renal Data System. Subgroup analysis was conducted by race. Risk factors for in-hospital mortality were identified with purposeful selection and multivariable logistic regression. RESULTS: From 2004 to 2016, the rate of parathyroidectomies for SHPT per 1000 ESRD patients decreased from 6.07 (95% CI: 4.83-7.32) to 3.67 (95% CI: 3.33-4.00). Black patients underwent parathyroidectomy for SHPT at a 1.8-fold higher rate than white and Hispanic patients (5.59 versus 3.04 and 3.07). Almost all tracked comorbidities increased in prevalence. In-hospital mortality trended lower (1.5% to 0.8%, P = 0.051). Risk factors for in-hospital mortality included weight loss (OR 4.19, 95% CI: 2.00-8.78) and cardiac arrhythmia (OR 3.38, 95% CI: 1.66-6.91), while additional calendar year (OR = 0.87, 95% CI: 0.80-0.95) was protective. CONCLUSIONS: The etiology of the declining parathyroidectomy rate for SHPT is unclear; possible factors include changing guidelines emphasizing medical management, widespread availability of cinacalcet, changing practice patterns, and inadequate surgical referral.

How Does SARS-CoV-2 Infection Affect Survival of Emergency Cardiovascular Patients? A Cohort Study From a German Insurance Claims Database.

OBJECTIVE: A previous study revealed a preliminary trend towards higher in hospital mortality in patients admitted as an emergency with acute stroke during the COVID-19 pandemic in Germany. The current study aimed to further examine the possible impact of a confirmed SARS-CoV-2 infection on in hospital mortality. METHODS: This was a retrospective analysis of health insurance claims data from the second largest insurance fund in Germany, BARMER. Patients hospitalised for ST elevation (STEMI) and non-ST elevation (NSTEMI) myocardial infarction, acute limb ischaemia (ALI), aortic rupture, acute stroke, or transient ischaemic attack (TIA) between 1 January 2017, and 31 October 2020, were included. Admission rates per 10 000 insured and mortality were compared between March - June 2017 - 2019 (pre-COVID) and March - June 2020 (COVID). Mortality rates were determined by the occurrence of a confirmed SARS-CoV-2 infection. RESULTS: A total of 316 718 hospitalisations were included (48.7% female, mean 72.5 years), and 21 191 (6.7%, 95% CI 6.6% - 6.8%) deaths occurred. In hospital mortality increased during the COVID-19 pandemic when compared with the three previous years for patients with acute stroke from 8.3% (95% CI 8.0 - 8.5) to 9.6% (95% CI 9.1 - 10.2), while no statistically significant changes were observed for STEMI, NSTEMI, ALI, aortic rupture, and TIA. When comparing patients with confirmed SARS-CoV-2 infection (2.4%, 95% CI 2.3 - 2.5) vs. non-infected patients, a higher in hospital mortality was observed for acute stroke (12.4% vs. 9.0%), ALI (14.3% vs. 5.0%), and TIA (2.7% vs. 0.3%), while no statistically significant differences were observed for STEMI, NSTEMI, and aortic rupture. CONCLUSION: This retrospective analysis of claims data has provided hints of an association between the COVID-19 pandemic and increased in hospital mortality in patients with acute stroke. Furthermore, confirmed SARS-CoV-2 infection was associated with increased mortality in patients with stroke, TIA, and ALI. Future studies are urgently needed to better understand the underlying mechanism and relationship between the new coronavirus and acute stroke.

Real-world anticancer medications for reproductive-age women with breast cancer by using a claims database in Japan.

Aim: To describe real-world breast cancer medications among reproductive-age women. Patients & methods: Using data from a Japanese claims database, anticancer prescriptions were classified into seven categories of amenorrhea risk based on fertility preservation guidelines. Results: We identified 2999 women with records of breast cancer and anticancer prescription from 2005 to 2018. The proportions of prescriptions were as follows: high, 4.1-12.9%; intermediate: 6.0-16.3%; low: 0.4-2.3%; very low/no: 0.3-12.2%; unknown: 33.9-45.5%; unlisted combination: 12.2-23.4%; and unlisted drug: 12.5-26.7%. The common drugs in the unknown category were trastuzumab (n = 1527), docetaxel (n = 1014), and paclitaxel (n = 995). For medications unlisted in the guidelines, various drugs and drug combinations were observed. Conclusion: Numerous anticancer drugs are currently being prescribed with insufficient evidence regarding amenorrhea risk.

Lay abstract The ability to have children for breast cancer patients is one of the key issues of cancer survivorship, especially because recent progress in anticancer treatments has enabled patients to achieve longer survival. The fertility preservation guidelines of the American Society of Clinical Oncology (2006) introduce some anticancer treatments that carry potential risks to future fertility. In this study, the anticancer prescriptions of 2999 patients with breast cancer aged between 15 and 49 years were examined. Results showed that several medications are prescribed despite the lack of information on the risk of infertility. This suggests that further research is required to fill the evidence gap, and that decision aid through adequate counseling should be undertaken.

Comprehensive Exploration of Medications That Affect the Bleeding Risk of Oral Anticoagulant Users.

Oral anticoagulants (OACs) pose a major bleeding risk, which may be increased or decreased by concomitant medications. To explore medications that affect the bleeding risk of OACs, we conducted a nested case-control study including 554 bleeding cases (warfarin, n = 327; direct OACs [DOACs], n = 227) and 1337 non-bleeding controls (warfarin, n = 814; DOACs, n = 523), using a Japanese health insurance database from January 2005 to June 2017. Major bleeding risk associated with exposure to concomitant medications within 30 d of the event/index date was evaluated, and adjusted odds ratios (aORs) were calculated using logistic regression analysis. Several antihypertensive drugs, such as amlodipine and bisoprolol, were associated with a decreased risk of bleeding (warfarin + amlodipine [aOR, 0.64; 95% confidence interval (CI): 0.41-0.98], DOACs + bisoprolol [aOR, 0.51; 95% CI, 0.33-0.80]). As hypertension is considered a significant risk factor for intracranial bleeding in antithrombotic therapy, antihypertensive drugs may suppress intracranial bleeding. In contrast, telmisartan, a widely used antihypertensive drug, was associated with an increased risk of bleeding [DOACs + telmisartan (aOR, 4.87; 95% CI, 1.84-12.91)]. Since telmisartan is an inhibitor of P-glycoprotein (P-gp), the elimination of rivaroxaban and apixaban, which are substrates of P-gp, is hindered, resulting in increased blood levels of both drugs, thereby increasing the risk of hemorrhage. In conclusion, antihypertensive drugs may improve the safety of OACs, and the pharmacokinetic-based drug interactions of DOACs must be considered.

Comparison of the Safety and Effectiveness of Four Direct Oral Anticoagulants in Japanese Patients with Nonvalvular Atrial Fibrillation Using Real-World Data.

Direct oral anticoagulants (DOACs) are widely used for the prevention of ischemic stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF). However, the differences in safety and effectiveness among four DOACs, dabigatran, rivaroxaban, apixaban, and edoxaban, in Japanese patients have not been clarified. Therefore, we conducted a retrospective cohort study to directly compare the safety and effectiveness among the four DOACs using the Japan Medical Data Center (JMDC) claims database. We identified 3823 patients with NVAF who started receiving a DOAC between March 2011 and June 2017. The safety outcome was major bleeding (a composite outcome of intracranial, gastrointestinal, respiratory, or renal/urinary tract bleeding) and the effectiveness outcome was the composite of ischemic stroke including transient ischemic attack (TIA) or systemic embolism. We constructed a Cox proportional hazard model to calculate the hazard ratio (HR) for all four DOAC combinations. The risk of major bleeding was significantly lower in the dabigatran group than in the apixaban group (HR, 0.55; 95% confidence interval (CI), 0.31-0.93; p = 0.03). In contrast, there was no significant difference in the risk of major bleeding among the other DOACs. In the composite risk of ischemic stroke including TIA or systemic embolism, there was no significant difference among the four DOACs. This study suggested that in the current use of DOACs in Japanese patients with NVAF, dabigatran had a significantly lower risk of major bleeding than apixaban, but there was no significant difference in effectiveness among the four DOACs.

Implementation Status of Liver Function Tests for Monitoring Benzbromarone-Induced Hepatotoxicity: An Epidemiological Survey Using the Japanese Claims Database.

A major adverse effect of benzbromarone is hepatotoxicity. Therefore, periodic liver function tests are required at least for the first 6 months of benzbromarone administration. However, it is not clear whether the relevant blood tests are implemented appropriately. Here, we performed a cross-sectional survey of the implementation status of liver function tests in patients who were newly prescribed benzbromarone, using the Japanese large claims database. Male patients who were newly prescribed benzbromarone from January 2010 to December 2016 were included. We targeted patients who continued benzbromarone during the observation period (up to 180 d from the start of administration). The primary endpoint was the proportion of patients in whom periodic liver function tests were implemented. A periodic liver function test was defined as one or more liver function tests performed during both 1-90 and 91-180 d of initial benzbromarone administration. We labeled the tests as a "periodic test" or "non-periodic test" based on whether periodic liver function tests were performed or not, respectively. Furthermore, factors influencing non-periodic test were analyzed. Periodic testing was implemented only in 28.7% of patients. Additionally, factors such as number of hospital beds ≤19 (compared to 100-199 beds) and duration of the first prescription of benzbromarone were associated with non-periodic testing. Our study revealed that periodic liver function tests are not performed sufficiently in Japan. Thus, clinicians prescribing benzbromarone should be educated about the test. Our blood-test-based approach should be applied to other drugs and countries in future research.

Association of tibolone and dementia risk: a cohort study using Korean claims data.

OBJECTIVE: Few studies have examined whether tibolone (TIB), a type of hormone replacement therapy widely used in Asia and Europe, affects dementia risk in postmenopausal women. Our study aims to investigate the association of TIB and dementia risk in Korean women aged 50-80 years. METHODS: A population-based longitudinal study was conducted using the Korean National Health Insurance Service claims database merged with national health examination data from 2002 to 2015. Among 13,110 participants, exposure to TIB was determined using the standardized defined daily dose (DDD) system from 2003 to 2007. Starting from 2007, participants were followed up for overall dementia, Alzheimer's disease (AD) and vascular dementia (VD) until 2015. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of dementia according to TIB use. RESULTS: TIB use was not significantly associated with the risk of total dementia (aHR = 1.040; 95% CI = 0.734-1.472; p = .827), AD (aHR = 0.949; 95% CI = 0.652-1.381; p = .785) and VD (aHR = 1.245; 95% CI = 0.631-2.457; p = .528). CONCLUSIONS: Our results suggest that TIB use does not have a significant association with dementia risk. Further randomized controlled trials are necessary to elucidate the role of exogenous hormones in the development of dementia.

BRCA testing in unaffected young women in the United States, 2006-2017.

BACKGROUND: The discovery of the BRCA gene in the 1990s created an opportunity for individualized cancer prevention. BRCA testing in young women before cancer onset enables early detection of those with an increased cancer risk and creates an opportunity to offer lifesaving prophylactic procedures and medications. This study assessed trends in BRCA testing in women younger than 40 years without diagnosed breast or ovarian cancer (unaffected young women [UYW]) for cancer prevention between 2006 and 2017 in the United States. METHODS: This study included 93,278 adult women 18 to 65 years old with insurance claims for BRCA testing between 2006 and 2017 from the de-identified Optum Clinformatics Data Mart database. The data contained medical claims and administrative information from privately insured individuals in the United States. The proportion of BRCA testing in UYW younger than 40 years among adult women aged 18 to 65 years who received BRCA testing was assessed. RESULTS: In 2006, only 10.5% of the tests were performed in UYW. The proportion of BRCA tests performed in UYW increased significantly to 25.5% in 2017 (annual percentage change for the 2006-2017 period, 6.9; 95% confidence interval, 6.4-7.3; P < .001). The increased trend in the proportion of BRCA tests in UYW significantly differed by region of residence and family history of breast or ovarian cancer. CONCLUSIONS: Over the past decade, there was increased use of BRCA testing for cancer prevention. Additional efforts are needed to maximize the early detection of women with BRCA pathogenic variants so that these cancers may be prevented.

Impact of patient factors and procedure on readmission after aortic dissection admission in the states of Florida and New York.

BACKGROUND: Readmissions after aortic dissection (AD) admission are not well described. Using state-based administrative claims data, we sought to define readmission rates after AD and to identify factors associated with them. METHODS: State Inpatient Databases for Florida (2007-2012) and New York (2008-2012) were queried for AD index admissions. Admissions were stratified by initial treatment strategy: type A open surgery repair (TAOR), type B open surgery repair (TBOR), thoracic endovascular aortic repair (TEVAR), or medical management (MM). All-cause readmission rates were calculated at 30 days, 90 days, and 2 years. Logistic regression was used to identify factors associated with readmission at each time point for all type A admissions (TAOR) or type B admissions (TBOR, TEVAR, MM). RESULTS: We identified 4670 patients with an AD index admission. Treatment was with TAOR in 1031 (22%), TBOR in 761 (16%), TEVAR in 412 (9%), and MM in 2466 (53%). Patients were predominantly male (59.4%) and white (61.9%), with a median age of 66 years. Overall mortality during AD index admission was 14.8% (TAOR, 15.8%; TBOR, 17.1%; TEVAR, 9.0%; MM, 14.7%; P = .002 across all groups). All-cause readmission rates were similar across treatment groups at 30 days (9.6%-11%; P = .56), 90 days (15.2%-20%; P = .26), and 2 years (49.2%-54.4%; P = .15). Higher income quartile (vs lowest) was associated with lower odds of early readmission (at 30 days and 90 days) after type B admissions but not after type A admissions. At 2 years, self-pay (vs Medicare) was associated with lower odds of readmission in both type A and type B admissions, whereas higher comorbidity count and black race (vs white) were associated with higher odds of readmission. TEVAR (vs MM) was also associated with higher odds of readmission. Cardiovascular disease was the most common cause for readmission at all time points. Emergency department readmission counts were highest after MM admissions, and ambulatory surgical admissions were highest after TBOR. Both TEVAR and MM initial costs were lower than TAOR and TBOR costs, but at 2 years, costs remained significantly lower only for MM. CONCLUSIONS: In-state 30-day, 90-day, and 2-year readmission rates after AD were not associated with initial treatment type. Two-year readmissions are common. Strategies to target socioeconomic, race, and geographic factors may reduce variations in readmission patterns after AD admission.