Trajectories of adherence to extended treatment with direct oral anticoagulants and risks of recurrent venous thromboembolism and major bleeding.

BACKGROUND: Little is known about medication adherence patterns and their association with effectiveness and safety among patients with venous thromboembolism (VTE) receiving direct oral anticoagulant (DOAC) therapy beyond 3-6 months of initial treatment. OBJECTIVE: To examine the associations between adherence trajectories of extended treatment with DOAC and the risks of recurrent VTE and major bleeding among patients with VTE. METHODS: We conducted a retrospective cohort study of patients with incident VTE who completed 6 months of initial anticoagulant treatment and received either DOAC extended therapy or no extended therapy using MarketScan Commercial and Medicare Supplemental databases (2013-2019). We used group-based trajectory models to identify distinct adherence patterns during extended treatment. Using inverse probability treatment weighted Cox proportional hazards models, we examined the association between the adherence trajectories and the risks of recurrent VTE and major bleeding. RESULTS: Among 10,960 patients with extended treatment with DOACs (rivaroxaban, apixaban, dabigatran, edoxaban) and 5,133 patients with no extended treatment, we identified 4 distinct trajectories (consistently high, gradually declining, rapidly declining, and no extended treatment). Compared with the no extended treatment group, the groups with consistently high adherence (hazard ratio = 0.09, 95% CI = 0.05-0.17) and with gradually declining adherence (0.13, 0.03-0.53) showed decreased recurrent VTE risk without increased major bleeding risk (consistently high adherence 1.19, 0.71-1.99; gradually declining adherence 1.96, 0.81-4.70). There was no difference in the risk of recurrent VTE (0.34, 0.10-1.16) for the group with rapidly declining adherence, but this group was associated with increased major bleeding risk (2.65, 1.01-6.92). CONCLUSIONS: Our findings underscore the clinical importance of continuing and remaining adherent to extended DOAC treatment without increased major bleeding risk for patients with VTE. DISCLOSURES: This research was supported by the BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program. The funding source had no role in the design, collection, analysis, or interpretation of the data or the decision to submit the article for publication. Dr Lo-Ciganic reported receiving research funding from Merck Sharp & Dohme Corp. Dr Dietrich reported receiving honorarium for training and education from BMS/Pfizer. Dr DeRemer is a stockholder of Portola Pharmaceuticals and reported receiving personal fees for advisory board meeting from BMS. No other disclosures were reported.

Nationwide trends in hospitalization, medical costs, and mortality for asthma after introduction of biologics: A cross-sectional study in the United States.

BACKGROUND: Asthma is the most common inflammatory lung disease in the United States. Since 2015, biologic therapies have provided targeted treatment for patients with severe asthma. OBJECTIVE: To evaluate the trends for in-hospital outcomes of asthma before (2012-2014) and after (2016-2018) the introduction of biologic therapies for asthma. METHODS: We conducted a nationwide cross-sectional analysis of patients aged 2 years or older who were hospitalized for asthma between 2012 and 2018 using data from the Nationwide Readmissions Database. Outcomes included rates of asthma hospital admission and asthma-related 30-day readmission, hospital length of stay, hospital costs, and inpatient mortality. Generalized linear models assessed trends in rates of asthma admission and readmission, length of stay, costs, and mortality quarterly during 2012-2014 and 2016-2018. RESULTS: Among 691,537 asthma-related admissions, quarterly asthma admission rates significantly decreased (-0.90%, 95% CI = -1.46% to - 0.34%; P = 0.002) during 2016-2018, mainly among adults, but not during 2012-2014. Quarterly assessed readmission rates decreased by 2.40% (-2.85% to -1.96%; P < 0.0001) during 2012-2014 and by 2.12% (-2.74% to - 1.50%; P < 0.0001) during 2016-2018. Mean length of stay for asthma admissions decreased quarterly by 0.44% (-0.49% to - 0.38%; P < 0.0001) during 2012-2014 and by 0.27% (-0.34% to - 0.20%; P < 0.0001) during 2016-2018. Quarterly hospital costs for admissions were unchanged during 2012-2014 but increased by 0.28% (0.21% to 0.35%; P < 0.0001) during 2016-2018. There were no significant trends in inpatient mortality during 2012-2014 and 2016-2018. CONCLUSIONS: After the introduction of new biologics for severe asthma in 2015, asthma-related hospital admissions decreased significantly, whereas hospital costs increased. Asthma-related 30-day readmission rates and length of stay for asthma admissions continuously decreased, whereas inpatient mortality rates remained stable. DISCLOSURES: This work was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number R01HL136945. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The data that support the findings of this study are available from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project.

Trajectories of adherence to extended treatment with warfarin and risks of recurrent venous thromboembolism and major bleeding.

Background: Little is published about warfarin therapy adherence patterns beyond 6 months of initial anticoagulant treatment and their association with effectiveness and safety for patients with venous thromboembolism (VTE). Objectives: To compare the risks of recurrent VTE and major bleeding during extended treatment between adherence patterns using MarketScan Commercial and Medicare Supplemental databases (2013-2019). Methods: In a retrospective cohort study, we included patients with incident VTE who completed an initial 6-month anticoagulant treatment and received either warfarin or no extended therapy. Group-based trajectory models were used to identify distinct extended treatment trajectories. Associations between the trajectories and risk of hospitalization due to recurrent VTE and major bleeding were assessed using inverse probability treatment-weighted Cox proportional hazards models. Results: Compared with no extended treatment, consistently high warfarin adherence was associated with a significantly decreased risk of hospitalization due to recurrent VTE (hazard ratio [HR] = 0.23; 95% CI, 0.12-0.45), but gradually (HR = 0.29; 95CI, 0.08-1.06) or rapidly declining (HR = 0.14; 95% CI, 0.02-1.24) adherence showed no association with the risk of hospitalization due to recurrent VTE. Compared with no extended treatment, warfarin extended therapy was associated with an increased risk of hospitalization due to major bleeding regardless of adherence patterns (consistently high: HR = 2.08; 95% CI, 1.18-3.64, gradually declining: HR = 2.10; 95% CI, 0.74-5.95, and rapidly declining: HR = 9.19; 95% CI, 4.38-19.29). However, compared with rapidly declining adherence, consistently high (HR = 0.23; 95% CI, 0.11-0.47) and gradually declining (HR = 0.23; 95% CI, 0.08-0.64) adherence were associated with decreased risk of hospitalization due to major bleeding. Conclusion: The findings indicated that consistently high adherence to extended warfarin treatment was associated with a decreased risk of hospitalization due to recurrent VTE but an increased risk of hospitalization due to major bleeding compared with no extended treatment.

Comparative effectiveness and safety of direct oral anticoagulants versus warfarin among patients with recurrent venous thromboembolism.

The comparative effectiveness and safety of oral anticoagulant therapies to prevent a second recurrent venous thromboembolism (VTE) remains undetermined. We aimed to compare the benefits and harms of direct oral anticoagulant (DOAC) and warfarin therapies in preventing second recurrent VTE and major bleeding events among patients with a recurrent VTE episode following anticoagulation therapy for incident VTE. A retrospective cohort analysis of two large national insurance claims databases was conducted for patients with two episodes of VTE. Cox proportional hazards models were used after inverse probability treatment weighting to compare risks of second recurrent VTE and major bleeding events. Compared with warfarin, DOAC therapy was associated with significantly decreased risk of second recurrent VTE with no significant difference in risk of major bleeding events. Our findings suggest that, compared with warfarin, DOACs may reduce risk of second VTE recurrence among patients who have experienced one recurrence.

Trajectories of Oral Anticoagulation Adherence and Associated Clinical Outcomes During Long-Term Anticoagulation Among Medicare Beneficiaries With Venous Thromboembolism.

BACKGROUND: Little is known about anticoagulation medication nonadherence patterns impacting effectiveness and safety outcomes in clinical practice. OBJECTIVE: We identified adherence trajectories of extended therapy with direct-acting oral anticoagulants (DOACs) and warfarin after 6 months initial anticoagulant therapy among Medicare beneficiaries with venous thromboembolism (VTE). We further assessed the associated recurrent VTE and major bleeding risks. METHODS: Using group-based trajectory models, this retrospective cohort study identified distinct beneficiary subgroups with similar adherence patterns of extended-phase anticoagulant treatment (DOACs or warfarin) for patients with VTE who completed 6 months of initial anticoagulant treatment. We examined associations between adherence trajectories and risks of recurrent VTE and major bleeding using inverse probability treatment weighted Cox proportional hazards models. RESULTS: Compared with no extended treatment, consistently high DOAC adherence was associated with decreased recurrent VTE risk (hazard ratio [HR] = 0.33, 95% confidence interval [CI] = 0.21-0.51) without increased major bleeding risk, and consistently high warfarin adherence was associated with decreased recurrent VTE risk (HR = 0.62, 95% CI = 0.40-0.95) and increased major bleeding risk (HR = 1.64, 95% CI = 1.12-2.41). Gradually declining adherence to DOACs (HR = 1.80, 95% CI = 1.07-3.03) or warfarin (HR = 2.34, 95% CI = 1.57-3.47) was associated with increased bleeding risk with no change in recurrent VTE risk. CONCLUSION AND RELEVANCE: This real-world evidence suggests persistently adhering to extended DOAC therapy is associated with lower recurrent VTE risk without increasing major bleeding among Medicare beneficiaries with VTE. Persistently adhering to extended warfarin therapy was associated with lower recurrent VTE risk but higher major bleeding risk.

Comparative effectiveness and safety of extended anticoagulant therapy among Medicare beneficiaries with venous thromboembolism.

Guidelines recommend an extended course of anticoagulation therapy for patients who experienced venous thromboembolism (VTE) without transient provocation, however, optimal duration remains uncertain. We assessed effectiveness and safety of extended use of apixaban and warfarin greater than 6 months of initial treatment in patients with VTE. We conducted a retrospective cohort study of Medicare beneficiaries aged greater than or equal to 18 years with deep vein thrombosis or pulmonary embolism. Patients were required to have initiated anticoagulants within 30 days of their first VTE diagnosis, completed 6 months of initial anticoagulant treatment, and received extended phase treatment with apixaban (the apixaban group) or warfarin (the warfarin group) or no extended therapy. Multivariable Cox proportional hazards modeling with inverse probability treatment weighting was used to compare recurrent VTE, mortality, and major bleeding risks among the three groups. Mean extended-treatment duration was up to 10 months and 14 months in apixaban and warfarin groups, respectively. Compared with no extended treatment, apixaban use was associated with decreased risks of recurrent VTE (hazard ratio [HR] = 0.08, [95% confidence interval [CI]: 0.01-0.41]) and mortality (HR = 0.37, [95% CI: 0.27-0.51]) without increased major bleeding risk (HR = 1.29, [95% CI: 0.68-2.45]); warfarin use was associated not with recurrent VTE risk change but with increased major bleeding risk (HR = 2.14, [95% CI: 1.26-3.65]) and decreased mortality risk (HR = 0.39, [95% CI: 0.29-0.51]). Compared with warfarin, apixaban use was associated with decreased recurrent VTE (HR = 0.13, [95% CI: 0.03-0.63]) and major bleeding (HR = 0.56, [95% CI: 0.32-0.98]) risks. Subgroup and sensitivity analyses (e.g., intention-to-treat) findings remained consistent. Compared with warfarin or no extended therapy, extended-apixaban use was associated with reduced risk of recurrent VTE without increased major bleeding risk. Continuing anticoagulant therapy with apixaban greater than 6 months may be effective and safe.

Effectiveness and Safety of Extended Oral Anticoagulant Therapy in Patients with Venous Thromboembolism: A Retrospective Cohort Study.

Limited real-world evidence exists for effectiveness and safety of extended oral anticoagulation beyond 6 months of initial treatment in prevention of recurrent venous thromboembolism (VTE) and adverse major bleeding events among patients with VTE. Using MarketScan Commercial and Medicare Supplemental databases (2013-2019), we conducted a retrospective cohort study to compare the risk of recurrent VTE and major bleeding events during extended treatment among patients with VTE who completed the 6-month initial treatment and received extended oral anticoagulant treatment with apixaban, warfarin, or no extended treatment. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards modeling with inverse probability treatment weighting. We identified 14,818 patients with extended treatment of apixaban (n = 4,338), warfarin (n = 5,298), or no extended treatment (n = 5,182). Compared with no extended treatment, apixaban use was associated with decreased risk of recurrent VTE (HR: 0.10, 95% CI: 0.04-0.26) without increased risk of major bleeding events (HR: 1.06, 95% CI: 0.52-2.17); warfarin use was associated with decreased risk of recurrent VTE (HR: 0.23, 95% CI: 0.12-0.44) but with increased risk of major bleeding events (HR: 2.64, 95% CI: 1.51-4.59). Compared with warfarin, apixaban use was associated with decreased risk of major bleeding events (HR: 0.42, 95% CI: 0.22-0.80) but no difference in risk of recurrent VTE (HR: 0.46, 95% CI: 0.15-1.36). In a real-world clinical setting, extended anticoagulation with apixaban or warfarin was associated with decreased risk of recurrent VTE compared with no extended treatment, and apixaban had a better safety profile with fewer major bleeding events compared with warfarin among commercially insured patients with VTE.

Comparison of effectiveness and safety for low versus full dose of apixaban during extended phase oral anticoagulation in patients with venous thromboembolism.

BACKGROUND: The optimal dose of apixaban therapy to prevent asecondary venous thromboembolism (VTE) event remains unconfirmed. To investigate the effects of extended phase use of apixaban (2.5 vs. 5 mg twice daily) beyond 6 months of initial treatment on the risk of recurrent VTE and major bleeding events among patients with a history of VTE. METHODS: A retrospective cohort analysis of two large national insurance claims databases was conducted for patients diagnosed with VTE. Cox proportional hazard models after propensity score matching were used to compare the risk of recurrent VTE and major bleeding. RESULTS: There were no detected differences in recurrent VTE or major bleeding events between patients prescribed low versus full dose apixaban. CONCLUSION: This study provides evidence that apixaban 2.5 mg twice daily is an alternative option for extended phase therapy for risk reduction of VTE recurrence compared to apixaban 5 mg twice daily.

Association between oseltamivir use and neuropsychiatric adverse events in influenza patients: a nationwide population-based cohort study.

Background: A potential risk of neuropsychiatric adverse events (NPAEs) of oseltamivir has remained controversial by retrospective cohort studies. This nationwide population-based cohort study aimed to assess the risk of NPAEs in influenza patients undergoing oseltamivir treatment (users) compared with a propensity score-matched cohort of patients not receiving oseltamivir (non-users). Research design and methods: Using the Korean National Health Service-Sample Cohort Database, patients diagnosed with incident influenza during 2003-2013 were divided into two cohorts: oseltamivir users and non-users. We calculated adjusted hazard ratios (aHRs) for the 5-day treatment course with oseltamivir using Cox regression analysis. Results: The incidence rate of NPAEs during 5-day oseltamivir treatment was 0.0029 and 0.0023 in oseltamivir users and non-users, respectively. The risk of NPAEs was different according to age, with an increased risk in patients aged 10-19 years (aHR 2.69, 95% CI 1.05-6.93) and a decreased risk in patients aged 0-9 years (aHR 0.46, 95% CI 0.24-0.88). The non-significant positive associations were observed in patients aged 20-64 years and those aged greater than 65 years. Conclusions: Although the reason for the inverse association in children aged 0-9 years is unknown, oseltamivir could increase the risk of NPAEs for children or adolescents aged greater than 10 years.

Cost-effectiveness of antiviral treatment in adult patients with immune-tolerant phase chronic hepatitis B.

OBJECTIVE: The cost-effectiveness of antiviral treatment in adult immune-tolerant (IT) phase chronic hepatitis B (CHB) patients is uncertain. DESIGN: We designed a Markov model to compare expected costs and quality-adjusted life-years (QALYs) of starting antiviral treatment at IT-phase ('treat-IT') vs delaying the therapy until active hepatitis phase ('untreat-IT') in CHB patients over a 20-year horizon. A cohort of 10 000 non-cirrhotic 35-year-old patients in IT-phase CHB (hepatitis B e antigen-positive, mean serum hepatitis B virus (HBV) DNA levels 7.6 log10 IU/mL, and normal alanine aminotransferase levels) was simulated. Input parameters were obtained from previous studies at Asan Medical Center, Korea. The incremental cost-effectiveness ratio (ICER) between the treat-IT and untreat-IT strategies was calculated. RESULTS: From a healthcare system perspective, the treat-IT strategy with entecavir or tenofovir had an ICER of US$16 516/QALY, with an annual hepatocellular carcinoma (HCC) incidence of 0.73% in the untreat-IT group. With the annual HCC risk ≥0.54%, the treat-IT strategy was cost-effective at a willingness-to-pay threshold of US$20 000/QALY. From a societal perspective considering productivity loss by premature death, the treat-IT strategy was extremely cost-effective, and was dominant (ICER <0) if the HCC risk was ≥0.43%, suggesting that the treat-IT strategy incurs less costs than the untreat-IT strategy. The most influential parameters on cost-effectiveness of the treat-IT strategy were those related with HCC risk (HBV DNA levels, platelet counts and age) and drug cost. CONCLUSION: Starting antiviral therapy in IT phase is cost-effective compared with delaying the treatment until the active hepatitis phase in CHB patients, especially with increasing HCC risk, decreasing drug costs and consideration of productivity loss.

Haematological cancer versus solid tumour end-of-life care: a longitudinal data analysis.

OBJECTIVE: To explore differences in end-of-life healthcare utilisation and medication costs between patients with haematological malignancies and patients with solid tumours. METHODS: Data on deceased patients with cancer were selected from the sample cohort data of health insurance claims from 2008 to 2015 in South Korea. They were categorised into two groups: patients with haematological malignancies and patients with solid tumours. Longitudinal data comprised the patient-month unit and aggregated healthcare utilisation and medication cost for 1 year before death. Healthcare utilisation included emergency room visits, hospitalisation and blood transfusions. Medication costs were subdivided into anticancer drugs, antibiotics, opioids, sedatives and blood preparation. Generalised linear mixed models were used to evaluate differences between the two groups and time trends. RESULTS: Of the 8719 deceased patients with cancer, 349 died from haematological malignancies. Compared with solid tumours, patients with haematological malignancies were more likely to visit the emergency room (OR=1.36, 95% CI 1.10 to 1.69) and receive blood transfusions (OR=5.44, 95% CI 4.29 to 6.90). The length of hospitalisation of patients was significantly different (difference=2.49 days, 95% CI 1.75 to 3.22). Medication costs, except for anticancer treatment, increased as death approached. The costs of antibiotics and blood preparations were higher in patients with haematological malignancies than in those with solid tumours: 3.24 (95% CI 2.14 to 4.90) and 4.10 (95% CI 2.77 to 6.09) times higher, respectively. CONCLUSIONS: Patients with haematological malignancies are at a higher risk for aggressive care and economic burden at the end of life compared with those with solid tumours. Detailed attention is required when developing care plans for end-of-life care of haematological patients.

Annona squamosa L. leaves inhibit alpha-melanocyte-stimulating hormone (α-MSH) stimulated melanogenesis via p38 signaling pathway in B16F10 melanoma cells.

BACKGROUND: Annona squamosa L. is a branched shrub, which is believed to be originated from the America and West Indies. Fruits of this plant are commonly known as custard apple, sugar apple, or sweetsops. A number of studies have proven a range of biological activities associated with various parts of A. squamosa. AIMS: The main aim of the present investigation was to evaluate potential inhibitory effects of A. squamosa leaf extract (ALE) on melanogenesis and its underlying mechanisms in B16F10 murine melanoma cells. METHODS: Inhibitory effects of A. squamosa leaf extract (ALE) on melanogenesis were primarily assessed by determining melanin contents. Effects of ALE on tyrosinase activity and the expression of proteins associated with melanogenesis were then determined. GC-MS analysis was carried out to identify the phytochemical profile of A. squamosa leaf extract. RESULTS: Antimelanogenic effects of ALE were found to exert through the inhibition of melanocyte inducing transcription factor (MITF) and activation of p38. GC-MS analysis identified ent-kaur-16-en-19-ol, 18-oxokauran-17-yl acetate, and ß-sitosterol as major phytochemicals. CONCLUSION: To our knowledge, this is the first study on the antimelanogenic effects of A. squamosa leaves, rationalizing the use A. squamosa leaf extract as a natural depigmentation agent for the treatment of skin diseases and the development of cosmetic products with enhanced skin-lightening capabilities.

Changes Over the Fermentation Period in Phenolic Compounds and Antioxidant and Anticancer Activities of Blueberries Fermented by Lactobacillus plantarum.

This study determined the effects of blueberry fermentation by Lactobacillus plantarum on antioxidant and anticancer activities. The fermented blueberries extracted with 80% ethanol (FBE) showed increased superoxide dismutase-like activity, increased scavenging of DPPH and alkyl radicals, and increased antiproliferative activity against human cervical carcinoma HeLa cells by inducing apoptosis. Seven representative phenolic compounds (malvidin 3-O-glucopyranoside, gallic acid, protocatechuic acid, catechol, chlorogenic acid, syringic acid, and epigallocatechin) in FBE were measured by high-performance liquid chromatography at different fermentation times. The content of each phenolic compound in the FBE was dependent on the fermentation period. Protocatechuic acid and catechol levels increased significantly with fermentation time. Of these three major compounds (protocatechuic acid, catechol, and chlorogenic acid), catechol showed the most significant anticancer activity when HeLa cells were treated with each of these three compounds alone or mixed in various ratios. Pearson's product-moment correlation analysis revealed that the increases in antioxidant and anticancer activities following blueberry fermentation were positively correlated with the phenolic acids present in FBE. PRACTICAL APPLICATION: Blueberries fermented with a tannase-producing lactic acid bacteria (LAB), Lactobacillus plantarum showed higher antioxidant activities and antiproliferative activities against human cervical carcinoma HeLa cells than did raw blueberries. L. plantarum fermentation biotransformed blueberry polyphenols into active phenol metabolites with strong antioxidant and antiproliferative activities. Our results suggest that fermented blueberries are rich in phenolic acids, which are a promising source of natural antioxidants and anticancer drugs and can be used as additives in food, pharmaceuticals, and cosmetic preparations.

Differences in the risk of mood disorders in patients with asthma-COPD overlap and in patients with COPD alone: a nationwide population-based retrospective cohort study in Korea.

BACKGROUND: Although feelings of anxiety and depression are common in patients with chronic obstructive pulmonary disease (COPD), little is known about the estimates of their incidence in patients with asthma-COPD overlap (ACO), which has been described and acknowledged as a distinct clinical entity. We aimed to estimate the risk of depression and anxiety among patients with ACO and compare it with the risk among those with COPD alone in the general population. METHODS: We conducted a nationwide population-based retrospective cohort study using the Korean National Sample Cohort database between 1 January, 2002, and 31 December, 2013. Patients who were diagnosed with COPD (International Classification of Diseases, 10th revision [ICD-10] codes J42-J44) at least twice and prescribed COPD medications at least once between 2003 and 2011 were classified into two categories: patients who were diagnosed with asthma (ICD-10 codes J45-J46) more than twice and at least once prescribed asthma medications comprised the ACO group, and the remaining COPD patients comprised the COPD alone group. Patients who had been diagnosed with depression or anxiety within a year before the index date were excluded. We defined the outcome as time to first diagnosis with depression and anxiety. Matched Cox regression models were used to compare the risk of depression and anxiety among patients with ACO and patients with COPD alone after propensity score matching with a 1:1 ratio. RESULTS: After propensity score estimation and matching in a 1:1 ratio, the cohort used in the analysis included 15,644 patients. The risk of depression during the entire study period was higher for patients with ACO than for patients with COPD alone (adjusted hazard ratio, 1.10; 95% confidence interval, 1.03-1.18; P value = 0.0039), with an elevated risk in patients aged 40-64 years (1.21; 1.10-1.34; 0.0001) and in women (1.18; 1.07-1.29; 0.0005). The risk of anxiety was higher for patients with ACO than for patients with COPD alone (1.06; 1.01-1.12; 0.0272), with a higher risk in patients aged 40-64 years (1.08; 1.00-1.17; 0.0392); however, the risk was not significant when stratified by sex. CONCLUSIONS: This population-based study revealed a higher incidence of depression and anxiety in patients with ACO than in patients with COPD alone.

A Comparison of Leukotriene Receptor Antagonists to Low-Dose Inhaled Corticosteroids in the Elderly with Mild Asthma.

BACKGROUND: Although elderly patients with asthma have clinical characteristics different from those of young adults, few studies or guidelines have focused on specific treatments for this population. OBJECTIVE: This study compared the effectiveness of leukotriene receptor antagonists (LTRAs) versus inhaled corticosteroids (ICSs) in elderly patients with asthma in real-world settings. METHODS: We extracted records for elderly patients with asthma who were newly prescribed LTRAs or low-dose ICSs from January 2003 to December 2010 from National Sample Cohort data of Korea. We defined the first prescription date for each medication as the index date. We compared the risks of asthma exacerbation between the 2 groups using Cox proportional-hazard regression after propensity score-based inverse probability of treatment weighting to balance covariates between treatment groups. We also compared asthma-related health care resource utilization and medication compliance in both groups using chi-square test and t test. RESULTS: The number of identified patients newly treated with LTRAs and low-dose ICSs was 1571 and 121, respectively. The risks of asthma exacerbation in the LTRA and low-dose ICS groups after weighting were not significantly different (hazard ratio, 0.98; 95% CI, 0.65-1.54). The proportion with high compliance (medication possession ratio ≥ 80%) in the LTRA group was higher than that in the low-dose ICS group. CONCLUSIONS: The effectiveness of LTRAs was not different from that of low-dose ICSs regarding the risk of asthma exacerbation in elderly patients with asthma in real-world settings. Given the practical benefits gained from convenient administration, LTRAs can be considered a reasonable alternative first-line therapy for elderly patients with mild asthma.

Risk of neuropsychiatric adverse events associated with the use of oseltamivir: a nationwide population-based case-crossover study.

Background: Although the potential risk of neuropsychiatric adverse events (NPAEs) upon administration of oseltamivir has been raised in case reports, the association between the use of oseltamivir and the risk of NPAEs is unclear. Objectives: We aimed to evaluate whether the use of oseltamivir triggers NPAEs. Patients and methods: We conducted a population-based case-crossover study using the National Sample Cohort data from the National Health Insurance Service in South Korea. From a total of 236 348 incident patients with NPAEs as either a primary or secondary diagnosis, our final case series included 5322 patients with a prior prescription for oseltamivir between 2009 and 2013. Exposure to oseltamivir was assessed during 2, 7, 14, 28 and 56 day hazard periods prior to each patient's NPAE. Three pre-consecutive control periods were matched using the same time windows. Conditional logistic regression analysis was used to estimate adjusted ORs (aORs), adjusting for time-variant diagnosis of influenza and concomitant medications. Results: Matched analyses found a consistently increased risk of NPAEs associated with the use of oseltamivir in the 2 day (aOR 1.90, 95% CI 1.29-2.81), 7 day (aOR 1.32, 95% CI 1.00-1.74), 14 day (aOR 1.28, 95% CI 1.03-1.60), 28 day (aOR 1.25, 95% CI 1.06-1.47) and 56 day (aOR 1.13, 95% CI 0.99-1.29) hazard periods compared with use in the three control periods. Conclusions: This study found that the short-term use of oseltamivir triggers the incidence of NPAEs. Early monitoring of NPAEs may be required when prescribing oseltamivir with careful consideration of the risk-benefit balance of oseltamivir.

Risk factors of asthma exacerbation based on asthma severity: a nationwide population-based observational study in South Korea.

OBJECTIVES: Asthma exacerbation, associated with many risks factors, can reflect management failure. However, little is known about how risk factors are associated with exacerbation, according to asthma severity. We aimed to investigate differences in risk factors in patients with different asthma severity and evaluate whether risk factors differed between frequent exacerbators and patients with single exacerbation. DESIGN: Nationwide population-based observational study. SETTING: Korean National Sample Cohort database. PARTICIPANTS: We included 22 130 adults with asthma diagnoses more than twice (ICD-10 (International Classification of Diseases, Tenth revision) codes J45 and J46) and one prescription for asthma medication from 2010 to 2011. OUTCOME MEASURES: Asthma exacerbation was defined as having a corticosteroid (CS) burst characterised by a prescription of high-dose oral CS for ≥3 days or one systemic CS injection, hospitalisation or emergency department visit. RESULTS: Among severities, history of CS bursts was significantly associated with exacerbation. In mild and moderate asthma, exacerbation was significantly associated with age ≥45 years, being female, gastro-oesophageal reflux disease and chronic rhinitis. High medication possession ratio (MPR≥50%), compared with low MPR (<20%) showed adjusted ORs of 0.828 (95% CI 0.707 to 0.971) and 0.362 (0.185 to 0.708) in moderate and severe asthma, respectively. In severe asthma, compared with mild asthma, only allergic rhinitis and history of hospitalisation were strongly associated with exacerbation. When comparing frequent exacerbators to patients with single exacerbation, age ≥45 years, atopic dermatitis, anxiety and history of CS burst were significant risk factors in mild and moderate asthma, whereas no risk factors were significant in severe asthma. CONCLUSIONS: Different associations between risk factors and asthma exacerbations based on asthma severity suggest that patients with mild asthma require greater attention to their age and comorbidities, whereas those with severe asthma require greater attention to hospitalisation history and drug adherence.

Relationship between lower urinary tract symptoms and cardiovascular risk scores including Framingham risk score and ACC/AHA risk score.

AIMS: This study attempted to investigate the association between lower urinary tract symptoms (LUTS) and cardiovascular disease (CVD) risk using International Prostate Symptom Score (IPSS) and CVD risk scores and to overcome the limitations of previous relevant studies. METHODS: A total of 2994 ostensibly healthy males, who participated in a voluntary health check in a health promotion center from January 2010 to December 2014, were reviewed. CVD risk scores were calculated using Framingham risk score and American College of Cardiology (ACC)/American Heart Association (AHA) score. Correlation and multivariate logistic regression analysis to predict the CVD risk severity were performed. RESULTS: Correlation between total IPSS with CVD risk scores demonstrated significant positive associations, which showed higher correlation with ACC/AHA score than the Framingham score (r = 0.18 vs 0.09, respectively). For ACC/AHA score, the partial correlation after adjustment of body mass index (BMI) showed significant positive correlations between all LUTS parameters and PSA. For the Framingham score, all variables, except IPSS Q2 and IPSS Q6, showed significant positive correlations. After adjustment of BMI, prostate volume and PSA, only the severe LUTS group showed significant relationship with intermediate-high CVD risk severity, as compared with normal LUTS group (OR = 2.97, 95%CI (1.35-6.99)). CONCLUSION: Using two validated CVD risk calculators, we observed that LUTS is closely associated with future CVD risk. To predict the intermediate-high CVD risk severity, severe LUTS was a sentinel sign, the presence of which warrants the importance of an earlier screening for CVD.

Comparison of Effectiveness Between Delamanid and Bedaquiline Among Patients with Multidrug-Resistant Tuberculosis: A Markov Model Simulation Study.

BACKGROUND: No clear evidence on the comparative effectiveness of delamanid (DLM) and bedaquiline (BDQ) has been published. OBJECTIVE: This study aims to estimate the incremental effectiveness of DLM versus BDQ in patients with multidrug-resistant tuberculosis (MDR-TB). METHODS: We developed a Markov model based on a cohort with MDR-TB, which consisted of success, failure, loss to follow-up, and death. The cohort simulation was conducted assuming each patient was 36 years old and, lived until age 82, and that the cycle length was 1 year. Patients with an inadequate response to DLM, the background regimen, or BDQ for 2 years were transitioned through the next treatment sequence. We evaluated the incremental effectiveness of the drugs using the quality-adjusted life-year (QALY) resulting from this Markov model over a lifetime. RESULTS: The incremental effectiveness of DLM (13.96 QALYs) was greater by 2.44 QALYs per patient than the background regimen (11.52 QALY), while the incremental effectiveness of BDQ (10.40 QALY) was higher by 1.14 QALY per patient than the background regimen (9.26 QALY). Consequently, the incremental effectiveness of DLM was relatively more positive by 1.30 QALY than those of BDQ per patient over a lifetime. LIMITATIONS: This study is a simulation study. Therefore, the treatment sequence for patients may be different in the real world. CONCLUSIONS: Our lifetime simulated data found that DLM was relatively more favorable than BDQ. A Markov model can be considered an alternative approach when there is an absence of head-to-head clinical data.