Protein-enriched soup and weekly exercise improve muscle health: A randomized trial in mid-to-old age with inadequate protein intake.

BACKGROUND: Prior research has highlighted the synergistic impact of protein supplementation on muscle function post-exercise in adults; however, evidence supporting the combined effects were less robust and inconsistent on those with protein insufficiency. This investigation aims to explore efficacy of protein-enriched soup coupled with exercise on muscle health and metabolism in middle-aged and older adults with suboptimal protein intake. METHODS: An open-label, 12-week, randomized controlled trial involving participants with insufficient protein intake (<1.0 g/kg/day) was done. The intervention group consumed protein-enriched soup (24-30 g protein daily) and 1-h weekly exercise, while controls received health education. Assessments included laboratory tests, functional assessments, and body composition. RESULTS: In this trial, 97 out of 100 randomized participants (mean age: 64.65 ± 4.84 years, 81.8% female) completed the study (47 in intervention group and 50 in control group). Compared results of baselines, at 1 and 3 months of intervention, significant improvements in waist circumference (83.48 ± 10.22 vs. 82.5 ± 9.88 vs. 82.37 ± 9.42 cm, P for trend = 0.046), 6-min walking distance (525.65 ± 58.46 vs. 534.47 ± 51.87 vs. 552.02 ± 57.66 m, P for trend = 0.001), five-time sit-to-stand time (7.63 ± 1.63 vs. 6.81 ± 1.8 vs. 6.4 ± 1.42 s, P for trend <0.001), grip strength (26.74 ± 6.54 vs. 27.53 ± 6.99 vs. 28.52 ± 7.09 kg, P for trend <0.001), and MNA score (26.8 ± 2.14 vs. 27.73 ± 1.74 vs. 27.55 ± 1.72, P for trend <0.001) were discerned within the intervention group. The intervention demonstrated a significant reduction in serum triglyceride (105.32 ± 49.84 vs. 101.36 ± 42.58 vs. 93.43 ± 41.49 mg/dL, P for trend = 0.023), increased HDL-C (60.04 ± 16.21 vs. 60 ± 17.37 vs. 62.55 ± 18.27 mg/dL, P for trend = 0.02), and DHEA-S levels (97.11 ± 54.39 vs. 103.39 ± 56.75 vs. 106.83 ± 60.56 µg/dL, P for trend = 0.002). Serum myostatin did not differ in both groups, but serum leptin levels significantly increased (9118.88 ± 5811.68 vs. 11508.97 ± 7151.08 vs. 11220.80 ± 7190.71 pg/mL, P for trend = 0.016) in controls. The intervention group showed greater improvements in 6 min walking distance (ß = 0.71, 95% CI: 6.88 to 40.79, P = 0.006), five-time sit-to-stand test (ß = -0.87, 95% CI: -1.59 to -0.15, P = 0.017), MNA score (ß = 0.96, 95% CI: 0.20 to 1.71, P = 0.013), serum triglycerides (ß = -15.01, 95% CI: -27.83 to -2.20, P = 0.022), LDL-C (ß = -9.23, 95% CI: -16.98 to -1.47, P = 0.020), and DHEA-S levels (ß = 9.98, 95% CI: 0.45 to 19.51, P = 0.04) than controls. CONCLUSIONS: Protein-enriched soup with weekly exercise over 12 weeks significantly improved physical performance, lipid profile, and DHEA-S levels among middle-aged and older adults with inadequate protein intake, while studies assessing long-term benefits of the intervention are needed.

Ten-year epidemiology and risk factors of cytomegalovirus infection in hematopoietic stem cell transplantation patients in Taiwan.

BACKGROUND: Cytomegalovirus (CMV) can cause infection and critical diseases in hematopoietic stem cell transplantation (HSCT) recipients. This study aimed to explore the cumulative incidence and risk factors for CMV infection and disease among HSCT recipients in Taiwan. METHODS: This retrospective cohort study using the Taiwan Blood and Marrow Transplantation Registry (TBMTR) included HSCT recipients between 2009 and 2018 in Taiwan. The primary outcome was cumulative incidence of CMV infection or disease at day 100 after HSCT. Secondary outcomes included day 180 cumulative incidence of CMV infection or disease, infection sites, risk factors for CMV infection or disease, survival analysis, and overall survival after CMV infection and disease. RESULTS: There were 4394 HSCT recipients included in the study (2044 auto-HSCT and 2350 allo-HSCT). The cumulative incidence of CMV infection and disease was significantly higher in allo-HSCT than in auto-HSCT patients at day 100 (53.7% vs. 6.0%, P < 0.0001 and 6.1% vs. 0.9%, P < 0.0001). Use of ATG (HR 1.819, p < 0.0001), recipient CMV serostatus positive (HR 2.631, p < 0.0001) and acute GVHD grades ≥ II (HR 1.563, p < 0.0001) were risk factors for CMV infection, while matched donor (HR 0.856, p = 0.0180) and myeloablative conditioning (MAC) (HR 0.674, p < 0.0001) were protective factors. CONCLUSION: The study revealed a significant disparity in terms of the incidence, risk factors, and clinical outcomes of CMV infection and disease between auto and allo-HSCT patients. These findings underscore the importance of considering these factors in the management of HSCT recipients to improve outcomes related to CMV infections.

The burden of frailty in heart failure: Prevalence, impacts on clinical outcomes and the role of heart failure medications.

BACKGROUND: Frailty often coexists with heart failure (HF), which significantly aggravates the clinical outcomes of older adults. However, studies investigating the interplay between frailty and HF in older adults are scarce. We aimed to assess the prevalence of frailty using the cumulative deficit approach and evaluate the impacts of frailty on health utilization, use of HF-related medications and adverse clinical outcomes (all-cause mortality, all-cause readmissions and HF readmissions) among older HF patients. METHODS: A total of 38 843 newly admitted HF patients were identified from Taiwan's National Health Insurance Research Database and categorized into three frailty subgroups (fit, mild frailty and severe frailty) based on the multimorbidity frailty index. Cox regression models and Fine and Gray subdistribution hazard models were used to estimate the impacts of frailty on clinical outcomes at 1 and 2 years of follow-up. Generalized estimating equation models were further conducted to evaluate the associations between longitudinal and time-varying use of HF-related medications and clinical outcomes among distinct frailty subgroups. RESULTS: Of 38 843 older HF patients (mean age 80.4 ± 8.5 years, 52.3% females) identified, 68.3% were categorized as frail (47.5% of mild frailty and 20.8% of severe frailty). The median number of readmissions (fit: 1 [inter-quartile range-IQR 2], mild frailty: 1 [IQR 2] and severe frailty: 2 [IQR 3]) increased with the severity of frailty. Only 27.3% of HF patients died of cardiovascular diseases regardless of their frailty status. Compared with the fit group, the severe frailty group was associated with increased risk of all-cause mortality (adjusted hazard ratio 1.16, 95% confidence interval [CI] 1.11-1.21), all-cause readmissions (subdistributional hazard ratio (sHR) 1.21, 95% CI 1.16-1.25) and HF-related readmissions (sHR 1.14, 95% CI 1.09-1.20) at 2 years of follow-up. Those who used triple or more HF-related medications were at lower risk for all-cause readmissions (adjusted odds ratio [aOR] 0.49, 95% CI 0.44-0.54) and HF-related readmissions (aOR 0.42, 95% CI 0.37-0.47) at 2 years of follow-up even in the severe frailty group. CONCLUSIONS: Frailty is highly prevalent and associated with increased risk of all-cause mortality, all-cause readmissions and HF readmissions among older HF patients. Those who were using triple or more HF-related medications were at lower risk of adverse clinical outcomes across distinct frailty subgroups. Further studies are needed to optimize the treatment strategies for older HF patients with distinct frailty status.

The incidences and clinical outcomes of cryptococcosis in Taiwan: A nationwide, population-based study, 2002-2015.

Large-scale epidemiological data on cryptococcosis other than cryptococcal meningitis (CM), human immunodeficiency virus (HIV)- or solid organ transplantation (SOT)-associated cryptococcosis are limited. This study investigated the disease burden of cryptococcosis in Taiwan over 14 years. Incident episodes of cryptococcosis, comorbidities, treatment, and outcomes were captured from Taiwan's National Health Insurance Research Database and National Death Registry between 2002 and 2015. Of 6647 episodes analyzed, the crude incidence rate per 100 000 population increased from 1.48 in 2002 to 2.76 in 2015, which was driven by the growing trend in the non-CM group (0.86-2.12) but not in the CM group (0.62-0.64). The leading three comorbidities were diabetes mellitus (23.62%), malignancy (22.81%), and liver disease (17.42%). HIV accounted for 6.14% of all episodes and was associated with the highest disease-specific incidence rate (269/100 000 population), but the value dropped 16.20% biennially. Within 90 days prior to cohort entry, 30.22% of episodes had systemic corticosteroid use. The in-hospital mortality of all episodes was 10.80%, which varied from 32.64% for cirrhosis and 13.22% for HIV to 6.90% for SOT. CM was associated with a higher in-hospital mortality rate than non-CM (19.15% vs. 6.33%). At diagnosis, only 48.53% of CM episodes were prescribed an amphotericin-based regimen. The incidence rate of cryptococcosis was increasing, especially that other than meningitis and in the non-HIV population. A high index of clinical suspicion is paramount to promptly diagnose, treat, and improve cryptococcosis-related mortality in populations other than those with HIV infection or SOT.

This nationwide study showed that the incidence rate of cryptococcosis doubled from 2002 to 2015. Non-meningeal cryptococcosis and non-HIV/nontransplant (NHNT)-associated cryptococcosis contributed to this increase. Our study highlighted the underestimated burden of cryptococcosis in the NHNT hosts.

Risk of thromboembolic events associated with different multiple myeloma regimens in Taiwan: a nested case-control study.

Although novel agents for multiple myeloma (MM) have a better response rate and survival in both newly diagnosed and relapsed/refractory MM patients, concerns regarding the association between MM treatments and thromboembolic events have been raised. The aim of this population-based study was to examine the association between different combinations of MM treatments and the risk of thromboembolic events. We conducted a nested case-control study using the Taiwan Cancer Registry (TCR) and National Health Insurance Research Database (NHIRD). Adult patients newly diagnosed with MM and treated with at least one of the immunomodulatory agents between 2008 and 2016 were identified. Among them, we further identified patients who developed thromboembolic events as cases and selected controls matched by age, sex and duration of MM diagnosis at a ratio of 1:5. The index date was defined as the day one year before the diagnosis date of thromboembolic events in the case group and the corresponding date in the control group. Conditional logistic regression was used to examine the association between different MM treatment regimens and the risk of thromboembolic events. A total of 4,180 newly diagnosed MM patients treated with at least one of the immunomodulatory agents were identified (mean age: 67.2 years; male: 55.7%). In this MM cohort, we further identified 388 cases and 1,940 matched controls (mean age: 71 years; male: 64.2%). The use of a thalidomide/bortezomib/steroid combination (odds ratio (OR) 2.95 [95% confidence interval (CI) 1.47-5.95]), thalidomide monotherapy (OR 3.33; 95% CI, 1.59-6.94), and a thalidomide/steroid combination (OR 4.24; 95% CI, 2.00-8.98) were associated with an increased risk of thromboembolic events. Other risk factors, particularly a history of thromboembolic events, including ischemic heart disease and pulmonary embolism, were significantly associated with increased risk of thromboembolic events. We found that the use of thalidomide alone and in specific combinations was associated with an increased risk of thromboembolic events.

Medication overload: A closer look at polypharmacy and potentially inappropriate medications among older people in Taiwan and Japan.

BACKGROUND: Polypharmacy and potentially inappropriate medications (PIM) are widely recognized as vital quality indicators of pharmacotherapy in older adults. As Taiwan and Japan grapple with the ongoing challenges of population aging, obtaining an accurate understanding of the prevalence of these indicators is crucial for developing effective strategies to optimize pharmacotherapy in older populations. The present study aims to comprehensively evaluate the prevalence of polypharmacy and PIMs in Taiwan and two Japanese cohorts, shedding light on the similarities and differences in prescribing practices across these populations. METHODS: This study employed a cross-sectional design to investigate individuals aged ≥65 years in Taiwan, as well as two Japanese cohorts: Japan Cohort 1 (dispensing data from chain pharmacies; year 2014 and 2019) and Japan Cohort 2 (claims data; year 2017 and 2019). The prescription records of these participants were collected from the national claims database in Taiwan for the years 2014, 2017, and 2019. To identify polypharmacy and hyper-polypharmacy, the study defined the use of 5-9 and 10+ drugs, respectively. Furthermore, the study identified PIMs based on the STOPP-J criteria. Notably, the study further explored the most frequently used PIMs (by categories) in Taiwan. RESULTS: In the year 2019, the prevalence of polypharmacy exhibited similar rates in Taiwan (35.4%) and Japan Cohort 2 (33.1%), while surpassing that of Japan Cohort 1 (25.6%). Nonetheless, the incidence of PIMs in Taiwan was the highest (66.5%), exceeding those of the two Japanese cohorts (Cohort 1: 43.7% and Cohort 2: 40.2%) in the same year. Notably, the top three categories of commonly used PIMs in Taiwan comprised non-steroidal anti-inflammatory drugs (NSAIDs), antithrombotic drugs, and benzodiazepines. CONCLUSIONS: This study highlights the varying prevalence of polypharmacy and PIMs between Taiwan and Japan, but emphasizes the need for collaborative efforts towards optimizing pharmacotherapy in older adults.

Health care utilization and potentially preventable adverse outcomes of high-need, high-cost middle-aged and older adults: Needs for integrated care models with life-course approach.

PURPOSE OF THE RESEARCH: The success of modern health care increases life expectancy and prolongs the days of having multimorbidity and functional limitations; the so-defined "high need, high cost (HNHC)" state represents the extreme scenarios of care burden and complexity. This study aims to explore health care utilization and the risk of preventable adverse outcomes stratified by age and HNHC state. MATERIALS AND METHODS: We conducted a retrospective cohort study using the National Health Insurance (NHI) database. People aged ≥40 years were included and further stratified by age (middle-aged: 40-64 and older adults: 65) and HNHC state (top 10% of spending). Health care utilization and drug consumption across different groups were obtained. The multimorbidity frailty index (mFI) was developed for further analysis. Cox regression models were used to examine the associations between HNHC and adverse clinical outcomes (preventable hospitalizations, preventable emergency department visits, and mortality). RESULTS: HNHC participants were older, had a higher mFI and drug consumption, and had higher health care utilization. Compared with non-HNHC participants, HNHC participants exhibited a 4.4-fold and 2.4-fold higher risk of preventable hospitalizations in middle-aged (HR=4.41; 95% CI, 4.17-4.65, p<0.01) and older adults (HR=2.44; 95% CI, 2.34-2.55, p<0.01). Similar risks were observed for preventable emergency department visits and mortality (all p<0.01). CONCLUSIONS: The HNHC state substantially increased health care utilization, polypharmacy, and potentially preventable adverse outcomes after adjustment for frailty. Intervention studies developing integrated care models using the life-course approach are needed to improve the quality of health care systems in super-aged societies.

Transitions in Frailty and 4-Year Mortality Risk in Taiwan Longitudinal Study on Aging.

OBJECTIVES: To explore the associations of (1) the frailty phenotype or frailty index transition with cause-specific mortality, and (2) different combinations of transition in frailty phenotype and frailty index with all-cause mortality. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Data from 3529 respondents aged >50 years who completed the 1999 and 2003 surveys of the Taiwan Longitudinal Study on Aging were analyzed. METHODS: Cox regression and subdistribution hazard models were constructed to investigate frailty phenotype or frailty index transitions (by categories of frailty phenotype, absolute and percentage changes in frailty index, and combined categories of the 2 measurements) and subsequent 4-year all-cause and cause-specific mortality, respectively. RESULTS: Among the frailty phenotype transition groups, the improved frailty group had overall mortality risk comparable to that of the maintained robustness/prefrailty group [hazard ratio (HR): 0.9; 95% CI: 0.7-1.2] and lower risk of mortality due to organ failure (HR: 0.4; 95% CI: 0.2-0.8; P = .015), whereas the worsened frailty group had the highest risk of all-cause mortality and death from infection, malignancy, cardiometabolic/cerebrovascular diseases, and other causes (HR: 1.8-3.7; all P < .03). The rapidly increased frailty index group had significantly higher all-cause and every cause-specific mortality than the decreased frailty index group (HR: 1.8-7.7; all P < .05). When frailty phenotype and frailty index transition groups were combined, participants with worsened frailty/rapidly increased frailty index had increased risk under the same frailty index/frailty phenotype transition condition, particularly for large changes in each factor (HR: 1.5-2.2; P < .01 for worsened frailty; 1.7-4.5, P < .03 for rapidly increased frailty index). CONCLUSIONS AND IMPLICATIONS: We found that considering both frailty phenotype and frailty index provided best mortality prediction. These associations were independent of baseline frailty status and comorbidities. Nevertheless, even capturing transitions in frailty phenotype or frailty index only can provide good mortality prediction, which supported adopting these approaches in different clinical settings.

Impact of Frailty on Survivals of Prostate Cancer Patients Treated with Radiotherapy.

BACKGROUND: Frailty has been linked to an increased risk of adverse outcomes among older men with prostate cancer (PCa), which in turn impacts survival. We evaluated the associations between frailty and risks of all-cause mortality and cancer-specific mortality in PCa patients treated with radiotherapy (RT). METHODS: We conducted a retrospective cohort study using the Taiwan Cancer Registry Database and National Health Insurance Research Database. Patients aged ≥65 years with newly-diagnosed PCa, and receiving RT as initial treatment between 2011 and 2015 were identified in the study. Frailty was measured using the multimorbidity frailty index (mFI), categorized as fit, mild frailty, moderate frailty, and severe frailty. Cox regression models were used to examine the association between frailty and mortality. RESULTS: Among 4,291 men with a median age of 75 years at PCa diagnosis, 21.87% were categorized as fit, 44.72% were mild frailty, 23.02% were moderate frailty, and 10.42% were severe frailty. With the mean follow-up duration of 4.8 years, patients in the severe frailty group had a significantly higher all-cause mortality risk (HR 1.86; 95% CI, 1.48-2.32) and cancer-specific mortality risk (HR 1.44; 95% CI, 1.05-1.98) than patients in the fit group, whereas no such association was found in the mild frailty group after adjustment. CONCLUSIONS: This is the first population-based cohort study to evaluate the feasibility of mFI on mortality of PCa patients treated with RT. We found that severe frailty was associated with a higher risk of both all-cause mortality and cancer-specific mortality.

The epidemiology, treatment patterns, healthcare utilizations and costs of Acute Myeloid Leukaemia (AML) in Taiwan.

BACKGROUNDS: An increasing incidence of Acute Myeloid Leukaemia (AML) has been reported in several Western countries. However, the epidemiology of AML in Asia is very limited. According to the National Comprehensive Cancer Network (NCCN) guideline of AML, a range of conventional therapy options is available to AML patients. Nevertheless, different treatment strategies may result in diverse healthcare utilization and costs. Understanding the treatment patterns, healthcare utilization and costs of AML would thus be essential for clinicians and policymakers to optimize the treatment strategies of AML. OBJECTIVES: The objective of this study was to investigate the incidence, treatment patterns, healthcare utilization and costs of AML in Taiwan using a nationwide population database. METHODS: We retrospectively identified AML patients diagnosed from 2006 to 2015 from the Taiwan Cancer Registry Database (TCRD) and estimated the epidemiology of AML in Taiwan. The TCRD was linked to National Health Insurance Research Database (NHIRD) to collect the treatment patterns and health care utilization. Patients diagnosed with AML from 2011 to 2015 were further identified to analyze treatment patterns, healthcare utilization and costs. RESULTS: The crude annual incidence of AML increased from 2.78 to 3.21 cases per 100,000 individuals from 2006 to 2015. However, the age-standardized rate (ASRs) of AML slightly declined from 2.47 to 2.41 cases per 100,000 individuals in the same period. Among 2,179 AML patients who received induction therapy (median age: 56 years), most of them (n = 1744; 80.04%) received standard-dose cytarabine (SDAC) regimen. The remaining 162 patients received high dose cytarabine (HDAC) and 273 patients received non-standard dose cytarabine (N-SDAC) regimen as the induction therapy. The median medical costs in our study for patients treated with chemotherapy alone was $42,271 for HDAC, $36,199 for SDAC and $36,250 for N-SDAC. For those who received hematopoietic stem cell transplantation (HSCT) after induction therapy, their median medical costs were $78,876 for HDAC, $78,593 for SDAC and $79,776 for N-SDAC. CONCLUSIONS: This study is the first population-based study conducted in Asia to provide updated and comprehensive information on epidemiology, treatment patterns and healthcare resource utilization and costs of AML.

Muscle-to-fat ratio identifies functional impairments and cardiometabolic risk and predicts outcomes: biomarkers of sarcopenic obesity.

BACKGROUND: Sarcopenic obesity aims to capture the risk of functional decline and cardiometabolic diseases, but its operational definition and associated clinical outcomes remain unclear. Using data from the Longitudinal Aging Study of Taipei, this study explored the roles of the muscle-to-fat ratio (MFR) with different definitions and its associations with clinical characteristics, functional performance, cardiometabolic risk and outcomes. METHODS: (1) Appendicular muscle mass divided by total body fat mass (aMFR), (2) total body muscle mass divided by total body fat mass (tMFR) and (3) relative appendicular skeletal muscle mass (RASM) were measured. Each measurement was categorized by the sex-specific lowest quintiles for all study participants. Clinical outcomes included all-cause mortality and fracture. RESULTS: Data from 1060 community-dwelling older adults (mean age: 71.0 ± 4.8 years) were retrieved for the study. Overall, 196 (34.2% male participants) participants had low RASM, but none was sarcopenic. Compared with those with high aMFR, participants with low aMFR were older (72 ± 5.6 vs. 70.7 ± 4.6 years, P = 0.005); used more medications (2.9 ± 3.3 vs. 2.1 ± 2.5, P = 0.002); had a higher body fat percentage (38 ± 4.8% vs. 28 ± 6.4%, P < 0.001), RASM (6.7 ± 1.0 vs. 6.5 ± 1.1 kg/m2 , P = 0.001), and cardiometabolic risk [fasting glucose: 105 ± 27.5 vs. 96.8 ± 18.7 mg/dL, P < 0.001; glycated haemoglobin (HbA1c): 6.0 ± 0.8 vs. 5.8 ± 0.6%, P < 0.001; triglyceride: 122.5 ± 56.9 vs. 108.6 ± 67.5 mg/dL, P < 0.001; high-density lipoprotein cholesterol (HDL-C): 56.2 ± 14.6 vs. 59.8 ± 16 mg/dL, P = 0.010]; and had worse functional performance [Montreal Cognitive Assessment (MoCA): 25.7 ± 4.2 vs. 26.4 ± 3.0, P = 0.143, handgrip strength: 24.7 ± 6.7 vs. 26.1 ± 7.9 kg, P = 0.047; gait speed: 1.8 ± 0.6 vs. 1.9 ± 0.6 m/s, P < 0.001]. Multivariate linear regression showed that age (ß = 0.093, P = 0.001), body mass index (ß = 0.151, P = 0.046), total percentage of body fat (ß = 0.579, P < 0001) and RASM (ß = 0.181, P = 0.016) were associated with low aMFR. Compared with those with high tMFR, participants with low tMFR were older (71.7 ± 5.5 vs. 70.8 ± 4.7 years, P = 0.075); used more medications (2.8 ± 3.3 vs. 2.1 ± 2.5, P = 0.006); had a higher body fat percentage (38.1 ± 4.7 vs. 28 ± 6.3%, P < 0.001), RASM (6.8 ± 1.0 vs. 6.5 ± 1.1 kg/m2 , P < 0.001), and cardiometabolic risk (fasting glucose: 104.8 ± 27.6 vs. 96.9 ± 18.7 mg/dL, P < 0.001; HbA1c: 6.1 ± 0.9 vs. 5.8 ± 0.6%, P < 0.001; triglyceride: 121.4 ± 55.5 vs. 108.8 ± 67.8 mg/dL, P < 0.001; HDL-C: 56.4 ± 14.9 vs. 59.7 ± 15.9 mg/dL, P = 0.021); and had worse functional performance (MoCA: 25.6 ± 4.2 vs. 26.5 ± 3.0, P = 0.056; handgrip strength: 24.6 ± 6.7 vs. 26.2 ± 7.9 kg, P = 0.017; gait speed: 1.8 ± 0.6 vs. 1.9 ± 0.6 m/s, P < 0.001). Low tMFR was associated with body fat percentage (ß = 0.766, P < 0.001), RASM (ß = 0.476, P < 0.001) and Mini-Nutritional Assessment (ß = -0.119, P < 0.001). Gait speed, MoCA score, fasting glucose, HbA1c and tMFR were significantly associated with adverse outcomes, and the effects of aMFR were marginal (P = 0.074). CONCLUSIONS: Older adults identified with low MFR had unfavourable body composition, poor functional performance, high cardiometabolic risk and a high risk for the clinical outcome.

Drug use at the end of life in older adults.

OBJECTIVE: To investigate symptom-relief and comorbid drug uses at the end of life for older people with different dying trajectories (cancer, organ failure, frailty and sudden death) in Taiwan. METHODS: In a retrospective observational study of older people aged 65 years and older who died in hospitals between 2008 and 2012, we used NHIRD to measure numbers, incremental changes and determinants of symptom-relief and comorbid drug use in the last month of outpatient care and last hospitalisation before death. RESULTS: We included 59 407 older adults (cancer 37%, organ failure 26%, frailty 35% and sudden death 2%) who died in hospitals for this study. In the last hospitalisation before death, individuals who died of cancer received greatest number of symptom-relief drugs (mean: 4.65, [SD 2.77]) and increased most the average change in the number of symptom-relief drug use (+1.60; SD 3.36). However, individuals who died of organ failure received the highest number of comorbid drugs (mean 2.88, [SD 1.95]) and also increased most the average change in the number of comorbid drug use (+0.17; SD 2.28) at last hospitalisation. Different dying trajectories were key determinants of receiving symptom-relief and comorbid drugs in our study. CONCLUSIONS: Our study suggests that the drug use of older adults at the end of life in the cancer group is different from that in the organ failure and frailty groups. Policymakers and health professionals should consider the different strategies to optimise drug use for older people with different dying trajectories near their end of life.

Tyrosine Kinase Inhibitors and Vascular Adverse Events in Patients with Chronic Myeloid Leukemia: A Population-Based, Propensity Score-Matched Cohort Study.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have shown long-term survival benefits in patients with chronic myeloid leukemia (CML). Nevertheless, significant concern has been raised regarding long-term TKI-associated vascular adverse events (VAEs). The objective of this retrospective cohort study was to investigate the incidence of VAEs in Taiwanese patients with CML treated with different TKIs (imatinib, nilotinib, and dasatinib) as well as potential risk factors. MATERIALS AND METHODS: We conducted a retrospective cohort study using the Taiwan Cancer Registry Database and National Health Insurance Research Database. Adult patients diagnosed with CML from 2008 to 2016 were identified and categorized into three groups according to their first-line TKI treatment (imatinib, nilotinib, and dasatinib). Propensity score matching was performed to control for potential confounders. Cox regressions were used to estimate the hazard ratio (HR) of VAEs in different TKI groups. RESULTS: In total, 1,111 patients with CML were included in our study. We found that the risk of VAEs in nilotinib users was significantly higher than that in imatinib users, with an HR of 3.13 (95% confidence interval (CI), 1.30-7.51), whereas dasatinib users also showed a nonsignificant trend for developing VAEs, with an HR of 1.71 (95% CI, 0.71-4.26). In multivariable logistic regression analysis, only nilotinib usage, older age, and history of cerebrovascular diseases were identified as significant risk factors. The annual incidence rate of VAEs was highest within the first year after the initiation of TKIs. CONCLUSION: These findings can support clinicians in making treatment decisions and monitoring VAEs in patients with CML in Taiwan. IMPLICATIONS FOR PRACTICE: This study found that patients with chronic myeloid leukemia (CML) treated with nilotinib and dasatinib may be exposed to a higher risk of developing vascular adverse events (VAEs) compared with those treated with imatinib. Thus, this study suggests that patients with CML who are older or have a history of cerebrovascular diseases should be under close monitoring of VAEs, particularly within the first year after the initiation of tyrosine kinase inhibitors.

Real-World Outcomes of Patients with Acute Myeloid Leukemia in Taiwan: A Nationwide Population-Based Study, 2011-2015.

BACKGROUND: Acute myeloid leukemia (AML) is a hematological malignancy originating from myeloid precursor cells, with different cytogenetic abnormalities, genetic mutations and diverse clinical prognoses. We investigated the clinical characteristics, treatment patterns, and outcomes of adult AML patients in Taiwan. MATERIALS AND METHODS: We retrospectively included 3851 patients with AML in the Taiwan Cancer Registry Database from 2011 to 2015. We excluded patients younger than 20 years, with acute promyelocytic leukemia, and with no pathological confirmation. RESULTS: Among the 3292 patients included, 2179 received induction chemotherapy and 1113 did not, because of older age and higher Charlson comorbidity index (CCI) score. Among the 2179 treated patients, 162 received high-dose cytarabine-based chemotherapy, 1535 received standard-dose cytarabine with anthracyclines, 209 received low-dose cytarabine-based chemotherapy, and 273 received chemotherapy without cytarabine. Patients in the low-dose cytarabine group had the oldest age and highest CCI scores compared with the other groups. In the analysis of overall survival (OS), the median OS of the overall study population was 6.27 months. Treated patients with AML had a longer OS than untreated ones (12.43 months treated vs. 2.03 months not treated; P < .0001). In the multivariate analyses of the treated patients with AML, several factors indicated better prognosis, including receiving standard-dose or high-dose cytarabine, female sex, younger age, lower CCI score, treatment at a medical center, favorable cytogenetic abnormalities, and allogeneic hematopoietic stem cell transplantation. CONCLUSION: Our study was a population-based study that illustrates the real-world outcomes of adult patients with AML in Taiwan.

Epidemiology, treatment patterns and survival of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) in Taiwan, 2006-2015.

AIM/OBJECTIVE: Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) is one of the most frequent types of leukaemia/lymphoma in adults in Western countries. However, there are few studies regarding its epidemiology and treatment patterns in Asian countries. METHODS: To investigate CLL/SLL in Asian populations, we identified CLL/SLL patients diagnosed during 2006 to 2015 from the Taiwan Cancer Registry Database and estimated the incidence. Further, patients diagnosed during 2008 to 2015 were included for the analysis of treatment patterns and survivals. Treatments for CLL/SLL were retrieved from the Taiwan's National Health Insurance Research Database and survival data from the National Death Registry. RESULTS: In total, 1497 patients who were older than 20 years and had newly diagnosed CLL/SLL during 2006-2015 were identified. The age-standardized incidence rates of CLL/SLL (0.36 per 100 000 persons in 2006, and 0.54 in 2015) increased during the 10-year period. The sex ratio was ranged from 1.21 to 2.63 with male predominant during 2006 and 2015. For the analysis of treatment patterns (n = 1236), 72.8% patients received chemotherapies. The median duration between the diagnosis and start of treatments was 27 days, and monotherapy of chlorambucil, bendamustine or cyclophosphamide was the most common regimen in initial treatments. The median follow-up duration for the patients receiving therapies was 29.6 months, and 45.0% patients experienced relapse or refractory. In patients with relapse/refractory CLL/SLL, 34.1% received rituximab-containing chemotherapies. Three hundred and ninety-nine (32.3%) patients received intensive treatments, and 175 (43.9%) of them received rituximab-containing chemotherapies. The 5-year overall survival (OS) rate was 61%, and age was an important prognostic factor for CLL/SLL patients. CONCLUSIONS: This study is the first population-based study in Asia and provides comprehensive evidence of epidemiology, treatment patterns and survivals of CLL/SLL in an Asian population.

Impact of Multiple Prescriptions With Anticholinergic Properties on Adverse Clinical Outcomes in the Elderly: A Longitudinal Cohort Study in Taiwan.

The cumulative effect of multiple pharmaceutics with anticholinergic properties (i.e., anticholinergic burden), can serve as an indicator of suboptimal prescribing in the elderly. Yet, no research is available concerning the effect of different compositions of score on adverse outcomes under the same anticholinergic burden. This population-based cohort study investigated whether different combinations of medications with anticholinergic properties have different impacts on adverse outcomes in the elderly using the Anticholinergic Risk Scale (ARS) and Anticholinergic Cognitive Burden Scale (ACB) scores. We included 116,043 people aged 65 years and older from Taiwan's Longitudinal Health Insurance Database and measured their monthly anticholinergic burden over a 10-year follow-up period (from January 1, 2002, to December 31, 2011). We analyzed the association between different anticholinergic score compositions and adverse outcomes (emergency department visits, all-cause hospitalizations, fracture-specific hospitalizations, and incident dementia) via generalized estimating equations. Cumulative effects of multiple medications with low anticholinergic activity were associated with a greater risk for emergency department visits and all-cause hospitalizations (emergency department visits for 65-74 year olds (y/o): ACB 1 + 1 + 1, adjusted odds ratio (aOR) 2.05 (1.99-2.12); ACB 1 + 2, aOR 2.04 (1.91-2.17); and ACB 3, aOR 1.62 (1.57-1.66)). In contrast, using medications with greater potency had a greater impact on central adverse outcomes (incident dementia for 65-74 y/o: ACB 1 + 1 + 1, aOR 3.30 (2.84-3.84); ACB 1 + 2, aOR 5.84 (4.59-7.41); and ACB 3, aOR 9.15 (8.38-9.99)). The quantity of anticholinergics (even with low score) an older person used matters in risk of emergency department visit and all-cause hospitalization but the potency of anticholinergics (i.e., those with high score) matters in risk of fracture-specific hospitalization and incident dementia.

Effects of incorporating multidomain interventions into integrated primary care on quality of life: a randomised controlled trial.

BACKGROUND: Integrating primary prevention into care pathways for older adults is a core strategy of healthy ageing, but evidence remains limited. We aimed to determine whether incorporating a multidomain intervention into primary health care could improve standard value-based health outcomes and quality of life. METHODS: For this Taiwan Integrated Geriatric Care (TIGER) study, a pragmatic randomised controlled trial, we recruited community-dwelling outpatients aged 65 years or older with at least three chronic medical conditions. We excluded people with malignancies undergoing chemotherapy, people with a life expectancy of less than 12 months, or people who were insufficiently able to communicate with study staff. Participants were randomly assigned (1:1) to usual care or to the integrated multidomain intervention using block randomisation. The integrated multidomain intervention entailed 16 2-h sessions per year, comprising communal physical exercise, cognitive training, nutrition and disease education, plus individualised treatment by specialists in integrated geriatric care. The primary outcome was changes from baseline quality of life, based on 36-item Short Form Health Survey (SF-36) scores, at 3, 6, 9, and 12 months. Intervention effects were analysed per protocol using a generalised linear mixed model. This trial is registered with ClinicalTrials.gov, NCT03528005. FINDINGS: Between June 25, 2018, and Feb 15, 2019, 628 participants were screened, of whom 398 were assigned to the integrated multidomain intervention (n=199) or to usual care (n=199). 335 (84%) participants completed the 12-month follow-up. Compared with the usual care group, the integrated multidomain intervention group had significantly higher mean SF-36 physical component scores across all timepoints (overall difference 0·8, 95% CI 0·2-1·5; p=0·010), but differences at 3, 6, 9, and 12 months did not reach statistical significance. The SF-36 mental component scores did not differ significantly overall, but were significantly higher in the integrated multidomain intervention group at the 12-month follow-up (55·3 [SD 7·6] vs 57·2 [7·0]; p=0·019). No serious adverse events occurred. INTERPRETATION: Incorporating multidomain interventions into integrated health care improved quality of life. Our standardised protocol is amenable to inclusion in policies to promote value-based care and healthy ageing. FUNDING: National Health Research Institutes, Taiwan, and Ministry of Science and Technology, Taiwan.

Combined Effects of Frailty and Polypharmacy on Health Outcomes in Older Adults: Frailty Outweighs Polypharmacy.

OBJECTIVES: Existing studies cannot evaluate the time-varying properties of frailty and polypharmacy despite raising concerns about their combined effects in older individuals. This study investigated the longitudinal association between different combined statuses of frailty and polypharmacy on risks of adverse outcomes. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Subjects aged between 65 and 100 years (n = 100,000) were identified from Taiwan's National Health Insurance Research Database. MEASURES: Frailty was categorized into fit, mild, moderate, and severe frailty based on the multimorbidity frailty index. Concomitant use of 5 to 9 and ≥10 chronic medications was considered polypharmacy and excessive polypharmacy. We used generalized estimating equation models to examine the association among 12 groups of combined effects of frailty and polypharmacy and risks of all-cause mortality, all-cause hospitalization, and unplanned hospitalization. Age-stratified analyses were conducted for those aged 65 to 74, 75 to 84, and 85+ years. RESULTS: Compared with fit without polypharmacy, severe frailty with excess polypharmacy was associated with increased risks of adverse outcomes, particularly unplanned hospitalization (adjusted relative risk (aRR): 20.01 [95% confidence interval (CI)] 19.30-20.75). However, the combined effects varied in distinct groups. Within each polypharmacy category, there were dose-response associations between frailty category and adverse outcomes. For instance, within the polypharmacy group, the aRRs of mortality were 1.58 (1.52-1.64), 2.70 (2.60-2.80), 4.62 (4.44-4.82), and 6.81 (6.50-7.13) for the fit and mild, moderate, and severe frailty groups, respectively. By contrast, within each frailty category, the dose-response association between polypharmacy and adverse outcomes was limited to fit and mildly frail people. Age-stratified analyses yielded similar results. CONCLUSIONS AND RELEVANCE: Both frailty and polypharmacy modified the risks of mortality and hospital admissions in older people, but the combined effects varied in distinct groups. This study thus highlights the potential to optimize care of older people by capturing the dynamic and combined changes related to frailty and polypharmacy.

Antiviral prophylaxis for hepatitis B carriers improves the prognosis of diffuse large B-cell lymphoma in Taiwan - a population-based study.

The prevention of hepatitis B virus (HBV) reactivation during rituximab treatment for diffuse large B-cell lymphoma (DLBCL) is important in the HBV-endemic area. This population-based study examines the impact of antiviral prophylaxis for DLBCL patients with HBV infections. We identified 3702 adult patients with newly diagnosed DLBCL between 2011 and 2015 receiving R-CHOP, R-CVP, CHOP or CVP from the Taiwan Cancer Registry. We further stratified them into three groups: HBsAg-negative patients (HBV-negative, N = 2921), HBV carriers who received antiviral prophylaxis (HBV + Px, N = 711), and HBV carriers who did not receive antiviral prophylaxis (HBV + No Px, N = 70). HBV + Px patients were the youngest, and 69·4% received entecavir for antiviral prophylaxis. The median overall survival (mOS) of HBV-negative and HBV + Px patients was similar (74·23 months and not reached, respectively). However, the mOS of HBV + No Px patients was only 35·61 months (P = 0·0028 compared with HBV + Px patients), indicating that antiviral prophylaxis improves OS in HBsAg-positive DLBCL patients. The multivariate analysis showed that the HBV status and antiviral prophylaxis was an independent prognostic factor. In conclusion, our population-based study illustrates the importance of antiviral prophylaxis in HBsAg-positive DLBCL patients. Under antiviral prophylaxis, the survival of DLBCL patients with HBV infections was comparable to that of HBV-negative patients.

Economic burden of cancers in Taiwan: a direct and indirect cost estimate for 2007-2017.

OBJECTIVE: Cancers result in significant economic burdens on patients, health sectors and society. Reliable burden estimates will help guide resource allocation. This study aimed to perform a nationwide cost analysis of the direct and indirect costs of the top ten most costly cancers, and acute coronary syndrome (ACS), as a comparison, in Taiwan. SETTING: A population-based cohort study. PARTICIPANTS: In total, 545 221 patients with newly diagnosed cancer (lung cancer, female breast cancer, colorectal cancer, liver cancer, oral cancer, leukaemia, prostate cancer, non-Hodgkin's lymphoma, gastric cancer and oesophageal cancer) and 170 879 patients with ACS between 2007 and 2014 were identified. PRIMARY AND SECONDARY OUTCOME MEASURES: Direct medical costs were calculated from claims recorded in the National Health Insurance Research Database . Indirect costs, comprising morbidity-associated and mortality-associated productivity losses, were estimated from public life expectancy, average wage and employment data. The costs incurred in the 3 years after diagnosis were assessed. As a comparison, the cost of ACS was also estimated using the same study frame. A cost driver analysis was conducted to identify factors impacting cancer costs. RESULTS: The cancers with the highest mean direct medical costs and total costs were leukaemia (US$28 464) and oesophageal cancer (US$81 775), respectively. Indirect costs accounted for over 50% of the total economic burden of most cancers, except for prostate cancer and female breast cancer. The costs of ACS were lower than those of most cancers. From the cost driver analysis, older age at diagnosis significantly (p<0.05) decreased the total cost of cancer; in contrast, male, tumour metastasis, comorbidities and treatment in medical centres increased the costs. CONCLUSIONS: This study demonstrates the comprehensive economic burden of the top 10 most costly cancers in Taiwan. These results are valuable for optimising healthcare resource allocation.