Effect of frailty on effectiveness and safety of GLP-1 receptor agonists versus SGLT2 inhibitors in people with type 2 diabetes in Taiwan: a retrospective, nationwide, longitudinal study.

BACKGROUND: GLP-1 receptor agonists and SGLT2 inhibitors are increasingly being used in people with type 2 diabetes on the basis of findings from randomised clinical trials; however, little is known of whether clinical outcomes are affected by frailty in real-world settings. We aimed to compare the clinical effectiveness and safety of GLP-1 receptor agonists and SGLT2 inhibitors in managing type 2 diabetes, with a specific focus on stratifying people by their frailty status. METHODS: In this retrospective, nationwide, longitudinal study, we identified people (aged ≥20 years) with type 2 diabetes who newly initiated either a GLP-1 receptor agonist or an SGLT2 inhibitor during the period Jan 1, 2017 to Dec 31, 2019 from the Taiwan National Health Insurance database. Individuals were excluded if they had been diagnosed with cancer, received dialysis for kidney failure, or had prescriptions for a GLP-1 receptor agonist or an SGLT2 inhibitor, within 1 year before the index date. Mortality data were collected from the Taiwan National Death Registry. Eligible individuals were categorised into three frailty subgroups-fit, mild frailty, and moderate or severe frailty-on the basis of the multimorbidity frailty index. Propensity score matching (1:1) was used to balance covariates between recipients of GLP-1 receptor agonists and SGLT2 inhibitors among each frailty subgroup. Clinical outcomes of interest included three-point major adverse cardiovascular events (non-fatal acute myocardial infarction, non-fatal stroke, and fatal cardiovascular disease), all-cause mortality, hospitalisation for heart failure, dialysis or renal transplant, severe diabetic foot complications, retinopathy, hospitalisation for severe hyperglycaemia, and hospitalisation for severe hypoglycaemia. The association between the use of a GLP-1 receptor agonist versus an SGLT2 inhibitor and the risk of the outcomes of interest among each frailty subgroup was examined using a subdistribution hazard model. FINDINGS: We identified 320 210 people with type 2 diabetes, of whom 280 163 met the eligibility criteria, who initiated either a GLP-1 receptor agonist (n=22 968; mean age 57·7 years [SD 13·9], 11 338 [49·4%] were female, and 11 630 [50·6%] were male) or SGLT2 inhibitor (n=257 195; mean age 58·8 years [12·3], 107 988 [42·0%] were female, and 149 207 [58·0%] were male) during 2017-19. After matching, 11 882, 7210, and 3414 pairs of GLP-1 receptor agonist and SGLT2 inhibitor users were assigned in the fit, mild frailty, and moderate or severe frailty subgroups. All clinical outcomes were comparable between users of GLP-1 receptor agonists and SGLT2 inhibitors among each frailty subgroup, except for a higher risk of hospitalisation for severe hyperglycaemia with GLP-1 receptor agonists than with SGLT2 inhibitors in the mild frailty subgroup (subdistribution hazard ratio 1·25 [95% CI 1·13-1·38]; p<0·0001) and a higher risk of dialysis or renal transplant with GLP-1 receptor agonists than with SGLT2 inhibitors in the fit (2·43 [1·82-3·23]; p<0·0001), mild frailty (3·93 [3·03 -5·09]; p<0·0001), and moderate or severe frailty (2·60 [2·03-3·31]; p<0·0001) subgroups. INTERPRETATION: Formulating clear and updated guidelines on the use of GLP-1 receptor agonists and SGLT2 inhibitors according to frailty status could improve management of type 2 diabetes. FUNDING: Ministry of Education, Taiwan.

Real world clinical outcomes when discontinuing denosumab or bisphosphonates in patients with surgically managed osteoporotic vertebral compression fractures: a population-based cohort study.

BACKGROUND CONTEXT: Osteoporotic vertebral compression fractures (OVCFs) are common fragility fractures. Patients who undergo surgical treatment for their initial OVCFs warrant particular attention because there is an elevated risk of subsequent vertebral fractures and other types of fragility fractures. However, the optimal osteoporosis treatment for this specific patient group is less investigated. PURPOSE: This study compares the risk of subsequent osteoporotic fractures and mortality rate for patients who are initiated with denosumab and bisphosphonates and determines the effect of adherence to treatment. STUDY DESIGN: Retrospective nationwide cohort study PATIENT SAMPLE: A total of 2,858 patients who had surgically-managed osteoporotic vertebral compression fractures. OUTCOME MEASURES: The risk of osteoporotic fractures, vertebral fractures, nonvertebral fractures and death. METHODS: This is a retrospective nationwide cohort study that uses the National Health Insurance Research Database. Patients aged ≥50 years who were admitted for surgical interventions for OVCF between 2012 and 2016 and subsequently received denosumab or bisphosphonates for one year were included. Patients were stratified according to their antiosteoporosis medications and adherence to treatment. A multivariable, time-varying Cox proportional hazards model was used to determine the risk of osteoporotic fractures, vertebral fractures, nonvertebral fractures and death. RESULTS: A total of 2,858 patients were included in this study: 1,123 patients in the denosumab group and 1,735 patients in the bisphosphonates group. Compared to persistent denosumab users, the nonpersistent denosumab users, persistent bisphosphonate users and nonpersistent bisphosphonate users had a greater risk of osteoporotic fractures, with respective hazard ratios of 1.64 (95% confidence interval [CI], 1.16-2.32), 1.74 (95% CI, 1.25-2.42) and 1.53 (95% CI, 1.14-2.06). If osteoporotic fractures were divided into nonvertebral and vertebral fractures, none of the groups exhibited an increased risk of vertebral fractures compared to persistent denosumab users, with an HR of 1.00 (95% CI: 0.54-1.88) for nonpersistent denosumab users, 1.64 (95% CI: 0.96-2.81) for persistent bisphosphonate users and 1.52 (95% CI: 0.95-2.43) for nonpersistent bisphosphonate users. However, there was a significantly greater risk of nonvertebral fracture, with respective hazard ratios of 2.04 (95% CI, 1.33-3.11), 1.80 (95% CI, 1.18-2.76) and 1.56 (95% CI, 1.06-2.27) for nonpersistent denosumab users, persistent bisphosphonate users and nonpersistent users. Noteworthy, nonpersistent denosumab users exhibited a significantly greater risk of mortality than persistent denosumab users, with a hazard ratio of 3.12 (95% CI, 2.22-4.38). CONCLUSIONS: In terms of patients with OVCFs who require hospitalization and surgical intervention, those who receive ongoing denosumab treatment exhibit less risk of developing subsequent osteoporotic fractures than those who receive bisphosphonates or nonpersistent denosumab treatment. However, discontinuation of denosumab is associated with a significantly increased risk of subsequent fractures and mortality. Therefore, adherence to the treatment is crucial for patients who are initiated with denosumab.

Activin A as a potential biomarker for preserved ratio impaired spirometry (PRISm) and clinical outcomes in community-dwelling adults.

INTRODUCTION: This study endeavors to decipher the association between Activin A and PRISm, thereby addressing the potential of Activin A as a serum biomarker for early detection and long-term clinical outcome prediction of PRISm and subsequent all-cause mortality. METHODS: The study sample comprised middle-aged and older adults from the I-Lan Longitudinal Aging Study. Pulmonary function including forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured. Demographic data and laboratory data (including serum Activin A levels) were also collected. Multivariate logistic regression and Cox proportional hazards models were used to identify independent predictors of PRISm and all-cause mortality, respectively. RESULTS: Among 711 eligible participants, 34 % had PRISm. The risk of PRISm elevated with Activin A levels in group quartiles (adjusted odds ratio (aOR), Q2: 1.606 [95 % CI 0.972-2.652], p = 0.064, Q3: 2.666 [1.635-4.348], p < 0.001, Q4: 3.225 [1.965-5.293], p < 0.001). On the other hand, lower hemoglobin (aOR: 1.122, p = 0.041) and higher blood urea nitrogen (BUN) levels (aOR: 1.033, p = 0.048) were associated with increased risk of PRISm. In addition, the PRISm group had a higher all-cause mortality rate (non-PRISm 4.5% vs. PRISm 8.3 %, p = 0.038). Multivariate Cox models also identify a higher level of Activin A as a risk factor of all-cause mortality (aHR: 1.001 [1.000-1.003], p = 0.042). CONCLUSIONS: Higher Activin A quartiles were linked to increased risk of PRISm, along with lower hemoglobin and higher BUN levels. Additonally, elevated Activin A was a significant risk factor of all-cause mortality.

Sequential multimodal treatments with chemotherapy and surgery for advanced soft tissue sarcoma may be associated with better survival than chemotherapy.

BACKGROUND: In patients with advanced soft tissue sarcoma (STS), surgery had been reported to be associated with superior overall survival (OS). Chemotherapy details for such patients were less reported, and whether multimodal treatment with surgery and chemotherapy provides extra survival benefit remains unclear. METHODS: We retrospectively reviewed patients with newly diagnosed advanced STS treated at National Taiwan University Hospital from January 1, 2011, to December 31, 2017. OS was calculated from the day of diagnosis of advanced STS to the day of death or last follow-up. Baseline patient characteristics and details regarding surgery and chemotherapy were recorded. RESULTS: A total of 545 patients were diagnosed with STS from 2011 to 2017, of which 226 patients had advanced STS. The median age was 54.7 years, and 54% of patients were women. Approximately 38% of patients with advanced STS underwent surgery and exhibited a trend of longer OS compared with who did not (median = 18.6 vs. 11.9 months, p = 0.083). In the chemotherapy subgroup, the benefit of surgery was more prominent (median = 21.9 vs. 16.5 months, p = 0.037). Patients who received chemotherapy prior to surgery exhibited numerically longer OS than those who underwent surgery first (median = 33.9 vs. 18.3 months, p = 0.155). After adjusting other clinical factors, chemotherapy remained an independent factor associated with favourable OS. CONCLUSION: Surgery may be more beneficial for the patients who receive chemotherapy. Our results support evaluation of sequential multimodal treatments strategy including surgery and chemotherapy in patients with advanced STS.

Cost and effectiveness analyses of the anti-osteoporosis medication in patients with hip fracture in Taiwan: A population-based national claims database analysis.

BACKGROUND: Real-world cost and effectiveness analyses of the anti-osteoporosis medications (AOM) using a nationwide database in Asia were limited. The aim of this study was to evaluate the cost and effectiveness of AOMs therapy under the reimbursement of National Health Insurance in Taiwan. METHODS: Using Taiwan's National Health Insurance Research Database, patients who had hospitalization due to incident hip fractures with related operation between 2008 and 2017 were identified as our study population. Patients who initiated AOMs within 1 year post incident hip fracture were matched with those did not according to the propensity score. The direct medical cost and subsequent fracture within three years were estimated. Statistically significant differences of risk for subsequent fracture between the AOM and non-AOM groups were estimated using the COX proportional hazards model. All costs were presented as New Taiwan Dollars (NTD). RESULTS: There were 27,357 new hip fracture patients who initiated AOMs, and 76% of them were women with a mean age of 77.7 years. Among patients ages ≥70 who encountered hip fractures, those who initiated AOMs experienced fewer non-vertebral fractures (HR = 1.07 (1.02-1.13), p = 0.0114 for those ages 70-79 years old; HR = 1.11 (1.06-1.17), p < 0.0001 for those ages ≥80 years) and mortality (HR = 1.18 (1.14-1.22), p < 0.0001 for those ages 70-79; HR = 1.20 (1.16-1.23), p < 0.0001) within 3 years post incident fracture; meanwhile, consuming fewer medical resources in the national insurance healthcare system. (Increment cost = -16011.2 NTD, p = 0.0248 for those ages 70-79; Increment cost = -17257.9 NTD, p = 0.0032 for those ages ≥80 years) CONCLUSION: Overall, under Taiwan's national health insurance, the use of AOMs is cost-saving, especially in the population aged ≥70 years. The finding of this research was valuable for policymakers in considering healthcare policy promotion and resource allocation in the future.

Osteoporosis care after hip fracture: Observation from national health insurance database and fracture liaison services.

BACKGROUND: The objective of this research was to report the trend of osteoporosis care after hip fractures from usual care (UC) and to compare the quality of care with those who received fracture liaison services (FLSs). METHODS: Data on osteoporosis care for patients with hip fracture were acquired from the National Health Insurance claims (UC group), and surveys from FLS programs (FLS group). A total of 183,300 patients receiving UC and 3010 patients receiving FLS were studied. For the two groups, common osteoporosis care indicators, such as bone mineral density (BMD) testing rate, antiosteoporosis medication commencement rate, and adherence rate were described. RESULTS: There were 2488 participants (82.7%) in the FLS group who completed Dual-energy X-ray absorptiometry (DXA) in 8 weeks, 155 (5.1%) who finished it between 8 weeks and 1 year. Even in 2018, when the DXA completion rate was at its highest, the completion rate in the UC group was only 23.5%. In terms of medication commencement, 2372 FLS patients (78.8%) received treatment within 3 months. Only 24.9% of the UC patients received antiosteoporosis medication within 3 months. Furthermore, antiosteoporosis medication adherence rate was 92.2% after 1 year and 83.9% after 2 years in the FLS group, but these were only 66.5% and 42.7%, respectively, in the UC group. CONCLUSION: Patients who received FLS had more timely BMD exams, antiosteoporosis medication treatment, and higher adherence to antiosteoporosis therapy than those who received UC. The discrepancy in rates of continuing treatment became more significant over time between both groups.

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.

Higher risk of future events, mortality and greater healthcare use among patients with increasingly recurrent atherosclerotic cardiovascular disease events in Taiwan: a retrospective cohort study.

OBJECTIVES: To describe the occurrence of recurrent atherosclerotic cardiovascular disease (ASCVD) events within 3 years after a new-onset event, the associated disease burden and statin prescribing in patients with ASCVD in Taiwan. DESIGN: Retrospective cohort study. SETTING: This was a retrospective cohort study using Taiwan's National Health Insurance Research Database. PARTICIPANTS: In total, 111 399, 133 538 and 21 572 patients who were hospitalised with diagnosis of coronary heart disease (CHD), cerebrovascular disease (CBVD) and peripheral artery disease (PAD), respectively, between 1 January 2012 and 31 December 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: For each index and recurrent event, patients were observed for 12 months after admission to quantify risks of mortality, recurrent events, statin treatment and healthcare use. RESULTS: We identified 97 321, 120 914 and 14 794 patients with new-onset CHD, CBVD and PAD, respectively. The proportions of developing first, second and third recurrent events were 22.5%, 25.6% and 30.9% for CHD; 20.9%, 26.2% and 32.4% for CBVD and 40.2%, 41.4% and 43.6% for PAD, respectively. Most patients had the same type of ASCVD for their recurrent events as their new-onset event. The mortality rates increased with each recurrent event (p<0.05 for all three ASCVD groups). The rates of hospital readmission and emergency room (ER) visit increased with increasing recurrent events. For example, in the CHD group, the 1-year readmission rates following the index, first and second recurrent events were 43.1%, 47.6% and 55.3%, respectively, and the proportions of visiting ER were 46.4%, 51.9% and 57.8%, respectively. Statin prescribing was suboptimal at time of index event and recurrent events. CONCLUSION: Recurrent ASCVD events were associated with a higher risk of recurrent event and mortality and greater healthcare use. However, statin prescriptions at index event and after each recurrent event were suboptimal.

The real-world adherence of the first-line anti-osteoporosis medications in Taiwan: Visualize the gap between reality and expectations.

BACKGROUND: Adherence to anti-osteoporosis medications (AOMs) is crucial. National Health Insurance (NHI) in Taiwan has its own rules of reimbursement rule for AOMs. The midterm adherence remained inconclusive. Here we investigated the adherence according to the initially used AOMs, for three consecutive years. METHODS: The nationwide cohort study from 2008 to 2018, based on Taiwan's National Health Insurance Research Database, included 336,229 patients. Their adherence, indicated by medication possession ratio (MPR), to the initial AOMs was investigated yearly for three consecutive years. The overall MPRs (OMPR), including the switched AOMs, were also calculated in the first year. The Sankey diagram further visualized the patient flows toward different adherence according to the initial AOMs. RESULTS: The OMPR in the first year improved if the patients used AOMs with longer dosing intervals. 100%, 68.9%, 40.7%, and 34.0% of the patients started the treatment with zoledronate, denosumab, alendronate, and raloxifene, respectively, had OMPR ≥75% in the first year. In the 3rd year, only 20.89%, 24.13%, and 12.83% of the patients continuously treated with zoledronate, denosumab, and alendronate, respectively, had MPR ≥75%. From the Sankey diagram, we also observed that patients who had poor adherence at one year were inclined to have poor adherence or discontinue antiosteoporosis treatment in the next year. CONCLUSION: The initial AOMs and the observed adherence may provide clues for optimizing patient treatment. The real-world adherence in Taiwan was far from satisfactory in our study.

Eleven years secular trend of the initiation of anti-osteoporosis medications and subsequent fractures in Taiwan: From 2008 to 2018.

BACKGROUND: Osteoporosis is a common metabolic bone disease that benefits from many newly developed anti-osteoporosis medications (AOMs). Reimbursement policies need to allocate medical budgets properly based on evidence-based data. This study aimed to investigate the 11-year secular trend, focusing on older age and males in this adjustment wave of the National Health Insurance reimbursement. METHODS: We adopted a nationwide cohort from Taiwan's National Health Insurance Research Database (NHIRD). Patients undergoing newly initiated AOMs from 2008 to 2018 were included. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. Patients <50 years, pathological fractures, missing data, and two AOMs prescribed were excluded. The real-world trends related to subsequent fragility fracture and death within 1 and 3 years were used to evaluate the potential effects due to revision of reimbursement policies. RESULTS: Of 393,092 patients, among them, 336,229 patients met the criteria, whose mean age ranged from 73.3 to 74.4 years, and nearly 80% were female. Further analysis showed a steady increase of AOMs from 5567 (17.1%) and 8802 (27.0%) in 2008-6697 (18.3%) and 10,793 (29.5%) in 2018 for males and 80+ years respectively. The subsequent fragility fracture within one and three years post AOMs initiation was 5.81% and 11.80% in 2018. CONCLUSION: This study showed an immediate drop in AOMs prescription after the implementation of a new stricter reimbursement policy. It took 5 years to return the annual prescription number.

Constraining in reimbursement criteria and the adherence to anti-osteoporosis medications (AOMs) in Taiwan: Urbanization makes the difference.

BACKGROUND: The Bureau of National Health Insurance in Taiwan implemented a new reimbursement scheme incorporating bone mineral density (BMD) criteria on Jan. 1, 2011. This study aimed to investigate a real-life 11-year secular trend of adherence in new AOMs users and evaluated the change of adherence to AOMs therapy in different urbanization areas after reimbursement criteria were restrained. METHODS: We used Taiwan's National Health Insurance Research Database to identify new AOMs users as our study population. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. The first prescription date of AOMs was defined as the cohort entry date. The adherence rates within one year after initiation were assessed. RESULTS: High adherence (≥75%) in the first year increased markedly after the new reimbursement scheme in 2011, changing from 31.8% in 2008, and 41.7% in 2011 to 54.2% in 2018. On the other hand, low adherence (<25%) decreased from 38.8% in 2008 to 14.6% in 2018. In addition, the switchers increased from 5.9% in 2008 to 9.3% in 2018, indicating a more flexible choice of AOMs. The proportion of high adherence to AOMs was highest in high-urbanization areas, and the proportion increased about two times from 30% in 2008 to 60% in 2018. CONCLUSION: The implementation of new reimbursement criteria in 2011 was associated with increased adherence to AOMs and the increase was most apparent in high-urbanization areas.

Longitudinal follow-up of pediatric Graves' disease in preschool children: Clinical characteristics and a case report.

RATIONALE: Pediatric Graves' disease at preschool age is a rare condition. Previous reports have indicated that adolescents with this disease are girls. Pediatric Graves' ophthalmopathy in young children is rare, and long-term follow-up reports are lacking. PATIENT CONCERNS: The patient had hyperthyroidism and bilateral proptosis for 2 years, but she was only 4 years old. DIAGNOSES: The blood test revealed hyperthyroidism and the ophthalmic examination revealed proptosis. The patient had Graves' disease and Graves' ophthalmopathy. INTERVENTIONS: Initially, she was followed up in the pediatric department. Bilateral proptosis developed, and she was brought to the ophthalmology department for assistance. Orbital computed tomography revealed borderline enlargement of the extraocular muscles bilaterally. Other initial clinical findings included bilateral upper and lower eyelid trichiasis and mild punctate epithelial erosions of the cornea. She received conservative medical treatment in the ophthalmology department. OUTCOMES: Remission of hyperthyroidism was achieved 2 years after medical control. No elevated intraocular pressure, strabismus, or optic neuropathy developed during follow-up. Significant cosmetic improvement and gradual resolution of punctate epithelial erosions were found over 10 years. Finally, the patient had only mild bilateral lower trichiasis. LESSONS: Longitudinal follow-up revealed that the ocular manifestations of proptosis and eyelid trichiasis may have good outcomes. Proptosis gradually improved as the patient grew up.

Epidemiology and clinical impact of osteoporosis in Taiwan: A 12-year trend of a nationwide population-based study.

BACKGROUND: Osteoporosis increases the fracture and mortality risk of patients and has a higher disease burden than some cancers. Therefore, global concerns regarding the prevention and treatment of osteoporosis have been raised. However, fast-aging Taiwan lacks national epidemiological data on osteoporosis in recent years. We aimed to establish and update epidemiological data on osteoporosis by analyzing national data from 2008 to 2019. METHODS: We estimated the prevalence and incidence of osteoporosis in patients aged ≥50 years based on claims data from Taiwan's National Health Insurance database from 2008 to 2019. We also analyzed the key parameters of fracture care (anti-osteoporosis medication use, bone mineral density examination rate, and length of hospital stay) to understand the secular trend of management and related clinical outcomes (imminent refracture rate and mortality). RESULTS: The number of prevalent osteoporosis increased from 2008 to 2015 and remained constant until 2019; however, the age-standardized prevalence and incidence rates declined from 2008 to 2019 (3.77%-2.91% and 2.08%-1.02%, respectively). The overall incidence rates of hip and spine fractures decreased significantly by 34% and 27%, respectively. For patients with hip and spine fractures, the immanent refracture rates were 8.5% and 12.9% and the 1-year mortality rate remained stable at approximately 15% and 6%, respectively. CONCLUSION: The age-standardized prevalence and incidence rates decreased remarkably from 2008 to 2019, while the number of prevalent osteoporosis remained steady. Patients with hip fractures encountered a high 1-year mortality rate, while the risk of imminent refracture was notable for patients with spine fractures.

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.

Anesthesia With Propofol Sedation Reduces Locoregional Recurrence in Patients With Breast Cancer Receiving Total Mastectomy Compared With Non-Propofol Anesthesia.

Purpose: We examined locoregional recurrence (LRR) in patients with breast invasive ductal carcinoma (IDC) receiving total mastectomy (TM) under propofol-based paravertebral block-regional anesthesia (PB-RA) versus sevoflurane-based inhalational general anesthesia (INHA-GA) without propofol. All-cause death and distant metastasis were secondary endpoints. Patients and Methods: Patients with breast IDC receiving TM were recruited through propensity score matching and categorized into INHA-GA with sevoflurane and PB-RA with propofol groups. Cox regression analysis was performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: In the multivariate Cox regression analysis, the adjusted HR (aHR; 95% CI) of LRR for the PB-RA with propofol group was 0.52 (0.28-0.96) compared with the INHA-GA with sevoflurane group. The aHRs of LRR for differentiation grade II, grade III, the American Joint Committee on Cancer clinical stage II, stage III, pathological tumor (pT) stage 2, pT stage 3-4, pathological nodal (pN) stage 1, and pN stage 2-3 were 1.16 (1.04-2.08), 1.28 (1.07-2.12), 3.71 (1.82-7.59), 4.67 (1.65-13.18), 1.09 (1.02-1.21), 1.17 (1.03-2.16), 1.10 (1.03-1.33), and 1.22 (1.06-2.41), respectively, compared with differentiation grade I, clinical stage I, pT1, and pN0. The aHR of LRR for adjuvant RT was 0.88 (0.64-0.94) compared with that for no adjuvant RT. Conclusion: PB-RA with propofol might be beneficial for reducing LRR in women with breast IDC receiving TM compared with INHA-GA without propofol.

Efficacy of Myopia Control and Distribution of Corneal Epithelial Thickness in Children Treated with Orthokeratology Assessed Using Optical Coherence Tomography.

The association between myopia control efficacy in children treated with orthokeratology and corneal epithelial thickness is still unknown. The aim of this study was to explore the corneal epithelial thickness and its association with axial length changes in children treated with orthokeratology. This retrospective cohort study enrolled children aged from 9 to 15 years who had received orthokeratology for myopia control and had been followed up for at least 1 year. Anterior segment optical coherence tomography was performed to generate wide epithelial thickness maps of the patients. Annual axial length changes were calculated from the axial length at 6 months after the initiation of orthokeratology lens wear and at final measurements. Corneal epithelial thickness data were obtained from 24 sectors and a central 2 mm zone of the wide epithelial thickness map. Associations between annual axial length changes and corneal epithelial thickness for each sector/zone of the wide epithelial thickness map, and orthokeratology treatment data were determined by generalized estimating equations. Finally, a total of 83 eyes of 43 patients (mean age 11.2 years) were included in the analysis. The mean annual axial length change was 0.169 mm; when regressing demographic and ortho-k parameters to mean annual axial length changes, age and target power were both negatively associated with them (ß = -14.43, p = 0.008; ß = -0.26, p = 0.008, respectively). After adjusting for age and target power, the annual axial length changes were positively associated with the corneal epithelium thickness of IT1, I1, SN2, and S2 sectors of the wide epithelial thickness map, and negatively with that of the I3 sector. In conclusion, we identified associations between annual axial length changes and the corneal epithelium thickness of certain sectors in children treated with orthokeratology. This may facilitate the design of orthokeratology lenses with enhanced efficacy for myopia control.

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.

Impact of the Requirement of Bone Mineral Density Evidence on Utilization of Anti-osteoporosis Medications, Clinical Outcome and Medical Expenditures of Patient With Hip Fracture in Taiwan.

BACKGROUND: Since 2011, Taiwan's National Health Insurance Administration (NHIA) issued a regulation on the reimbursement to anti-osteoporosis medications (AOMs). This study aimed to evaluate the impact of this regulation in reimbursement on the utilization of AOMs, clinical outcomes and associated medical expenditures of patients with incident hip fractures. METHODS: By using the National Health Insurance Research Database (NHIRD), patients with incident hip fracture from 2006 to 2015 were identified as our study cohort. Patients younger than 50 years old or prescribed with AOMs within one year prior to incident fracture were excluded. Outcomes of interest were quarterly estimates of the proportion of patients who received bone mineral density (BMD) examination, who were prescribed AOMs, as well as who encountered subsequent osteoporotic fracture-related visits and associated medical expenditures. Particularly, age- and gender specific estimates were reported. An interrupted time series study design with segmented regression model was used to quantitatively explore the impact of the changes of the reimbursement criteria on the level (immediate) and trend (long-term) changes of these outcomes. RESULTS: Our study enrolled 118 493 patients with incident hip fracture with those patients aged older than 80 years old accounting for the largest proportion. A significantly decreased trend of AOMs prescription rates was observed immediately post regulation except for female aged between 65 and 80, while the long-term pattern showed no significant difference. However, the percentage of patients encountered subsequent osteoporotic fracture-related visit was not statistically different between pre- and post-regulation periods. Noteworthy, the policy regulation was associated with an increasing trend of osteoporotic fracture associated medical expenditures, especially for patients older than 80 years old. CONCLUSION: The regulation on the reimbursement for AOMs decreased the prescribing rate of AOMs immediately although the effect did not sustain thereafter. However, higher subsequent osteoporotic fracture-related medical expenditures were introduced, especially among those very old population.

Impact of pneumococcal conjugate vaccination on hospitalized childhood pneumonia in Taiwan.

BACKGROUND: A national 13-valent pneumococcal conjugate vaccine (PCV13) catch-up program among children aged 2-5 years in 2013, before routine infant immunization in 2015, successfully reduced serotype 19A-related invasive pneumococcal diseases in Taiwan. We aimed to investigate its impact on hospitalized childhood pneumonia. METHODS: We analyzed the National Health Insurance Research Database, 2001-2017, for hospitalized children aged <18 years with the diagnoses of all-cause pneumonia, lobar/pneumococcal pneumonia, and pneumococcal parapneumonic diseases. The study period was divided into 2001-2005 (pre-PCV), 2006-2012 (private sectors), and 2013-2017 (universal PCV13 vaccination). RESULTS: On pneumococcal parapneumonic diseases, the national PCV13 vaccination program was associated with an immediate decline in 2-4-year-old children and significant decreasing trends in all ages. The incidence rate ratios of 2016-2017/2011-2012 were 0.16 (95% confidence interval [CI], 0.06-0.40) and 0.18 (95% CI, 0.13-0.23) in children aged < 2 and 2-4 years, respectively. We observed an increase of lobar/pneumococcal pneumonia cases after an early decline. The intensive/invasive medical needs and the fatality of all-cause pneumonia decreased significantly in children of all ages. CONCLUSIONS: Pneumococcal parapneumonic diseases and the disease burden of lobar/pneumococcal pneumonia and lower respiratory tract infections declined after the national PCV13 vaccination program. IMPACT: The impact study of the PCV13 immunization program on childhood pneumonia in Asian countries remained limited. The unique PCV13 immunization program in Taiwan, catch-up before primary infantile series, reduced severe childhood pneumococcal pneumonia at 5 years post PCV13. The intensive and invasive medical needs and fatality of all-cause pneumonia decreased significantly in children of all ages. We observed an increase in lobar/pneumococcal pneumonia after an early decline.