RESUMEN
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, non-vertebral 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 anti-osteoporosis medications and adherence to treatment. A multivariable, time-varying Cox proportional hazards model was used to determine the risk of osteoporotic fractures, vertebral fractures, non-vertebral 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 non-persistent denosumab users, persistent bisphosphonate users and non-persistent 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 non-vertebral 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 non-persistent denosumab users, 1.64 (95% CI: 0.96-2.81) for persistent bisphosphonate users and 1.52 (95% CI: 0.95-2.43) for non-persistent bisphosphonate users. However, there was a significantly greater risk of non-vertebral 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 non-persistent denosumab users, persistent bisphosphonate users and non-persistent users. Noteworthy, non-persistent 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 non-persistent 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.
RESUMEN
BACKGROUND: Male hypogonadism is not uncommon in people with HIV (PWH), with estimated prevalence ranging from 9% to 16%. Existing data are limited on the serum testosterone levels in PWH in Asian populations. METHODS: We enrolled HIV-positive men who have sex with men (MSM) and had been on stable antiretroviral therapy and MSM without HIV between February 2021 and November 2022. Serum free testosterone levels, sex hormone-binding globulins and other associated hormones were measured. Multiple linear regression analysis was performed to assess the association between serum free testosterone levels and clinical variables collected. RESULTS: A total of 447 MSM with HIV and 124 MSM without HIV were enrolled. Compared with MSM without HIV, MSM with HIV had a higher age (median, 41 versus 29.5 years) and prevalence of symptomatic hypogonadism (8.3% versus 1.6%). Among MSM who were aged <35 years, there were no significant differences in the serum free testosterone levels and prevalences of hypogonadism between the two groups. In multiple linear regression analysis, serum free testosterone level significantly decreased with advanced age (a decrease of 1.14 pg/mL per 1-year increase) and a higher body-mass index (BMI) (a decrease of 1.07 pg/mL per 1-kg/m2 increase), but was not associated with HIV serostatus. CONCLUSION: We found that MSM with HIV had a higher prevalence of symptomatic hypogonadism than MSM without HIV in Taiwan, which could be attributed to age difference. Serum free testosterone levels were negatively correlated with age and BMI, but did not show a significant correlation with HIV serostatus.
RESUMEN
OBJECTIVES: Exosomes are membrane vesicles that are actively secreted in response to microenvironmental stimuli. In this study, we quantified the amount of exosomes in patients with significant coronary artery disease (CAD) and evaluated its relationship with myocardial perfusion imaging (MPI) results. METHODS: Patients who underwent both MPI and coronary angiography were recruited. Plasma was collected during angiography, and exosomes were extracted via the precipitation method. The summed stress scores (SSS), summed difference scores, and ventricular functional parameters were calculated from the MPI and compared with the amounts of exosomes and extracted miRNAs. RESULTS: In total, 115 patients were enrolled (males: 78 %; mean age: 66.6 ± 10.6 years). Those with abnormal SSS according to the MPI had significantly fewer exosomes (p = 0.032). After multivariate analysis, the SSS remained significantly related to the amount of exosomes (p = 0.035). In forty randomly selected samples, miRNA-432-5p and miRNA-382-3p were upregulated in patients with abnormal SSS. CONCLUSIONS: Patients with compromised poststress myocardial perfusion on MPI tended to have fewer exosomes in association with CAD-related miRNAs. This is the first study to clarify the fundamental and pathophysiological causes of CAD using radiographic examinations.
RESUMEN
Low physical activity has been associated with poor prognosis in hemodialysis (HD) patients. Interventions to maintain healthy lifestyle in this population are important to reduce mortality. This study aimed to evaluate the effectiveness of digital health interventions (DHIs) for improving the physical activity and health-related quality of life (HRQoL) in HD patients. The 24-week prospective study enrolled 31 clinically stable HD patients. All participants were assigned home exercises and provided with wearable devices. Dietary and exercise information was uploaded to a health management platform. Suggestions about diet and exercise were provided, and a social media group was created. Physical performance testing was performed at baseline and during weeks 4, 8, 12, 16 and 24. HRQoL and nutritional status were evaluated. A total of 25 participants completed the study. After the interventions, the daily step count increased 1658 steps. The 10-time-repeated sit-to-stand test reduced by 4.4 s, the sit-to-stand transfers in 60 s increased 12 repetitions, the distance of six-minute walk test (6MWT) increased by 55.4 m. The mental health components and burden of kidney disease of the Kidney Disease Quality of Life survey, and subjective global assessment (SGA) scores improved. By Spearman correlation, the monthly step count correlated positively with 6MWT and SGA. DHIs that combined wearable devices, a health management platform, and social media could strengthen physical activity and improve the HRQoL and nutrition of maintenance HD patients. The results outline a new model to promote healthy lifestyle behaviors in HD patients.
Asunto(s)
Enfermedades Renales , Calidad de Vida , Humanos , Proyectos Piloto , Estudios Prospectivos , Salud Digital , Diálisis Renal/métodos , Estilo de Vida SaludableRESUMEN
Biological plausibility suggests that fluoroquinolones may lead to mitral valve regurgitation or aortic valve regurgitation (MR/AR) through a collagen degradation pathway. However, available real-world studies were limited and yielded inconsistent findings. We estimated the risk of MR/AR associated with fluoroquinolones compared with other antibiotics with similar indications in a population-based cohort study. We identified adult patients who initiated fluoroquinolones or comparison antibiotics from the nationwide Taiwanese claims database. Patients were followed for up to 60 days after cohort entry. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of MR/AR comparing fluoroquinolones to comparison antibiotics after 1:1 propensity score (PS) matching. All analyses were conducted by type of fluoroquinolone (fluoroquinolones as a class, respiratory fluoroquinolones, and non-respiratory fluoroquinolones) and comparison antibiotic (amoxicillin/clavulanate or ampicillin/sulbactam, extended-spectrum cephalosporins). Among 6,649,284 eligible patients, the crude incidence rates of MR/AR ranged from 1.44 to 4.99 per 1,000 person-years across different types of fluoroquinolones and comparison antibiotics. However, fluoroquinolone use was not associated with an increased risk in each pairwise PS-matched comparison. HRs were 1.00 (95% CI, 0.89-1.11) for fluoroquinolones as a class, 0.96 (95% CI, 0.83-1.12) for respiratory fluoroquinolones, and 0.87 (95% CI, 0.75-1.01) for non-respiratory fluoroquinolones, compared with amoxicillin/clavulanate or ampicillin/sulbactam. Results were similar when fluoroquinolones were compared with extended-spectrum cephalosporins (HRs of 0.96, 95% CI, 0.82-1.12, HR, 1.05, 95% CI, 0.86-1.28, and HR, 0.88, 95% CI, 0.75-1.03, respectively). This large-scale cohort study did not find a higher risk of MR/AR with different types of fluoroquinolones in the adult population.
Asunto(s)
Válvula Aórtica , Fluoroquinolonas , Adulto , Humanos , Fluoroquinolonas/efectos adversos , Estudios de Cohortes , Sulbactam , Antibacterianos/efectos adversos , Combinación Amoxicilina-Clavulanato de Potasio , Ampicilina , CefalosporinasRESUMEN
BACKGROUND: It is common to support cardiovascular function in critically ill patients with extracorporeal membrane oxygenation (ECMO). The purpose of this study was to identify patients receiving ECMO with a considerable risk of dying in hospital using machine learning algorithms. METHODS: A total of 1342 adult patients on ECMO support were randomly assigned to the training and test groups. The discriminatory power (DP) for predicting in-hospital mortality was tested using both random forest (RF) and logistic regression (LR) algorithms. RESULTS: Urine output on the first day of ECMO implantation was found to be one of the most predictive features that were related to in-hospital death in both RF and LR models. For those with oliguria, the hazard ratio for 1 year mortality was 1.445 (p < 0.001, 95% CI 1.265-1.650). CONCLUSIONS: Oliguria within the first 24 h was deemed especially significant in differentiating in-hospital death and 1 year mortality.
Asunto(s)
Oxigenación por Membrana Extracorpórea , Bosques Aleatorios , Adulto , Humanos , Mortalidad Hospitalaria , Oliguria , AlgoritmosRESUMEN
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.
RESUMEN
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.
Asunto(s)
Conservadores de la Densidad Ósea , Osteoporosis , Humanos , Taiwán , Urbanización , Osteoporosis/tratamiento farmacológico , Alendronato/uso terapéutico , Ácido Ibandrónico/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéuticoRESUMEN
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.
Asunto(s)
Conservadores de la Densidad Ósea , Fracturas Óseas , Osteoporosis , Fracturas Osteoporóticas , Masculino , Humanos , Femenino , Anciano , Conservadores de la Densidad Ósea/uso terapéutico , Taiwán , Osteoporosis/tratamiento farmacológico , Fracturas Óseas/tratamiento farmacológico , Alendronato/uso terapéutico , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/prevención & controlRESUMEN
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.
Asunto(s)
Conservadores de la Densidad Ósea , Osteoporosis , Humanos , Conservadores de la Densidad Ósea/uso terapéutico , Conservadores de la Densidad Ósea/efectos adversos , Alendronato/uso terapéutico , Estudios de Cohortes , Denosumab/uso terapéutico , Ácido Zoledrónico/uso terapéutico , Taiwán , Motivación , Cumplimiento de la Medicación , Osteoporosis/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
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.
RESUMEN
BACKGROUND: Genome-wide association studies (GWASs) have linked RRBP1 (ribosomal-binding protein 1) genetic variants to atherosclerotic cardiovascular diseases and serum lipoprotein levels. However, how RRBP1 regulates blood pressure is unknown. METHODS: To identify genetic variants associated with blood pressure, we performed a genome-wide linkage analysis with regional fine mapping in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) cohort. We further investigated the role of the RRBP1 gene using a transgenic mouse model and a human cell model. RESULTS: In the SAPPHIRe cohort, we discovered that genetic variants of the RRBP1 gene were associated with blood pressure variation, which was confirmed by other GWASs for blood pressure. Rrbp1- knockout (KO) mice had lower blood pressure and were more likely to die suddenly from severe hyperkalemia caused by phenotypically hyporeninemic hypoaldosteronism than wild-type controls. The survival of Rrbp1-KO mice significantly decreased under high potassium intake due to lethal hyperkalemia-induced arrhythmia and persistent hypoaldosteronism, which could be rescued by fludrocortisone. An immunohistochemical study revealed renin accumulation in the juxtaglomerular cells of Rrbp1-KO mice. In the RRBP1-knockdown Calu-6 cells, a human renin-producing cell line, transmission electron and confocal microscopy revealed that renin was primarily retained in the endoplasmic reticulum and was unable to efficiently target the Golgi apparatus for secretion. CONCLUSIONS: RRBP1 deficiency in mice caused hyporeninemic hypoaldosteronism, resulting in lower blood pressure, severe hyperkalemia, and sudden cardiac death. In juxtaglomerular cells, deficiency of RRBP1 reduced renin intracellular trafficking from ER to Golgi apparatus. RRBP1 is a brand-new regulator of blood pressure and potassium homeostasis discovered in this study.
Asunto(s)
Proteínas Portadoras , Hiperpotasemia , Hipertensión , Hipoaldosteronismo , Animales , Humanos , Ratones , Aldosterona , Óxido de Aluminio , Presión Sanguínea , Estudio de Asociación del Genoma Completo , Homeostasis , Hiperpotasemia/complicaciones , Hipoaldosteronismo/complicaciones , Potasio , Renina/genética , Proteínas Portadoras/genética , Proteínas Portadoras/fisiologíaRESUMEN
BACKGROUND & AIMS: Data regarding the long-term evolution of estimated glomerular filtration rate (eGFR) in patients receiving antiviral treatment for hepatitis C virus are limited. METHODS: A total of 1987 patients with eGFR ≥15 mL/min/1.73m2 who received interferon or direct-acting antiviral treatment were prospectively enrolled in this cohort study. The eGFR was assessed biannually by the Chronic Kidney Disease Epidemiology Collaboration equation from the time point of sustained virologic response (SVR12). Multivariate generalized estimated equation was used to assess the association between the factors of interest and evolution of eGFR following antiviral treatment. Multivariate Cox regression analysis was used to assess the relative risk of end-stage renal disease (ESRD), defined as an eGFR <15 mL/min/1.73m2. RESULTS: Patients who achieved SVR12 (adjusted slope coefficient difference: 2.36 mL/min/1.73 m2/year; 95% confidence interval [CI], 1.50 to 3.32; P < .001) were associated with eGFR improvement, compared with those who did not achieve SVR12. Among patients who achieved SVR12, the eGFR evolution was comparable (adjusted slope coefficient difference: 0.31 mL/min/1.73m2/year; 95% CI, -0.34 to 0.96; P = .35) in those treated with interferon or direct-acting antiviral. The incidence rates of ESRD in patients who achieved and did not achieve SVR12 were 0.06 per 100 person-years and 0.37 per 100 person-years. Patients who achieved SVR12 were associated with a lower risk of ESRD (adjusted hazard ratio, 0.24; 95% CI, 0.05-0.68; P = .021). CONCLUSIONS: The long-term eGFR evolution and risk of ESRD are significantly improved in patients who achieve SVR12 with anti- hepatitis C virus treatment.
Asunto(s)
Hepatitis C Crónica , Hepatitis C , Fallo Renal Crónico , Humanos , Antivirales/uso terapéutico , Hepacivirus , Tasa de Filtración Glomerular/fisiología , Estudios de Cohortes , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/complicaciones , Interferones/uso terapéuticoRESUMEN
Background: Both sodium glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have cardiovascular protective effects in patients with type 2 diabetes mellitus. However, the comparative risk of GLP-1RA versus SGLT-2i for major adverse limb events remains unknown. Materials and methods: We studied a nationwide cohort involving 123,048 diabetes patients 20-100 years of age who initiated a SGLT-2i or GLP-1RA during 2012 and 2017. The patients in the two groups were matched by propensity score (PS), and incidence rates for hospitalization for major adverse limb events, critical limb ischemia (CLI) and lower extremity amputation (LEA), were assessed. Cox proportional hazards regression was applied to estimate hazard ratios (HRs) between patients receiving SGLT-2i as compared with GLP-1RA. The modification effects of age, a history of established cardiovascular disease, and chronic kidney disease were examined. In addition, use of dipeptidyl peptidase-4 inhibitor (DPP-4i) was chosen as a second active comparator. Results: After PS-matching, a total of 13,378 SGLT-2i and 13,378 GLP-1RA initiators were identified. Use of SGLT-2i was not associated with an increased risk for hospitalization for CLI and LEA, either compared with GLP-1RA (HR, 1.13; 95% CI, 0.77-1.65 and 1.27; 95% CI, 0.63-2.55, respectively) or compared with DPP-4i use (HR, 1.06; 95% CI, 0.75-1.50 and HR, 0.80; 95% CI, 0.42-1.53, respectively). Although the study was underpowered to explore potential effect modification, a trend of higher risks for LEA was noted among SGLT-2i users with cardiovascular disease as compared with either GLP-1RA or DPP-4i. Conclusion: Use of SGLT-2i was not associated with higher risks for hospitalization for CLI and LEA as compared with reference drugs. Further large-scale studies are needed for a precise risk estimation.
RESUMEN
BACKGROUND: Mechanical circulatory support (MCS) has been widely utilized in critically ill cardiac transplant candidates. Few studies have investigated the impact of duration of MCS before heart transplantation (HTx) on long-term patient survival. METHODS: A retrospective HTx database was reviewed between 2009 and 2019. Patients who did not or did undergo MCS before HTx were categorized into two groups: (1) A (did not) and (2) B (did), respectively. A receiver operating characteristic (ROC) curve was plotted to assess the cutoff level of MCS duration before HTx in evaluating 5-year survival. RESULT: A total of 270 HTx patients (group A: 120, group B: 150) were analyzed. Group B patients had a higher percentage of blood type O, a higher incidence of resuscitation, a shorter listing duration, and a higher likelihood of having United Network for Organ Sharing (UNOS) 1A status than group A. The ROC curve revealed 24 days as a good cut-off level for determining the best MCS before HTx timing. Group B was categorized into two subgroups: (1) B1 (MCS < 24 days, n = 65) and (2) B2 (MCS > 24 days, n = 85). B2 had a higher incidence of cardiopulmonary resuscitation (CPR), hemodialysis, longer waiting time after MCS, and better ventricular assist device implantation than B1. However, the survival curves showed that B1 outcomes were significantly worse than in groups A and B2. Groups A and B2 had similar survival curves without an increased incidence of infection. CONCLUSION: The preliminary data demonstrated that a longer duration of MCS may be associated with better outcomes than urgent HTx.
Asunto(s)
Insuficiencia Cardíaca , Trasplante de Corazón , Corazón Auxiliar , Humanos , Estudios Retrospectivos , Resultado del Tratamiento , Factores de Tiempo , Insuficiencia Cardíaca/cirugíaRESUMEN
AIMS: To examine the comparative effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for select cardiovascular outcomes and to examine whether the relative risks varied across different patient subgroups in patients with type 2 diabetes. MATERIALS AND METHODS: We conducted a nationwide cohort study of patients with type 2 diabetes who initiated GLP-1RAs or SGLT2 inhibitors between 2012 and 2018 in Taiwan. The study outcomes included myocardial infarction and total stroke, further classified into ischaemic or haemorrhagic stroke. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for each outcome, comparing GLP-1RAs with SGLT2 inhibitors using Cox proportional hazards models after 1:1 propensity-score (PS) matching. We also examined if there was effect modification by age, underlying chronic kidney disease, or coexisting cardiovascular disease in prespecified subgroup analyses. RESULTS: Among 26 032 PS-matched patients, GLP-1RA initiators and SGLT2 inhibitor initiators showed similar risks of myocardial infarction (HR 0.99, 95% CI 0.65-1.52), total stroke (HR 0.90, 95% CI 0.69-1.17), ischaemic stroke (HR 0.86, 95% CI 0.65-1.14) and haemorrhagic stroke (HR 0.88, 95% CI 0.63-1.25). However, GLP-1RA treatment was associated with an increased risk of total stroke (HR 1.76, 95% CI 1.06-2.94) and ischaemic stroke (HR 1.88, 95% CI 1.09-3.23) among patients with chronic kidney disease, but not among patients without chronic kidney disease. GLP-1RA therapy seemed to have a lower risk of haemorrhagic stroke among patients with cardiovascular disease (HR 0.64, 95% CI 0.43-0.97), but not in patients without cardiovascular disease. CONCLUSIONS: Glucagon-like peptide-1 receptor agonists and SGLT2 inhibitors appeared to have comparable effectiveness with regard to several cardiovascular outcomes overall, but their comparative effectiveness may vary in certain patient subgroups.
Asunto(s)
Isquemia Encefálica , Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Accidente Cerebrovascular Hemorrágico , Accidente Cerebrovascular Isquémico , Infarto del Miocardio , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Accidente Cerebrovascular , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Estudios de Cohortes , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Glucosa , Humanos , Hipoglucemiantes/uso terapéutico , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/epidemiología , Infarto del Miocardio/prevención & control , Insuficiencia Renal Crónica/complicaciones , Sodio , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Accidente Cerebrovascular/inducido químicamente , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & controlRESUMEN
STUDY OBJECTIVE: Clinical trials have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may be associated with a higher risk of biliary-related diseases in patients with type 2 diabetes. Limited real-world studies have examined the comparative biliary safety of GLP-1RAs versus other antihyperglycemic drugs. We aimed to estimate the comparative risk of biliary-related diseases between GLP-1RAs and sodium glucose cotransporter 2 inhibitors (SGLT2is), which are indicated for patients with similar diabetes severity in Taiwan. DESIGN: Retrospective cohort study. DATA SOURCE: Taiwan National Health Insurance Database during 2011 to 2018. PATIENTS: Patients with type 2 diabetes who initiated GLP-1RAs or SGLT2is. INTERVENTION: GLP-1RAs versus SGLT2is. MEASUREMENTS AND MAIN RESULTS: We used an on-treatment approach to examine the effect of continuous use and an intention-to-treat approach to assess the effect of initiation of GLP-1RAs versus SGLT2is. We used Coxregression models to estimate the hazard ratios (HRs) and 95% confidenceintervals (CIs) for the composite hospitalized biliary-related diseases, including acute cholecystitis or cholecystectomy, choledocholithiasis, and acute cholangitis, after matching each GLP-1RA initiator to up to 10 SGLT2iinitiators using propensity scores (PSs). Among 78,253 PS-matched patients, GLP-1RA use was associated with a numerically higher risk of biliary-related diseases versus SGLT2i use in the on-treatment analysis, with an HR of 1.20 (95% CI, 0.93-1.56) for the composite outcome, an HR of 1.22 (95% CI, 0.92-1.62) for acute cholecystitis or cholecystectomy, an HR of 1.20 (95% CI, 0.69-2.07) for choledocholithiasis, and an HR of 1.14 (95% CI,0.82-2.42) for acute cholangitis. The HRs were more pronounced in theintention-to-treat analysis (1.27 [95% CI, 1.05-1.53] for the composite outcome, 1.29 [95% CI, 1.04-1.58] foracute cholecystitis or cholecystectomy, 1.74 [95% CI, 1.23-2.46] for choledocholithiasis, and 1.31 [95% CI, 0.89-1.94] for acute cholangitis). The increased risk of the composite outcome associated with GLP-1RAs was more evident in patients aged ã60 years, women, and 120 days after treatment initiation. Liraglutide, but not dulaglutide, was associated with an elevated risk. CONCLUSIONS: GLP-1RAs might be associated with an elevated risk of biliary-related diseases compared to SGLT2is in Asian patients with type 2 diabetes.
Asunto(s)
Colangitis , Colecistitis Aguda , Coledocolitiasis , Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Colangitis/inducido químicamente , Colangitis/tratamiento farmacológico , Colecistitis Aguda/inducido químicamente , Colecistitis Aguda/tratamiento farmacológico , Coledocolitiasis/inducido químicamente , Coledocolitiasis/tratamiento farmacológico , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Receptor del Péptido 1 Similar al Glucagón/agonistas , Humanos , Hipoglucemiantes/efectos adversos , Estudios Retrospectivos , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversosRESUMEN
Melatonin exerts a wide range of effects among various tissues and organs. However, there is currently no study to investigate the genetic determinants of melatonin secretion. Here, we conducted a genome-wide association study (GWAS) for melatonin secretion using morning urine 6-hydroxymelatonin sulfate-to-creatinine ratio (UMCR). We initially enrolled 5000 participants from Taiwan Biobank in this study. After excluding individuals that did not have their urine collected in the morning, those who had history of neurological or psychiatric disorder, and those who failed to pass quality control, association of single nucleotide polymorphisms with log-transformed UMCR adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for estimated glomerular filtration rate (eGFR). A total of 2373 participants underwent the genome-wide analysis. Five candidate loci associated with log UMCR (P value ranging from 6.83 × 10-7 to 3.44 × 10-6) encompassing ZFHX3, GALNT15, GALNT13, LDLRAD3 and intergenic between SEPP1 and FLJ32255 were identified. Similar results were yielded with further adjustment for eGFR. Interestingly, the identified genes are associated with circadian behavior, neuronal differentiation, motor disorders, anxiety, and neurodegenerative diseases. We conducted the first GWAS for melatonin secretion and identified five candidate genetic loci associated with melatonin level. Replication and functional studies are needed in the future.
Asunto(s)
Estudio de Asociación del Genoma Completo , Melatonina , Ritmo Circadiano , Sitios Genéticos , Humanos , Melatonina/genética , Melatonina/metabolismo , Polimorfismo de Nucleótido SimpleRESUMEN
RATIONALE, AIMS, AND OBJECTIVES: A more effective allocation of critical care resources is important as the cost of intensive care increases. A model has been developed to predict the probability of in-hospital death among patients who received extracorporeal membrane oxygenation (ECMO). Cost-effectiveness analyses (CEA) were performed regarding the relationship between hospitalization expenses and predicted survival outcomes. METHODS: Adult patients who received ECMO in a medical center in Taiwan (2005-2016) were included. A logistic regression model was applied to a spectrum of clinical measures obtained before and during ECMO institutions to identify the risk variables for in-hospital mortality. CEA were reported as a predictive risk in quintiles and defined as the cost of each quality-adjusted life-year (QALY). The distribution of the cost-effectiveness ratio (CER) was measured by the ellipse and acceptability curve methods. RESULTS: A total of 919 patients (659 males, mean age: 53.7 years) were enrolled. Ten variables emerged as significant predictors of in-hospital death. The area under the receiver operating characteristic curve was 0.75 (95% confidence interval: 0.72-0.79). In-hospital and total follow-up times were 40,366 and 660,205 person-days, respectively. The total in-hospital expense was $31,818,701 USD and the total effectiveness was 1687.3 QALY. For the lowest to the highest risk quintile, the mean mortality risks were 0.30, 0.48, 0.61, 0.75, and 0.88, and mean adjusted CER were $24,230, $43,042, $54,929, $84,973, and $149,095 per QALY, respectively. CONCLUSIONS: The efficient allocation of limited and costly resources is most important when one is forced to decide between groups of critically ill patients. The current analyses of ECMO outcomes should assist in identifying candidates with the greatest prospect for survival while avoiding futile treatments.
Asunto(s)
Oxigenación por Membrana Extracorpórea , Adulto , Análisis Costo-Beneficio , Oxigenación por Membrana Extracorpórea/métodos , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Años de Vida Ajustados por Calidad de Vida , Estudios Retrospectivos , Medición de RiesgoRESUMEN
Background: This 12-year study aimed to compare the longitudinal change in left ventricular diastolic dysfunction (LVDD) between healthy elderly, coronary artery disease (CAD), and hypertension (HTN) patients. Methods: From 2008 to 2020, 1476 patients were included, and 3181 echocardiography examinations were conducted. Finally, 130 participants (36 healthy elderly (79.39 ± 9.51 years old), 51 with CAD (68.31 ± 12.09 years old), and 43 with HTN (68.31 ± 12.09 years old)) with more than a 10-year follow-up period were included in the final analysis. Results: The change in diastolic function was different among these subjects according to the integrated score index (elderly vs. HTN, p = 0.01; CAD vs. HTN, p = 0.01), septal E/e' ratio (elderly vs. HTN, p < 0.001; CAD vs. HTN, p = 0.01), lateral E/e' ratio (elderly vs. HTN, p < 0.001; CAD vs. HTN, p < 0.001), and NYHA functional class (elderly vs. HTN, p = 0.03; CAD vs. HTN, p < 0.001). Additionally, per one-year increase in age, the integrated score index increased 0.2 in the healthy elderly, 0.15 in the CAD, and 0.06 in the HTN patients (all p < 0.05). Conclusion: Under aggressive treatment, diastolic function was relatively preserved in HTN subjects with aging in comparison with elderly and CAD subjects.