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1.
Anal Chem ; 96(25): 10380-10390, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38860916

RESUMO

To reduce the risk of atherosclerotic disease, it is necessary to not only diagnose the presence of atherosclerotic plaques but also assess the vulnerability risk of plaques. Accurate detection of the reactive oxygen species (ROS) level at plaque sites represents a reliable way to assess the plaque vulnerability. Herein, through a simple one-pot reaction, two near-infrared (NIR) fluorescent dyes, one is ROS responsive and the other is inert to ROS, are coassembled in an amphiphilic amino acid-assembled nanoparticle. In the prepared NIR fluorescent amino acid nanoparticle (named FANP), the fluorescent properties and ROS-responsive behaviors of the two fluorescent dyes are well maintained. Surface camouflage through red blood cell membrane (RBCM) encapsulation endows the finally obtained FANP@RBCM nanoprobe with not only further reduced cytotoxicity and improved biocompatibility but also increased immune escape capability, prolonged blood circulation time, and thus enhanced accumulation at atherosclerotic plaque sites. In vitro and in vivo experiments demonstrate that FANP@RBCM not only works well in probing the occurrence of atherosclerotic plaques but also enables plaque vulnerability assessment through the accurate detection of the ROS level at plaque sites in a reliable ratiometric mode, thereby holding great promise as a versatile tool for the diagnosis and risk assessment of atherosclerotic disease.


Assuntos
Aminoácidos , Corantes Fluorescentes , Nanopartículas , Placa Aterosclerótica , Espécies Reativas de Oxigênio , Placa Aterosclerótica/diagnóstico por imagem , Animais , Espécies Reativas de Oxigênio/metabolismo , Corantes Fluorescentes/química , Nanopartículas/química , Camundongos , Aminoácidos/química , Humanos , Medição de Risco , Imagem Óptica , Raios Infravermelhos , Células RAW 264.7
2.
J Formos Med Assoc ; 122 Suppl 1: S92-S100, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37574339

RESUMO

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.

3.
Neurology ; 100(9): e921-e931, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36450606

RESUMO

BACKGROUND AND OBJECTIVES: Delayed or missed antiseizure medications (ASMs) doses are common during long-term or lifelong antiepilepsy treatment. This study aims to explore optimal individualized remedial dosing regimens for delayed or missed doses of 11 commonly used ASMs. METHODS: To explore remedial dosing regimens, Monte Carlo simulation was used based on previously identified and published population pharmacokinetic models. Six remedial strategies for delayed or missed doses were investigated. The deviation time outside the individual therapeutic range was used to evaluate each remedial regimen. The influences of patients' demographics, concomitant medication, and scheduled dosing intervals on remedial regimens were assessed. RxODE and Shiny in R were used to perform Monte Carlo simulation and recommend individual remedial regimens. RESULTS: The recommended remedial regimens were highly correlated with delayed time, scheduled dosing interval, and half-life of the ASM. Moreover, the optimal remedial regimens for pediatric and adult patients were different. The renal function, along with concomitant medication that affects the clearance of the ASM, may also influence the remedial regimens. A web-based dashboard was developed to provide individualized remedial regimens for the delayed or missed dose, and a user-defined module with all parameters that could be defined flexibly by the user was also built. DISCUSSION: Monte Carlo simulation based on population pharmacokinetic models may provide a rational approach to propose remedial regimens for delayed or missed doses of ASMs in pediatric and adult patients with epilepsy.


Assuntos
Epilepsia , Adulto , Humanos , Criança , Epilepsia/tratamento farmacológico , Método de Monte Carlo , Simulação por Computador , Modelos Biológicos , Esquema de Medicação
4.
ERJ Open Res ; 8(4)2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36411792

RESUMO

Owing to condensed development processes, expanding evidence and differences in healthcare system characteristics, many COVID-19 guidelines differ in their quality and treatment recommendations, which has consequences for clinical practice. This review aimed to identify COVID-19 treatment guidelines, assess their quality and summarise their recommendations. Guidelines were identified for five therapies most commonly used among inpatients with COVID-19 (remdesivir, dexamethasone, tocilizumab, baricitinib and casirivimab/imdevimab) from 11 countries. Guideline quality was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE-II) tool. Full details of recommendations and supporting evidence were analysed for high-quality guidelines, defined as those scoring ≥50% in Domain 3 (Rigour of Development) of AGREE-II. Overall, guidelines differed substantially in their quality and, even among high-quality guidelines using the same evidence, recommendations regarding specific therapeutics varied. Potential reasons for this heterogeneity, including the availability and consistency of clinical data, visibility of trial end-points and context-specific factors, are discussed.

5.
Medicine (Baltimore) ; 101(32): e29718, 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-35960054

RESUMO

BACKGROUND: The negative impacts of COVID-19 (ImpactCOVID) on public health are commonly assessed using the cumulative numbers of confirmed cases (CNCCs). However, whether different mathematical models yield disparate results based on varying time frames remains unclear. This study aimed to compare the differences in prediction accuracy between 2 proposed COVID-19 models, develop an angle index that can be objectively used to evaluate ImpactCOVID, compare the differences in angle indexes across countries/regions worldwide, and examine the difference in determining the inflection point (IP) on the CNCCs between the 2 models. METHODS: Data were downloaded from the GitHub website. Two mathematical models were examined in 2 time-frame scenarios during the COVID-19 pandemic (the early 20-day stage and the entire year of 2020). Angle index was determined by the ratio (=CNCCs at IP÷IP days). The R2 model and mean absolute percentage error (MAPE) were used to evaluate the model's prediction accuracy in the 2 time-frame scenarios. Comparisons were made using 3 visualizations: line-chart plots, choropleth maps, and forest plots. RESULTS: Exponential growth (EXPO) and item response theory (IRT) models had identical prediction power at the earlier outbreak stage. The IRT model had a higher model R2 and smaller MAPE than the EXPO model in 2020. Hubei Province in China had the highest angle index at the early stage, and India, California (US), and the United Kingdom had the highest angle indexes in 2020. The IRT model was superior to the EXPO model in determining the IP on an Ogive curve. CONCLUSION: Both proposed models can be used to measure ImpactCOVID. However, the IRT model (superior to EXPO in the long-term and Ogive-type data) is recommended for epidemiologists and policymakers to measure ImpactCOVID in the future.


Assuntos
COVID-19 , COVID-19/epidemiologia , Surtos de Doenças , Humanos , Modelos Teóricos , Pandemias , SARS-CoV-2
6.
PLoS One ; 17(8): e0269006, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35951654

RESUMO

OBJECTIVE: This study aims to investigate the cost-effectiveness of the add-on exenatide to conventional pharmacotherapy in patients with Parkinson's disease (PD) when considering the coexistence of diabetes mellitus (DM). METHODS: We used the Keelung and Community-based Integrated Screening databases to understand the medical utilisation in the Hoehn and Yahr stages of patients with PD. A Markov model with 1-year cycle length and 50-year time horizon was used to assess the cost-effectiveness of add-on exenatide to conventional pharmacotherapy compared to conventional pharmacotherapy alone. All costs were adjusted to the value of the new Taiwanese dollar (NT$) as of the year 2020. One-way sensitivity and probability analyses were performed to test the robustness of the results. RESULTS: From a societal perspective, the add-on exenatide brought an average of 0.39 quality-adjusted life years (QALYs) gained, and a cost increment of NT$104,744 per person in a 50-year horizon compared to conventional pharmacotherapy. The incremental cost-effectiveness ratio (ICER) was NT$268,333 per QALY gained. As the ICER was less than the gross domestic product per capita (NT$839,558), the add-on exenatide was considered to be very cost-effective in the two models, according to the World Health Organization recommendation. Add-on exenatide had a 96.9% probability of being cost-effective in patients with PD, and a 100% probability of being cost-effective in patients with PD and DM. CONCLUSION: Add-on exenatide is cost-effective in PD combined with DM. Considering that DM may be a risk factor for neurodegenerative diseases, exenatide provides both clinical benefits and cost-effectiveness when considering both PD and DM.


Assuntos
Diabetes Mellitus , Doença de Parkinson , Análise Custo-Benefício , Exenatida/uso terapêutico , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Anos de Vida Ajustados por Qualidade de Vida
7.
PLoS One ; 17(1): e0261871, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35061709

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Atenção à Saúde/economia , Transplante de Células-Tronco Hematopoéticas/economia , Leucemia Mieloide Aguda , Sistema de Registros , Adulto , Idoso , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Custos e Análise de Custo , Feminino , Humanos , Incidência , Leucemia Mieloide Aguda/economia , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taiwan/epidemiologia
8.
Int J Health Policy Manag ; 11(4): 470-478, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33059424

RESUMO

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.


Assuntos
Fraturas do Quadril , Osteoporose , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Feminino , Gastos em Saúde , Fraturas do Quadril/complicações , Fraturas do Quadril/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Taiwan/epidemiologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-34639575

RESUMO

Few large-scale studies have focused on tracheostomy in patients with prolonged mechanical ventilation. This retrospective population-based study extracted data from the longitudinal National Health Insurance Research Database in Taiwan to compare long-term mortality between patients on prolonged mechanical ventilation with and without tracheostomy and their related medical expenditures. Data on newly developed respiratory failure in patients on ventilator support were extracted from 1 January 2002 to 31 December 2008. Of 10,705 patients included, 1372 underwent tracheostomy (n = 563) or translaryngeal intubation (n = 779). Overall survival of the patients with tracheostomy was followed for 5 years. Average survival was 4.98 years for the patients with tracheostomy and 5.48 years for the patients with translaryngeal intubation (not significant). Sex, age, premium-based monthly salary difference, occupation, urbanization level, chronic obstructive pulmonary disease, chronic heart failure, chronic renal disease, and cerebrovascular diseases were significantly associated with mortality for endotracheal intubation. Male sex, chronic heart failure, chronic renal disease, age ≥45 years, and low income were associated with significantly higher mortality. Although total medical expenditures were higher for the patients with tracheostomy, annual medical expenditures were not significantly different. There were no differences in long-term mortality between the two groups.


Assuntos
Insuficiência Respiratória , Traqueostomia , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Insuficiência Respiratória/terapia , Estudos Retrospectivos
10.
Expert Rev Clin Pharmacol ; 14(9): 1153-1163, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34058934

RESUMO

BACKGROUND: Rivaroxaban is an oral anticoagulant widely used for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). During long-term anticoagulant therapy, delayed or missed doses are common. This study aimed to explore appropriate remedial dosing regimens for non-adherent rivaroxaban-treated patients. METHODS: Monte Carlo simulation based on a previously established rivaroxaban population pharmacokinetic/pharmacodynamic (PK/PD) model for patients with NVAF was employed to design remedial dosing regimens. The proposed regimens were compared with remedial strategies in the European Heart Rhythm Association (EHRA) guide by assessing deviation time in terms of drug concentration, factor Xa activity, and prothrombin time. RESULTS: The proposed remedial dosing regimens were dependent on delay duration. The missed dose should be taken immediately when the delay does not exceed 6 h; a half dose is advisable when the delay is between 6 and 20 h. A missed dose should be skipped if less than 4 h remains before the next dose. The proposed regimens resulted in shorter deviation time than that of the EHRA guide. CONCLUSION: PK/PD modeling and simulation provide valid evidence on the remedial dosing regimen of rivaroxaban, which could help to minimize the risk of bleeding and thromboembolism.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Modelos Biológicos , Rivaroxabana/administração & dosagem , Idoso , Fibrilação Atrial/complicações , Simulação por Computador , Relação Dose-Resposta a Droga , Inibidores do Fator Xa/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Adesão à Medicação , Pessoa de Meia-Idade , Método de Monte Carlo , Rivaroxabana/efeitos adversos , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Fatores de Tempo
11.
Crit Care ; 25(1): 45, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531020

RESUMO

BACKGROUND: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. METHOD: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. RESULTS: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. CONCLUSIONS: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.


Assuntos
Acidose/tratamento farmacológico , Bicarbonato de Sódio/administração & dosagem , APACHE , Acidose/epidemiologia , Idoso , Austrália/epidemiologia , Feminino , Humanos , Incidência , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Internacionalidade , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Bicarbonato de Sódio/farmacologia , Bicarbonato de Sódio/uso terapêutico , Taiwan/epidemiologia
12.
Acta Pharmacol Sin ; 42(8): 1368-1375, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33154554

RESUMO

Camrelizumab, a programmed cell death 1 (PD-1) inhibitor, has been approved for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma, nasopharyngeal cancer and non-small cell lung cancer. The aim of this study was to perform a population pharmacokinetic (PK) analysis of camrelizumab to quantify the impact of patient characteristics and to investigate the appropriateness of a flat dose in the dosing regimen. A total of 3092 camrelizumab concentrations from 133 patients in four clinical trials with advanced melanoma, relapsed or refractory classical Hodgkin lymphoma and other solid tumor types were analyzed using nonlinear mixed effects modeling. The PKs of camrelizumab were properly described using a two-compartment model with parallel linear and nonlinear clearance. Then, covariate model building was conducted using stepwise forward addition and backward elimination. The results showed that baseline albumin had significant effects on linear clearance, while actual body weight affected intercompartmental clearance. However, their impacts were limited, and no dose adjustments were required. The final model was further evaluated by goodness-of-fit plots, bootstrap procedures, and visual predictive checks and showed satisfactory model performance. Moreover, dosing regimens of 200 mg every 2 weeks and 3 mg/kg every 2 weeks provided similar exposure distributions by model-based Monte Carlo simulation. The population analyses demonstrated that patient characteristics have no clinically meaningful impact on the PKs of camrelizumab and present evidence for no advantage of either the flat dose or weight-based dose regimen for most patients with advanced solid tumors.


Assuntos
Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/sangue , Ensaios Clínicos como Assunto , Simulação por Computador , Relação Dose-Resposta a Droga , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Método de Monte Carlo , Neoplasias/sangue , Adulto Jovem
13.
Epilepsy Behav ; 111: 107265, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32640410

RESUMO

OBJECTIVE: Delayed or missed doses are unavoidable in the pharmacotherapy of epilepsy and significantly compromise the efficacy of antiepileptic drug treatment. An inappropriate remedial regimen can cause seizure relapse or serious adverse events. This study investigated the effect of delayed or missed doses on the pharmacokinetics (PK) of valproic acid (VPA) in patients with epilepsy and established remedial dosing recommendations for nonadherent patients. METHODS: Monte Carlo simulations are based on all previous population pharmacokinetic models for pediatric, adult and elderly patients with epilepsy. The following four remedial strategies were investigated for each delayed dose: A) A partial dose or a regular dose is taken immediately; a regular dose is taken at the next scheduled time. B) The delayed dose was administered immediately, followed by a partial dose at the next scheduled time. C) The delayed dose and a partial dose are taken; the next scheduled time is skipped, and the regular regimen is resumed. D) Double doses are taken when missed one dose or two doses, and the regular regimen at the subsequent scheduled time is resumed. RESULTS: The recommended remedial dose was related to the delay duration and daily dose. Remedial dosing strategies A and B were almost equivalent, whereas Strategy C was recommended when the delayed dose was close to the next scheduled dose. Strategy D was only suggested for delayed two doses. CONCLUSION: Simulations provide quantitative insight into the remedial regimens for nonadherent patients, and clinicians should select the optimal regimen for each patient based on the individual's status.


Assuntos
Anticonvulsivantes/administração & dosagem , Epilepsia/diagnóstico , Epilepsia/tratamento farmacológico , Método de Monte Carlo , Ácido Valproico/administração & dosagem , Adulto , Idoso , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Humanos , Lactente , Masculino , Convulsões/tratamento farmacológico
14.
J Pain Symptom Manage ; 58(6): 968-976, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31404645

RESUMO

CONTEXT: Nearly 70% of do-not-resuscitate (DNR) directives for chronic obstructive pulmonary disease (COPD) patients are established during their terminal hospitalization. Whether patient use of end-of-life resources differs between early and late establishment of a DNR is unknown. OBJECTIVES: The objective of this study was to compare end-of-life resource use between patients according to DNR directive status: no DNR, early DNR (EDNR) (established before terminal hospitalization), and late DNR (LDNR) (established during terminal hospitalization). METHODS: Electronic health records from all COPD decedents in a teaching hospital in Taiwan were analyzed retrospectively with respect to medical resource use during the last year of life and medical expenditures during the last hospitalization. Multivariate linear regression analysis was used to determine independent predictors of cost. RESULTS: Of the 361 COPD patients enrolled, 318 (88.1%) died with a DNR directive, 31.4% of which were EDNR. COPD decedents with EDNR were less likely to be admitted to intensive care units (12.0%, 55.5%, and 60.5% for EDNR, LDNR, and no DNR, respectively), had lower total medical expenditures, and were less likely to undergo invasive mechanical ventilator support during their terminal hospitalization. The average total medical cost during the last hospitalization was nearly twofold greater for LDNR than for EDNR decedents. Multivariate linear regression analysis revealed that nearly 60% of medical expenses incurred were significantly attributable to no EDNR, younger age, longer length of hospital stay, and more comorbidities. CONCLUSION: Although 88% of COPD decedents died with a DNR directive, 70% of these directives were established late. LDNR results in lower quality of care and greater intensive care resource use in end-of-life COPD patients.


Assuntos
Custos de Cuidados de Saúde , Hospitalização/economia , Doença Pulmonar Obstrutiva Crônica/economia , Doença Pulmonar Obstrutiva Crônica/terapia , Ordens quanto à Conduta (Ética Médica) , Diretivas Antecipadas , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Comorbidade , Cuidados Críticos/economia , Cuidados Críticos/estatística & dados numéricos , Registros Eletrônicos de Saúde , Feminino , Humanos , Tempo de Internação/economia , Masculino , Pessoa de Meia-Idade , Respiração Artificial/economia , Respiração Artificial/estatística & dados numéricos , Assistência Terminal
15.
Epilepsy Behav ; 96: 132-140, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31132614

RESUMO

OBJECTIVE: This study investigated the effect of delayed or missed doses on the pharmacokinetics (PK) of lamotrigine (LTG) in children with epilepsy and established remedial dosing recommendations for nonadherent patients. METHODS: The Monte Carlo simulation based on a published LTG population PK model was used to assess the effect of different scenarios of nonadherence and the subsequently administered remedial regimens. The following three remedial approaches were investigated for each delayed dose: A) A partial dose was administered immediately, and the regular dose was administered at the next scheduled time. B) The delayed dose was administered immediately, followed by a partial dose at the next scheduled time. C) The delayed and partial doses were coadministered immediately, the next scheduled dose was skipped, and the regular dosing was resumed at the subsequent scheduled time. The most appropriate remedial regimen was that with the shortest deviation time from the individual therapeutic window. RESULTS: The effect of nonadherence on PK was dependent on the delay duration and daily dose, and the recommended remedial dose was related to the delay duration and concomitant antiepileptic drugs. Remedial dosing strategies A and B were almost equivalent, whereas C showed a larger PK deviation time. If one dose was missed, double doses were not recommended for the next scheduled time. CONCLUSIONS: Simulations provide quantitative insight into the remedial regimens for nonadherent patients, and clinicians should select the optimal regimen based on the status of patients.


Assuntos
Anticonvulsivantes/administração & dosagem , Epilepsia/tratamento farmacológico , Lamotrigina/administração & dosagem , Método de Monte Carlo , Adolescente , Criança , Pré-Escolar , Esquema de Medicação , Epilepsia/diagnóstico , Feminino , Humanos , Masculino
16.
Int J Clin Pract ; 72(10): e13246, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30144247

RESUMO

AIMS: Recent clinical guidelines have suggested that patients experience an osteoporotic fracture should initiate anti-osteoporosis medications (AOMs). However, whether clinical guidelines translate well in "real-world" practices remain questioned. This study aimed to evaluate the "real-world" prescription pattern of AOMs and visualise the unmet treatment needs in different geographical areas in Taiwan. METHODS: Using Taiwan's National Health Insurance Research Database, we identified patients diagnosed with a hip or vertebral fracture between 2009 and 2012. The treatment rate was defined as the proportion of patients receiving AOMs within 1 year after their index fracture. The qualitative geographical information systems approach was adopted to visualise the treatment needs of postfracture patients in different geographical areas. RESULTS: Our study included 276,492 patients diagnosed with a hip or vertebral fracture between 2009 and 2012. The proportion of patients who received AOMs within 1 year after their index fracture increased with age and differed with fracture types and sex. For patients with hip fractures, the treatment rate ranged from 3.43% to 20.88% for female patients and from 0.69% to 10.04% for male patients in different age groups. For patients with vertebral fractures, the treatment rate ranged from 3.23% to 37.08% for female patients and from 1.85% to 23.05% for male patients. Cities in the mid-northern and southern areas of Taiwan had the highest unmet treatment need, with a treatment rate of less than 15%. CONCLUSION: The treatment rate of osteoporotic fractures with AOMs was diverse and suboptimal in Taiwan, especially among male patients. This study used a visualisation technique to display information about the treatment status in different geographical areas and help policymakers allocate resource appropriately.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Necessidades e Demandas de Serviços de Saúde , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Prevenção Secundária/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Sistemas de Informação Geográfica , Fraturas do Quadril/etiologia , Fraturas do Quadril/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde/estatística & dados numéricos , Avaliação das Necessidades , Osteoporose/complicações , Fraturas por Osteoporose/etiologia , Estudos Retrospectivos , Fatores Sexuais , Análise Espacial , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/prevenção & controle , Taiwan
17.
Arch Osteoporos ; 12(1): 92, 2017 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-29067572

RESUMO

This nationwide study investigated the epidemiology, treatment patterns, and economic burden of osteoporosis and associated fracture in Taiwan. The treatment of osteoporosis is alarmingly suboptimal, considering the significantly increased economic burden of major osteoporotic fracture. Osteoporosis men received lesser anti-osteoporosis drugs but had higher incremental costs attributable to osteoporotic fractures. PURPOSE: This nationwide study investigated the epidemiology, treatment patterns, and economic burden of osteoporosis and associated fracture between 2009 and 2013 in Taiwan. METHODS: We used the National Health Insurance Research Database as our data source. The prevalence of diagnosed osteoporosis and major osteoporotic fractures was calculated annually from 2009 to 2013, stratified by age and gender. Osteoporosis patients who received any prescription of anti-osteoporosis drugs during each fiscal year were defined as osteoporosis patients under treatment. Healthcare utilization and associated direct medical costs were used to quantify the economic burden of osteoporosis. For patients who encountered major osteoporotic fracture, the incremental changes of direct medical costs attributable to fracture using a pre- and post-quasi-experimental design were estimated. Furthermore, we compared the annual direct medical costs of patients who encountered major osteoporotic fracture with those diagnosed osteoporosis only and with the general population. RESULTS: The prevalence of diagnosed osteoporosis increased with age, with the highest rate among those aged 80 and older. Overall, less than one-third of women and only 10% of men received anti-osteoporosis drugs among osteoporosis patients. The annual direct medical costs for osteoporosis patients increased steadily from 2009 to 2013. The total medical costs and incremental change of direct medical costs were higher in men than those in women. CONCLUSION: We found the treatment of osteoporosis to be alarmingly suboptimal, considering the significantly increased economic burden of major osteoporotic fracture also identified in this study. Osteoporosis men received lesser anti-osteoporosis drugs but had higher incremental costs attributable to major osteoporotic fractures.


Assuntos
Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde/estatística & dados numéricos , Osteoporose/epidemiologia , Fraturas por Osteoporose/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Seguro Saúde/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Osteoporose/economia , Osteoporose/terapia , Fraturas por Osteoporose/economia , Fraturas por Osteoporose/terapia , Prevalência , Distribuição por Sexo , Taiwan/epidemiologia
18.
BMJ Open ; 6(6): e010973, 2016 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-27279477

RESUMO

OBJECTIVES: To investigate the association between the trends of CT utilisation in an emergency department (ED) and changes in clinical imaging practice and patients' disposition. SETTING: A hospital-based retrospective observational study of a public 1520-bed referral medical centre in Taiwan. PARTICIPANTS: Adult ED visits (aged ≥18 years) during 2009-2013, with or without receiving CT, were enrolled as the study participants. MAIN OUTCOME MEASURES: For all enrolled ED visits, we retrospectively analysed: (1) demographic characteristics, (2) triage categories, (3) whether CT was performed and the type of CT scan, (4) further ED disposition, (5) ED cost and (6) ED length of stay. RESULTS: In all, 269 239 adult ED visits (148 613 male patients and 120 626 female patients) were collected during the 5-year study period, comprising 38 609 CT scans. CT utilisation increased from 11.10% in 2009 to 17.70% in 2013 (trend test, p<0.001). Four in 5 types of CT scan (head, chest, abdomen and miscellaneous) were increasingly utilised during the study period. Also, CT was increasingly ordered annually in all age groups. Although ED CT utilisation rates increased markedly, the annual ED visits did not actually increase. Moreover, the subsequent admission rate, after receiving ED CT, declined (59.9% in 2009 to 48.2% in 2013). CONCLUSIONS: ED CT utilisation rates increased significantly during 2009-2013. Emergency physicians may be using CT for non-emergent studies in the ED. Further investigation is needed to determine whether increasing CT utilisation is efficient and cost-effective.


Assuntos
Serviço Hospitalar de Emergência/organização & administração , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Tomografia Computadorizada por Raios X/tendências , Triagem/classificação , Adolescente , Adulto , Idoso , Análise Custo-Benefício , Bases de Dados Factuais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Encaminhamento e Consulta , Estudos Retrospectivos , Taiwan , Adulto Jovem
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