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BACKGROUND: Narrative medicine demonstrated positive impact on empathy in medicine and nursing students. However, this pedagogical approach had not been evaluated in pharmacy education. This study sought to apply and evaluate the narrative medicine approach in extending empathy in Asian undergraduate pharmacy students. METHODS: Narrative medicine was applied through workshops which used narratives of people with different experiences and perspectives. First-year undergraduate pharmacy students who volunteered and attended these workshops formed the intervention group (N = 31) and the remaining first-year cohort formed the control group (N = 112). A sequential explanatory mixed methods approach was adopted in which quantitative methods were first used to measure impact on pharmacy students' empathy using the Jefferson Scale of Empathy- Health Professions Student (JSE-HPS), and qualitative methods (i.e. group interviews) were then used to assess pharmacy students' emotional responses to narratives, and the perspectives of pharmacy students and faculty of this pedagogical approach. RESULTS: There was no difference in JSE-HPS scores between intervention and control groups across baseline (i.e. upon matriculation), pre-intervention, and post-intervention timepoints. Pharmacy students in the intervention group had lower scores in Factor 3 ("Standing in People's Shoes") following the intervention. Five themes, guided by internal and external factors in cognition, emerged from the Group Interviews: (1) incongruence between students' motivation and faculty's perception, (2) learning context, (3) academic context, (4) cognitive system, and (5) affective system. Themes 1, 4 and 5 referred to internal factors such as students' motivation, perceived learnings, and feelings. Themes 2 and 3 referred to external factors including workshop materials, activities, content, and facilitation. CONCLUSION: This study is the first to demonstrate that pharmacy students engaged with the narrative medicine approach as narratives elicited emotional responses, exposed them to diverse perspectives, and deepened their appreciation of the importance of empathy and complexities of understanding patients' perspectives. Scaffolded educational interventions using narratives and real-life patient encounters, alongside longitudinal measurements of empathy, are necessary to bring about meaningful and sustained improvements in empathy.
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Educación en Farmacia , Medicina Narrativa , Estudiantes de Medicina , Humanos , Singapur , Estudiantes de Medicina/psicología , Empatía , Personal de SaludRESUMEN
Pharmacological agents used to treat or manage diseases can modify the level of heat strain experienced by chronically ill and elderly patients via different mechanistic pathways. Human thermoregulation is a crucial homeostatic process that maintains body temperature within a narrow range during heat stress through dry (i.e., increasing skin blood flow) and evaporative (i.e., sweating) heat loss, as well as active inhibition of thermogenesis, which is crucial to avoid overheating. Medications can independently and synergistically interact with aging and chronic disease to alter homeostatic responses to rising body temperature during heat stress. This review focuses on the physiologic changes, with specific emphasis on thermolytic processes, associated with medication use during heat stress. The review begins by providing readers with a background of the global chronic disease burden. Human thermoregulation and aging effects are then summarized to give an understanding of the unique physiologic changes faced by older adults. The effects of common chronic diseases on temperature regulation are outlined in the main sections. Physiologic impacts of common medications used to treat these diseases are reviewed in detail, with emphasis on the mechanisms by which these medications alter thermolysis during heat stress. The review concludes by providing perspectives on the need to understand the effects of medication use in hot environments, as well as a summary table of all clinical considerations and research needs of the medications included in this review. SIGNIFICANCE STATEMENT: Long-term medications modulate thermoregulatory function, resulting in excess physiological strain and predisposing patients to adverse health outcomes during prolonged exposures to extreme heat during rest and physical work (e.g., exercise). Understanding the medication-specific mechanisms of altered thermoregulation has importance in both clinical and research settings, paving the way for work toward refining current medication prescription recommendations and formulating mitigation strategies for adverse drug effects in the heat in chronically ill patients.
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Calentamiento Global , Calor , Humanos , Anciano , Regulación de la Temperatura Corporal/fisiología , Temperatura Corporal/fisiología , Enfermedad CrónicaRESUMEN
AIMS: This study attempts to identify predictors associated with bleeding and stroke and systemic embolism (SSE) in Singaporean Asians taking rivaroxaban and apixaban. METHODS: A total of 134 Singaporean patients on either rivaroxaban or apixaban for non-valvular atrial fibrillation were included for this study. Baseline characteristics were recorded at recruitment while bleeding and SSE events were recorded during a 1-year follow-up. Peak and trough drug plasma concentrations were collected based on the dosing interval and pharmacokinetics of the drugs and quantified using high performance liquid chromatography. Characteristics of patients with or without bleeds were compared using relevant statistical tests. Multivariable regression that included covariates with p < 0.1 from an initial univariable regression was performed to analyse predictors that resulted in higher risk of bleeding in patients. RESULTS: Median creatinine clearance (CrCl) was significantly lower in patients on rivaroxaban who experienced bleeds as compared to patients who did not experience bleeds (61.5 vs 70.8 mL/min, p = 0.047), while concomitant simvastatin use was found to be independently associated with a sixfold increased risk of bleeding (adjusted OR = 6.14 (95% CI: 1.18-31.97), p = 0.031) for rivaroxaban after controlling for body mass index, CrCl and having experienced a previous SSE. CONCLUSION: Our findings suggest that concomitant use of simvastatin with rivaroxaban may be associated with bleeding events in an Asian cohort. Further studies using physiologically based pharmacokinetic modelling are required to investigate the drug-drug interactions between these drugs.
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Fibrilación Atrial , Hemorragia , Rivaroxabán , Simvastatina , Accidente Cerebrovascular , Humanos , Anticoagulantes/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Estudios de Cohortes , Dabigatrán , Hemorragia/inducido químicamente , Rivaroxabán/efectos adversos , Rivaroxabán/sangre , Singapur/epidemiología , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/prevención & control , Pueblo Asiatico , Simvastatina/efectos adversos , Quimioterapia Combinada , AtorvastatinaRESUMEN
Pharmacogenetics play an important role in determining the anti-hypertensive effects of blood pressure-lowering medications and have the potential to improve future patient care. Current literature on the topic, however, has a heavy focus on Caucasians and may not be generalisable to the Asian populations. Therefore, we have conducted this systematic review to summarise and evaluate the literature of the past decade. PubMed, Embase, and the Cochrane Register of Controlled Trials were searched for relevant studies from 1 January 2011 to 23 July 2021. The outcome of interest was the response to anti-hypertensive treatment in Asians according to each genetic polymorphism. A total of 26 studies with a total of 8837 patients were included in our review, covering five classes of anti-hypertensive agents-namely, angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), beta-blockers (BB), calcium channel blockers (CCB), and thiazide-like diuretics. Response to ACEI therapy was most susceptible to genotypic variations, while the efficacy of ARB and CCB were affected by pharmacogenetic differences to varying extent. For BB, only variations in the ADRB1 genotype significantly affects therapeutic response, while the therapeutic efficacy of thiazide-like diuretics was correlated with genotypic variations in the REN and ACE. This systematic review evaluated the impact of pharmacogenetic variations on the therapeutic efficacy of anti-hypertensive treatment in Asians and has described numerous drug-gene pairs that are potentially clinically important. Future prospective studies with larger sample sizes and longer follow-up periods are needed to better elucidate the impact of these drug-gene pairs.
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Antihipertensivos , Hipertensión , Humanos , Antihipertensivos/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Estudios Prospectivos , Bloqueadores de los Canales de Calcio/uso terapéutico , Bloqueadores de los Canales de Calcio/farmacología , Diuréticos/uso terapéutico , Tiazidas/uso terapéutico , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Hipertensión/genéticaRESUMEN
OBJECTIVES: The aim of this study was to characterize the benefits of converting Electronic Medical Records (EMRs) to a common data model (CDM) and to assess the potential of CDM-converted data to rapidly generate insights for benefit-risk assessments in post-market regulatory evaluation and decisions. METHODS: EMRs from January 2013 to December 2016 were mapped onto the Observational Medical Outcomes Partnership-CDM (OMOP-CDM) schema. Vocabulary mappings were applied to convert source data values into OMOP-CDM-endorsed terminologies. Existing analytic codes used in a prior OMOP-CDM drug utilization study were modified to conduct an illustrative analysis of oral anticoagulants used for atrial fibrillation in Singapore and South Korea, resembling a typical benefit-risk assessment. A novel visualization is proposed to represent the comparative effectiveness, safety and utilization of the drugs. RESULTS: Over 90% of records were mapped onto the OMOP-CDM. The CDM data structures and analytic code templates simplified the querying of data for the analysis. In total, 2,419 patients from Singapore and South Korea fulfilled the study criteria, the majority of whom were warfarin users. After 3 months of follow-up, differences in cumulative incidence of bleeding and thromboembolic events were observable via the proposed visualization, surfacing insights as to the agent of preference in a given clinical setting, which may meaningfully inform regulatory decision-making. CONCLUSIONS: While the structure of the OMOP-CDM and its accessory tools facilitate real-world data analysis, extending them to fulfil regulatory analytic purposes in the post-market setting, such as benefit-risk assessments, may require layering on additional analytic tools and visualization techniques.
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We evaluated the cost-effectiveness of a genotype-guided strategy among patients with acute coronary syndromes using a decision-tree model based on the Singapore healthcare payer's perspective over a 1-year time horizon. Three dual antiplatelet strategies were considered: universal clopidogrel, genotype-guided, and universal ticagrelor. The prevalence of loss-of-function alleles was assumed to be 61.7% and model inputs were identified from the literature. Our primary outcome of interest was incremental cost-effectiveness ratio (ICER) compared to universal clopidogrel. Both genotype-guided (72,158 SGD/QALY) and universal ticagrelor (82,269 SGD/QALY) were considered cost-effective based on a willingness-to-pay (WTP) threshold of SGD 88,991. In our secondary analysis, the ICER for universal ticagrelor was 114,998 SGD/QALY when genotype-guided was taken as a reference. Probabilistic sensitivity analysis revealed that genotype-guided was the most cost-effective strategy when the WTP threshold was between SGD 70,000 to 100,000. Until more data are available, our study suggests that funding for a once-off CYP2C19 testing merits a consideration over 1 year of universal ticagrelor.
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Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/genética , Citocromo P-450 CYP2C19/genética , Inhibidores de Agregación Plaquetaria/economía , Inhibidores de Agregación Plaquetaria/uso terapéutico , Síndrome Coronario Agudo/economía , Clopidogrel/economía , Clopidogrel/uso terapéutico , Análisis Costo-Beneficio/economía , Costos de los Medicamentos , Genotipo , Humanos , Años de Vida Ajustados por Calidad de Vida , Singapur , Ticagrelor/economía , Ticagrelor/uso terapéutico , Ticlopidina/economía , Ticlopidina/uso terapéuticoRESUMEN
BACKGROUND: Patients with ischemic stroke are often treated with clopidogrel monotherapy as part of secondary stroke prevention. The prevalence of loss of function (LOF) mutations in the CYP2C19 gene is higher in Asians than in Western populations. Patients with loss of function (LOF) mutations are at risk for poorer secondary outcomes when prescribed clopidogrel. OBJECTIVE: We aimed to determine the cost effectiveness of genotype-guided antiplatelet therapy in an Asian population with the aim of prescribing ticagrelor as an alternative to patients with LOF mutations. METHODS: Markov models were developed to look at the cost effectiveness of genetic testing of CYP2C19, with patients who screened positive for LOF alleles being switched to ticagrelor compared to universal clopidogrel treatment. Effect ratios were obtained from the literature and incidence rates and costs were obtained from the national data published by the Singapore Ministry of Health. Lifetime costs and quality-adjusted life-years (QALYs) were calculated. The primary endpoints were the incremental cost-effectiveness ratios (ICERs). RESULTS: The prevalence of the LOF mutations was 61% in the population, with 65% of ethnic Chinese, 60% of ethnic Indian, and 53% of ethnic Malay patients having LOF mutations. Based on this prevalence, the overall ICER of genetic testing was S$33,839/QALY with ICERS of S$30,755/QALY, S$33,177/QALY, and S$41,470/QALY for Chinese, Indians, and Malays, respectively. CONCLUSION: This study suggests that it is cost effective to screen for LOF mutations in the CYP2C19 gene in ischemic stroke populations, with ticagrelor as a substitute for clopidogrel in those with LOF mutations.
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Clopidogrel/administración & dosificación , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Ticagrelor/administración & dosificación , Anciano , Pueblo Asiatico , Isquemia Encefálica/tratamiento farmacológico , Análisis Costo-Beneficio , Citocromo P-450 CYP2C19/genética , Genotipo , Humanos , Mutación con Pérdida de Función , Persona de Mediana Edad , Años de Vida Ajustados por Calidad de VidaRESUMEN
Genetic polymorphisms significantly affect individual responses to warfarin, contributing to unpredictability and challenges in managing anticoagulation. Although numerous studies have demonstrated that pharmacogenetic testing improves anticoagulation-related outcomes in the Caucasian population, its effect in the Asian population has not been well studied. This article discusses controversies surrounding tailoring warfarin therapy using pharmacogenetic testing and its role in clinical practice, with a focus on the Asian context. Using the Singapore experience as an example, the authors propose how pharmacogenetic testing can be a means to reduce dose titrations in select patient populations, and how it may be positioned as an enabler to reduce healthcare resources needed for anticoagulation management.
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Aim: Identify factors patients consider regarding CYP2C19 genotyping test to guide choice of antiplatelet therapy. Patients & methods: Patient's perception and attitude toward use of CYP2C19 genotyping test was gathered according to an interview guide. Thematic analysis was conducted. Results: A total of 14 patients were interviewed. The main factors found to influence uptake of CYP2C19 genotyping test are, convenience of genotyping test (n = 4), physician's recommendation (n = 11), prior explanation of genetic testing by medical personnel (n = 5) and inclination toward clopidogrel, with three sub-factors; less frequent dosing (n = 3), lower cost (n = 7) and lower risk of bleeding (n = 9). Conclusion: This study provided the information needed to develop a discrete choice experiment to empirically quantify patients' preference and willingness to pay for genetic testing and to simulate uptake.
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Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Síndrome Coronario Agudo/genética , Citocromo P-450 CYP2C19/genética , Genotipo , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéuticoRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Several Caucasian cohort studies have associated at least one loss-of-function CYP2C19 on Clopidogrel (LoF-Clopidogrel) with major adverse cardiovascular events (MACE), and only a couple have used Clinical Pharmacogenetics Implementation Consortium (CPIC® ) phenotype grouping to study the associations. We primarily aimed to study the impact of use of platelet reactivity testing to escalate antiplatelet therapy and secondarily to study the association of CPIC phenotype with MACE outcomes in South-East Asian Acute Coronary Syndrome (ACS) subjects. METHOD: A retrospective genotype study was performed on 238 percutaneous coronary intervention subjects, originally planned for escalation of antiplatelets using platelet reactivity testing. RESULTS AND DISCUSSION: There was no difference in MACE between the switched and unswitched groups; however, 'all bleeds' and 'clinically significant bleeds' (CSB) were statistically higher in the patients who were switched to prasugrel. The subgroup of patients who remained on clopidogrel (n = 199) were analysed using phenotype categories and MACE. Eleven percent (11.4%) of CYP2C19 poor metabolizers (PM) suffered MACE, compared with 1.3% of extensive metabolizers (EM). LoF-Clopidogrel patients are significantly more likely to experience MACE compared with non-LoF subjects (8.0% vs 5.4%, P: .041). WHAT IS NEW AND CONCLUSION: In our multivariate analysis, LoF-Clopidogrel, malay ethnicity, diabetics and use of proton pump inhibitors were independent predictors of MACE. There were numerically more bleeds in LoF subjects who were on prasugrel compared with Clopidogrel (23.5% vs 11%, P = .082). Our data corroborate with current findings on platelet reactivity testing, suggesting that the assay would not be sensitive enough to pick up sufficient 'at-risk' subjects as compared to the use of CYP2C19 genotyping.
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Síndrome Coronario Agudo/terapia , Citocromo P-450 CYP2C19/genética , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Anciano , Pueblo Asiatico/genética , Enfermedades Cardiovasculares/epidemiología , Clopidogrel/administración & dosificación , Clopidogrel/efectos adversos , Femenino , Genotipo , Hemorragia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Farmacogenética , Fenotipo , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/administración & dosificación , Clorhidrato de Prasugrel/efectos adversos , Estudios RetrospectivosRESUMEN
AIMS: Non-vitamin K antagonist oral anticoagulants (NOACs) require dose reductions according to patient or clinical factors for patients with atrial fibrillation (AF). In this meta-analysis, we aimed to assess outcomes with reduced-dose NOACs when given as pre-specified in pivotal trials. METHODS AND RESULTS: Aggregated data abstracted from Phase III trials comparing NOACs with warfarin in patients with AF were assessed by treatment using risk ratios (RRs) and 95% confidence intervals (CIs) stratified by patient eligibility for NOAC dose reduction. Irrespective of treatments, annualized rates of stroke or systemic embolism and major bleeding were higher in patients eligible for reduced-dose NOACs than in those eligible for full-dose NOACs (2.70% vs. 1.60% and 4.35% vs. 2.87%, respectively). Effects of reduced-dose NOACs compared with warfarin in patients eligible for reduced-dose NOACs on stroke or systemic embolism [RR 0.84 (95% CI 0.69-1.03)] and on major bleeding [RR 0.70 (95% CI 0.50-0.97)] were consistent with those of full-dose NOACs relative to warfarin in those eligible for full-dose NOACs [RR 0.86 (95% CI 0.77-0.96) for stroke or systemic embolism and RR 0.87 (95% CI 0.70-1.08) for major bleeding; interaction P, 0.89 and 0.26, respectively]. In addition, NOACs were associated with reduced risks of haemorrhagic stroke, intracranial haemorrhage, fatal bleeding, and death regardless of patient eligibility for NOAC dose reduction (interaction P > 0.05 for each). CONCLUSIONS: Patients eligible for reduced-dose NOACs were at elevated risk of thromboembolic and haemorrhagic complications when treated with anticoagulants. NOACs, when appropriately dose-adjusted, had an improved benefit-harm profile compared with warfarin. Our findings highlight the importance of prescribing reduced-dose NOACs for indicated patient populations.
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Fibrilación Atrial/tratamiento farmacológico , Inhibidores del Factor Xa/administración & dosificación , Hemorragia/inducido químicamente , Accidente Cerebrovascular/prevención & control , Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Relación Dosis-Respuesta a Droga , Embolia/etiología , Embolia/prevención & control , Hemorragia Gastrointestinal/inducido químicamente , Humanos , Hemorragias Intracraneales/inducido químicamente , Pirazoles/administración & dosificación , Piridinas/administración & dosificación , Piridonas/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Rivaroxabán/administración & dosificación , Accidente Cerebrovascular/etiología , Tiazoles/administración & dosificación , Warfarina/uso terapéuticoRESUMEN
The objectives of this study are to compare steady-state trough (Cmin,ss) and peak (Cmax,ss) concentrations of rivaroxaban between Asians and Caucasians and to evaluate the relationship between rivaroxaban concentrations and prothrombin time/international normalized ratio (PT/INR). Recruited patients were advised on the time to take rivaroxaban. Cmin,ss and PT/INR were taken when patients arrived. Cmax,ss and PT/INR were drawn between 2 and 4 h later after the patient took rivaroxaban with food. Thirty patients were included in the analyses: 57% (n = 17) males and 43% (n = 13) females, 77% (n = 23) on 20 mg and 23% (n = 7) on 15 mg. Median PTtrough and PTpeak are moderately correlated with Cmin,ss (r2 = 0.43) and Cmax,ss (r2 = 0.49), respectively. Patients on 15 mg have lower Cmin,ss and Cmax,ss versus Caucasians [12 ng/ml vs. 57 ng/ml (Cmin,ss); 87 ng/ml vs. 229 ng/ml (Cmax,ss), p < 0.01 for both]. Patients on 20 mg also have lower Cmin,ss and Cmax,ss versus Caucasians [14 ng/ml vs. 44 ng/ml (Cmin,ss); 101 ng/ml vs. 249 ng/ml (Cmax,ss), p < 0.01 for both]. Subgroup analysis shows patients with BMI ≥ 30 have lower Cmax,ss than patients with BMI < 30 [80.47 ng/ml vs. 124 (p = 0.014)]. Cmin,ss and Cmax,ss were lower in Singaporeans than Caucasians. This may have an impact on the effectiveness of rivaroxaban in Singaporeans. Patients with higher BMI may not benefit similarly as patients with lower BMI. Lastly, the Dade Innovin reagent's measure of PT/INR is not sensitive towards changes in rivaroxaban concentrations.
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Pueblo Asiatico , Pruebas de Coagulación Sanguínea , Rivaroxabán/sangre , Población Blanca , Adulto , Índice de Masa Corporal , Femenino , Humanos , Relación Normalizada Internacional , Masculino , Tiempo de ProtrombinaRESUMEN
BACKGROUND: Direct oral anticoagulants (DOACs) have a better risk benefit profile in Asian patients with atrial fibrillation (AF). Whether treatment effects could be modified by drug class and dependency on renal elimination of studied agents has not yet been explored. METHODS: We searched PubMed, CENTRAL, and CINAHL databases through November 2016 for phase III randomized controlled trials comparing DOACs with warfarin in patients with AF. Efficacy and safety outcomes were pooled according to drug class and dependency on renal elimination of DOACs and were compared with the Mantel-Haenszel fixed-effects model. Effect differences were assessed with Bucher's indirect comparisons using common estimates, once heterogeneity was low, and with the Bayesian method. RESULTS: Among 6496 Asian patients from 6 trials, both direct thrombin inhibitors and factor Xa inhibitors, compared with warfarin, were associated with lower risks of stroke or systemic embolism and major bleeding (risk ratio [95% confidence interval], 0.51 [0.33-0.78], 0.74 ([0.58-0.96], 0.60 [0.41-0.86], and 0.59 [0.47-0.76], respectively). There was no between-group difference in direct thrombin inhibitors and factor Xa inhibitors or in DOACs with renal elimination less than 50% and 50% or greater (all I2 < 25% and interaction P > .05). Indirect comparisons within strata of drug class and dependency on renal elimination showed no preferential effect of any given regimen over another. There was no difference in effects on ischemic and hemorrhagic stroke, intracranial hemorrhage, myocardial infarction, and all-cause mortality between DOACs stratified by pharmacologic characteristics. CONCLUSIONS: DOACs, as a therapeutic class, outperform warfarin in efficacy and safety in Asian patients with AF.
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Anticoagulantes/administración & dosificación , Anticoagulantes/farmacocinética , Antitrombinas/administración & dosificación , Antitrombinas/farmacocinética , Pueblo Asiatico , Fibrilación Atrial/tratamiento farmacológico , Eliminación Renal , Accidente Cerebrovascular/prevención & control , Administración Oral , Anticoagulantes/clasificación , Antitrombinas/clasificación , Fibrilación Atrial/sangre , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/etnología , Coagulación Sanguínea/efectos de los fármacos , Ensayos Clínicos Fase III como Asunto , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/clasificación , Inhibidores del Factor Xa/farmacocinética , Hemorragia/inducido químicamente , Humanos , Oportunidad Relativa , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/etnología , Resultado del Tratamiento , Warfarina/administración & dosificación , Warfarina/clasificación , Warfarina/farmacocinéticaRESUMEN
BACKGROUND: Real-world effectiveness and safety of antithrombotics in nonvalvular atrial fibrillation (NVAF) patients in Singapore has not been thoroughly studied. HYPOTHESIS: Users of various antithrombotics experience a significantly different risk of stroke and major bleed compared with warfarin users. METHODS: This multicenter retrospective cohort study included patients age ≥ 21 years newly diagnosed with NVAF between July 2012 and September 2015. Using electronic medical records, data on patients' demographics, antithrombotics prescribed, and CHA2 DS2 -VASc and HAS-BLED risk factors were collected. Patients were followed for 1 year from diagnosis for the primary effectiveness and safety endpoints of incident stroke or systemic embolism and major bleed, respectively. The secondary safety endpoint was overall bleed. Hazard ratios (HR) were determined from Cox regression. RESULTS: Of 743 patients included, 224 were on warfarin, 156 on direct oral anticoagulants (DOACs), 277 on single antiplatelet therapy (SAPT), 28 on dual antiplatelet therapy (DAPT), and 58 on no therapy. Mean age (±SD) was 68.7 ± 13.0 years. Compared with warfarin users, SAPT (adjusted [adj.] HR: 3.70, 95% confidence interval [CI]: 1.21-11.3) and DAPT users (adj. HR: 10.1, 95% CI: 1.51-67.2) were more likely to develop thromboembolic outcomes. Also, DOAC users (adj. HR: 0.304, 95% CI: 0.158-0.585), SAPT users (adj. HR: 0.142, 95% CI: 0.0680-0.295), and DAPT users (adj. HR: 0.112, 95% CI: 0.0146-0.857) were less likely to experience any bleed compared with warfarin users. CONCLUSIONS: SAPT and DAPT are less effective than warfarin in NVAF patients. DOACs may be considered in view of lower risk of overall bleed.
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Fibrilación Atrial/diagnóstico , Fibrinolíticos/farmacología , Hemorragia/epidemiología , Medición de Riesgo , Accidente Cerebrovascular/prevención & control , Tromboembolia/epidemiología , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/complicaciones , Femenino , Estudios de Seguimiento , Hemorragia/inducido químicamente , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Singapur/epidemiología , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Tromboembolia/etiología , Tromboembolia/prevención & controlRESUMEN
BACKGROUND: Stratifying patients according to 15-day readmission risk would be useful in identifying those who may benefit from targeted interventions during and/or following hospital discharge that are designed to reduce the likelihood of readmission. METHODS: A prediction model was derived via a case-control analysis of patients discharged from a tertiary hospital in Singapore using multivariate logistic regression. The model was validated in two independent external cohorts separated temporally and geographically. Model discrimination was assessed using the C-statistic, while calibration was assessed using the Hosmer-Lemeshow χ2 and the Brier score statistics. RESULTS: A total of 1291 patients were included with 670, 101, and 520 patients in the derivation, temporal, and geographical validation cohorts, respectively. Age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.03, p=0.008), anemia (OR 2.08, 95% CI 1.15-8.05, p=0.015), malignancy (OR 3.37, 95% CI 1.16-9.80, p=0.026), peptic ulcer disease (OR 3.05, 95% CI 1.12-8.26, p=0.029), chronic obstructive pulmonary disease (OR 3.16, 95% CI 1.24-8.05, p=0.016), number of discharge medications (OR 1.06, 95% CI 1.01-1.12, p=0.026), discharge to nursing homes (OR 3.57, 95% CI 1.57-8.34, p=0.003), and premature discharge against medical advice (OR 5.05, 95% CI 1.20-21.23, p=0.027) were independent predictors of 15-day readmission risk. The model demonstrated reasonable discrimination on the temporal and geographical validation cohorts with a C-statistic of 0.65 and 0.64, respectively. Model miscalibration was observed in both validation cohorts. CONCLUSION: A 15-day readmission risk prediction model is proposed and externally validated. The model facilitates the targeting of interventions for patients who are at high risk of an early readmission.
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Algoritmos , Modelos Estadísticos , Readmisión del Paciente/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Alta del Paciente , Factores de Riesgo , Singapur , Centros de Atención Terciaria , Factores de TiempoRESUMEN
INTRODUCTION: As the effectiveness of intensive glycaemic control is unclear and recommended glycaemic targets are inconsistent, this study aimed to ascertain the prevalence of dysglycaemia among hospitalised patients with diabetes mellitus in an Asian population and evaluate the current standards of inpatient glycaemic control. METHODS: A retrospective observational study was conducted at a secondary hospital. Point-of-care blood glucose (BG) values, demographic data, medical history, glycaemic therapy and clinical characteristics were recorded. Dysglycaemia prevalence was calculated as proportions of BG-monitored days with at least one reading exceeding the cut points of 8, 10 and 15 mmol/L for hyperglycaemia, and below the cut point of 4 mmol/L for hypoglycaemia. RESULTS: Among the 288 patients recruited, hyperglycaemia was highly prevalent (90.3%, 81.3% and 47.6% for the respective cut points), while hypoglycaemia was the least prevalent (18.8%). Dysglycaemic patients were more likely than normoglycaemic patients to have poorer glycated haemoglobin (HbA1c) levels (8.4% ± 2.6% vs. 7.3% ± 1.9%; p = 0.002 for BG > 10 mmol/L) and longer lengths of stay (10.1 ± 8.2 days vs. 6.8 ± 4.7 days; p = 0.007 for BG < 4 mmol/L). Hyperglycaemia was more prevalent in patients on more intensive treatment regimens, such as basal-bolus combination therapy and the use of both insulin and oral hypoglycaemic agents (100.0% and 96.0%, respectively; p < 0.001 for BG > 10 mmol/L). CONCLUSION: Inpatient glycaemic control is suboptimal. Factors (e.g. type of treatment regimen, discipline and baseline HbA1c) associated with greater prevalence of dysglycaemia should be given due consideration in patient management.
Asunto(s)
Diabetes Mellitus/tratamiento farmacológico , Hiperglucemia/complicaciones , Hipoglucemia/complicaciones , Pacientes Internos , Anciano , Glucemia/análisis , Femenino , Hospitales , Humanos , Hiperglucemia/tratamiento farmacológico , Hipoglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Sistemas de Atención de Punto , Prevalencia , Estudios Retrospectivos , Singapur , Resultado del TratamientoRESUMEN
OBJECTIVE: To report a case of erythema multiforme secondary to dimenhydrinate and pamabrom cross-sensitivity. CASE SUMMARY: A 22-year-old Chinese female presented with a complaint of lip mucosal ulceration with necrosis and stomatitis, worsening over the past 24 hours and associated with reduced oral intake and incomplete opening of the mouth. Presentation was accompanied by a generalized rash and genital mucosal involvement. The only new systemically ingested agent was dimenhydrinate approximately 4 days prior to admission. She had no significant medical history, but was labeled to be allergic to acetaminophen. She had a positive history of 2 similar presentations secondary to Panadol Menstrual (acetaminophen and pamabrom), once 3 years ago and again 5 months prior to the current admission. An objective causality assessment revealed that the adverse drug event was "probable" to dimenhydrinate. A detailed history revealed a negative drug challenge to acetaminophen. She had previously taken plain acetaminophen and Beserol (acetaminophen and chlormezanone) with no reaction. DISCUSSION: A comprehensive history taking facilitated the diagnosis of erythema multiforme secondary to dimenhydrinate without the need to perform invasive testing, and the removal of erroneous allergy labeling to acetaminophen. Dimenhydrinate and pamabron both contain theophylline-related structures in their chemical composition. Similar reactions to pamabrom strongly suggested cross-sensitivity to theophylline-related structures. CONCLUSIONS: To our knowledge, this is the first report of erythema multiforme due to dimenhydrinate with pamabron cross-sensitivity. We recommend that comprehensive medication-history taking be carried out for all drug-allergy patients to ensure greater informed decision making when choosing medications to use for that patient in the future.