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Some guidelines had recommended "thrombolysis first" in ST-elevated myocardial infarction (STEMI) during the Coronavirus Disease 2019 (COVID-19) outbreak. The impact of COVID-19 solely on STEMI thrombolysis is lacking as most studies reported outcomes related to percutaneous coronary intervention (PCI) setting. Thus, this study aimed to assess the impact of the COVID-19 pandemic on STEMI thrombolysis outcomes and the Emergency Department's performance in a non-PCI capable centre.This single-centre retrospective study analysed data on consecutive STEMI patients who received thrombolytic therapy from May 2019 to December 2020 (20 months) in a non-PCI capable tertiary hospital. Total population sampling was used in this study. We compared all patients' characteristics and outcomes ten months before and during the pandemic. Regression models were used to assess the impact of COVID-19 pandemic on door-to-needle time (DNT), mortality, bleeding events, and the number of overnight stays.We analysed 323 patients with a mean age of 52.9 ± 12.9 years and were predominantly male (n = 280, 88.9%). There was a 12.5% reduction in thrombolysis performed during the pandemic. No significant difference in timing from symptoms onset to thrombolysis and DNT was observed. In-hospital mortality was significantly higher during the pandemic (OR 2.02, 95% CI 1.02-4.00, p = 0.044). Bleeding events post thrombolysis remained stable and there was no significant difference in the number of overnight stays during the pandemic.STEMI thrombolysis cases were reduced during the COVID-19 pandemic, with an inverse increase in mortality despite the preserved Emergency Department performance in timely thrombolysis.

Fibrinolysis remains the primary reperfusion strategy for ST-elevation myocardial infarction (STEMI) in many Asian countries. The outcomes and factors affecting mortality in STEMI fibrinolysis in the Asian population are lacking despite being widely used.This study aimed to assess the clinical profile of patients and predictors affecting STEMI mortality in an Asian population.This single-center retrospective study analyzed data from STEMI patients who received fibrinolytic therapy from 2016 to 2020 in a tertiary hospital. Logistic regression analysis was performed to identify the significant predictors of the 30-day all-cause mortality, the primary outcome.A total of 859 patients were included. Their mean age was 53.6 ±12.1 years and they were predominantly male (n=769, 89.4%). The majority of them had anterior involvement STEMI (n = 477, 55.5%) and presented with Killip ≥ II (n = 424, 49.4%). The 30-day all-cause mortality was 12.0% (n = 103). The final model found six predictors for 30-day mortality: age ≥75 (aOR 4.784, p 0.001), female gender (aOR 2.869, p = 0.001), pre-existing hypertension (aOR 1.623, p = 0.046), anterior myocardial infarction (MI) (aOR 1.947, p 0.001), Killip class (p 0.001) and heart rate ≥100 at presentation (aOR 1.823, p = 0.016). Following fibrinolytic therapy, five predictors were found to affect 30-day mortality, i.e. failed fibrinolysis (aOR 2.094, p = 0.041), bleeding events, congestive heart failure (aOR 3.554, p = 0.046), ventricular fibrillation/ tachycardia (aOR 5.920, p 0.001), and atrial fibrillation/ flutter (aOR 2.968, p = 0.016).Our STEMI patients were younger and more ill at presentation. The risk predictors on 30-day all-cause mortality identified in our Asian population allow the clinicians to better triage and manage STEMI patients.

Several types of cardiovascular cells use microRNA-21 ( miR-21 ), which has been linked to cardioprotection. In this study, we systematically reviewed the results of published papers on the therapeutic effect of miR-21 for myocardial infarction. Studies described the cardioprotective effects of miR-21 to reduce infarct size by improving angiogenesis, antiapoptotic, and anti-inflammatory mechanisms. Results suggest that cardioprotective effects of miR-21 may work synergistically to prevent the deterioration of cardiac function during postischemia. However, there are other results that indicate that miR-21 positively regulates tissue fibrosis, potentially worsening a postischemic injury. The dual functionalities of miR-21 occur through the targeting of genes and signaling pathways, such as PTEN , PDCD4 , KBTBD7 , NOS3 , STRN , and Spry-1 . This review provides insights into the future advancement of safe miR-21 -based genetic therapy in the treatment of myocardial infarction.

Dabigatran etexilate is an oral direct thrombin inhibitor used in preventing thromboembolism in patients with atrial fibrillation and several other conditions. Routine dabigatran concentration monitoring is not recommended in clinical practice; however, measurement of dabigatran concentration may be required in several conditions. This study aims to pool the peak and trough dabigatran concentration from real-world studies. A systematic review was performed to identify studies that measured the peak and trough dabigatran concentrations. Observational studies reporting dabigatran peak or trough concentrations and patients' clinical characteristics of either sex, age or weight were included. Random-effect meta-analyses and metaregression were conducted to pool dabigatran concentrations and to identify the correlation between factors affecting dabigatran concentrations. Fifteen studies with a total of 1226 patients were included. The pooled peak dabigatran concentration was 133 ng/mL (95% CI: 113-154, I

Rivaroxaban and apixaban are effective oral anticoagulants, but their usage has been associated with an increased risk of bleeding events. This study examined the bleeding and thromboembolic events of rivaroxaban and apixaban. Medical records from 114 patients (rivaroxaban n = 64, apixaban n = 80) treated for stroke prevention in atrial fibrillation at a tertiary hospital in Malaysia were retrospectively reviewed. Patients with bleeding or stroke/ systemic embolism events were identified and the bleeding risk factors were investigated using logistic regression analysis. Stroke or systemic embolism after treatment with Factor Xa (FXa) inhibitor occurred in 12 (8.33%) of the patients, 5 (3.47%) were ischaemic stroke and 7 (4.86%) of them were presented with myocardial infarction. Bleeding occurred in 32 (22.20%) patients, where 7 (4.90%) were presented with major bleeding (rivaroxaban n = 3, apixaban n = 4), while another 25 (17.40%) experienced clinically relevant non-major bleeding. Furthermore, concomitant antiplatelet used and serum creatinine level were significant predictors of bleeding events (P < 0.05). In conclusion, stroke or systemic embolism events were low for both drugs, but this may be an underestimate of the true prevalence due to the small sample size in the present study.

Aims There is considerable interpatient variability in the pharmacokinetics (PK) of intravenous immunoglobulin G (IVIG), causing difficulty in optimizing individual dosage regimen. This study aims to estimate the population PK parameters of IVIG and to investigate the impact of genetic polymorphism of the FcRn gene and clinical variability on the PK of IVIG in patients with predominantly antibody deficiencies. Methods Patients were recruited from four hospitals. Clinical data were recorded and blood samples were taken for PK and genetic studies. Population PK parameters were estimated by nonlinear mixed-effects modeling in Monolix®. Models were evaluated using the difference in objective function value, goodness-of-fit plots, visual predictive check and bootstrap analysis. Monte Carlo simulation was conducted to evaluate different dosing regimens for IVIG. Results A total of 30 blood samples were analyzed from 10 patients. The immunoglobulin G concentration data were best described by a one-compartment model with linear elimination. The final model included both volume of distribution (Vd) and clearance (CL) based on patient's individual weight. Goodness-of-fit plots indicated that the model fit the data adequately, with minor model mis-specification. Genetic polymorphism of the FcRn gene and the presence of bronchiectasis did not affect the PK of IVIG. Simulation showed that dosing intervals of 3 to 4-weekly was sufficient to maintain IgG levels of 5 g L-1 , with more frequent intervals needed to achieve higher trough levels. Conclusions Body weight significantly affects the PK parameters of IVIG. Genetic and other clinical factors investigated did not affect the disposition of IVIG.

Background/Aims: G73A polymorphism in the CST3 gene of cystatin C has been associated with Alzheimer’s disease, age-related macular degeneration, and cardiovascular disease. However, studies investigating the influence of this genetic variability on serum cystatin C and cystatin-based renal function estimate are limited. Therefore, the aim of this study is to investigate the possible association of single-nucleotide polymorphism (rs1064039) of the CST3 gene on the serum cystatin C level and cystatin C-based estimated glomerular filtration rate (eGFR). Methods: Study subjects include patients with various levels of renal function recruited from the nephrology clinic and wards of a tertiary hospital. The blood samples collected were analyzed for serum cystatin C and creatinine levels by particle-enhanced turbidimetric immunoassay and kinetic alkaline picrate method, respectively. DNA was extracted using a commercially available kit. ­Polymerase chain reaction results were confirmed by direct DNA Sanger sequencing. Results: The genotype percentage (G/G = 73%, G/A = 24.1%, and A/A = 2.9%) adhere to the Hardy-Weinberg equilibrium. The dominant allele found in our population was CST3 73G allele (85%). The regression lines’ slope of serum cystatin C against creatinine and cystatin C-based eGFR against creatinine-based eGFR, between G and A allele groups, showed a statistically significant difference (z-score = 3.457, p < 0.001 and z-score = 2.158, p = 0.015, respectively). Patients with A allele had a lower serum cystatin C level when the values were extrapolated at a fixed serum creatinine value, suggesting the influence of genetic factor. Conclusion: Presence of CST3 gene G73A polymorphism affects serum cystatin C levels.

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas’ original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300–600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75–150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175–300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100–200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250–400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150–300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300–600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.

Background Fibrinolysis using streptokinase or tenecteplase remains the primary reperfusion strategy for ST-elevation myocardial infarction (STEMI) in many Asian countries, including Malaysia. Comparative outcomes of these two fibrinolytic agents in the Asian population were inconclusive despite being widely used. Aim We aimed to assess and compare the outcomes of streptokinase versus tenecteplase in STEMI reperfusion of an Asian population. Method This single-centre retrospective study analysed data on STEMI patients who received fibrinolytic therapy from 2016 to 2020 in the Emergency Department of the largest tertiary hospital in Malaysia. Total population sampling was used in this study. Based on the propensity score matching, 359 patients receiving streptokinase were matched against 359 patients receiving tenecteplase by incorporating 16 variables that potentially affect mortality. 30-day mortality, stroke and major bleeding were the primary outcome measures. Results There was no significant difference in 30-day mortality between streptokinase (n = 39, 11.2%) and tenecteplase (n = 46, 13.2%) groups (p = 0.418). The rates of ischemic strokes [streptokinase (n = 1, 0.3%) versus tenecteplase (n = 3, 0.9%), p = 0.624], intracranial haemorrhage [streptokinase (n = 3, 0.9%) versus tenecteplase (n = 1, 0.3%), p = 0.624] and major bleeding [streptokinase (n = 4, 1.1%) versus tenecteplase (n = 3, 0.9%), p = 0.624], were comparable for the two groups. The incidences of failed thrombolysis were significantly higher in the tenecteplase arm. Hypotension and allergic reaction were significantly higher in the streptokinase arm. Conclusion Streptokinase and tenecteplase are fibrinolytic agents with similar efficacy and safety in STEMI reperfusion therapy in our Asian population.

PurposeTo estimate the vitamin D status of participants residing in Malaysia.MethodsPubMed, Scopus, Web of Science, and MyJurnal were searched up to June 2022 without language restrictions. Studies that reported the 25-hydroxyvitamin D [25(OH)D] concentrations and defined their cut-off for deficiency or insufficiency from healthy participants residing in Malaysia were included. The random effects model was used to pool vitamin D status using established cut-offs of ResultsFrom 299 studies screened, 32 studies were included in the meta-analysis. The pooled proportion for n = 2,438 from 10 studies), while the pooled proportion n = 13,977 from 30 studies), and n = 1,376 from five studies). Heterogeneity was high (I2 ranged from 98–99%). Higher proportions of vitamin D insufficiency (defined as ConclusionMore than half of Malaysians have insufficient vitamin D levels, despite being a country that is close to the equator. We strongly urge prompt public health measures to improve the vitamin D status in Malaysia.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021260259].

Background Population pharmacokinetics (popPK) using the nonlinear mixed-effect (NLME) modeling approach is an essential tool for guiding dose individualization. Several popPK analyses using the NLME have been conducted to characterize the pharmacokinetics of immunoglobulin G (IgG). Objective To summarize the current information on popPK of polyclonal IgG therapy. Method A systematic search was conducted in the PubMed and Web of Science databases from inception to December 2020. Additional relevant studies were also included by reviewing the reference list of the reviewed articles. All popPK studies that employed the NLME modeling approach were included and data were synthesized descriptively. Results This review included seven studies. Most of the popPK models were developed in patients with primary immunodeficiency (PID). IgG pharmacokinetics was described as a two-compartment model in five studies, while it was described as a one-compartment model in two other studies. Among all tested covariates, weight was consistently identified as a significant predictor for clearance (CL) of IgG. Whereas, weight and disease type were found to be significant predictors for the volume of distribution in central compartment (Vc). In a typical 70 kg adult, the median estimated values of Vc and CL were 4.04 L and 0.144 L/day, respectively. The between subject variability of Vc was considered large. Only two studies evaluated their models using external data. Conclusions Seven popPK studies of IgG were found and discussed, with only weight being a significant covariate across all studies. Future studies linking pharmacokinetics with pharmacodynamics in PID and other patient populations are required.

Background The objective of this study was to compare the performance of cystatin C- and creatinine-based estimated glomerular filtration rate (eGFR) equations in predicting the clearance of vancomycin. Methods MEDLINE and Embase databases were searched from inception up to September 2019 to identify all studies that compared the predictive performance of cystatin C- and/or creatinine-based eGFR in predicting the clearance of vancomycin. The prediction errors (PEs) (the value of eGFR equations minus vancomycin clearance) were quantified for each equation and were pooled using a random-effects model. The root mean squared errors were also quantified to provide a metric for imprecision. Results This meta-analysis included evaluations of seven different cystatin C- and creatinine-based eGFR equations in total from 26 studies and 1,234 patients. The mean PE (MPE) for cystatin C-based eGFR was 4.378 mL min−1 (95% confidence interval [CI], −29.425, 38.181), while the creatinine-based eGFR provided an MPE of 27.617 mL min−1 (95% CI, 8.675, 46.560) in predicting clearance of vancomycin. This indicates the presence of unbiased results in vancomycin clearance prediction by the cystatin C-based eGFR equations. Meanwhile, creatinine-based eGFR equations demonstrated a statistically significant positive bias in vancomycin clearance prediction. Conclusion Cystatin C-based eGFR equations are better than creatinine-based eGFR equations in predicting the clearance of vancomycin. This suggests that utilising cystatin C-based eGFR equations could result in better accuracy and precision to predict vancomycin pharmacokinetic parameters., Graphical Abstract

We conducted a systematic review and meta-regression analysis to evaluate the impact of increasing immunoglobulin G (IgG) trough levels on the clinical outcomes in patients with PID receiving intravenous immunoglobulin G (IVIG) treatment. Systematic search was conducted in PubMed and Cochrane. Other relevant articles were searched by reviewing the references of the reviewed article. All clinical trials with documented IgG trough levels and clinical outcome of interest in patients receiving IVIG treatment were eligible to be included in this review. Meta-regression analysis was conducted using Comprehensive Meta-analysis Software. Additional sensitivity analyses were undertaken to evaluate the robustness of the overall results. Twenty-eight clinical studies with 1218 patients reported from year 2001 to 2018 were included. The mean IVIG dose used ranges from 387 to 560 mg/kg every 3 to 4 weekly, and mean IgG trough obtained ranges from 660 to 1280 mg/dL. Random-effects meta-regression slope shows that IgG trough level increases significantly by 73 mg/dL with every increase of 100 mg/kg dose of IVIG (p

There is preliminary evidence to suggest that some published warfarin dosing algorithms produce biased maintenance dose predictions in patients who require higher than average doses. We conducted a meta-analysis of warfarin dosing algorithms to determine if there exists a systematic under- or overprediction of dose requirements for patients requiring ≥7 mg/day across published algorithms. Medline and Embase databases were searched up to September 2015. We quantified the proportion of over- and underpredicted doses in patients whose observed maintenance dose was ≥7 mg/day. The meta-analysis included 47 evaluations of 22 different warfarin dosing algorithms from 16 studies. The meta-analysis included data from 1,492 patients who required warfarin doses of ≥7 mg/day. All 22 algorithms were found to underpredict warfarin dosing requirements in patients who required ≥7 mg/day by an average of 2.3 mg/day with a pooled estimate of underpredicted doses of 92.3% (95% confidence interval 90.3–94.1, I2 = 24%).

Background: Gynura species have been used traditionally to treat various ailments, such as fever, pain, and to control blood glucose level. This systematic review critically discusses studies regarding Gynura species that exhibited antioxidant and anti-inflammatory effects, thus providing perspectives and instructions for future research of the plants as a potential source of new dietary supplements or medicinal agents. Methods: A literature search from internet databases of PubMed, Scopus, Science Direct, e-theses Online Service, and ProQuest was carried out using a combination of keywords such as “Gynura,” “antioxidant,” “anti-inflammatory,” or other related words. Research articles were included in this study if they were experimental (in vitro and in vivo) or clinical studies on the antioxidant or anti-inflammatory effects of Gynura species and if they were articles published in English. Results: Altogether, 27 studies on antioxidant and anti-inflammatory effects of Gynura species were selected. The antioxidant effects of Gynura species were manifested by inhibition of reactive oxygen species production and lipid peroxidation, modulation of glutathione-related parameters, and enzymatic antioxidant production or activities. The anti-inflammatory effects of Gynura species were through the modulation of inflammatory cytokine production, inhibition of prostaglandin E2 and nitric oxide production, cellular inflammatory-related parameters, and inflammation in animal models. The potential anti-inflammatory signaling pathways modulated by Gynura species are glycogen synthase kinase-3, nuclear factor erythroid 2-related factor 2, PPARγ, MAPK, NF-κB, and PI3K/Akt. However, most reports on antioxidant and anti-inflammatory effects of the plants were on crude extracts, and the chemical constituents contributing to bioactivities were not clearly understood. There is a variation in quality of studies in terms of design, conduct, and interpretation, and in-depth studies on the underlying mechanisms involved in antioxidant and anti-inflammatory effects of the plants are in demand. Moreover, there is limited clinical study on antioxidant and anti-inflammatory effects of Gynura species. Conclusion: This review highlighted antioxidant and anti-inflammatory effects of genus Gynura and supported their traditional uses to treat oxidative stress and inflammatory-related diseases. This review is expected to catalyze further studies on genus Gynura. However, extensive preclinical data need to be generated from toxicity and pharmacokinetic studies before clinical studies can be pursued for their development into clinical medicines to treat oxidative stress and inflammatory conditions.

Personalised medicine is potentially useful to delay the progression of chronic kidney disease (CKD). The aim of this study was to determine the effects of CYP3A5 polymorphism in rapid CKD progression. This multicentre, observational, prospective cohort study was performed among adult CKD patients (≥18 years) with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, who had ≥4 outpatient, non-emergency eGFR values during the three-year study period. The blood samples collected were analysed for CYP3A5*3 polymorphism. Rapid CKD progression was defined as eGFR decline of &gt, 5 mL/min/1.73 m2/year. Multiple logistic regression was then performed to identify the factors associated with rapid CKD progression. A total of 124 subjects consented to participate. The distribution of the genotypes adhered to the Hardy–Weinberg equilibrium (X2 = 0.237, p = 0.626). After adjusting for potential confounding factors via multiple logistic regression, the factors associated with rapid CKD progression were CYP3A5*3/*3 polymorphism (adjusted Odds Ratio [aOR] 4.190, 95% confidence interval [CI]: 1.268, 13.852), adjustments to antihypertensives, young age, dyslipidaemia, smoking and use of traditional/complementary medicine. CKD patients should be monitored closely for possible factors associated with rapid CKD progression to optimise clinical outcomes. The CYP3A5*3/*3 genotype could potentially be screened among CKD patients to offer more individualised management among these patients.

Background: \ud A previously established Bayesian dosing tool for warfarin was found to produce biased maintenance dose predictions. In this study, we aimed (1) to determine whether the biased warfarin dose predictions previously observed could be replicated in a new cohort of patients from 2 different clinical settings, (2) to explore the influence of CYP2C9 and VKORC1 genotype on predictive performance of the Bayesian dosing tool, and (3) to determine whether the previous population used to develop the kinetic–pharmacodynamic model underpinning the Bayesian dosing tool was sufficiently different from the test (posterior) population to account for the biased dose predictions.\ud \ud Methods: \ud The warfarin maintenance doses for 140 patients were predicted using the dosing tool and compared with the observed maintenance dose. The impact of genotype was assessed by predicting maintenance doses with prior parameter values known to be altered by genetic variability (eg, EC50 for VKORC1 genotype). The prior population was evaluated by fitting the published kinetic–pharmacodynamic model, which underpins the Bayesian tool, to the observed data using NONMEM and comparing the model parameter estimates with published values.\ud \ud Results: \ud The Bayesian tool produced positively biased dose predictions in the new cohort of patients (mean prediction error [95% confidence interval]; 0.32 mg/d [0.14–0.5]). The bias was only observed in patients requiring ≥7 mg/d. The direction and magnitude of the observed bias was not influenced by genotype. The prior model provided a good fit to our data, which suggests that the bias was not caused by different prior and posterior populations.\ud \ud Conclusions: \ud Maintenance doses for patients requiring ≥7 mg/d were overpredicted. The bias was not due to the influence of genotype nor was it related to differences between the prior and posterior populations. There is a need for a more mechanistic model that captures warfarin dose–response relationship at higher warfarin doses.

Background: An assay for the quantification of dabigatran and its active metabolites, dabigatran acylglucuronides, has not previously been described in detail. Results: For the quantification of total dabigatran concentration (free dabigatran and acylglucuronides), samples were subjected to alkaline hydrolysis. For the quantification of free dabigatran, samples were acidified with ammonium formate. Following acetonitrile protein precipitation, the samples were analyzed by LC–MS/MS using gradient elution to ensure separation of dabigatran from dabigatran acylglucuronides. Mean recoveries ≥98% were achieved. The assay was validated over the range 2.5–1000 ng/ml dabigatran, imprecision was

The aim of this study was to compare the predictive performance of different warfarin dosing methods.Data from 46 patients who were initiating warfarin therapy were available for analysis. Nine recently published dosing tools including 8 dose prediction algorithms and a Bayesian forecasting method were compared with each other in terms of their ability to predict the actual maintenance dose. The dosing tools included 4 algorithms that were based on patient characteristics (2 clinical and 2 genotype-driven algorithms), 4 algorithms based on international normalized ratio (INR) response feedback and patient characteristics (2 clinical and 2 genotype-driven algorithms), and a Bayesian forecasting method. Comparisons were conducted using measures of bias (mean prediction error) and imprecision [root mean square error (RMSE)].The 2 genotype-driven INR feedback algorithms by Horne et al and Lenzini et al produced more precise maintenance dose predictions (RMSE, 1.16 and 1.19 mg/d, respectively; P0.05) than the genotype-driven algorithms by Gage et al and Klein et al and the Bayesian method (RMSE, 1.60, 1.62, and 1.81 mg/d respectively). The dose predictions from clinical and genotype-driven algorithms by Gage et al, Klein et al, and Horne et al were all negatively biased. Only the INR feedback algorithms (clinical and genotype) by Lenzini et al produced unbiased dose predictions. The Bayesian method produced unbiased dose predictions overall (mean prediction error, +0.37 mg/d; 95% confidence interval, 0.89 to -0.15) but overpredicted doses in patients requiring8 mg/d.Overall, warfarin dosing methods that included some measure of INR response (INR feedback algorithms and Bayesian methods) produced unbiased and more precise dose predictions. The Bayesian forecasting method produced positively biased dose predictions in patients who required doses8 mg/d. Further research to assess differences in clinical endpoints when warfarin doses are predicted using Bayesian or INR-driven algorithms is warranted.