Cisplatin-induced ototoxicity: a novel approach to an ancient problem.

With the scarcity of pharmacological otoprotective agents against cisplatin-induced ototoxicity (CIO), researchers find themselves compelled to look at and navigate all possible strategies to identify ways to prevent CIO. One of these promising strategies is pharmacogenomic implementation. This strategy aims for identifying and detecting high-risk genetic variants to tailor cisplatin therapy to reach the best survival outcomes with the least risk of ototoxicity.

Trends in prescribing and outcomes in obese versus non-obese patients receiving rivaroxaban therapy: an observational study using real-world data.

PURPOSE: To investigate real-world prescribing trends and clinical outcomes based on body mass index (BMI) categorization in patients who received rivaroxaban therapy. METHODS: This was a retrospective cohort study involving all patients who received rivaroxaban therapy across all Hamad Medical Corporation (HMC) hospitals from 2015 to 2020. RESULTS: The number of patients initiated on rivaroxaban therapy significantly increased from 152 (3.3%) in 2015 to 1342 (28.9%) in 2020 (p <0.001). Within BMI categories, a similar increasing trend was observed in underweight, normal, and overweight patients, while from 2018 to 2020, there was a decreasing trend in rivaroxaban prescribing in all obese classes. The prevalence rate of all-cause mortality differed significantly between the BMI groups, with the highest mortality being among morbidly obese patients (BMI ≥ 40 kg/m2) (p< 0.001). On the other hand, no significant differences were found between the BMI groups in terms of bleeding, pulmonary embolism, deep vein thrombosis and stroke incidences. Multivariate logistic regression analyses showed that the likelihood of all-cause mortality was significantly higher in overweight and all categories of obese patients compared to underweight patients: overweight (OR: 5.3, 95% CI: 2.3-11.9, p< 0.001); obese class 1 (OR: 5.4, 95% CI: 2.3 - 12.2, p< 0.001); obese class 2 (OR: 6.5, 95% CI: 2.7 - 15.6, p< 0.001); and obese class 3 (OR: 3.7, 95% CI: 1.6 - 8.7, p = 0.003). CONCLUSIONS: Rivaroxaban prescribing has significantly increased over the years across general population, with a noticeable decline in obese population during the last few years (from 2018 onwards). Furthermore, an appreciable association was evident between all-cause mortality and BMI of these patients.

Effect of CYP2C19 genetic variants on bleeding and major adverse cardiovascular events in a cohort of Arab patients undergoing percutaneous coronary intervention and stent implantation.

INTRODUCTION: One-third of patients have clopidogrel resistance that may lead to major adverse cardiac events (MACEs). By contrast, it was found that some clopidogrel-treated patients have hyperresponsive platelets that are associated with higher bleeding risk. Several studies have shown that polymorphisms in the gene encoding the CYP2C19 contribute to the variability in response to clopidogrel. Data on genetic and nongenetic factors affecting clopidogrel response in the Arab population are scarce. In this prospective cohort study, we sought to assess the association between the increased function allele (CYP2C19*17) and bleeding events, and validate the effect of the CYP2C19 genetic variants and nongenetic factors on the incidence of MACEs. METHODS: Blood samples were collected from patients that were undergoing percutaneous coronary intervention and receiving clopidogrel at the Heart Hospital, a specialist tertiary hospital in Doha, Qatar. Patients were followed for 12 months. Genotyping was performed for CYP2C19*2, *3, and *17 using TaqMan assays. RESULTS: In 254 patients, the minor allele frequencies were 0.13, 0.004, and 0.21 for *2, *3, and *17, respectively. Over a 12-month follow-up period, there were 21 bleeding events (8.5 events/100 patient-year). CYP2C19*17 carriers were found to be associated with increased risk of bleeding (OR, 21.6; 95% CI, 4.8-96.8; P < 0.0001). CYP2C19*2 or *3 carriers were found to be associated with increased risk of baseline and incident MACE combined (OR, 8.4; 95% CI, 3.2-23.9; P < 0.0001). CONCLUSION: This study showed a significant association between CYP2C19*17 allele and the increased risk of bleeding, and CYP2C19*2 or *3 with MACE outcomes.

Anticoagulation clinic drive-up service during COVID-19 pandemic in Qatar.

Coronavirus Disease 2019 (COVID-19) is a pandemic affecting many countries worldwide. Given the increasing incidence especially in elderly and individuals with comorbid conditions, it is advised by health authorities to stay home if possible, maintain social distancing and stay away from those who are sick or could be infected. Patients with comorbidities especially cardiovascular disease are at higher risk of getting infected with COVID-19 and have worse prognosis. Among efforts to safely manage warfarin patients during this pandemic, we introduced a hospital drive-up anticoagulation testing service. This service can reduce the risk of exposure of anticoagulation patients to COVID-19 by reducing the contact time with the different personnel at the hospital and by maintaining those patients at a safe distance from others.

Comparative effectiveness and safety of direct oral anticoagulants compared to warfarin in morbidly obese patients with acute venous thromboembolism: systematic review and a meta-analysis.

Direct oral anticoagulant (DOAC) agents are becoming the anticoagulation strategy of choice. However, their use in the treatment of acute venous thromboembolism (VTE) in morbidly obese patients (bodyweight of > 120 kg or BMI > 40 kg/m2) guarded. This is due to the scarce data supporting their use in this population. As a result, the International Society on Thrombosis and Haemostasis recommended against their use in this cohort of patients. New data emerged supporting the use of DOACs in these patients. Hence, we aimed to systematically review the literature exploring the efficacy and safety of these agents compared to warfarin in VTE treatment in morbidly obese patients. A systematic review of PubMed and EMBASE since inception until 01/04/2020. Subsequently, a non-inferiority (NI of 1.75) meta-analysis utilizing the random-effects model. Five observational studies (6585 patients) were included in our meta-analysis. DOAC analogs were non-inferior compared to warfarin in reducing the primary efficacy outcome of VTE recurrence (OR 1.07, 95% CI 0.93-1.23) and the primary safety outcome (major bleeding events) (OR 0.80, 95% CI 0.54-1.17). Our meta-analysis comprising real-world observational data concludes that the use of DOAC analogs in morbidly obese patients (bodyweight of > 120 kg or BMI > 40 kg/m2) is non-inferior with regards to efficacy and safety compared to warfarin. This finding helps to resolve the uncertainty associated with the use of DOACs in this cohort. Additionally, it invites for a confirmatory non-inferiority randomized controlled trial testing DOAC vs. Warfarin in this group of patients.

The effect of genetic and nongenetic factors on warfarin dose variability in Qatari population.

The objective of this study is to estimate the prevalence of VKORC1, CYP2C9, and CYP4F2 genetic variants and their contribution to warfarin dose variability in Qataris. One hundred and fifty warfarin-treated Qatari patients on a stable dose and with a therapeutic INR for at least three consecutive clinic visits were recruited. Saliva samples were collected using Oragene DNA self-collection kit, followed by DNA purification and genotyping via TaqMan Real-Time-PCR assay. The population was stratified into derivation and validation cohorts for the dosing model. The minor allele frequency (MAF) of VKORC1 (-1639G>A) was A (0.47), while the MAF's for the CYP2C9*2 and *3 and CYP4F2*3 were T (0.12), C (0.04) and T (0.43), respectively. Carriers of at least one CYP2C9 decreased function allele (*2 or *3) required lower median (IQR) warfarin doses compared to noncarriers [24.5 (14.5) mg/week vs. 35 (21) mg/week, p < 0.001]. Similarly, carriers of each additional copy of (A) variant in VKORC1 (-1639G>A) led to reduction in warfarin dose requirement compared to noncarriers [21(7.5) vs. 31.5(18.7) vs. 43.7(15), p < 0.0001]. CYP4F2*3 polymorphism on the other hand was not associated with warfarin dose. Multivariate analysis on the derivation cohort (n = 104) showed that a dosing model consisting of hypertension (HTN), heart failure (HF), VKORC1 (-1639G>A), CYP2C9*2 & *3, and smoking could explain 39.2% of warfarin dose variability in Qataris (P < 0.001). In the validation cohort (n = 45), correlation between predicted and actual warfarin doses was moderate (Spearman's rho correlation coefficient = 0.711, p < 0.001). This study concluded that VKORC1 (-1639G>A), CYP2C9*2 & *3 are the most significant predictors of warfarin dose along with HTN, HF and smoking.

Effect of SAMe-TT2R2 score and genetic polymorphism on the quality of anticoagulation control in Qatari patients treated with warfarin.

There is no strong evidence on pharmacogenetics role on the quality of INR control after the initiation phase and on the maintenance of stable INR on the long term as measured by the time in therapeutic range (TTR). The benefit of a score such as SAMe-TT2R2 is that it can preemptively guide clinicians on whether to start the patient on warfarin or direct oral anticoagulant. To determine the association between genetic variants in CYP2C9, VKORC1, and CYP4F2 and TTR. To validate SAMe-TT2R2 score predictive ability on the quality of anticoagulation in Qatari patients. This is an observational nested case-control study that was conducted on a cohort of Qatari patients treated with warfarin with previously identified genotype for the CYP2C9, VKORC1, and CYP2F4. The sample size of this cohort was 148 patients. Mean TTR was 62.7 ± 21%. TTR was not significantly different among carriers of the CYP2C9*2 &*3, VKORC1(-1639G>A) or CYP4F2*3 compared to their non-carriers alleles. None of the factors in the SAMe-TT2R2 score had a significant effect on the TTR except for the female gender where TTR was significantly lower in females (n = 89) compared to males (n = 59) (59.6 ± 21% vs. 67.2 ± 20%, p = 0.03). Furthermore, patients with SAMe-TT2R2 score of zero had significantly better TTR compared to those with higher scores (76.5 ± 17% vs. 61.8 ± 21%, p = 0.04). Logistic regression analysis showed that high SAMe-TT2R2 score was the only statistically significant predicting factor of poor INR control (odds ratio (OR) 5.7, 95% confidence interval (CI) 1.1-28.3, p = 0.034). Genetic variants have no contribution to the quality of INR control. SAMe-TT2R2 score was predictive for the poor quality of anticoagulation in a cohort of Qatari patients.

Assessment of the attitude, awareness and practice of periprocedural warfarin management among health care professional in Qatar. A cross sectional survey.

It is estimated that 10-15% of oral anticoagulant (OAC) patients, would need to hold their OAC for scheduled surgery. Especially for warfarin, this process is complex and requires multi-layer risk assessment and decisions across different specialties. Clinical guidelines deliver broad recommendations in the area of warfarin management before surgery which can lead to different trends and practices among practitioners. To evaluate the current attitude, awareness, and practice among health care providers (HCPs) on warfarin periprocedural management. A multiple-choice questionnaire was developed, containing questions on demographics and professional information and was completed by187 HCPs involved in warfarin periprocedural management. The awareness median (IQR) score was moderate [64.28% (21.43)]. The level of awareness was associated with the practitioner's specialty and degree of education (P = 0.009, 0.011 respectively). Practice leans to overestimate the need for warfarin discontinuation as well as the need for bridging. Participants expressed interest in using genetic tests to guide periprocedural warfarin management [median (IQR) score (out of 10) = 7 (5)]. In conclusion, the survey presented a wide variation in the clinical practice of warfarin periprocedural management. This study highlights that HCPs in Qatar have moderate awareness. We suggest tailoring an educational campaign or courses towards the identified gaps.

Fixed-dose combination associated with faster time to smear conversion compared to separate tablets of anti-tuberculosis drugs in patients with poorly controlled diabetes and pulmonary tuberculosis in Qatar.

BACKGROUND: Diabetes is associated with increased risk of tuberculosis (TB) treatment failure, death, and relapse compared to patients without diabetes. Current TB regimens are available as fixed dose combination (FDC) and separate tablets (ST), in which using the former is purported to make it easier to adhere and complete treatment. So far there are no studies assessing the performance of FDC compared to ST in diabetic patients with pulmonary TB. METHODOLOGY: A retrospective cohort study was conducted, and included eight hospitals in Qatar in which patients diagnosed with pulmonary TB received rifampin, isoniazid, pyrazinamide, and ethambutol (as FDC or ST) given as directly observed therapy. Sputum smears for acid fast bacilli were tested weekly. We included patients admitted between December 2012 and December 2015, ≥18 years old, diagnosed with TB with pretreatment positive sputum smears, and having diabetes. Patients with Mycobacterium tuberculosis that was resistant to any first-line drug were excluded. Blood glucose was monitored closely and controlled to < 180 md/dL using oral hypoglycemic agents and/or insulin. We assessed the effectiveness of TB regimens by comparing time to confirmed negative smears between those treated with FDC or ST, and the impact of adding metformin. RESULTS: 103 patients met inclusion criteria. Mean age and body mass index were 45.6 ± 9.1 years and 22.1 ± 3.6 kg/m2, respectively. Fifty-four (52%) patients received the FDC. There was no difference between groups in baseline characteristics and sputum bacillary loads. Patients prescribed FDC showed faster times to sputum smear conversion compared to ST (32 ± 19 vs. 46 ± 31 days, p = 0.01). The difference was greater among patients with pretreatment bacillary load of 3+ (FDC 36.6 ± 19.5 vs. ST 56.1 ± 28.8, p = 0.008). Receipt of metformin≥2000 mg/day altered the difference in time to smear conversion (FDC 30.7 ± 13.4 vs. ST 62 ± 35.5, p = 0.016), which was of greatest difference in those with pretreatment bacillary load 3+ and who received metformin≥2000 mg/day (FDC 36 ± 12.1 vs. ST 92.2 ± 26 days, p = 0.001). CONCLUSION: Patients with diabetes and prescribed FDC showed faster smear conversion during treatment for pulmonary TB compared to ST which was more pronounced in those with 3+ bacillary load pretreatment and which appeared to be modified by higher dose metformin.

Direct Oral Anticoagulant Use in Atypical Thrombosis-Related Conditions.

OBJECTIVE: To review the published literature for evidence of the efficacy and safety of direct oral anticoagulants (DOACs) when used in the management of atypical thrombosis-related conditions. DATA SOURCES: A comprehensive MEDLINE database search (1948 to July 2017) and EMBASE search (1980 to July 2017) were conducted using the search terms direct oral anticoagulant in combination with acute coronary syndrome (ACS), antiphospholipid antibody syndrome (APLAS), and cancer-associated thrombosis (CAT). STUDY SELECTION AND DATA EXTRACTION: The literature search was limited to studies that were conducted in humans and published in English. Clinical trials, observational studies, and case series were selected. DATA SYNTHESIS: A total of 20 published studies were selected from the literature. Only 1 randomized controlled study showed a significant reduction in cardiovascular outcomes on DOAC use in ACS patients but at the expense of increased bleeding. For the use of DOACs in APLAS, the evidence from case series seems to suggest low incidence of thromboembolic events or recurrent thrombosis in low-risk patients. Finally, in cancer patients, DOACs were comparable to warfarin in preventing CAT in 8 studies of different designs. Major bleeding with DOACs was not significantly lower than in patients who received an enoxaparin/warfarin regimen. CONCLUSIONS: Until more evidence from the ongoing clinical trials is available, DOACs may not be favorable add-on therapy in ACS patients receiving standard antiplatelet therapy but may be alternative to warfarin in preventing or treating thrombosis in low-risk APLAS patients as well as in cases of CAT in which patients have to be managed with warfarin.

Treatment outcomes of fixed-dose combination versus separate tablet regimens in pulmonary tuberculosis patients with or without diabetes in Qatar.

BACKGROUND: Tuberculosis is considered the second most common cause of death due to infectious agent. The currently preferred regimen for treatment of pulmonary tuberculosis (PTB) is isoniazid, rifampin, pyrazinamide, and ethambutol, which has been used either as separate tablets (ST) or as fixed-dose combination (FDC). To date, no studies have compared both regimens in Qatar. We aim to evaluate the safety and effectiveness of FDC and ST regimen for treating PTB, in addition to comparing safety and efficacy of FDC and ST regimens in patients with diabetes treated for TB. METHODS: A retrospective observational study was conducted in two general hospitals in Qatar. Patients diagnosed with PTB received anti-tuberculosis medications (either as FDC or ST) administered by the nurse. Sputum smears were tested weekly. We assessed the time to negative sputum smear and incidence of adverse events among FDC and ST groups. RESULTS: The study included 148 patients. FDC was used in 90 patients (61%). Effectiveness was not different between FDC and ST regimens as shown by mean time to sputum conversion (29.9 ± 18.3 vs. 35.6 ± 23 days, p = 0.12). Similarly, there was no difference in the incidence of adverse events, except for visual one that was higher in ST group. Among the 33 diabetic patients, 19 received the FDC and had faster sputum conversion compared to those who received ST (31 ± 12 vs. 49.4 ± 30.9 days, p = 0.05). Overall, diabetic patients needed longer time for sputum conversion and had more hepatotoxic and gastric adverse events compared to non-diabetics. CONCLUSION: ST group had higher visual side effects compared to FDC. FDC may be more effective in diabetic patients; however, further studies are required to confirm such finding.

Trends in oral anticoagulant use in Qatar: a 5-year experience.

In Qatar, dabigatran was introduced in 2011 followed by rivaroxaban in 2014. In this study, we aim to explore the trends in oral anticoagulant use in Qatar over the past 5 years and to what extent did DOACs replace warfarin. We also explored the extent of switching between different anticoagulants (from warfarin to DOACs and vice versa). We collected all anticoagulant prescriptions dispensed as in- or out-patient from 2011 to 2015 in all Hamad Medical Corporation (HMC) hospitals. Overall number of patients using warfarin, dabigatran and rivaroxaban over the last 5 years collectively was calculated. Per each calendar year, we calculated the number of all 3 OAC used (warfarin, dabigatran and rivaroxaban), frequency of use of each one of the OAC prescribed and compared the change in proportion of DOACs to warfarin prescriptions over the years. Overall, 6961 patients were using OAC over the past 5 years among which 5849 (84%) used warfarin, 496 (7.1%) used dabigatran and 616 (8.8%) used rivaroxaban. Oral anticoagulants use increased gradually from 2091 in 2011 to 3688 in 2015. Number of patients receiving DOACs increased significantly compared to warfarin [11 (0.5%) in 2011 vs. 849 (23%) in 2015 (p < 0.0001)]. Since its introduction in 2014, number of rivaroxaban users increased significantly compared to dabigatran [212 (40.9%) in 2014 vs. 544 (64.1%) in 2015]. DOACs have been gradually replacing warfarin in Qatar and the trend of their use is similar to that reported in other countries. Warfarin remains the most commonly used oral anticoagulant.

Triple Oral Antithrombotic Therapy in Atrial Fibrillation and Coronary Artery Stenting: Searching for the Best Combination.

Patients with atrial fibrillation (AF) who are treated with oral anticoagulants often have concurrent coronary artery disease. Triple oral antithrombotic therapy (TOAT) is often necessity to prevent stent thrombosis or myocardial infarction associated with percutaneous coronary intervention or acute coronary syndrome in patients with comorbid coronary artery disease and AF. Although the use of TOAT (aspirin, clopidogrel, and warfarin) has excellent efficacy against thrombotic complications, this comes on the expense of increased bleeding risk. This review discusses potential strategies to improve TOAT benefit-risk ratio evidence from the literature. These strategies include: (1) dropping aspirin; (2) reducing the duration of TOAT; (3) switching warfarin to a direct oral anticoagulant (DOAC); (4) the use of DOAC in combination with a single antiplatelet agent; and (5) switching clopidogrel to a novel antiplatelet agent. Although dropping aspirin and reducing TOAT duration should be considered in selected AF patients at low risk of thrombosis, the role of DOACs and novel antiplatelets in TOAT has not been thoroughly studied, and there is limited evidence to support their use currently. Ongoing studies will provide safety and efficacy data to guide clinicians who frequently face the challenge of determining the best TOAT combination for their patients.

Patients satisfaction with warfarin and willingness to switch to dabigatran: a patient survey.

Warfarin is an anticoagulant medication that is challenging to manage. Dabigatran has been approved by the FDA for stroke and systemic embolism prevention in non-valvular atrial fibrillation as an alternative to warfarin. Dabigatran does not require routine monitoring, has an established dose, and lacks many of the drug, herbal, and food interactions that afflict warfarin. To evaluate patients' satisfaction with their current warfarin treatment and their opinion on switching to a newly marketed medication (dabigatran) through a brief survey. Two separate surveys were administered to (1) evaluate the patients' opinion of their warfarin therapy and (2) evaluate their thoughts on switching to a newer anticoagulant. Responses were recorded on a rating scale of 1-5; 1 being the least and 5 being the highest. Study was conducted at the Georgia Regents Health System (GRHS) pharmacy-based anticoagulation clinic. Two hundred sixty patients on warfarin treatment were enrolled. Patients expressed high satisfaction with warfarin treatment (4.7 ± 0.78). However, a vast majority of the patients were willing to switch to an agent that: requires less frequent follow-up visits (3.9 ± 1.35); lacks interaction with food and/or beverage (4.1 ± 1.25); is as efficacious as warfarin (3.7 ± 1.38). Patients expressed that out-of-pocket cost would be a major barrier to switch to this new medication (1.3 ± 0.58). Patients are satisfied with their warfarin treatment but willing to consider a new anticoagulant. Cost was highlighted as the most significant barrier. Efficacy, dietary freedom and less frequent visits are the major factors affecting the patients' decision.

Pharmacokinetics of single-dose rivaroxaban under fed state in obese vs. non-obese subjects: An open-label controlled clinical trial (RIVOBESE-PK).

The evidence of rivaroxaban's pharmacokinetics in obese compared with non-obese populations remains inconclusive. We aimed to compare the pharmacokinetic profile of rivaroxaban between obese and non-obese populations under fed state. Participants who met the study's eligibility criteria were assigned into one of two groups: obese (body mass index ≥35 kg/m2) or non-obese (body mass index 18.5-24.9 kg/m2). A single dose of rivaroxaban 20 mg was orally administered to each participant. Nine blood samples over 48 h, and multiple urine samples over 18 h were collected and analyzed for rivaroxaban concentration using ultra-performance liquid chromatography coupled with tandem mass detector. Pharmacokinetic parameters were determined using WinNonlin software. Thirty-six participants were recruited into the study. No significant changes were observed between obese and non-obese participants in peak plasma concentration, time to reach peak plasma concentration, area under the plasma concentration-time curve over 48 h or to infinity, elimination rate constant, half-life, apparent volume of distribution, apparent clearance, and fraction of drug excreted unchanged in urine over 18 h. Rivaroxaban's exposure was similar between the obese and non-obese subjects, and there were no significant differences in other pharmacokinetic parameters between the two groups. These results suggest that dose adjustment for rivaroxaban is probably unwarranted in the obese population.

QPGx-CARES: Qatar pharmacogenetics clinical applications and research enhancement strategies.

Pharmacogenetic (PGx)-informed medication prescription is a cutting-edge genomic application in contemporary medicine, offering the potential to overcome the conventional "trial-and-error" approach in drug prescription. The ability to use an individual's genetic profile to predict drug responses allows for personalized drug and dosage selection, thereby enhancing the safety and efficacy of treatments. However, despite significant scientific and clinical advancements in PGx, its integration into routine healthcare practices remains limited. To address this gap, the Qatar Genome Program (QGP) has embarked on an ambitious initiative known as QPGx-CARES (Qatar Pharmacogenetics Clinical Applications and Research Enhancement Strategies), which aims to set a roadmap for optimizing PGx research and clinical implementation on a national scale. The goal of QPGx-CARES initiative is to integrate PGx testing into clinical settings with the aim of improving patient health outcomes. In 2022, QGP initiated several implementation projects in various clinical settings. These projects aimed to evaluate the clinical utility of PGx testing, gather valuable insights into the effective dissemination of PGx data to healthcare professionals and patients, and identify the gaps and the challenges for wider adoption. QPGx-CARES strategy aimed to integrate evidence-based PGx findings into clinical practice, focusing on implementing PGx testing for cardiovascular medications, supported by robust scientific evidence. The current initiative sets a precedent for the nationwide implementation of precision medicine across diverse clinical domains.

Clinical versus fixed warfarin dosing and the impact on quality of anticoagulation (The ClinFix trial).

Different dosing strategies exist to initiate warfarin, most commonly fixed warfarin dosing (FWD), clinical warfarin dosing (CWD), and genetic-guided warfarin dosing (GWD). Landmark trials have shown GWD to be superior when compared to FWD in the EU-PACT trial or CWD in the GIFT trial. COAG trial did not show differences between GWD and CWD. We aim to compare the anticoagulation quality outcomes of CWD and FWD. This is a prospective cohort study with a retrospective comparator. Recruited subjects in the CWD (prospective) arm were initiated on warfarin according to the clinical dosing component of the algorithm published in www.warfarindosing.org. The primary efficacy outcome was the percentage time in the therapeutic range (PTTR) from day 3 to 6 till day 28 to 35. The study enrolled 122 and 123 patients in the CWD and FWD, respectively. The PTTR did not differ statistically between CWD and FWD (62.2 ± 26.2% vs. 58 ± 25.4%, p = 0.2). There was also no difference between both arms in the percentage of visits with extreme subtherapeutic international normalized ratio (INR) (<1.5; 15 ± 18.3% vs. 16.8 ± 19.1%, p = 0.44) or extreme supratherapeutic INR (>4; 7.7 ± 14.7% vs. 7.5 ± 12.4%, p = 0.92). We conclude that CWD did not improve the anticoagulation quality parameters compared to the FWD method.

Cost-Benefit Analysis of Genotype-Guided Interruption Days in Warfarin Pre-Procedural Management.

Warfarin is commonly used in thromboembolic conditions. Warfarin interruption represents a significant challenge in pre-operative warfarin management as it is associated with major consequences. Genetics polymorphism demonstrated to be a significant predictor of the required days of warfarin interruption. This study sought to assess the economic benefit of implementing a pharmacogenetic-guided approach in the preprocedural warfarin management. From the hospital's perspective, a cost-benefit analysis was conducted based on a 1-year decision-analytic follow-up model of the economic implications of using a pharmacogenetic algorithm vs standard of care in pre-operative warfarin management in the Hamad Medical Corporation, Qatar. The benefit of the interventional algorithm was based on estimated reduction in the probabilities of clinical events and their cost, added to the avoided cost because of canceled procedures. The cost of the algorithm was the cost of the genotyping assay. The model event probability inputs were extracted from major literature clinical trials, and the setting-specifc and cost inputs were locally obtained. The model was based on a multivariate analysis at its base case. As per 10.3% prevalence of genetic variants, 82% bridging, and a calculated 20% optimization in the preparative period of warfarin management, the benefit to cost ratio was 4.0 in favor genotype-guided approach. This positive benefit to cost ratio was maintained in 100% of the simulated study cases. Sensitivity analyses confirmed the robustness and generalizability of the study conclusion. A pharmacogenetic- guided pre-operative warfarin interruption management is a cost-beneficial approach in the Qatari practice.

Prescribing patterns of antihypertensive medications: A systematic review of literature between 2010 and 2020.

Background: Hypertension has affected over 1.13 billion people worldwide in 2015 and it's one of the most preventable risk-factors for morbidity and mortality. Antihypertensives significantly reduce cardiovascular risks. Several studies on antihypertensives' prescribing patterns were conducted worldwide, and guidelines were developed on hypertension management. However, no systematic reviews were conducted globally to synthesize the evidence from these studies. This review aims to evaluate antihypertensives' prescription patterns, and adherence to international guidelines for hypertension management worldwide. Methods: Full-text antihypertensives' prescribing patterns evaluation studies were included. Reviews, commentaries, guidelines, and editorials were excluded. Various databases were searched including PubMed, Embase, and others. Studies were limited to English only and to articles published from (01/01/2010) to (20/03/2020). Crowe Critical Appraisal Tool (CCAT) was used for quality assessment. Results: The most commonly prescribed antihypertensives as monotherapy in adult patients with no comorbidities were ACEIs/ARBs (Angiotensin converting enzyme inhibitors/Angiotensin receptor blockers), followed by CCBs (Calcium channel blockers), and BBs (Beta Blockers). Most commonly prescribed dual combinations were thiazide diuretics+ACEIs/ARBs, BBs + CCBs and CCBs+ACEIs/ARBs. Among diabetic patients, the most common agents were ACEIs/ARBs. Among patients with heart diseases, CCBs were prescribed frequently. While patients with kidney diseases, CCBs and ARBs were most prescribed. Of the 40 studies included in the review, only four studies directly assessed the prescribing patterns of antihypertensives in adherence to clinical practice guidelines. And only two studies confirmed adherence to guidelines. Furthermore, the quality of the majority of studies was moderate (50%), while 25% of articles were reported as either high or low quality. Conclusion: This review revealed that there are areas for improvement for prescribing practices of antihypertensives in concordance with the latest evidence and with clinical practice guidelines.