PRISMA Flow Chart of Included Studies.

<p>PRISMA Flow Chart of Included Studies.</p

study Characteristics.

<p>study Characteristics.</p

Minor Allele Frequency (MAF) of Most Common Genetic Variants.

<p>Minor Allele Frequency (MAF) of Most Common Genetic Variants.</p

Warfarin dosing strategies evolution and its progress in the era of precision medicine, a narrative review

Background For decades, vitamin K antagonists and specifically warfarin, have been the sole agents used orally to manage thromboembolic conditions, including stroke and venous thromboembolism (VTE). Several factors lead to warfarin dose variability, including genetic and non-genetic factors which made warfarin management challenging especially at the initiation phase. To overcome the challenges with warfarin dosing at initiation, strategies other than conventional or fixed dosing were introduced and explored. Aim In this narrative review, we aim to discuss and critique the different dosing strategies for warfarin at initiation with more focus on genotype-guided warfarin dosing and the most recent supporting evidence for and against its use. Method Medline database was searched from 1965 to July 2021. Articles addressing different warfarin dosing methods were screened for inclusion. Results A number of methods exist for warfarin initiation. Studies comparing different dosing methods for initiation yielded conflicting outcomes due to differences in study design, population studied, comparator, and outcomes measured. Conclusions Looking at the big picture, the use of genetic dosing for warfarin initiation can lead to better outcomes. Whether these better outcomes are clinically or economically beneficial remains controversial.Other Information Published in: International Journal of Clinical Pharmacy License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s11096-022-01386-8</p

A 5-year trend in the use of sodium-glucose co-transporter 2 inhibitors and other oral antidiabetic drugs in a Middle Eastern country

Background Sodium glucose co-transporter 2 inhibitors (SGLT2is) are a novel class of oral antidiabetic drugs. To date, there are no pharmacoepidemiologic studies investigating the pattern of use of SGLT2is compared to other oral antidiabetic drugs in the Middle East, including Qatar. Aim This study aimed to explore the trends in the use of SGLT2is compared to other oral antidiabetic drugs in Qatar from 2016 to 2020. Method This is a descriptive, retrospective cross-sectional study where information on all oral antidiabetic drugs dispensed as in- or out-patient prescriptions from 2016 to 2020 in Hamad Medical Corporation hospitals, Qatar were collected. Outcomes included the number and relative frequency of quarterly prescriptions of different oral antidiabetic drug classes [biguanides, sulfonylureas, dipeptidyl peptidase 4 inhibitors, thiazolidinediones, meglitinides, α-glucosidase inhibitors, and SGLT2is] prescribed from 2016 to 2020. Results SGLT2is prescriptions increased from 1045 (2.13%) in 2017 to 8375 (12.39%) in 2020, while sulfonylureas prescriptions declined from 10,436 (21.25%) to 9158 (13.55%) during the same period. Metformin use decreased from 23,926 (48.71%) in 2017 to 30,886 (45.70%) in 2020. The proportions of thiazolidinediones, meglitinides, α-glucosidase inhibitors prescriptions remained stable over the years. Among SGLT2is, empagliflozin prescriptions showed an increase from 537 (10.65%) to 2881 (34.40%) compared to dapagliflozin, which decreased by the end of 2018 from 4505 (89.35%) to 5494 (65.6%). Conclusion SGLT2is have largely replaced sulfonylureas in Qatar. The increasing trend in their use over the years is similar to that reported in other countries. The trend among SGLT2is suggests greater preference for empagliflozin over dapagliflozin.Other Information Published in: International Journal of Clinical Pharmacy License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s11096-022-01464-x</p

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 othersOther Information Published in: Journal of Thrombosis and Thrombolysis License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s11239-020-02206-4</p

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.Other Information Published in: Journal of Thrombosis and Thrombolysis License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s11239-020-02102-x</p

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.Other Information Published in: Journal of Thrombosis and Thrombolysis License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s11239-020-02179-4</p

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.Other Information Published in: Journal of Thrombosis and Thrombolysis License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s11239-020-02111-w</p

Clinical and Pharmacokinetic Outcomes of Peak–Trough-Based Versus Trough-Based Vancomycin Therapeutic Drug Monitoring Approaches: A Pragmatic Randomized Controlled Trial

Vancomycin therapeutic drug monitoring (TDM) is based on achieving 24-h area under the concentration–time curve to minimum inhibitory concentration cure breakpoints (AUC24/MIC). Approaches to vancomycin TDM vary, with no head-to-head randomized controlled trial (RCT) comparisons to date. We aimed to compare clinical and pharmacokinetic outcomes between peak–trough-based and trough-only-based vancomycin TDM approaches and to determine the relationship between vancomycin AUC24/MIC and cure rates. A multicentered pragmatic parallel-group RCT was conducted in Hamad Medical Corporation hospitals in Qatar. Adult non-dialysis patients initiated on vancomycin were randomized to peak–trough-based or trough-only-based vancomycin TDM. Primary endpoints included vancomycin AUC24/MIC ratio breakpoint for cure and clinical effectiveness (therapeutic cure vs therapeutic failure). Descriptive, inferential, and classification and regression tree (CART) statistical analyses were applied. NONMEM.v.7.3 was used to conduct population pharmacokinetic analyses and AUC24 calculations. Sixty-five patients were enrolled [trough-only-based-TDM (n = 35) and peak–trough-based-TDM (n = 30)]. Peak–trough-based TDM was significantly associated with higher therapeutic cure rates compared to trough-only-based TDM [76.7% vs 48.6%; p value = 0.02]. No statistically significant differences were observed for all-cause mortality, neutropenia, or nephrotoxicity between the two groups. Compared to trough-only-based TDM, peak–trough-based TDM was associated with less vancomycin total daily doses by 12.05 mg/kg/day (p value = 0.027). CART identified creatinine clearance (CLCR), AUC24/MIC, and TDM approach as significant determinants of therapeutic outcomes. All patients [n = 19,100%] with CLCR ≤ 7.85 L/h, AUC24/MIC ≤ 1256, who received peak–trough-based TDM achieved therapeutic cure. AUC24/MIC > 565 was identified to be correlated with cure in trough-only-based TDM recipients [n = 11,84.6%]. No minimum AUC24/MIC breakpoint was detected by CART in the peak–trough-based group. Maintenance of target vancomycin exposures and implementation of peak–trough-based vancomycin TDM may improve vancomycin-associated cure rates. Larger scale RCTs are warranted to confirm these findings.Other Information Published in: European Journal of Drug Metabolism and Pharmacokinetics License: https://creativecommons.org/licenses/by-nc/4.0See article on publisher's website: http://dx.doi.org/10.1007/s13318-019-00551-1</p