Switching of oral anticoagulants in patients with nonvalvular atrial fibrillation: A narrative review.

Approval of direct-acting oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation (AF) was an important milestone, providing a wider range of treatment options and creating the possibility for drug switching after initiation. In addition to improved utilisation of oral anticoagulants (OACs) for stroke prevention, reports of switching among OACs are growing in the literature; switching may influence clinical outcomes, healthcare costs and patient satisfaction. This review aimed to summarise the current literature on the pattern of OAC switching in patients with AF, including reasons for switching and clinical consequences following switching. A literature search was conducted in PubMed, Scopus and Embase on 27 June 2020. We included 39 articles published after 2013, following the introduction of apixaban. The review found that switching among OACs was common in clinical practice, significantly varying with the type of OAC. Studies reporting the reason for switching and clinical outcomes were comparatively limited. The decision to switch was often related to safety issues (usually bleeding), poor anticoagulation control and ease of use. Patient characteristics, clinical conditions and drug interactions were found to be associated with switching from OACs. Findings regarding bleeding outcomes following switching were inconsistent, possibly confounded by the rationale for switching and the switching protocol. Noting the limited number of studies included and their relatively short follow-up periods, switching did not have a significant impact on the risk of stroke and other thrombotic outcomes. Further prospective studies are needed to understand better potential rationales for switching and the clinical outcomes.

Availability of essential medicines and pharmaceutical inventory management practice at health centers of Adama town, Ethiopia.

BACKGROUND: Good inventory management practices in the health facilities are one of the critical aspects that influence the availability of essential medicines (EMs). This study aimed to assess EMs availability and inventory management practices at health centers (HCs) of Adama town, Ethiopia. METHOD: Institution based cross sectional survey was conducted among six HCs in Adama Town from March 19 to April 12, 2017. Self-administered questionnaire and observational checklists were used to collect quantitative information. Eleven tracer drugs (TDs) that were selected by the Federal ministry of health and included in the TD list of the HCs were used to assess the availability of EMs at the time of the survey; and during the past 12 months. The data were entered and analyzed using SPSS version 21. The accuracy of record keeping was assessed using inventory management assessment tool (IMAT) indicators. RESULT: Five HCs had Essential drug list and the procurement was made as per the list. Out of six HCs, four of them procured EMs from both pharmaceutical fund and supply agency (PFSA) of Ethiopia and private suppliers. Stock status of PFSA and transportation were the major challenges during the procurement process. The overall average availability of TDs on the day of the survey was 76.3%. Average length of stock out days for TDs during the past 12 months from each HC was 40.6 days. Among the TDs assessed at HCs, oral rehydrating salt was stock outed for 144 days while paracetamol was stock outed only for 1.4 days. The discrepancy of TDs between physical count and on bincard for which physical inventory less than the balance on bincard ranges from 0 to 33.3%. CONCLUSION: The availability of EMs was low and there was also poor inventory management practice in some of the HCs during the study period.

Clinical outcomes of oral anticoagulant discontinuation in atrial fibrillation: a systematic review and meta-analysis.

INTRODUCTION: Oral anticoagulants (OACs) should generally be continued lifelong in patients with atrial fibrillation (AF) to ensure optimal benefits, unless contraindications arise. However, discontinuation of OACs might occur for various reasons, potentially affecting clinical outcomes. In this review, we synthesized evidence on the clinical outcomes following OAC discontinuation in patients with AF. METHODS: We conducted a systematic review and meta-analysis using PubMed, Embase and Scopus. Cohort or case-control studies were included if data were available on clinical outcomes of OAC discontinuation, compared with continuation, in patients with AF. A random-effect meta-analyses were conducted for key outcomes of stroke, mortality, and major bleeding. RESULTS: Eighteen observational studies having a total of 283,418 patients were included. Discontinuation significantly increased the risk of stroke (hazard ratio [HR] 1.88; 95% confidence interval [CI] 1.58-2.23), all-cause (HR 1.90; 95% CI 1.40-2.59) and cardiovascular (HR 1.83; 95% CI 1.06-3.18) mortality. The risk of major bleeding was not significantly different between the discontinued and continued groups (HR 1.04; 95% CI 0.72-1.52). CONCLUSIONS: Discontinuation of OAC therapy was associated with an increased risk of stroke and mortality, with no difference in the risk of major bleeding. Acknowledging heterogeneity among the studies, the findings underline the need to ensure continuity of OAC therapy in patients with AF to prevent thrombotic complications and associated mortality. PROSPERO REGISTRATION NUMBER: CRD42020186116.

Oral Anticoagulant Use in Patients with Atrial Fibrillation at Low Risk of Stroke and Associated Bleeding Complications.

BACKGROUND: The use of oral anticoagulants (OACs) in patients with atrial fibrillation (AF) and low stroke risk might cause more harm than benefit. Little attention has been given to address its prevalence and associated consequences. This study aimed to investigate the prescription rate of OACs, identify associated factors, and describe incident bleeding events in low-risk patients. METHODS: We included patients with a new diagnosis of AF between 1 January 2011 and 31 December 2018 having a low risk of stroke (CHA2DS2-VASc score of 0 for males and 1 for females) from Australian general practice data (MedicineInsight). Patients were classified as OAC users if there was a recorded prescription of an OAC within 60 days of AF diagnosis, and factors associated with the prescription of an OAC were assessed using logistic regression. Recorded incident bleeding events were identified within 6 months after AF diagnosis or after OAC initiation for OAC non-users and users, respectively. The risk of bleeding was compared between the two groups by adjusting their baseline differences using propensity score matching. RESULTS: The study included 2810 low-risk patients (62.3% male) with a mean age of 49.3 ± 10.8 years. Of the total, 705 (25.1%) patients had a record of OAC prescription within 60 days of diagnosis of AF. Older age (odds ratio [OR] 1.03; 95% confidence interval [CI] 1.03-1.04) and diagnosis periods (2015-2016 [OR 1.46; 95% CI 1.10-1.94] and 2017-2018 [OR 1.65; 95% CI 1.17-2.23] vs. 2011-2012) were associated with higher odds of OAC initiation. Female sex (OR 0.71; 95% CI 0.59-0.85), higher bleeding risk (ORBIT score; OR 0.80; 95% CI 0.68-0.94), and higher socioeconomic index for areas (SEIFA) quintiles (SEIFA quintiles; 2 [OR 0.65; 95% CI 0.48-0.88], 3 [OR 0.74; 95% CI 0.56-0.98], 4 [OR 0.70; 95% CI 0.52-0.94], 5 [OR 0.69; 95% CI 0.52-0.91] compared with quintile 1) were associated with lower odds of OAC prescription. A total of 52 (in 1.8% of patients) incident bleeds were identified, with 18 (2.6%) among OAC users. The rate of bleeding was not significantly different between users and non-users after matching. However, within OAC users, commencement of OAC was associated with an increased risk of bleeding compared to the period before OAC initiation (p = 0.006). CONCLUSIONS: One in four patients at low risk of stroke received an OAC within 60 days of AF diagnosis. Older age and the period following the widespread availability of direct-acting OACs were associated with an increased likelihood of OAC prescription. Positively, using OACs was not associated with an increased rate of bleeding compared to non-users.

Oral Anticoagulant Discontinuation and Its Predictors in Patients with Atrial Fibrillation.

BACKGROUND: Oral anticoagulants (OACs) are important in reducing the risk of ischaemic stroke in people with atrial fibrillation (AF). Although patients need to take their OAC continuously, it has been suggested that discontinuation is common in clinical practice, and this could predispose patients to thrombotic complications. AIMS: To investigate the rate of OAC discontinuation and its predictors in patients with AF, using national data from Australian general practices. METHODS: We analysed data obtained from NPS MedicineWise's MedicineInsight dataset. We included patients with a recorded diagnosis of AF who newly started an OAC between 1 January 2013 and 31 December 2017. Patients were considered persistent if an OAC was prescribed continuously without discontinuing more than 60 days gap in therapy. The follow-up period was 12 months post-initiation. Multivariable models were used for the analysis of predictors. RESULTS: Of 16,075 patients included in the cohort, 47.3% were females, and the mean age was 74.6 (SD 10.2) years. The overall OAC discontinuation rate was 13.2% (confidence interval (CI) 12.6-13.7%) by 12 months post-initiation. The discontinuation rates for warfarin, apixaban, dabigatran and rivaroxaban were 18.3% (95% CI 17.2-19.5%), 10.1% (95% CI 9.2-11.0%), 10.9% (95% CI 9.4-12.5%) and 12.2% (95% CI 11.4-13.2%), respectively. Warfarin had a significantly higher risk of discontinuation compared to direct-acting OACs. Factors that are known to increase the risk of stroke (older age, diabetes, and hypertension) were associated with better persistence. CONCLUSIONS: A relatively high proportion of patients with AF continued OAC therapy by 12 months post-initiation. Positively, patients with the highest risk of stroke and lowest risk of bleeds seemed to have better persistence.

Switching of oral anticoagulants in atrial fibrillation: a cohort study using Australian general practice data.

BACKGROUND: We assessed switching patterns of oral anticoagulants (OACs) in patients with atrial fibrillation (AF) in the period following widespread availability of the direct-acting oral anticoagulants (DOACs). RESEARCH DESIGN AND METHODS: A retrospective cohort study was conducted using NPS MedicineWise's MedicineInsight dataset, collected from Australian general practices. Patients with AF who newly commenced an OAC between 1 January 2013 and 30 September 2017 were included. The switching rate was calculated within 12 months post-initiation. Switching rates between OACs were compared, and predictors of switching were identified. RESULTS: We included 15,020 patients who were recorded as having been commenced on warfarin or a DOAC. Overall, 5.7% of patients switched their OAC within 12 months. The switching rates from warfarin, apixaban, dabigatran and rivaroxaban were 9.4%, 2.6%, 8.9% and 4.0%, respectively. Compared to apixaban, commencement on warfarin, dabigatran or rivaroxaban was associated with a higher risk of switching to another OAC. Patients with an estimated glomerular filtration rate (eGFR) <30 mL/min were more likely to switch from DOACs to warfarin and less likely to switch from warfarin, compared to those with an eGFR >60 mL/min. CONCLUSION: There was a low switching rate between OACs in Australian general practice patients with AF. A key determinant of switching appeared to be kidney disease.

Health related quality of life of people receiving highly active antiretroviral therapy in Southwest Ethiopia.

BACKGROUND: Highly Active Antiretroviral Therapy (HAART) is a standard of HIV management to suppress viral load and delay progression to AIDS. However, questions have been raised about the use of antiretroviral therapy and how it affects quality of life (QoL) of people living with HIV/AIDS (PLWHA). The study hence aimed to assess the QoL of PLWHA who were taking HAART at Mizan-Tepi University Teaching Hospital (MTUTH) and identify factors associated with QoL. METHODS: A cross sectional study was conducted among PLWHA receiving HAART at MTUTH from March 04-April 1, 2018. Patients were recruited consecutively and interviewed with structured questionnaire. A data abstraction tool was used to extract data from patient medical records. Quality of life was assessed using the World Health Organization Quality of Life HIV- BREF (WHOQOL-HIV-BREF) standard tool. Data was entered to Epi-Info version 3.5.3 and analyzed using SPSS version 22 for windows. A multivariable logistic regression analysis was fitted to identify factors associated with QoL. A statistical significance was established at a p value <0.05. RESULTS: A total of 240 participants with the mean age of 35.11 (SD = 9.08) years were included in the study. This study found that 57.1% of the patients had high global score of QoL. Patients with normal current health (AOR = 3.38, 95% CI = 1.56-7.31)) and having family support (AOR = 3.12, 95% CI = 1.51-6.46) were positively associated with high global score of QoL, while patients with low HAART adherence (AOR = 0.40, 95%, CI = 0.19-0.86) were negatively associated with high global score of QoL. CONCLUSION: The study revealed that more than half of the participants had high global score of QoL. Normal current health and family support were associated with better global score of QoL, while low HAART adherence was found to be associated with the lower global score of QoL.

Evaluation of Abortifacient Effect of Rumex nepalensis Spreng Among Pregnant Swiss Albino Rats: Laboratory-Based Study.

BACKGROUND: Rumex nepalensis Spreng (Amharic: Yewsha Tult) belongs to the Polygonaceae (buckwheat) family. In Ethiopia, the plant is traditionally used for the treatment of stomach ache, tonsillitis, ascariasis, uterine bleeding, etc. An ethnobotanical study from Mizan-Tepi University also reported the use of the plant by "Shekicho" people as an abortifacient. As a result, this study aimed at the assessment of the outcome of hydro-ethanolic leaves extract of R. nepalensis on Swiss albino pregnant rats and confirm its abortifacient activity. METHODS: The hydro-alcoholic leaves extract of Rumex nepalensis Spreng was evaluated for its abortifacient activity in Swiss albino rats. The mature female rats were mated overnight to male rats in mating cages. Two different dosage regimens (300 mg/kg, 600 mg/kg) of the extract were administered. Laparotomy was performed on the rats to assess the uterus and ovary, the viable, non-viable, adsorbing sites, and corpora lutea. Differences between the experimental and control groups were compared using one-way analysis of variance (ANOVA), followed by Dunnett's T-test to determine their level of significance. RESULTS AND DISCUSSION: This study revealed that Rumex nepalensis Spreng had anti-implantation and abortifacient activities at both 300 and 600 mg/kg doses, which was statistically significant as compared with the controls. It was relatively safe up to the dose of 5000 mg/kg, where no mortality and organ toxicity were manifested. Phytochemicals identified were alkaloids, flavonoids, saponins, tannins, steroids, and anthraquinones. CONCLUSION: In general, our study showed that R. nepalensis had a significant abortifacient activity that testifies its traditional dibs. Therefore, the use of this plant should be avoided in pregnant women to minimize unintended abortion and further studies are needed to know its mechanism of activity and to identify the phytochemicals corresponding to this activity. Checking its efficacy on other species is also needed.

Appropriateness of insulin commencement and adequacy of glycemic control among ambulatory patients with type 2 diabetes in Ethiopia.

BACKGROUND: Knowing when to start insulin is central to optimal management of Type 2 diabetes mellitus (T2DM) but a real clinical challenge. Poor glycemic control is critical for development of the deadly diabetic complications. OBJECTIVE: The aim of the study was to assess the appropriateness of insulin commencement, adequacy of glycemic control and associated factors among patients with T2DM. SETTINGS: The study was conducted at three public hospitals in Southwest Ethiopia. METHODS: Cross sectional study was conducted using structured questionnaire and data abstraction format. All patients with T2DM who were available during the data collection period and fulfilling study criteria were included. MAIN OUTCOME MEASURE: Multivariable binary logistic regression analysis was done for identifying factors associated with poor glycemic control by taking statistical significance at p value ≤0.05. RESULTS: One hundred sixty nine patient data was considered for analysis. Insulin was initiated in 28 patients, but only 10(35.7%) insulin commencements were appropriate. More than two third (70.4%) of the studied population had poor glycemic control. Addition of second antidiabetic medication (Adjusted Odds Ratio (AOR) = 2.5, 95% CI = 1.3-6.2) and living in urban areas (AOR = 2.5, 95% CI = 1.1-5.7) were associated with poor glycemic control while having regular diabetic care follow up of every >1 month (AOR = 0.4, 95% CI = 0.2-0.9) was negatively associated with poor glycemic control. CONCLUSIONS: About two third of insulin commencements were inappropriate and majority of patients could not stay on optimal glycemic control. Addition of second antidiabetic medication and living in urban areas were found to be associated with poor glycemic control. IMPACT OF FINDINGS ON PRACTICE STATEMENTS: • Initiation of insulin before optimization of oral agents increase cost of care.• Proper titration of the first oral agent is important prior to adding other antidiabetic agents.• Emphasis should be given to improve glycemic control, and hence halt subsequent complications.

Treatment Outcome and Adverse Events of Tenofovir Disoproxil Fumarate Based Regimens as Compared to Zidovudine Based Regimens Among People Living with HIV/AIDS: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: Findings from different studies report inferior clinical and virologic efficacy with TDF/3TC/NVP. But, some studies show that, there was no statistically significant difference in mortality among ZDV and TDF based regimens. The objective of this review was to systematically identify, appraise and synthesize the best available evidence on efficacy and safety of TDF based regimen as compared to ZDV based regimens. METHODS: A three-step search strategy was used to locate published and unpublished studies. First, an initial limited search of google was undertaken followed by analysis of text words. A second extensive search was undertaken. We searched the PubMed, EMBASE, Google Scholar, Medline, and CINHAL. We did the initial search for articles on July 11-18, 2016, and updated the results on May 13, 2017.Third, the reference lists of all identified articles was searched for additional studies. RESULTS: ZDV based regimens had better outcome on prevention of mortality (OR=1.31, 95%CI (1.14, 1.50), I2 = 0%, Chi2 = 2.51), and lower virologic failure (OR = 1.44, 95% CI [1.18, 1.76], chi2 = 5.91, P= 0.003, I2 =83%) while, TDF based regimens were more tolerable (OR=0.15, 95%CI (0.08, 0.30), I2 = 40%, Chi2 = 3.31). The difference in incidence of opportunistic infection is not significant (OR = 0.83, 95% CI [0.52, 1.32], chi2 = 0.11, P= 0.42, I2 =0%). CONCLUSION: There is lower mortality and lower virologic failure in ZDV group, but better safety profile among TDF based regimens.

Antidiabetic Effects of Artemisia Species: A Systematic Review.

BACKGROUND: Over the last century, human life style and food habits have drastically changed which lead to various chronic diseases. Diabetes mellitus is one such disease which is causing serious problems to human health. Allopathic drugs are not much effective in handling the disease and its complications. Hence focus has been turned towards the traditional system of medicine. Medicinal plants play an important role in the management of diabetes mellitus. METHODS: Experimental studies conducted on species of Artemisia on diabetic animal models and human published since the year 2000 until April, 2017 were reviewed. Each article was critically appraised by two independent reviewers for their methodological quality using the JBIMAStARI tool. RESULT: A total of 14 studies were included in this review and the blood glucose data obtained from these critically reviewed studies clearly showed that both the aqueous and alcoholic extracts of species of Artemisia produced significant hypoglycemic effects in alloxan, Streptozotocin and high fat diet induced diabetic animals and diabetic humans with different mechanisms of action as compared to standard antidiabetic medications. DISCUSSION AND CONCLUSION: The antidiabetic effect of single or multiple doses of aqueous and alcoholic extracts of Artemisia species was due to the active compounds of these plants and they all are effective in lessening the blood glucose level in all of those experimental studies. Despite the presence of known antidiabetic medicines in the pharmaceutical market, therapeutic remedies from these medicinal plants have been utilized with success to treat this disorder and its complications with a relatively less side effects.

Efficacy and Tolerability of Tenofovir Disoproxil Fumarate Based Regimen as Compared to Zidovudine Based Regimens: A Systematic Review and Meta-Analysis.

BACKGROUND: Although tenofovir (TDF)/emtricitabine (FTC)/efavirenz (EFV) and zidovudine (ZDV)/lamivudine (3TC)/efavirenz (EFV) are used as preferred first line regimen, their head-to-head comparison in terms of their efficacy and tolerability was limited. This review aimed to synthesize the best available evidence on the comparative efficacy and tolerability of the two regimens. METHODS: Seven sites and databases in addition to Google search until August 20, 2016, were searched. Only randomized clinical trials conducted on adult population were included in this study. Our primary outcome was viral load suppression while secondary outcomes were death and tolerability. Undetectable viral load is defined as <50 Human Immunodeficiency Virus (HIV) ribonucleic acid (RNA) copies/ml. Joanna Briggs institute meta-analysis of statistics assessment and review instrument (JBI-MAStARI) and critical appraisal and data extraction tool were applied for critical assessment and data extraction, respectively. We performed a random effect meta-analysis to pool the relative risk (RR) for viral load suppression (<50 HIV RNA copies/ml and <400 HIV RNA copies/ml), tolerability, and death. RESULT: Data was extracted from four articles, which included a total of 2381 participants. We found superior viral load suppression among tenofovir (TDF) arm compared to zidovudine (ZDV) arm. Tenofovir arm achieves viral load <50 HIV RNA copies/ml (RR = 1.12, 95% confidence interval (CI) [1.04, 1.21], I2 = 0%) higher than zidovudine arm. Similarly TDF arm is superior in viral load suppression to <400 HIV RNA copies/ml (RR = 1.19, 95% CI [1.11, 1.27], I2 = 0%). Moreover, TDF based regimens were more likely to be tolerated than ZDV based regimens (4 trials, 2381 participants (RR = 1.06, 95% CI [1.02, 1.10], I2 = 51%)). However, forest plot of death shows that it was not significant (RR = 0.91, 95% CI [0.51, 1.62]). CONCLUSION: The use of TDF/FTC/EFV as first line regimen for naïve HIV-1 infected adult patient showed superior viral load suppression and tolerability as compared to ZDV/3TC/EFV. In order to compare the death outcome of both ZDV/3TC/EFV and TDF/FTC/EFV further research is needed.