Comparative Effectiveness and Safety of Direct Oral Anticoagulants in Low Body Weight Patients with Atrial Fibrillation: A Systematic Review and Meta-analysis.

INTRODUCTION: Direct oral anticoagulant (DOAC) agents are established as the anticoagulation strategy of choice for a variety of clinical risks. Despite this, uncertainty still exists with regard to their efficacy and safety for the prevention of stroke and systemic embolism in some patient populations; most notably those with low body weight (LBW) (<60 kg or body mass index [BMI] <18 kg/m2). Currently, there is a paucity of trial and non-trial data to support a prescriptive recommendation for their use in these patient cohorts. We have carried out a pooled systematic review of the most up to date published data of patients stabilized on various DOAC analogs with the view to ascertaining the exact matrices of their efficacy and safety in these cohorts of patients. METHODS: We initially carried out a comprehensive search of databases from inception to June 2023 for eligible studies exploring the efficacy and safety of various analogs of direct oral anticoagulants in patients with atrial fibrillation who had low body weight. Databases accessed include PubMed, EMBASE, the Science Citation Index, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effectiveness. We carried out a weighted comparison of derived pooled odd ratios (with their corresponding confidence intervals) of mortality outcomes between various DOACs using the random effects model. RESULTS: Thirteen studies (n = 165,205 patients) were included in our meta-analysis. DOAC analogs were associated with increased stroke-related events, composite outcome, and mortality in low body weight patients compared to non-low body weight patients (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.17-1.92), (OR 1.55, 95% CI 1.29-1.86), (OR 2.92, 95% CI 1.87-4.58), respectively. There was no significant difference in the safety outcome (major bleeding events) between the DOAC analogs (OR 1.19, 95% CI 0.93-1.52). DISCUSSION: In this meta-analytical review comprising both real-world and randomized controlled studies, the use of DOAC analogs in low body weight patients (body weight of <60 kg or BMI<18 kg/m2) with atrial fibrillation was associated with increased risks of stroke-related events, composite outcomes, and mortality compared to non-low body weight cohorts patients. At the same time, there was no significant difference in terms of major bleeding events. This finding has provided the first resolution of pervading uncertainty surrounding the use of DOAC analogs in these patient cohorts and suggests the need for follow-up confirmatory systematic studies in this group of patients.

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.

The effects of thrombocytopenia, type 2 diabetes mellitus, and endothelial dysfunction on clinical outcomes in patients with COVID-19.

Diabetes mellitus is a well-recognized contributor to increased COVID-19 severity. Endothelial dysfunction has been implicated in the pathogenesis of COVID-19, while thrombocytopenia has been identified as a potential risk factor for severe COVID-19. In this study, we evaluated the combined effect of thrombocytopenia and other markers of endothelial dysfunction on disease outcomes in patients with type 2 diabetes and active COVID-19 infection. Our aim was to risk stratify patients with COVID-19 and type 2 diabetes mellitus, which can help identify patients with high-risk features who will benefit the most from hospital admission and a high level of care. This cross-sectional study was performed after reviewing secondary data of 932 patients with COVID-19 and type 2 diabetes mellitus in the outpatient and inpatient settings across Qatar between March 1, 2020 and May 7, 2020. Univariate and multivariate analyses, with adjustment for low platelet counts, were performed for the following variables: age, hemoglobin, white blood cells (WBC), lymphocytes, monocytes, eosinophils, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, ferritin, D-dimer, and interleukin 6. Increasing age was associated with an increased risk for death and/or intensive care unit admission in diabetic patients with COVID-19 who have low platelet counts. These findings support the evidence found in the literature and give special attention to COVID-19 patients with low platelet counts and diabetes mellites. These results can guide physicians in making clinical decisions regarding hospital admission and escalation of care during follow-up in this population of patients.

Seroconversion and safety of Covid-19 vaccines in pa-tients with chronic liver disease and liver transplant: A systematic review.

BACKGROUND AND AIMS: As part of the COVID-19 control strategy, a growing number of vaccine portfolios evolved and got fast-tracked through regulatory agencies, with a limited examination of their efficacy and safety in vulnerable populations, such as patients with chronic conditions and immunocompromised states. Patients with chronic liver disease (CLD), and cohorts post liver transplant (LT) in particular, were underrepresented in the determinant trials of vaccine development, hence the paucity of data on their efficacy and safety in published literature. This systematic review aims to examine the available evidence and ascertain the effectiveness and safety of Covid-19 vaccination in patients with CLD and those with LT. METHODS: A systematic review of PubMed (Medline), Google Scholar, Cochrane Library, and ScienceDirect from inception until 1st March 2022 was conducted. We included observational studies and assessed vaccine efficacy regarding seroconversion or immunological rate, whereas serious or significant adverse effects have been considered safety outcomes when reported. RESULTS: Studies comprised 45275 patients, performed in 11 different countries. Seroconversion or immunological rate after Covid-19 vaccination was mostly the primary endpoint, whereas other endpoints like covid-19 related adverse effects were also reported. Twenty-four of the final analyzed studies are prospective cohort studies, while four are retrospective cohort studies. Twenty-one studies included patients who underwent LT and received the Covid vaccine; nine included patients who had CLD due to various etiologies. The median age range of all included patients varied from 43-69 years. All patients with LT who received at least two doses of Covid vaccine had a seroconversion rate of around 60%. Patients with CLD had a seroconversion rate of about 92% post two doses of Covid vaccination. The average seroconversion rate in post-transplant recipients was around 45% after two doses of the significant Covid vaccines: Pfizer, AstraZeneca, Moderna, and Jansen. Only two studies have reported a higher seroconversion rate of 75% and 73% after the third dose of Covid vaccine. No significant adverse effects were reported in all studies; the most commonly reported negative effect was local injection site pain. CONCLUSION: The present systematic review, comprising real-world observational data studies, concludes that Covid-19 vaccination was associated with 92% and 60% seroconversion rates in patients with CLD and LT, respectively. No significant side effects were reported in all studies. This finding helps to resolve the uncertainty associated with Covid-19 vaccination in this cohort of patients.

The impact of enteric coating of aspirin on aspirin responsiveness in patients with suspected or newly diagnosed ischemic stroke: prospective cohort study: results from the (ECASIS) study.

BACKGROUND AND PURPOSE: Uncertainty remains regarding the impact of enteric-coated aspirin (EC-ASA) on secondary prevention of ischemic stroke compared to plain aspirin (P-ASA). Hence, this study was designed to investigate the effect of EC formulation on ASA response via evaluating thromboxane B2 (TXB2) levels in patients with suspected or newly diagnosed stroke. METHODS: A prospective cohort study on suspected or newly diagnosed ischemic stroke patients who are aspirin-naive was conducted. Patients were received either EC aspirin or plain aspirin for at least 3 days. The primary outcome was the proportion of aspirin non-responsiveness between two groups (level of residual serum TXB2 associated with elevated thrombotic risk (< 99.0% inhibition or TXB2 > 3.1 ng/ml) within 72 h after three daily aspirin doses, while secondary outcomes were the incidence of early gastrointestinal tract (GIT) bleeding with the various aspirin preparations. (Trial registration: Clinicaltrials.gov NCT04330872 registered on 02 April 2020). RESULTS: Of 42 patients, ischemic strokes were confirmed in both P-ASA (81%) and EC-ASA (67%) arms. ASA non-responsiveness showed no significant difference between the two formulations (P-ASA vs. EC-ASA; 28.6% vs 23.8%; P = 0.726). Univariate and multivariate logistic regression analysis showed that patients treated with EC-ASA were more likely to have a lower rate of non-responders compared to P-ASA (unadjusted OR 0.78; 95% CI 0.20, 3.11); with the risk highest in type 2 diabetic patients with HBA1c > 6.5% (adjusted OR 6; 95% CI 1.02, 35.27; P = 0.047). No incidence of GIT bleeding observed throughout the study. CONCLUSION: A significant proportion of ASA non-responsiveness was recorded regardless of ASA formulation administered. The increased risk of ASA non-responsiveness in diabetic patients needs further exploration by larger prospective studies.

What is polypharmacy in people living with HIV/AIDS? A systematic review.

Polypharmacy in people living with HIV/AIDS (PLWHA) is a rising morbidity that exacts hefty economic burden on health budgets in addition to other adverse clinical outcomes. Despite recent advances, uncertainty remains around its exact definition in PLWHA. In this systematic review and Meta-analysis, we explored relevant databases (PUBMED, EMBASE, CROI) for studies evaluating polypharmacy in PLWHA from January 2000 to August 2021 to ascertain the exact numerical threshold that defines this morbidity. Two independent reviewers extracted and reviewed relevant variables for analyses. The review included a total of 31 studies involving n = 53,347 participants with a mean age of 49.5 (SD ± 17.0) years. There was a total of 36 definitions, with 93.5% defining polypharmacy as the concomitant use of 5 or more medications. We found significant variation in the numerical definition of polypharmacy, with studies reporting it as "minor" (N = 3); "major" (N = 29); "severe" (N = 2); "excessive" (N = 1); and "higher" (N = 1). Most studies did not incorporate a duration (84%) in their definition and excluded ART medications (67.7%). A plurality of studies in PLWHA have established that polypharmacy in this cohort of patients is the intake of ≥ 5 medications (including both ART and non-ART). To standardize the approach to addressing this rising morbidity, we recommend incorporation of this definition into national and international PLWHA treatment guidelines.

Critical care tele-pharmacy services during COVID-19 pandemic: A qualitative exploration of healthcare practitioners' perceptions.

WHAT IS KNOWN AND OBJECTIVE: The scope of clinical pharmacy services has changed during COVID-19 pandemic with the view to mitigating both exposure and spread of the virus. The performance of novel pandemic-driven services such as tele-pharmacy has remained unexplored, until now. The aim of this study is to investigate the perceptions of healthcare providers of the impact of tele-pharmacy services provided in critical care units during COVID-19. METHODS: A qualitative study of semi-structured interviews conducted with healthcare practitioners who worked in COVID-19 intensive care units and remotely interacted with clinical pharmacists at the Weill Cornell-affiliated Hamad Medical Corporation, Doha, Qatar. Random sampling technique was employed to recruit participants, with the resultant interview guide piloted before commencement of data collection process. RESULTS AND DISCUSSION: From a total 129 and 200 physicians and nurses, respectively, 20 interviews were conducted with physicians (n = 15), and nurses (n = 5). From these interactions, a number of major themes emerged including: satisfactory understanding across clinical environment and personnel (physician and nurses) about remote clinical pharmacists' roles; additional robust feedback on the perception of the remote clinical pharmacy service; an understanding by 'frontline' health personnel on the discernible differences between remote and in-person coverage of clinical pharmacists; a reflection by both physicians and nurses on the novel challenges involved in the implementation of such pandemic-driven service; and solutions to overcome these challenges. WHAT IS NEW AND CONCLUSION: In this novel qualitative study of pandemic-driven tele-pharmacy service, we found a positive perception amongst healthcare practitioners towards this service; with residual challenges that will need further evaluation by large sampled sized surveys or mixed methods research.

Clinical, Radiological, and Outcome Characteristics of Acute Pulmonary Embolism: A 5-year Experience from an Academic Tertiary Center.

BACKGROUND: Acute pulmonary embolism (PE) is a common and potentially life-threatening condition. This comprehensive study from a Gulf Cooperation Council (GCC) country aimed to evaluate the clinical, radiological, and outcome characteristics associated with acute PE. METHODS: This retrospective observational study analyzed data of patients with confirmed acute PE who were admitted to the largest academic tertiary center in the State of Qatar from January 1, 2014, to December 31, 2018. Data on the clinical presentation, radiologic, and echocardiographic findings, as well as outcomes were collected. RESULTS: A total of 436 patients were diagnosed with acute PE during the study period (male, 53%). Approximately 56% of the patients were < 50 years old at presentation, with a median age of 47 years. In approximately 69% of cases, the PE occurred outside the hospital. The main associated comorbidities were obesity (34.6%), hypertension (29.4%), and diabetes (25%). Immobilization (25.9%) and recent surgery (20.6%) were the most common risk factors. The most frequent presenting symptom was dyspnea (39.5%), and the most frequent signs were tachycardia (49.8%) and tachypnea (45%). Cardiac arrest was the initial presentation in 2.2% of cases. Chest X-ray findings were normal in 41%. On computed tomography pulmonary angiography (CTPA), 41.3% of the patients had segmental PE, 37.1% had central PE, and 64.1% had bilateral PE. The main electrocardiographic (ECG) abnormality was sinus tachycardia (98%). In patients who underwent echocardiography, right ventricular (RV) enlargement was the main echocardiographic finding (36.4%). Low-, intermediate-, and high-risk PE constituted 49.8%, 31.4%, and 18.8% of the cases, respectively. Thrombolysis was prescribed in 8.3% of the total and 24.4% of the high-risk PE cases. Complications of PE and its treatment (from admission up to 6 months post-discharge) included minor bleeding (14%), major bleeding (5%), PE recurrence (4.8%), and chronic thromboembolic pulmonary hypertension (CTEPH) (5%). A total of 15 (3.4%) patients died from PE. CONCLUSIONS: Acute PE can manifest with complex and variable clinical and radiological syndromes. Striking findings in this study are the younger age of acute PE occurrence and the low PE-related mortality rate.

Colchicine use might be associated with lower mortality in COVID-19 patients: A meta-analysis.

BACKGROUND: Colchicine was recently repurposed for the management of coronavirus disease 2019 (COVID-19). This rapid review and meta-analysis aimed to assess colchicine's impact on mortality outcomes in COVID-19 patients. MATERIALS AND METHODS: We systematically searched PubMed, EMBASE, Google Scholar since their inception till 25/03/2021 for observational or controlled studies that reported mortality as an outcome. The mortality odd ratios were generated with their corresponding 95% confidence intervals utilizing the random-effects model. RESULTS: Nine studies comprising 5522 patients met our inclusion criteria. Our meta-analysis revealed significantly lower mortality in the colchicine group (OR 0.35, 95% CI 0.25-0.48, I2 0%) compared with controls. A subgroup analysis limited to hospitalized patients (OR 0.35, 95% CI 0.25-0.50, I2 0%) revealed similarly lower mortality in the colchicine group. CONCLUSIONS: This meta-analysis suggests a mortality benefit with colchicine when used in the treatment of COVID-19 patients. The majority of included studies were observational; thus, the findings of this review need to be further supported by the results of ongoing trials.

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.

Avoidability of drug-induced liver injury (DILI) in an elderly hospital cohort with cases assessed for causality by the updated RUCAM score.

BACKGROUND: Drug-induced liver injury (DILI) represents an increasing morbidity in the general population, but more so in the elderly cohort of patients. Despite this, the concept of its prevention through prospective analysis has largely remained unexamined. We evaluated the utility of recently validated adverse drug reactions (ADR) avoidability tool in a cohort of elderly patients with DILI. METHODS: We examined 38 DILI-drug pairs from n=38 patients in a prospective cohort of patients presenting with adverse drug reactions to a Weill Cornell-affiliated tertiary hospital between February 2019 and January 2020. DILI outcomes were adjudicated by the updated Roussel Uclaf Causality Assessment Method (RUCAM). Two clinical pharmacologists and two general physicians utilized the Liverpool adverse drug reactions avoidability tool (LAAT) and the modified Hallas tools to rate the preventability of DILI-drug pairs. Inter-rater, exact agreement proportions, as well as intraclass correlation coefficients were generated and expressed as ordinal outcomes. RESULTS: The cases examined for the determination of DILI avoidability had probability likelihood of "probable" or "highly probable" by the updated RUCAM scale. Examination of the 38 DILI-drug pairs (n= 38 patients) resulted in a total of 152 ordinal outcome decisions. We found about 32.3% (50/152) and 34.2% (52/152) of DILI-drug pairs were rated as "avoidable" ("probable" or "definite") by the LAAT and the modified Hallas tools respectively. The overall median Krippendorf's kappa with the LAAT was 0.61 (SE 0.12, CI 0.36, 0.85) and for modified Hallas tool was 0.53 (SE 0.18; CI 0.16, 0.89). The inter-rater correlation coefficient (ICC) for the LAAT and modified Hallas were 0.50 [0.32, 0.65] and 0.63 [0.48, 0.76] respectively. Exact pairwise agreement was present in 30/38 (IQR 29.5, 34.5), and 28/38 (IQR 27.5-35.5) of DILI-ADR pairs using the LAAT and modified Hallas tools respectively. CONCLUSION: We found a significant proportion of drug-induced liver injury adjudicated by the updated RUCAM scale in elderly hospitalized cohort of patients were avoidable with significant implication for therapeutic commissioning as well as cost effectiveness interventions in this cohort of patients.

Converging indications of aldosterone antagonists (spironolactone and eplerenone): a narrative review of safety profiles.

The converging clinical effectiveness of mineralocorticoid receptor antagonists (MRAs) Spironolactone and Eplerenone has made their safety profiles/cost-effectiveness key determinants of "agents of choice" across a broad range of clinical indications. The clinical biology of the aldosterone molecule and its range of effects in varied organ systems have been well elucidated from recent mechanistic and systematic studies. Clinical experience with Spironolactone is well established, as is its adverse effects profile. The range of adverse effects experienced with Spironolactone subsequently led to its modification and synthesis of Eplerenone. Recent published reports have confirmed lower prevalence rates of sex-related adverse effects attributable to Eplerenone compared to Spironolactone. There is, however, not much to choose between these agents in regards to other adverse effects including hyperkalemia and kidney failure. As was the experience with Spironolactone, as more robust observational data on Eplerenone accrues, it is possible that the real-life experience of its adverse profile may be discordant with that reported by randomized controlled clinical trials (RCTs). In addition, its metabolism by the vulnerable and highly polymorphic cytochrome dependent pathway also makes it susceptible to various drug interactions. The potential implication of the latter (including morbidity and mortality) may take years to evolve.

Infectious Mononucleosis Revealed by Non-steroidal Anti-inflammatory Drug: A First Clinical Report.

Infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV), is a common viral illness among adolescents and young adults. IM typically presents with symptoms such as fever, lymphadenopathy, and pharyngitis. We present a case of a 32-year-old woman who developed a maculopapular rash following ibuprofen administration, revealing an underlying undiagnosed IM. Laboratory investigations confirmed EBV infection. This represents the first documented case linking non-steroidal anti-inflammatory drugs (NSAIDs) to IM presentation. Awareness of this association is crucial for timely diagnosis and management, especially when evaluating patients with unexplained skin reactions to medications.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants Compared with Warfarin in Patients with Low Bodyweight who have Atrial Fibrillation: A Systematic Review and Meta-analysis.

INTRODUCTION: oral anticoagulant (DOAC) agents are becoming the anticoagulation strategy of choice for most clinical risks for which they are indicated. However, residual uncertainty remains regarding their use in preventing stroke in patients with low bodyweight [< 60 kg or body mass index (BMI) < 18 kg/m2]. We have carried out pooled systematic analyses of published studies to determine the efficacy and safety of these agents compared with warfarin in stroke prevention in patients with low bodyweight. METHODS: We carried out a comprehensive search of electronic databases from inception to June 2023 for eligible studies reporting on the efficacy and safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation who had low bodyweight. These include PubMed, EMBASE, the Cochrane Database of Systematic Reviews, the Science Citation Index, and the Database of Abstracts of Reviews of Effectiveness. Using the random effects model, derived pooled odd ratios (with their corresponding confidence intervals) of mortality outcomes in patient cohorts exposed to direct oral anticoagulants versus warfarin in patients with atrial fibrillation who had low bodyweight. RESULTS: Nine studies (n = 159,514 patients) were included in our meta-analysis. DOAC analogs were associated with lower stroke recurrence compared with warfarin [odds ratio (OR) 0.66, 95% confidence interval (CI) 0.49-0.9]; however, there was no significant difference in the composite outcome (OR 0.81, 95% CI 0.59-1.09) and mortality (OR 0.82, 95% CI 0.48-1.41). Additionally, DOAC analogs showed a significant reduction in major bleeding events by 30% compared with warfarin (OR 0.70, 95% CI 0.62-0.80). CONCLUSION: In this pooled meta-analytical synthesis of studies comprising both real-world and randomized controlled data, the use of DOAC analogs in patients with atrial fibrillation and low bodyweight (< 60 kg or BMI < 18 kg/m2) was associated with a significant reduction in risks of stroke and major bleeding compared with patient cohorts stabilized on warfarin-based therapy. There was uncertainty regarding the composite outcome and mortality point estimate between these two anticoagulation strategies. This finding helps to resolve the uncertainty associated with the use of DOACs in this cohort. Additionally, it suggests the need for confirmatory non-inferiority randomized controlled trials evaluating DOACs versus warfarin in this cohort of patients.