In patients with chronic heart failure which polypharmacy pheno-groups are associated with adverse health outcomes? (Polypharmacy pheno-groups and heart failure outcomes).

BACKGROUND: Patients with heart failure are living longer with the inevitable morbidity of rising medication counts. It remains uncertain what fraction of this ensuing polypharmacy exactly predicts adverse clinical outcomes. METHODS: This prospective study examined records of patients admitted to a Weill Cornell-affiliated tertiary medical institution with a confirmed diagnosis of heart failure between January 2018 to January 2022. Each patient's medications for the past four months were tallied, and a definitional threshold of ≤4, ≥5, ≥10 medications was established. The primary outcome was all-cause mortality within the study period. RESULTS: Out of a total of 7354 patients included in the study, 70 % were males with a median age of 59 years IQR (48-71). The median (IQR) age-adjusted Charlson Comorbidity Index (CCI) was 21-5. A total of 1475 (20 %) participants died within the study period. Patient cohorts with excessive polypharmacy (≥9 medications) had the highest probability of survival up to 1.6 years compared to those with lower medication thresholds (≤4); the mortality rate decreased by 18 % for patients with excessive polypharmacy [HR = 0.82, 95 % CI: 0.71-0.94]). Conversely, patients with non-heart failure-related polypharmacy had increased risks of ICU admissions (aOR = 1.78, 95 % CI: 1.13-2.70). CONCLUSION: In an examination of a database of patients with chronic heart failure, major non-heart failure-related polypharmacy was associated with increased risks in intensive care admissions. Excessive polypharmacy was associated with increased rates of survival.

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.

What is Polypharmacy in Patients with Chronic Kidney Disease? A Systematic Review.

PURPOSE: Polypharmacy presents an increasing therapeutic challenge for physicians managing patients with chronic kidney disease (CKD). However, there is a lack of consensus regarding the specific medication count threshold that defines polypharmacy in this population. The objective of this review is to establish a unified definition of polypharmacy in the CKD population by examining the diverse definitions used in previously published studies. METHODS: A comprehensive search was conducted in relevant databases (PubMed, SCOPUS, Cochrane, and disease-specific databases) from 2000 to May 2022 to identify studies with polypharmacy threshold definitions in patients with CKD. Studies meeting the inclusion criteria were included in this review, and their methodologic quality was assessed. FINDINGS: Following the screening of the search results, duplicate records and studies that did not meet the inclusion criteria were removed, resulting in a total of 18 studies included in this review. Among these, 61.1% specified the polypharmacy definition to be a threshold of ≥5 medications. In addition, 22.2% specified a high polypharmacy definition at a threshold of ≥10 medications. However, none of the studies reported on the dichotomy between kidney-related and non-kidney-related polypharmacy. IMPLICATIONS: This review indicates that a numerical threshold of ≥5 medications is commonly used to define polypharmacy in patients with CKD. Nevertheless, it remains uncertain whether a kidney-related polypharmacy definition or a high polypharmacy definition would better identify patients with CKD at risk for polypharmacy-related complications.

Prevalence and global trends of polypharmacy in patients with chronic liver disease: A systematic review and meta-analysis.

BACKGROUND: Despite its central role in drug metabolism, the exact prevalence estimates and factors affecting global trends of polypharmacy in patients with chronic liver disease (CLD) have remained unexamined. The aim of this systematic review and meta-analysis is to estimate the prevalence of polypharmacy in patients with CLD and to comprehensively synthesize the socio-demographic factors that drive this. METHODS: We conducted a comprehensive search of relevant databases (PubMed, EMBASE, Science citation index, Cochrane Database of Systematic Reviews, and database of abstracts of reviews of effectiveness) for studies published from inception to May 30, 2022 that reported on prevalence estimates of polypharmacy in patients with CLD. The risk of bias was conducted utilizing Loney criteria. The primary outcome was the pooled prevalence of polypharmacy in patients with CLD. We subsequently performed a systematic review and weighted meta-analysis to ascertain the exact pooled prevalence of polypharmacy among patients with CLD. RESULTS: We identified approximately 50 studies from the initial literature search, of which 7 (enrolling N = 521,435 patients) with CLD met the inclusion criteria; of these, 58.7% were male, with a mean age of 53.9 (SD ±â€…12.2) years. The overall pooled prevalence of polypharmacy among patients with CLD was 31% (95% confidence interval [CI]: 4%-66%, I2 = 100%, τ2 ≤ 0.001, P ≤ .0001). We found higher pooled prevalence estimates among patients aged 50 years and older compared to their younger cohorts (42%, [CI 10-77]; I2 = 100%, P = <.001 vs 21%, [CI 0-70]; I2 = 100%, P = <.001). CONCLUSION: In an examination of multiple community- and hospital-based databases of patients with CLD, we found a pooled prevalence estimate of polypharmacy of approximately 31%. This represents a case burden within the range reported in the general population and will likely respond to mitigation strategies employed thus far for patients in that population.

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.

An investigation into the avoidability of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rising morbidity amongst hospitalized patients. Whilst clinical protocols for the management of individual DRESS cases have been well established, determination of potential prevention of these cases by utilizing novel "avoidability" tools has remained unexplored. This retrospective study reviewed records of patients who presented to the emergency department of Weill Cornell Medicine-affiliated Hamad General Hospital, Doha Qatar with suspected DRESS syndrome. These cases were independently adjudicated (utilizing the RegiSCAR, and JSCAR tools) as DRESS-drug pairs by a team of two clinical pharmacists and two General Physicians. They were then rated for potential avoidability with the Liverpool adverse drug reactions avoidability tool (LAAT) by the same team of raters. A total of 16 patients satisfied RegiSCAR criteria for DRESS syndrome. The mean age of the study population was 41.5 years (SD ± 13.3). The study population was predominantly male (n = 12; [75%]). The median latent period from drug ingestion to clinical presentation was 14 days (interquartile range [IQR] 6.5, 29). The median RegiSCAR and J-SCAR scores were 6 (IQR 5, 6.8), 5 (IQR 4, 5.8) respectively. Utilizing the LAAT, about 60% of the DRESS syndrome-drug pairs were rated as "avoidable" ("probable" or "definite"). The overall Krippendorf's alpha with the LAAT was 0.81 (SE 0.10, CI 0.59-1.00); with an intraclass correlation coefficient (ICC) of 0.90 (CI 0.77, 0.96.). In a randomly selected cohort of DRESS syndrome-drug pairs, a significant proportion was potentially avoidable ("possibly" and "definitely") utilizing the LAAT. This will need validation by larger sample-sized prospective studies utilizing the updated LAAT proposed by this study.

Median arcuate ligament syndrome masquerading as mesenteric angina.

Patients with recurrent unclear causes of postprandial abdominal pain should have median arcuate ligament syndrome as a differential diagnosis which is thought to be caused by celiac artery compression. Diagnosis is by imaging such as CT angiography.

The Net Clinical Benefit of Rivaroxaban Compared to Low-Molecular-Weight Heparin in the Treatment of Cancer-Associated Thrombosis: Systematic Review and Meta-Analysis.

Cancer-associated thrombosis (CAT) carries significant morbidity and mortality. Low-molecular-weight heparin (LMWH) remains the standard of care, with recent systematic studies suggesting the efficacy and safety of rivaroxaban in the treatment of CAT. Uncertainty, however, remains regarding rivaroxaban efficacy and safety in real-world settings. We performed a systematic review and meta-analysis of studies comparing rivaroxaban to LMWH. We searched PubMed, MEDLINE, and EMBASE. The primary outcome was the net clinical benefit (NCB), while rates of major bleeding (MB), venous thromboembolism (VTE), clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality events were secondary outcomes. Seventeen studies were included in the final analysis. Rivaroxaban had a better NCB (relative risk [RR] = 0.82; 95% CI = 0.75-0.89, Q = 10.51, I 2 = 0%), less VTE events (RR = 0.73, 95% CI = 0.65-0.82, Q = 6.76, I 2 = 0%), and lower all-cause mortality (RR = 0.72, 95% CI = 0.57-0.91, Q = 32.8, I 2 = 79%) compared to LMWH. Additionally, comparable MB events (RR = 1.07, 95% CI = 0.85-1.33, Q = 16.9, I 2 = 11%). However, CRNMB events were higher in the rivaroxaban group (RR = 2.02, 95% CI = 1.46-2.80, Q = 9.9, I 2 = 19%). Additional analyses demonstrated consistency of results. Our review encompassing data from randomized and real-world data suggested rivaroxaban superiority compared to LMWH in terms of a better NCB, fewer VTE events, lower all-cause mortality, and comparable MB risk while carrying a higher risk of CRNMB. These findings support the use of rivaroxaban in the treatment of CAT. Additionally, it warrants a sizable randomized controlled study testing the superiority of rivaroxaban versus LMWH formulation and ascertaining bleeding outcomes according to cancer type and site.

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.

Comparative effectiveness and safety of direct-acting oral anticoagulants (DOACS) for the reduction of recurrent venous thromboembolism in cancer patients: A protocol for systematic review and network meta-analysis using a generalized pairwise modeling methodology.

BACKGROUND: There has been a significant improvement in both our understanding and therapeutic choices available to clinicians for the management of cancer associated thrombosis (CAT). Even with the recent publication of a systematic review and landmark trials demonstrating the non-inferiority of DOACS-based anticoagulation strategy compared to the standard of care in patients with CAT, there is unresolved uncertainty regarding the exact hierarchy of risks and effectiveness of various DOAC analogues in these cohorts of patients. METHOD: We will carry out a network meta-analyses, utilizing a novel generalized pairwise methodology to generate direct and indirect comparisons between the various DOAC analogues. We will search the following databases for studies that satisfies pre-specified inclusions criteria; these include PubMed, EMBASE, Cochrane library, Clinicaltrials.gov, conference abstracts among other sources. The primary efficacy and safety outcomes are recurrent VTE and major hemorrhagic events, respectively. Two reviewers will Search the databases independently with the view to identify studies that meet eligibility criteria. The methodological quality of the included studies will be determined using a recently validated risk of bias assessment tool. RESULTS: We expect that the result of this review will ascertain the hierarchy of risks and effectiveness of various DOAC analogues in patients with CAT. CONCLUSION: Results of this review will assist in informed decisions making regarding therapeutic guidelines of DOAC in CAT.

An investigation into the avoidability of adverse drug reactions using the LAAT and modified Hallas tools.

An adverse drug reactions avoidability tool called the Liverpool ADR avoidability assessment tool (LAAT) was recently developed (for research purposes), and subsequently validated with mixed interrater reliability (IRR). We investigated the comparative IRR of this tool in an inpatient cohort to ascertain its practical application in this setting.The patient population was comprised of 44 ADR drug pairs drawn from an observational prospective cohort of patents with ADR attending a Weill Cornell Medicine-affiliated tertiary medical Centre in Doha Qatar (Hamad General Hospital). Using the LAAT, and modified Hallas tools, 4 independent raters (2 Clinical Pharmacologists, and 2 General Physicians) assessed and scored the 44 ADR-drug pairs. Agreement proportions between the rating pairs were evaluated as well individual/overall kappa statistics and intraclass correlation coefficients. We evaluated the weight of each of the 7 questions on the LAAT tool to ascertain its determinative role.Across 44 ADR-drug pairs, the overall median Fleiss kappa using the LAAT, and modified Hallas tools were 0.67 (interquartile range (IQR) 0.55, 0.76), 0.36 (IQR, 0.23-0.71) respectively. The overall percentage pairwise agreement with the LAAT and modified Hallas tools were 78.5%, and 62.2% respectively. Exact pairwise agreement occurred in 37 out of 44 (range 0.71-1), and 27 of 44 (0.53-0.77) ADR-drug pairs using the LAAT and modified Hallas tools respectively. Using the LAAT tool, the overall intraclass correlation coefficient was 0.68 (CI 0.55, 0.79), and 0.37 (CI 0.22, 0.53) with the modified Hallas tool.We report a higher proportion of "possible" and "definite" avoidability outcomes of adverse drug reactions compared with the modified Hallas, or that reported by developers of the LAAT tool. Although initially developed for research purposes, our report has suggested for the first time a potential applicability of this tool in clinical environment as well.

Novel biomarkers for potential risk stratification of drug induced liver injury (DILI): A narrative perspective on current trends.

BACKGROUND: Drug induced liver injury (DILI) is an increasing cause of acute liver injury especially with increasing need for pharmacotherapy of widening comorbidities amongst our ever-aging population. Uncertainty however remains regarding both acceptable and widely agreeable diagnostic algorithms as well a clear understanding of mechanistic insights that most accurately underpins it. In this review, we have explored the potential role of emerging novel markers of DILI and how they could possibly be integrated into clinical care of patients. METHODS: We explored PUBMED and all other relevant databases for scientific studies that explored potential utility of novel biomarkers of DILI, and subsequently carried out a narrative synthesis of this data. As this is a narrative review with no recourse to patient identifiable information, no ethics committee's approval was sought or required. RESULTS: Novel biomarkers such as microRNA-122 (miR-122) profiles, high mobility group box-1 (HMGB1), glutamate dehydrogenase (GLDH), and cytokeratin-18 (K-18), amongst others do have the potential for reducing diagnostic uncertainties associated with DILI. CONCLUSION: With the increasing validation of some of the novel liver biomarkers such as K-18, mir-122, HMGB-1, and GLDH, there is the potential for improvement in the diagnostic uncertainty commonly associated with cases of DILI.

Efficacy of sodium-glucose co-transporter 2 inhibitors in patients with type II diabetes: A protocol for systematic review of randomised controlled clinical trials utilising a generalised pairwise modelling methodology.

BACKGROUND: Recent systematic reviews have evaluated the efficacy of sodium-glucose co-transporter 2 inhibitors (SGLT2) inhibitors (SGLT2I) in improving glycaemic control and mortality in patients with type II diabetes mellitus. None have incorporated the most recent study or utilized the generalized pairwise modeling methodology network meta-analysis (NMA), as well as a novel bias risk assessment approach. METHODS: We propose to conduct literature search of all randomized controlled clinical trials published in English language evaluating the efficacy of (SGLT2I) versus placebo or usual standard of care from the inception of following databases to September 30, 2019: Controlled Clinical Trials Cochrane Controlled Trials Register (CCTR), Cochrane Database of Systematic Reviews (CDSR), EMBASE, Database of Abstracts of Reviews of Effectiveness (DARE), PubMed. Two reviewers will independently search these databases to identify studies that satisfy pre-specified eligibility criteria. Study bias risk assessment amongst other methodology quality evaluation of the studies will be carried out using a novel risk bias assessment tool. RESULTS: We anticipate that the result of this review will provide additional insight into the ranking of the efficacy of various (SGLT2I) in type II diabetic patients especially as it relates to mortality, glycemic control, and body weight reduction. CONCLUSION: The result of this review will be useful informing therapeutic decisions by policy makers with regards to commissioning of diabetic care.Prospero registration number: CRD42019139708.