Concomitant Medication Use Research Articles

Adverse cardiovascular outcomes due to potential drug-drug interactions in statin therapy: a population-based study

Abstract Background Statins have been proven to reduce morbidity and mortality in patients with known atherosclerotic cardiovascular disease (ASCVD) and in primary prevention. Given their unique role in ASCVD, concomitant use of statins and other medications are inevitable. Our clinicians’ duty is to identify clinically important drug-drug interactions (DDI) with statins and to minimize potential life-threatening adverse drug reactions. Purpose To understand the clinical relevance of statin related DDI, we aimed to analyse the prevalence and level of severity of potential statin DDI in a real-world territory-wide population-based study. Methods We retrospectively analysed 95278 patients (mean age 64.3±11.4, female 45.0%) prescribed simvastatin (N=56111, 59%), atorvastatin (N=33902, 36%), or rosuvastatin (N=5265, 5%) from 2013-2022 among 16 public hospitals. Covariates were balanced with 1:1 propensity score matching for patients with and without potential DDI, resulting in 35907 patients in each arm. A composite 4-point MACE (major adverse cardiovascular events) was used as the primary outcome, which included coronary revascularisation, stroke, myocardial infarction (MI), and cardiovascular-related death (CV death). Cox proportional-hazard model with competing risk regression was performed to estimate adjusted hazards ratio (aHR) with corresponding 95% confidence intervals (CI). Secondary analyses would be focusing on adverse drug reactions in these three different statin subgroups. Results At 1-year follow up, subjects with potential statin related DDI have higher propensities of deranged liver function (ALT>=3x ULN, 4.9% vs 3.4%; p<0.001), elevated creatine kinase (CK>=5x ULN, 0.9% vs 0.5%, p<0.001) and deranged renal function (creatinine level >=2X ULN, 0.3% vs 0.2%, p<0.001) than non-DDI group. At 5-year follow up, the statin DDI group had higher incidences of MI (2.9% vs 1.9%, p<0.01), stroke (4.0% vs 2.3%, p<0.001) and CV death (1.7 % vs 1.5%, p=0.038). Potential DDI had most significant effect seen on simvastatin compared to other statins. Simvastatin DDI cohort had strong association with subsequent coronary vascularization (aHR 1.41, 95% CI 1.21–1.64, p<0.005), MI (aHR 1.66, 95% CI 1.46–1.88, p<0.005), stroke (aHR 1.95, 95% CI 1.76–2.16, p<0.005), and CV-related death (aHR 1.18, 95% 1.00–1.38, p=0.05) as compared to control. Atorvastatin DDI cohort was associated with higher rates of MI (aHR 1.81, 95% CI 1.54–2.12, p<0.005) and stroke (aHR 1.64, 95% CI 0.39–1.94, p<0.005) than control. Rosuvastatin DDI cohort was weakly associated with higher rates of MI (aHR 1.75, 95% CI 1.02–3.01, p=0.04). Conclusion Potential statin related drug-drug interactions are prevalent and were associated with major adverse cardiovascular events. Our real-world data demonstrated that simvastatin related drug-drug interaction pose a significant threat to our patients with association with CV death, myocardial infarction, stroke and future coronary revascularization.4-point MACE

Long-term efficacy and safety of stapokibart for moderate-to-severe atopic dermatitis: 52-week results from a phase 3 trial.

Management of moderate-to-severe atopic dermatitis (AD) needs long-term therapy. Stapokibart is a humanized monoclonal antibody targeting interleukin-4 receptor α subunit (IL-4Rα), a shared receptor for IL-4 and IL-13 which are key pathogenic drivers of AD. In a pivotal phase 3 trial (NCT05265923), significant higher proportions of adult AD patients receiving stapokibart than placebo achieved ≥75% improvement from baseline in Eczema Area and Severity Index (EASI-75; 66.9% vs. 25.8%) and Investigator's Global Assessment (IGA) score of 0/1 with ≥2-point reduction (44.2% vs. 16.1%) at Week 16. Herein, we report long-term (52 weeks) efficacy and safety of stapokibart from this trial. After 16-week double-blind treatment completed, patients in both stapokibart and placebo groups entered a 36-week maintenance treatment period and received stapokibart 300 mg every 2 weeks. Concomitant use of topical medications for AD was permitted throughout the maintenance period. Of 476 patients entering maintenance period, 430 completed the treatment. At Week 52, EASI-75 was achieved in 92.5% of patients continuing stapokibart and 88.7% of those switching from placebo to stapokibart, respectively; an IGA score of 0 or 1 with a ≥2-point reduction was achieved in 67.3% and 64.2% of patients, respectively; a ≥4-point reduction in weekly average of daily Peak Pruritus Numerical Rating Scale (PP-NRS) was achieved in 67.3% and 60.5% of patients, respectively. Over the 52-week treatment period, 88.1% of patients reported treatment-emergent adverse events, most were mild or moderate. Long-term treatment with stapokibart demonstrated a sustained efficacy and favorable safety profile in adults with moderate-to-severe AD.

Post-marketing safety concerns with rimegepant based on a pharmacovigilance study

PurposeThis study aimed to comprehensively assess the safety of rimegepant administration in real-world clinical settings.MethodsData from the Food and Drug Administration Adverse Event Reporting System (FAERS) spanning the second quarter of 2020 through the first quarter of 2023 were retrospectively analyzed in this pharmacovigilance investigation. This study focuses on employing subgroup analysis to monitor rimegepant drug safety. Descriptive analysis was employed to examine clinical characteristics and concomitant medication of adverse event reports associated with rimegepant, including report season, reporter country, sex, age, weight, dose, and frequency, onset time, et al. Correlation analysis, including techniques such as violin plots, was utilized to explore relationships between clinical characteristics in greater detail. Additionally, four disproportionality analysis methods were applied to assess adverse event signals associated with rimegepant.ResultsA total of 5,416,969 adverse event reports extracted from the FAERS database, 10, 194 adverse events were identified as the “primary suspect” (PS) drug attributed to rimegepant. Rimegepant-associated adverse events involved 27 System Organ Classes (SOCs), and the significant SOC meeting all four detection criteria was “general disorders and administration site conditions” (SOC: 10018065). Additionally, new significant adverse events were discovered, including “vomiting projectile” (PT: 10047708), “eructation” (PT: 10015137), “motion sickness” (PT: 10027990), “feeling drunk” (PT: 10016330), “reaction to food additive” (PT: 10037977), etc. Descriptive analysis indicated that the majority of reporters were consumers (88.1%), with most reports involving female patients. Significant differences were observed between female and male patients across age categories, and the concomitant use of rimegepant with other medications was complex.ConclusionThis study has preliminarily identified potential new adverse events associated with rimegepant, such as those involving the gastrointestinal system, nervous system, and immune system, which warrant further research to determine their exact mechanisms and risk factors. Additionally, significant differences in rimegepant-related adverse events were observed across different age groups and sexes, and the complexity of concomitant medication use should be given special attention in clinical practice.

Evaluation of the Potential for Cytochrome P450 and Transporter-Mediated Drug-Drug Interactions for Firsocostat, a Liver-Targeted Inhibitor of Acetyl-CoA Carboxylase.

Firsocostat is an oral, liver-targeted inhibitor of acetyl-CoA carboxylase in clinical development for the treatment of metabolic dysfunction-associated steatohepatitis. This work evaluated the potential drug-drug interactions (DDIs) of firsocostat as a victim and as a perpetrator, to inform concomitant medication use. In this phase I study, healthy participants (n=13-30 in each of four cohorts) received firsocostat alone or in combination with either victims or perpetrators of cytochrome P450 (CYP) enzymes and drug transporters to evaluate firsocostat as both a victim and perpetrator of DDIs, respectively. Overall, 80 participants completed the study. As a victim of DDI, firsocostat plasma exposure (area under the plasma concentration-time curve [AUC] from 0 to infinity [AUC∝]) was 19-fold, 22-fold, 63%, and 38% higher when administered with single-dose rifampin 600 mg (organic anion transporting polypeptide [OATP] 1B1/B3 inhibitor), single-dose cyclosporine A 600 mg (OATP/P-glycoprotein/CYP3A inhibitor), multiple-dose probenecid 500 mg twice daily (evaluated as a uridine diphosphate glucuronosyltransferase [UGT] inhibitor), and multiple-dose voriconazole 200 mg twice daily (CYP3A inhibitor), respectively, compared with the administration of firsocostat alone. As a perpetrator of DDI, multiple-dose administration of firsocostat did not affect the exposure of midazolam 2 mg (CYP3A substrate) or drospirenone/ethinylestradiol 3 mg/0.02 mg (combined oral contraceptive). Study treatments were well-tolerated and all adverse events were mild. Firsocostat can be administered with CYP3A and UGT inhibitors without dose adjustment. However, firsocostat should not be coadministered with strong OATP1B/3 inhibitors, such as rifampin and cyclosporine A. Firsocostat can be administered with CYP3A substrates or combined oral contraceptives without dose modification.

Association Between Long- Versus Short-Acting Angiotensin II Receptor Antagonists and Hypotension During Anesthesia Induction: A Retrospective Study.

The withdrawal or continuation of angiotensin II receptor blockers (ARBs) before surgery continues to be debated. We hypothesized that this is because ARBs with different half-lives have not been studied individually. This retrospective study aimed to clarify whether the degree of hypotension during anesthesia induction differs among ARBs with different half-lives. We included patients who received general anesthesia with regular oral administration of telmisartan (group T) or valsartan (group V), which have half-lives of approximately 24 and 6 hours, respectively. The frequency of hypotension and vasopressor frequency and dose during anesthesia induction were compared between the two groups. At our hospital, ARBs were withdrawn on the day of surgery in all patients. Groups T and V included 190 and 132 patients, respectively. Patient backgrounds in group V were significantly more strongly associated with the use of calcium channel blockers. No significant differences were observed in the use of other concomitant antihypertensive medications, cardiovascular complications, or renal function. The time during which the mean arterial blood pressure was < 60 mmHg during anesthesia induction was significantly greater in group T than in group V (11 min vs. 7 min, P=0.030). The proportion of patients who used vasopressors was significantly higher in group T than that in group V (74.2% vs. 56.0%, P < 0.001). Patients taking telmisartan showed more hypotensive during the induction of general anesthesia than those taking valsartan, even after withdrawal on the day of surgery.

SP5.10 - Statin use during neoadjuvant therapy is an independent marker for a favourable Neoadjuvant Rectal (NAR) score in locally advanced rectal cancer when analysing common concomitant medications

Abstract Aim The extent of neoadjuvant therapy (NAT) response is an important prognosticator in locally advanced rectal cancer (LARC). The Neoadjuvant Rectal (NAR) is validated as a pseudo-continuous measurement of response, and a surrogate marker of long-term outcomes. We investigated the impact of common concomitant medications (statins, antiplatelets, metformin) on the extent of response using the NAR score. Methods A retrospective review of regional cancer centre LARC patients undergoing NAT was performed between June 2016 - 2021. The NAR score was calculated as previously described by George et al (2015). Results 253 patients were included. 104(34%), 52(17%), and 19(6%) patients took statins, antiplatelets, and metformin respectively. 90% of those on an antiplatelet are also on a statin. Of those on statins, 45.2% and 14.4% also took antiplatelets or metformin respectively. There was no significant association with concomitant medication use and disease stage or tumour size. Only metformin use associated with the absence of Extramural vascular invasion (EMVI) (p=0.031) on pre-NAT MRI. Neither antiplatelets nor metformin use associated with the extent of NAT response. Statin use associated with a favourable NAR score (p=0.008). On multivariate analysis with pre-NAT mrEMVI and nodal status, concomitant statin use independently predicted a favourable NAR score of &amp;lt;16 (OR 2.019, 95%CI 1.11-3.67, p=0.021). Conclusion Concomitant statin use at time of neoadjuvant therapy associates with a favourable response. Antiplatelet and metformin use does not appear to influence response. Analysis through a clinical trial of statin use combined with neoadjuvant therapy may give more insight into how it influences response.

PCSK9 Inhibitors and Anthracyclines: The Future of Cardioprotection in Cardio-Oncology.

The field of cardio-oncology is an expanding frontier within cardiovascular medicine, and the need for evidence-based guidelines is apparent. One of the emerging focuses within cardio-oncology is the concomitant use of medications for cardioprotection in the setting of chemotherapy regimens that have known cardiovascular toxicity. While clinical trials focusing on cardioprotection during chemotherapy are sparse, an inaugural trial exploring the prophylactic potential of Sodium-Glucose Cotransporter-2 inhibitors (SGLT2is) for anthracycline (ANT)-induced cardiotoxicity has recently commenced. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, though less studied in this oncology demographic, have exhibited promise in preclinical studies for conferring cardiac protection during non-ischemic toxic insults. While primarily used to reduce low-density lipoprotein, PCSK9 inhibitors exhibit pleiotropic effects, including the attenuation of inflammation, reactive oxygen species, and endothelial dysfunction. In ANT-induced cardiotoxicity, these same processes are accelerated, resulting in premature termination of treatment, chronic cardiovascular sequelae, heart failure, and/or death. This review serves a dual purpose: firstly, to provide a concise overview of the mechanisms implicated in ANT-induced cardiotoxicity, and, finally, to summarize the existing preclinical data supporting the theoretical possibility of the cardioprotective effects of PCSK9 inhibition in ANT-induced cardiotoxicity.

The use of concomitant medications on nephrotoxicity associated with teicoplanin: A retrospective observational study

BackgroundTeicoplanin (TEIC) is a nephrotoxic agent. However, little is known about the effects of concomitant medications on nephrotoxicity. In this study, we investigated the effects of concomitant drugs on nephrotoxicity. MethodsA retrospective observational case-control study was conducted on patients (≥18 years) who started TEIC at the Tokyo Dental College, Ichikawa General Hospital, between January 2013 and April 2023. The primary outcome was nephrotoxicity, defined as an increase in serum creatinine levels of ≥50 % or ≥0.5 mg/dL from baseline. Logistic regression analysis was used to determine the risk factors for nephrotoxicity associated with TEIC. In addition, we investigated the relationship between nephrotoxicity and predicted free TEIC concentrations. ResultsOf 305 patients, 43 (14.1 %) developed nephrotoxicity. The multivariate logistic regression analysis identified that serum albumin (odds ratio [OR] = 0.50, 95 % confidence interval [CI] 0.27–0.89, p = 0.02), concomitant use of loop diuretics (OR = 2.22, 95 % CI 1.10–4.59, p = 0.03), antivirals (OR = 3.24, 95 % CI 1.32–7.62, p < 0.01), and vasopressors (OR = 2.57, 95 % CI 1.10–5.78, p = 0.03) were the associated risk factors for nephrotoxicity in patients administered with TEIC. In 216 patients, predicted TEIC concentrations were 3.6 [interquartile range (IQR), 2.6–4.9] μg/mL in the nephrotoxicity group versus 3.6 [IQR, 2.5–4.7] μg/mL in the non-nephrotoxicity group, with no significant difference (p = 0.69). ConclusionOur results indicate the importance of modifying the concomitant use of loop diuretics, antivirals, and vasopressors.

Impact of metformin, statin, aspirin and insulin on the prognosis of uHCC patients receiving first line Lenvatinib or Atezolizumab plus Bevacizumab

Recently, in Hepatocellular carcinoma (HCC) setting, the use of metformin has been associated to a trend toward worse response rate, overall survival and progression free survival in patients who received immunotherapy. The study population included individuals from both Eastern and Western regions with a confirmed diagnosis of HCC and receiving first line treatment with Atezolizumab plus bevacizumab or Lenvatinib. Univariate and multivariate analyses were performed by Cox proportional. For the analysis, patients were stratified based on their use of concomitant medication or not. At the time of database lock, 319 deaths were observed: 209 in the Lenvatinib cohort, 110 in the Atezolizumab plus bevacizumab cohort. In the Atezolizumab plus Bevacizumab arm, 50 (16.5%) patients were on chronic metformin use. At the univariate analysis for OS, patients who used metformin showed significantly shorter OS compared to patients who did not use metformin (HR 1.9, 95% CI 1.1–3.2). Multivariate analysis confirmed that patients in metformin group had significantly shorter OS compared to patients in no-metformin group (HR 1.9; 95% CI 1.1–3.1). At the univariate analysis for PFS, patients in metformin group had significantly shorter PFS compared to patients in no-metformin group (HR 1.6, 95% CI 1.0–2.6). Multivariate analysis confirmed that patients in metformin group had significantly shorter PFS compared to patients in no-metformin group (HR 1.7; 95% CI 1.1–2.7; p = 0.0147). No differences were reported in terms of ORR and DCR between patients in metformin group and those in no-metformin group. In the Lenvatinib cohort, 65 (15%) patients were recorded to chronically use metformin. No statistically significant differences in terms of both OS and PFS were found between patients in metformin group and patients in no-metformin group. This analysis unveils a negative prognostic role associated with metformin use specifically within the Atezolizumab plus Bevacizumab group.

Real-world risk factors for herpes zoster in patients with rheumatoid arthritis undergoing tofacitinib treatment.

This study sought to assess the risk factors of herpes zoster (HZ) in rheumatoid arthritis (RA) patients treated with tofacitinib (TOFA). This retrospective study reviewed RA patients receiving TOFA. We compared clinical characteristics, laboratory profiles, concomitant medication use, and HZ incidence in patients with and without recent biologic synthetic disease-modifying anti-rheumatic drugs (bDMARDs) treatment, which is defined as their administration ≤ 180 days prior to the initiation of TOFA treatment. We used univariate Cox proportional hazards models and Kaplan-Meier analysis to assess risk factors. Among 304 RA patients, 97 had recent bDMARDs use and 207 did not. Patients with recent bDMARDs use typically had lower weekly doses of methotrexate, less hydroxychloroquine use, and shorter follow-up times. In the recent bDMARDs group, 64 (66.0%) used tumor necrosis factor inhibitors (TNFi), 19 (19.6%) used tocilizumab, and 14 (14.4%) used abatacept. The overall incidence rate (IR) of HZ was 5.62 per 100 person-years. Patients with recent bDMARDs use exhibited a higher HZ risk compared to those without recent bDMARDs use (IR ratio: 2.34, 95% confidence interval [CI]: 1.04-5.19, p = 0.028). Recent bDMARDs use (hazard ratio: 2.4, 95% CI: 1.12-4.95, p = 0.024) was an independent risk factor for HZ among multivariable analysis. Kaplan-Meier analysis confirmed increased HZ risk in RA patients on TOFA with recent bDMARDs use (log-rank p = 0.015). HZ is common in RA patients treated with TOFA, and recent bDMARDs (TNFi, tocilizumab and abatacept) use is a risk factor of HZ. HZ vaccination, therefore, should be recommended for this group.

Effects of titration speed, gender, obesity and concomitant medications on the risk and onset time of clozapine-associated fever among Japanese patients with schizophrenia: retrospective review of charts from 21 hospitals.

Clozapine-induced inflammation, such as myocarditis and pneumonia, can occur during initial titration and can be fatal. Fever is often the first sign of severe inflammation, and early detection and prevention are essential. Few studies have investigated the effects of clozapine titration speed and concomitant medication use on the risk of clozapine-induced inflammation. We evaluated the risk factors for clozapine-associated fever, including titration speed, concomitant medication use, gender and obesity, and their impact on the risk of fever and the fever onset date. We conducted a case-control study. The medical records of 539 Japanese participants with treatment-resistant schizophrenia at 21 hospitals in Japan who received clozapine for the first time between 2010 and 2022 were retrospectively investigated. Of these, 512 individuals were included in the analysis. Individuals were divided into three groups according to the titration rate recommended by international guidelines for East Asians: the faster titration group, the slower titration group and the ultra-slower titration group. The use of concomitant medications (such as antipsychotics, mood stabilisers, hypnotics and anxiolytics) at clozapine initiation was comprehensively investigated. Logistic regression analysis was performed to identify the explanatory variables for the risk of a fever of 37.5°C or higher lasting at least 2 days. Fever risk significantly increased with faster titration, male gender and concomitant use of valproic acid or quetiapine. No increased fever risk was detected with the use of other concomitant drugs, such as olanzapine, lithium or orexin receptor antagonists. Fever onset occurred significantly earlier with faster titration. Multivariate analysis identified obesity as being a factor that accelerated fever onset. A faster titration speed and concomitant treatment with valproic acid and quetiapine at clozapine initiation increased the risk of clozapine-associated fever. Clinicians should titrate clozapine with caution and consider both the titration speed and concomitant medications.

Clinical features associated with immune checkpoint inhibitor nephritis: a single-center clinical case series

BackgroundAcute kidney injury (AKI) has been well described as a complication of immune checkpoint inhibitor therapy. We present a series of patients, the majority with lung adenocarcinoma, who developed AKI while actively receiving immune checkpoint inhibitors.MethodsThis is a retrospectively analyzed clinical case series of six patients treated at City of Hope Comprehensive Cancer Center. Data were collected on gender, age, ethnicity, comorbidities, concomitant medications, type of malignancy, treatments, and renal function. All patients underwent renal biopsy for classification of the mechanism of AKI. Comprehensive genomic profiling (CGP) was performed on tumor tissue for all patients.ResultsPatterns of AKI included acute interstitial nephritis and acute tubular necrosis. Contributing factors included the use of concomitant medications known to contribute to AKI. All but two patients had full resolution of the AKI with the use of steroids. There were several mutations found on CGP that was notable including an Exon 20 insertion as well as multiple NF1 and TP53 mutations. There was high PD-L1 expression on tumor tissue noted in two out of six patients. In addition to AKI, a subset of patients had proteinuria with biopsies revealing corresponding glomerular lesions of minimal change disease and focal and segmental glomerulosclerosis.ConclusionsOur case series demonstrates that AKI from immune checkpoint inhibitors has a variable presentation that may require an individualized treatment approach. Further studies are needed to identify biomarkers that may help identify those at risk and guide the management of this condition.

Prior herpes zoster occurrence and high-dose corticosteroids increase herpes zoster risk in rheumatoid arthritis patients receiving janus kinase inhibitors in a retrospective and observational study.

Herpes zoster (HZ) risk is increased in rheumatoid arthritis (RA) patients receiving Janus kinase inhibitors (JAKi) therapy. Identifying and evaluating the risk factors of HZ development in patients receiving JAKi therapy would be clinically helpful. We investigated HZ's incidence rates (IR), identified the risk factors, and further assessed their influence on HZ development in RA patients undergoing JAKi therapy. We retrospectively evaluated 249 RA patients who received JAKi therapy between 2015 and 2023. Data regarding clinical characteristics, HZ reactivation, HZ vaccination status, and concomitant medication use were collected. Among 249 JAKi-treated patients, 44 developed new-onset HZ (tofacitinib, 28/142; baricitinib, 6/35; upadacitinib,10/72), with an IR of 5.11/100patient-years. Multivariate analysis revealed significant predictors of HZ development: a long JAKi exposure period, prior HZ or COVID-19 history, and concomitant high-dose corticosteroids use. The interval between JAKi initiation and HZ development was significantly shorter in patients with prior HZ history than in those without (median, 6.5months versus 33.5months, p < 0.001), suggesting "biphasic" emergence of HZ. Only one patient who had experienced an HZ episode while receiving JAKi developed recurrent HZ. None of the seventeen patients immunized with the non-live recombinant zoster vaccine developed HZ. Our JAKi-treated patients had elevated HZ risks, a class effect across different JAKi. A long exposure period, prior history of HZ or COVID-19, and concomitant high-dose corticosteroid treatment may further increase the risk. The emergence of HZ shows a biphasic pattern: early HZ development in patients with prior HZ and late development in those without. Key Points • An increased risk of HZ was observed in Taiwanese RA patients treated with JAKi, presenting as a class effect. • Patients with a long JAKi exposure period, prior history of HZ or COVID-19, and concomitant use of high-dose corticosteroids were at high risk of HZ while receiving JAKi therapy. • The interval between JAKi initiation and HZ occurrence was shorter in patients with prior HZ than in those without, showing "biphasic" emergence.

Deprescribing in an outpatient medical clinic at a tertiary care hospital in Sri Lanka

Introduction: Use of multiple concomitant medications or ‘polypharmacy’ is linked to decreased medication adherence, adverse drug reactions and increased financial burden on patients and the economy. Deprescribing by experienced healthcare personnel can ensure safe and effective use of medications. Many medications, prescribed during hospital stay or at clinic level are continued for unnecessarily long periods, highlighting the necessity for deprescribing. The objectives of this audit were to identify and deprescribe inappropriate medications in patients, identify their comorbidities and explore reasons for the inappropriate medication use.Methods: This deprescribing audit was conducted by systematic sampling in selected adult patients &gt;18 years, attending a medical clinic at National Hospital, Kandy over one month. The audit standard was the American Academy of Family Physicians (AAFP) ‘5-step process in deprescribing’. Our study was based only on the first 3 steps of the AAFP deprescribing process.Results: Out of a total of 402 patients, deprescribing was carried out in 135 (33.58%). In this deprescribed group, 59.3% of patients were female and the mean age was 62.3 (±10.9) years. Furthermore, of the deprescribed patients, 52.6% had hypertension, 44.4% had ischaemic heart disease, and 34.1% had diabetes mellitus. The most deprescribed medication was antiplatelets (37.8%), followed by analgesics (24.4%) and diuretics (20%). A clear indication for using the drug was lacking in 68.9%, while 31.1% of patients continued taking the medication for longer than recommended. Conclusions: In this audit, over one third of patients underwent deprescribing. It provides just a glimpse of the broader issue of inappropriate polypharmacy and the necessity of deprescribing. Future research involving multiple centres is recommended to enhance understanding of medication patterns necessitating deprescribing.

Prevalence and Factors Associated with De-escalation of Anti-TNFs in Older Adults with Rheumatoid Arthritis: A Medicare Claims-Based Observational Study.

The aim was to evaluate prevalence and factors associated with anti-tumor necrosis factor (anti-TNF) de-escalation in older adults with rheumatoid arthritis (RA). We identified adults ≥66 years of age with RA on anti-TNF therapy within 6 months after RA diagnosis with at least 6-7 months duration of use (proxy for stable use), using 20% Medicare data from 2008-2017. Patient demographic and clinical characteristics, including concomitant use of glucocorticoid (GC), were collected. Anti-TNF use was categorized as either de-escalation (identified by dosing interval increase, dose reduction, or cessation of use) or continuation. We used (1) an observational cohort design with Cox regression to assess patient characteristics associated with de-escalation and (2) a case-control design with propensity score-adjusted logistic regression to assess the association of de-escalation with different clinical conditions and concomitant medication use. We identified 5106 Medicare beneficiaries with RA on anti-TNF, 65.5% of whom had de-escalation. De-escalation was more likely with older age (hazard ratio [HR] 1.01, 95% confidence interval [CI] 1.01-1.02) or greater comorbidity (HR 1.07, 95% CI 1.05-1.09), but was less likely with low-income subsidy status (HR 0.85, 95% CI 0.78-0.92), adjusting for patient sex and race/ethnicity. Lower odds of de-escalation were associated with serious infection (odds ratio [OR] 0.79, 95% CI 0.66-0.94), new heart failure diagnosis (OR 0.70, 95% CI 0.52-0.95), and long-term GC use (OR 0.84, 95% CI 0.74-0.95), whereas higher odds were associated with concomitant methotrexate use (OR 1.16, 95% CI 1.03-1.31). Anti-TNFs are de-escalated in two-thirds of older adults with RA in usual care. Further study is needed on RA outcomes after anti-TNF de-escalation.

RWD40 Concomitant Use of Opioids and Psychotropic Medications in Mississippi Medicaid Beneficiaries

RWD40 Concomitant Use of Opioids and Psychotropic Medications in Mississippi Medicaid Beneficiaries

Impact of Azithromycin on the Predisposition to Cardiac Arrhythmias in Adult Patients: A Systematic Review

Background: Azithromycin is a macrolide antibiotic that can lead to QT interval prolongation, which may trigger ventricular tachycardia, also known as torsades de pointes (TdP), the most common cardiac arrhythmia associated with these drugs. All macrolides are linked to QTc interval prolongation, with apparently higher risk with erythromycin and clarithromycin compared to azithromycin. Macrolides can extend QT and QTc intervals and cause cardiac arrhythmias, including TdP, ventricular tachycardia, and ventricular fibrillation, through their affinity for binding to the delayed rectifier potassium channel, IKr, inducing QT prolongation and risk of TdP. However, it is crucial to assess the risk-benefit ratio of prescribing azithromycin, especially in patients with preexisting cardiovascular disease or taking concomitant medications that prolong the QT interval. Objectives: The aim of this study is to determine whether azithromycin is genuinely associated with the occurrence of ventricular arrhythmias in adult patients. Materials and Methods: This systematic review is based on meticulous searching across Medline and Google Scholar databases, analysis of publications, and synthesis of available evidence regarding the risk of arrhythmias with the use of azithromycin. Results: We reviewed 6 articles that met the criteria, including 20.510.653 patients and 66 articles. While some studies suggest an increased risk of ventricular arrhythmias in certain subgroups of patients, others have not found a significant association between azithromycin and these arrhythmias. These discrepancies could be attributed to differences in the definition of arrhythmias, the duration of follow-up, or the characteristics of the groups of patients evaluated. The results point toward the need for a more thorough risk assessment before initiating this antibiotic in adult patients, especially those with known cardiovascular risk factors or those with a history of heart disease. Several risk factors, such as hypokalemia, pre-existing heart conditions, and concomitant use of other QT-prolonging medications, have been identified as increasing vulnerability to macrolide-induced arrhythmias. Conclusion: The results of the systematic review and cohort studies analyzed consistently suggest an association between the use of azithromycin and an increased risk of developing ventricular arrhythmias. This risk appears to be most evident in the elderly, with different studies showing variations in the magnitude of the risk. It is crucial to evaluate the risks and benefits of these antibiotics in each clinical situation, considering the information provided by observational studies and systematic reviews

Factors associated with the use of benzodiazepine and opioid prescription drug in the student population: a cross-sectional study

The misuse of benzodiazepines and opioid medications is frequent in students. To improve our understanding of this behavior, we aimed to identify factors associated with separate and concomitant use of these substances. Anonymous self-reported questionnaires were e-mailed to students enrolled at a French university between March and July 2021, covering: sociodemographic characteristics, academics, psychoactive substance use, ADHD symptomatology (adulthood and childhood), and psychiatric/psychological or addiction follow-up. Factors associated with the use of benzodiazepines and opioid medications included female sex (OR = 1.41 [1.08; 1.86]) and OR = 1.38 [1.06; 1.79], respectively), older age (OR = 1.65 [1.04; 2.6] and OR = 2.17 [1.4; 3.36], respectively), current psychiatric/psychological follow-up (OR = 6.53 [5.18; 8.24] and OR= 1.5 [1.12; 2.0], respectively), ADHD symptomatology (OR= 2.33 [1.71;3.16] and OR= 1.61 [1.15; 2.24], respectively), polyconsumption (tobacco use for benzodiazepine users, OR = 1.38 [1.04; 1.82]; alcohol use OR = 1.67 [1.17; 2.39] and tobacco use OR = 1.62 [1.23; 2.14] for opioid users). These factors were even more strongly associated with the concomitant use of benzodiazepines and opioid medications: older age (OR = 3.64 [2.22; 5.99]), female sex (OR = 1.54 [1.1; 2.14]), grade repetition (OR = 1.7 [1.14; 2.54]), psychiatric/psychological follow-up (OR = 4.51 [3.35;6.06]), ADHD symptomatology (OR = 5.3 [3.69; 7.63]), polyconsumption (tobacco use OR = 2.05 [1.39; 3] and cannabis use, OR = 2.07 [1.97; 4.16]. The factors associated with the use of benzodiazepines and prescription opioids identified in this study could lead to the development of targeted prevention methods.

Electrocardiographic Findings in Children Treated with Leuprolide Acetate for Precocious Puberty: Does it Cause Prolonged QT?

Central precocious puberty is treated with long-acting GnRH analogues. Some adult patients undergoing GnRHa treatment experienced prolonged QT syndrome, which is associated with an increased risk of serious cardiac events such as myocardial infarction, stroke, arrhythmias, and sudden cardiac death. Seventy-four patients, aged between 5 and 11 years and diagnosed with central precocious puberty but with no other concomitant disease or medication use, underwent electrocardiogram assessment. They had been receiving 3.75 mg leuprolide acetate (Lucrin® Depot) injections every 28 days for at least three months. The electrocardiograms of all patients showed a QTc interval within normal limits, consistent with the data of healthy Turkish children of the same age and gender. No other pathological physical examination or ECG findings were observed. Furthermore, there was no significant difference in QTc interval in relation to age, anthropometric data, or the duration or cumulative dose of the treatment. The study found no correlation between QTc interval values and age, treatment duration, total cumulative dose, and anthropometric data. The findings suggest that cardiovascular adverse events associated with GnRHa may be related to age and other underlying physiopathological conditions rather than the drug.

Influence of the glutamate-glutamine cycle on valproic acid-associated hepatotoxicity in pediatric patients with epilepsy

Introduction Although valproic acid is generally well tolerated, hepatotoxicity is a common side effect in patients receiving long-term treatment. However, the mechanisms underlying valproic acid-associated hepatotoxicity remain elusive. Methods To investigate the mechanisms and explore the potential risk factors for valproic acid-associated hepatotoxicity, 165 age-matched pediatric patients were recruited for laboratory tests and glutamate-glutamine cycle analysis. Results The concentration of glutamate in patients with hepatotoxicity was significantly greater than that in control patients, while the concentration of glutamine in patients with hepatotoxicity was significantly lower than that in control patients (P <0.05). In addition, the frequencies of the heterozygous with one mutant allele and homozygous with two mutant alleles genotypes in glutamate-ammonia ligase rs10911021 were significantly higher in the hepatotoxicity group than those in the control group (47.1 percent versus 32.5 percent, P = 0.010; 17.6 percent versus 5.2 percent, P = 0.001, respectively). Moreover, heterozygous carriers with one mutant allele and homozygous carriers with two mutant alleles genotypes of glutamate-ammonia ligase rs10911021 exhibited significant differences in the concentrations of glutamine and glutamate concentrations (P ˂ 0.001 and P = 0.001, respectively) and liver function indicators (activities of aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase, P <0.001, respectively). Furthermore, logistic regression analysis indicated that glutamate-ammonia ligase rs10911021 (P = 0.002, odds ratio: 3.027, 95 percent confidence interval, 1.521 − 6.023) and glutamate (P = 0.001, odds ratio: 2.235, 95 percent confidence interval, 1.369 − 3.146) were associated with a greater risk for hepatotoxicity, while glutamine concentrations were negatively associated with hepatotoxicity (P = 0.001, odds ratio: 0.711, 95 percent confidence interval, 0.629 − 0.804). Discussion Understanding pharmacogenomic risks for valproic acid induced hepatotoxicity might help direct patient specific care. Limitations of our study include the exclusive use of children from one location and concomitant medication use in many patients. Conclusion Perturbation of the glutamate-glutamine cycle is associated with valproic acid-associated hepatotoxicity. Moreover, glutamate-ammonia ligase rs10911021, glutamate and glutamine concentrations are potential risk factors for valproic acid-associated hepatotoxicity.