Higher Risk Of Adverse Events Research Articles

Efficacy and safety of veliparib plus chemotherapy for the treatment of lung cancer: A systematic review of clinical trials.

As a poly-ADP ribose polymerase (PARP) inhibitor, veliparib has been identified as a potential therapeutic agent for lung cancer. The present study aimed to conduct a systematic review of clinical trials investigating the efficacy and safety of veliparib for treating lung cancer. PubMed, Scopus, the Web of Science, and Google Scholar were systematically searched up to October 30, 2022. Only randomized controlled trials (RCTs) evaluating the efficacy or safety of veliparib in the treatment of lung cancer patients were included. Studies were excluded if they were not RCTs, enrolled healthy participants or patients with conditions other than lung cancer, or investigated therapeutic approaches other than veliparib. The Cochrane risk-of-bias tool was used for quality assessment. The seven RCTs (n = 2188) showed that patients treated with a combination of veliparib and chemotherapy had a significantly higher risk of adverse events, when compared to the control arm. There was no statistically significant difference in overall survival (OS) between those treated with veliparib plus chemotherapy and those receiving the standard therapies. Only two trials demonstrated an improvement in progression-free survival (PFS), and only one study found an increase in objective response rate (ORR). Furthermore, adding veliparib to standard chemotherapy showed no benefit in extending the duration of response (DoR) in any of the studies. Only a small number of studies have found veliparib to be effective, in terms of improved OS, PFS, and ORR, while the majority of studies found no benefit for veliparib over standard treatment.

Impact of Obstructive Sleep Apnea on Disease Severity and Adverse Outcomes in Patients with Acute Pulmonary Embolism.

Acute pulmonary embolism (PE) poses a life-threatening risk with high mortality rates. While the coexistence of PE and obstructive sleep apnea (OSA) is gaining recognition, its influence on PE severity and prognosis remains uncertain. This study aims to investigate the associations between OSA and disease severity, as well as outcomes, in patients with acute PE. We conducted a retrospective cohort study on patients diagnosed with acute PE who had undergone previous cardiorespiratory polygraphy. OSA severity was assessed using the apnea-hypopnea index (AHI) derived from cardiorespiratory polygraphy. The severity of acute PE was evaluated using the simplified Pulmonary Embolism Severity Index (sPESI) score. Logistic regression analysis was performed to investigate the associations between AHI and the risk of belonging to the sPESI≥1 group. Cox regression analysis was used to examine the relationship between AHI and long-term adverse events, defined as a composite of all-cause mortality and non-fatal cardiovascular events. Among 145 acute PE patients (mean age 62.2 years, 49.7% male), 94 (64.8%) had OSA. Patients with OSA had a significantly higher proportion of sPESI≥1 (89.4% vs 68.6%, p=0.002) than non-OSA patients. Each unit increase in AHI was associated with a 15% increased risk of severe PE (sPESI≥1) (odds ratio: 1.15, 95% CI 1.05-1.26, p=0.002) after adjusting for confounders. During a median follow-up of 15.2 months, 27 (18.6%) patients experienced adverse events. Increased AHI independently predicted a higher risk of adverse events (hazard ratio: 1.03, 95% CI: 1.00-1.05, p=0.026), even after adjusting for potential confounders. AHI ≥8 events/h was associated with a significantly higher adjusted hazard ratio of 2.56 (95% CI: 1.15-5.72, p=0.022) for adverse events compared to AHI <8 events. OSA is common in acute PE patients and is linked to increased disease severity and adverse outcomes. Implementing routine OSA screening and management may aid risk stratification and improve outcomes in acute PE patients.

Incremental Benefit of Lipid Lowering in a Large Chinese Population Aged 75 Years and Older With Established Atherosclerotic Cardiovascular Disease

ObjectiveTo explore the optimal low-density lipoprotein cholesterol (LDL-C) level in patients aged 75 years and older with established atherosclerotic cardiovascular disease (ASCVD). Patients and MethodsWe conducted a retrospective multicenter cohort study of veterans aged 75 years and older with ASCVD who were regularly hospitalized or medically examined in 15 medical institutions in southern China from January 1, 2006, to December 31, 2013. Follow-up continued through October 1, 2021. The time-weighted average (TWA) LDL-C level represented the average LDL-C level during follow-up. Participants were divided into TWA LDL-C groups of 55.0 mg/dL or lower, 55.1 to 70.0 mg/dL, 70.1 to 85.0 mg/dL, 85.1 to 100.0 mg/dL, and greater than 100.0 mg/dL. The subgroup with LDL-C levels lower than 55.0 mg/dL was further subdivided into groups with LDL-C levels from 40.1 to 55.0 mg/dL and 40.0 mg/dL or less. The association of TWA LDL-C levels with outcomes was evaluated with Cox proportional hazards models. ResultsOverall, 6387 patients aged 75 years or older with ASCVD were included (mean age, 79.4 years). In total, 4267 major adverse cardiovascular events, 1518 stroke events, and 515 myocardial infarction events occurred during a mean follow-up of 12.7 years. Generally, lower TWA LDL-C level was associated with a lower risk of cardiovascular events but was not associated with a higher risk of adverse events in elderly individuals with ASCVD, with the lowest cardiovascular risk observed for LDL-C levels of less than 55.0 mg/dL. After multivariable adjustment, the risk of a major adverse cardiovascular event was 1.30 (95% CI, 1.26 to 1.34; P<.001) for a per SD increment in TWA LDL-C level. Compared with TWA LDL-C levels of 40.1 to 55.0 mg/dL, TWA LDL-C levels of 40.0 mg/dL or less were associated with an increased risk of hemorrhagic stroke (hazard ratio, 3.71; 95% CI, 1.89 to 7.26). ConclusionLow-density lipoprotein cholesterol levels from 40.1 to 55.0 mg/dL exhibited the maximum cardiovascular benefit in patients aged 75 years and older who had ASCVD. Lowering LDL-C levels to 40.0 mg/dL or less might increase the risk of hemorrhagic stroke.

Association of Supine Hypertension Versus Standing Hypotension With Adverse Events Among Middle-Aged Adults.

Management of orthostatic hypotension (OH) prioritizes prevention of standing hypotension, sometimes at the expense of supine hypertension. It is unclear whether supine hypertension is associated with adverse outcomes relative to standing hypotension. To compare the long-term clinical consequences of supine hypertension and standing hypotension among middle-aged adults with and without OH. The ARIC study (Atherosclerosis Risk in Communities) measured supine and standing blood pressure (BP) in adults aged 45 to 64 years, without neurogenic OH, between 1987 and 1989. We defined OH as a positional drop in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg, supine hypertension as supine BP≥140/≥90 mm Hg, and standing hypotension as standing BP≤105/≤65 mm Hg. Participants were followed for >30 years. We used Cox regression models to examine associations with cardiovascular disease events, all-cause mortality, falls, and syncope. Of 12 489 participants (55% female, 26% Black, mean age 54 years, SD 6), 4.4% had OH. Among those without OH (N=11 943), 19% had supine hypertension and 21% had standing hypotension, while among those with OH (N=546), 58% had supine hypertension and 38% had standing hypotension. Associations with outcomes did not differ by OH status (P-interactions >0.25). Supine hypertension was associated with heart failure (hazard ratio, 1.83 [95% CI, 1.68-1.99]), falls (hazard ratio, 1.12 [95% CI, 1.02-1.22]), and all-cause mortality (hazard ratio, 1.45 [95% CI, 1.37-1.54]), while standing hypotension was only significantly associated with mortality (hazard ratio, 1.06 [95% CI, 1.00-1.14]). Supine hypertension was associated with higher risk of adverse events than standing hypotension, regardless of OH status. This challenges conventional OH management, which prioritizes standing hypotension over supine hypertension.

Clinical Outcomes in Metabolically Healthy and Unhealthy Obese and Overweight Patients With Atrial Fibrillation: Findings From the GLORIA-AF Registry

ObjectiveTo explore the association between metabolic status, body mass index (BMI), and natural history of patients with atrial fibrillation (AF). MethodsThe global, prospective GLORIA-AF Registry Phase II and III included patients with recent diagnosis of AF between November 2011 and December 2014 for Phase II and between January 2014 and December 2016 for Phase III. With this analysis, we categorized patients with AF according to BMI (normal weight [18.5 to 24.9 kg/m2], overweight [25.0 to 29.9 kg/m2], obese [30.0 to 60.0 kg/m2]) and metabolic status (presence of hypertension, diabetes, and hyperlipidemia). We analyzed risk of major outcomes using multivariable Cox regression analyses; the primary outcome was the composite of all-cause death and major adverse cardiovascular events. ResultsThere were 24,828 (mean age, 70.1±10.3 years; 44.6% female) patients with AF included. Higher BMI was associated with metabolically unhealthy status and higher odds of receiving oral anticoagulants and other treatments. Normal-weight unhealthy patients showed a higher risk of the primary composite outcome (adjusted hazard ratio [aHR], 1.20; 95% CI, 1.01 to 1.42) and thromboembolism, whereas a lower risk of cardiovascular death (aHR, 0.35; 95% CI, 0.14 to 0.88) and major adverse cardiovascular events (aHR, 0.56; 95% CI, 0.33 to 0.93) was observed in metabolically healthy obese individuals. Unhealthy metabolic groups were also associated with increased risk of major bleeding (aHR, 1.51 [95% CI, 1.04 to 2.20] and aHR, 1.96 [95% CI, 1.34 to 2.85] in overweight and obese groups, respectively). ConclusionIncreasing BMI was associated with poor metabolic status and with more intensive treatment. Prognosis was heterogeneous between BMI groups, with metabolically unhealthy patients showing higher risk of adverse events.

Effectiveness and safety of reduced-dose rivaroxaban for elderly patients with non-valvular atrial fibrillation: A subanalysis of the EXPAND study

BackgroundEstablishing the appropriate rivaroxaban dose in older patients with non-valvular atrial fibrillation (NVAF) is important because of the high risk of adverse events. In this EXPAND study subanalysis, we examined the safety and efficacy of standard-dose (15 mg/day) and non-recommended reduced-dose (10 mg/day) rivaroxaban in patients aged ≥65 years with NVAF and preserved renal function. MethodsThe entire analysis population (ALL cohort [n = 3982]; ≥65 years) was divided into early elderly (ELD) (65–74 years [n = 1444]) and late ELD (≥75 years [n = 2386]) sub-cohorts. Each sub-cohort was divided into reduced-dose and standard-dose groups. Kaplan–Meier survival curves with adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were used to assess efficacy (thromboembolic events) and safety (hemorrhagic events) outcomes. ResultsThe aHR for major bleeding did not differ between the dosages in any of the cohorts (aHRs: 0.86–0.93). There were no significant differences in the occurrence of stroke + systemic embolism (SE) or stroke + SE + myocardial infarction (MI) + cardiovascular (CV) death among the cohorts. The aHR for MI/unstable angina + interventional/CV surgery + CV death was higher with 10-mg/day rivaroxaban than 15-mg/day rivaroxaban in the ALL cohort (aHR: 1.56 [95% CI 1.02–2.37], p = 0.039) and the late ELD sub-cohort (aHR: 1.86 [95% CI 1.01–3.42], p = 0.045). ConclusionsReduced-dose rivaroxaban may increase the risk of coronary artery events. The use of rivaroxaban 15 mg/day in patients with NVAF aged ≥75 years with preserved renal function was supported.

Utilidad y seguridad de los ingresos directos a una unidad hospitalaria de agudos de un servicio de geriatría valorados por atención geriátrica en residencias

Background and objectiveMore than half of institutionalized older people need a emergency department visit annually, with high resources consumption and higher risk of adverse events, due to high complexity. Direct admission to Acute Geriatric Unit (AGU), after geriatric consultant and nursing home medical team assessment, could be a safety and effective alternative to emergency department (ED) admission. MethodsRetrospective observational study of AGU patients admitted by Nursing Home Geriatric Team between January, 1st and December, 31st, 2021. Planned admissions and SARS-CoV-2 positive patients were excluded. Medical (sociodemographic, clinical, functional and cognitive) records and outcomes data (inpatient mortality, hospital and ED lenght of stay, transfer to ED and delirium within 48h after admission, hospital discharge location) were collected. ResultsTwo hundred and six patients directly admitted, 101 through ED (N 307). 62.5% with Barthel index <40, 65% with dementia, 56.4% with Charlson index ≥3. Inpatient mortality was 14.6% in direct admission, 20.8% in ED referral group, p=0.14. Hospital lenght of stay was 9.61±6.01 days in direct admission, 11.22±5.36 days in ED group, p=0.02. 27.7% of patients with delirium in direct admission and 36.6% in ED group; only one patient was transferred to ED, within 48h after admission. ConclusionsDirect admission is a safety and effective alternative to ED referral in institutionalized older people after geriatric assessment, due to no increased mortality, shorter length of stay and hospital cost reduction.

Association of Age and Frailty With 30-Day Outcomes Among Patients Undergoing Oral Cavity Cancer Surgery.

To evaluate the impact of age and frailty on 30-day outcomes following surgery for oral squamous cavity carcinoma (OSCC). Retrospective cross-sectional analysis. American College of Surgeons' National Quality Improvement Program (NSQIP) database. Patients who underwent OSCC resection were queried via NSQIP (2015-2020). Cases were stratified by age (18-65, 65-75, and older than 75) as well as by modified frailty index scores (mFI 0, mFI 1, and mFI 2+) for comparative analyses. Univariate and multivariable analyses were conducted to examine demographics, perioperative outcomes, and 30-day postoperative adverse events. A total of 3238 patients who underwent OSCC surgery were identified and categorized as nongeriatric ("NGA," age 18-65), younger geriatric ("YGA," age 65-75), and older geriatric ("OGA," age >75) adults. Compared to NGA, geriatric patients had higher the American Society of Anesthesiologists classification, higher modified frailty index scores, and more comorbidities such as hypertension, congestive heart failure, chronic obstructive disease, and diabetes (p < .001). YGAs and OGAs were also less likely to undergo neck dissection (p < .001), composite resection (p = .006), and free flap reconstruction compared to NGAs (p < .001). When controlling for confounders, age was not independently associated with an increased risk of poor outcomes. On the other hand, frailty was found to be independently associated with a higher risk of adverse events (odds ratio: 1.40 [1.15-1.70], p < .001 for mFI 1, odds ratio: 1.45 [1.04-2.02], p = .027 for mFI 2+). A higher mFI score, not older age, is associated with an increased risk of 30-day complications following OSCC surgery.

Egg allergy and yellow fever vaccination

ObjectiveEvaluate biomarkers capable of safely guiding Yellow fever vaccine (YFV) vaccination among individuals suspicious of hen's egg allergy, and identify factors associated with a higher risk for adverse events after immunization (AEAI). MethodsPatients underwent skin prick test (SPT) for standardized allergens: whole egg, egg white, egg yolk; YFV (1:10 dilution; Biomanguinhos-Fiocruz), and intradermal test (IDT; YFV 0.02 mL, 1:100 dilution) and positive and negative controls. Serum levels of specific IgE (sIgE) for a whole egg, egg white, egg yolk, egg albumin, ovomucoid, lysozyme, and conalbumin (ImmunoCap®; ThermoFisher®) were obtained. Patients sensitized to YFV were submitted to YFV desensitization, and those negatives received YFV (0.5mL) and remained under surveillance for at least one hour. Results103 patients were enrolled, 95% under 12 years old. 71% (81/103) of patients had reactions: 80% immediate, 11% mixed, and 9% delayed. There was an association between positive skin test results with YFV and the severity of the reaction (OR:7.64; 95%CI:1.61-36.32; p = 0,011). Only the presence of sIgE to ovomucoid was associated with clinical symptoms (p = 0,025). Thirty patients underwent the YFV desensitization protocol. ConclusionThere is a relationship between the positivity of the egg's components and the severity of the clinical reaction. Furthermore, the relationship between the positivity of the tests with the YFV and egg's components may show a tendency to look at ovomucoid and conalbumin, but it is not a certainty. Therefore, further studies are needed to confirm these associations, and for now, the authors still recommend using the vaccine for testing when necessary.

The Efficacy and Safety of Teprotumumab in Thyroid Eye Disease: Evidence from Randomized Controlled Trials.

In this study, we conducted a meta-analysis to assess the efficacy and safety of teprotumumab in treating thyroid eye disease. We searched the Cochrane Library, PubMed, and Embase databases from inception to May 25, 2022, and included all randomized controlled trials. Odds ratios (ORs) were calculated using fixed- or random-effect models. A total of three studies involving 341 patients were identified. Overall, the analysis revealed that teprotumumab demonstrated superior integrated proptosis response compared to placebo in both the intention-to-treat (ITT) population (OR = 17.81, 95% CI = [10.32, 30.76], I2 = 50%) and per-protocol population (OR = 24.53, 95% CI = [12.96, 46.45], I2 = 14%). Furthermore, patients receiving teprotumumab showed significant improvement in overall response (OR = 8.35, 95% CI = [4.74, 14.71], I2 = 79%), diplopia response (OR = 5.53, 95% CI = [3.24, 9.44], I2 = 0%), and achieving a clinical activity score (CAS) of 0 or 1 (OR = 6.26, 95% CI = [3.87, 10.12], I2 = 0%). Moreover, patients treated with teprotumumab experienced greater improvements in proptosis (MD = -2.49, 95% CI = [-2.54, -2.45], I2 = 98%) and Graves' ophthalmopathy-specific quality of life (GO-QOL, MD = 11.48, 95% CI = [11.03, 11.93], I2 = 95%). However, it is important to note that patients receiving teprotumumab had a higher risk of adverse events, including serious adverse events, gastrointestinal adverse reactions, and muscle spasms. In summary, teprotumumab demonstrated greater improvement in proptosis response, proptosis, diplopia response, overall response, GO-QOL, and CAS. Nonetheless, it should be considered that its use is associated with a higher risk of adverse events.

LEFT VENTRICULAR REMODELING IN HEART FAILURE (PART ІI): PHENOTYPIC HETEROGENEITY AS A RATIONALE FOR PERSONALIZED PATIENTS` MANAGEMENT

Aim: to provide a literature review of the current conсepts on phenotypic heterogeneity of left ventricular (LV) remodeling in heart failure (HF), and highlight the significance of such a diversity for an implementation of personalized patients` management. This paper is a second part of the review, devoted to the current state of pathophysiology of LV remodeling in HF.&#x0D; Material and methods. The thematic scientific papers, published predominantly during the last decade, constituted the study material. The research methodology involved bibliosemantic method and structural and logical analysis.&#x0D; Results and discussion. HF is a heterogeneous, multifactorial and rising epidemic syndrome. To date, the LV ejection fraction (EF) is used as a substantial criterion for HF classification and management. However, the existing research data has revealed the significant overlapping between different LV EF-based HF patterns in terms of the risk factors, comorbidities and disease modifiers; bidirectional transitions of LV EF due to disease treatment and progression; myocardial fibrosis and dysfunction; effectiveness of neurohumoral inhibitors etc.&#x0D; Moreover, the «spectrum» paradigm has been recently proposed, positioning HF as a spectrum across different phenotypes. Particularly, each HF phenotype is the result of a patient-specific trajectory, being an exceptional and unique «track» for the heart transition towards different remodeling patterns.&#x0D; The HF phenotyping may be an innovative approach to the study of myocardial remodeling and HF, which is potentially an important prerequisite for the development of individualized patients` treatment. Personalized medicine can offer the particular options for managing HF patients, that, in turn, will better identify responders, non-responders, and those at high risk of adverse events, and ultimately improve of the treatment efficacy and safety.&#x0D; Conclusions. The baseline heterogeneity of the structural and functional patients` characteristics, including those describing the LV remodeling, and their dynamic change over time, creates a spectrum across overlapping HF phenotypes, challenging a categorical HF classification based solely on LV EF. Such an approach to treat the HF phenotypic heterogeneity may provide further insights into the pathomechanisms, related to LV remodeling in HF, and has the potential to improve the personalized patients` management.

Gender differences in adverse events related to Osimertinib: a real-world pharmacovigilance analysis of FDA adverse event reporting system

ABSTRACT Objective We analyze and identify the signals of gender differences in adverse events (ADEs) related to Osimertinib and provide reference for clinical implementation of individualized drug use. Methods ADE reports of Osimertinib received from FAERS database from the first quarter of 2016 to the fourth quarter of 2022 were extracted. Reporting odds ratio (ROR) data analysis strategy was used for mining of signal strength that represents gender differences in ADEs related to Osimertinib. Results The number of Osimertinib ADE reports included in the analysis was 7968 in females and 7570 in males, respectively. According to ROR, men were more likely to develop pneumonia aspiration, lung infection, interstitial lung disease, pulmonary toxicity, dyspnea, ventricular extrasystoles, and pulmonary thrombosis, while women were more likely to develop cardiac failure congestive, stomatitis, diarrhea, muscle spasms, nail disorder, onycholysis, skin disorder, dry skin, and rash. Conclusion Gender differences existed in ADE signals related to Osimertinib. The higher risk of ADEs in male patients was lung diseases that seem more serious than those nail toxicities or skin problems that occurred in female patients. In order to ensure the safety of medication, we should be alert to the differences between different genders and take corresponding preventive measures to reduce the occurrence of serious ADEs.

Iron deficiency in cardiac surgery patients and the possibility of its correction at the preoperative stage

Among cardio-surgical patients, the prevalence of iron deficiency conditions reaches 70 %, and anemia is detected in less than 50% cases. Meanwhile, both anemia and latent iron deficiency are risk factors for adverse outcomes in cardio-surgical patients. These conditions are associated with a high frequency and greater volume of blood transfusions as well as with a longer stay in the hospital. Timely diagnosis and correction of iron deficiency, regardless of the presence of anemia, are mandatory at the stage of preoperative preparation. The use of oral iron medicines is limited by their low efficacy in this category of patients and a high risk of adverse events. Intravenous iron medicines have a high potential for correcting iron deficiency, and their efficacy and safety have been previously demonstrated. Administration of ferric carboxymaltose has proved beneficial in studies on iron deficiency correction in cardiological and cardio-surgical patients. In these patients, ferric carboxymaltose improved the dynamics of ferritin and hemoglobin, reduced the risk of blood transfusion, and decreased the duration of stay in the hospital. Preoperative intravenous administration of ferric carboxymaltose to cardio-surgical patients can improve clinical outcomes and the cost effectiveness of cardiac surgery.

Anticholinergic burden risk and prevalence of medications carrying anticholinergic properties in elderly cancer patients in Jordan

BackgroundGeriatric cancer patients are susceptible to adverse drug events due to the complexity of their chemotherapy regimens and collateral treatments for their comorbid conditions. Prescribing medications with anticholinergic burden characteristics can complicate their condition, leading to negative impacts on their health outcomes and quality of life, including an increase in adverse drug event frequency, physical and cognitive impairments. ObjectiveThis study aims to examine the prevalence of anticholinergic prescribing and identify the cumulative anticholinergic load risk associated with drugs prescribed to elderly cancer patients. Also, to identify the predictors that might lead to raised anticholinergic burden in these patients. MethodologyThis retrospective cross-sectional study included elderly patients (age ≥ 65) diagnosed with cancer and admitted to the adult oncology unit at King Abdullah University Hospital (KAUH) in Jordan during the period between (January 1st, 2019, and January 1st, 2022). The medication charts of 420 patients were evaluated for study outcomes. ResultsOf the total subjects, females represented 49.3%, and the average age was 72.95 (SD = 7.33). A total of 354 (84.3%) patients were prescribed at least one drug carrying anticholinergic burden properties. Median for anticholinergic medications was 3 (IQR = 4). Our study found that 194 (46.2%) patients were at a high risk of adverse events associated with anticholinergic load (cumulative score ≥ 3). Metoclopramide, furosemide, and tramadol were the most frequently prescribed drugs with anticholinergic properties. Alimentary tract drugs with anticholinergic action were the most commonly encountered items in our study population. ConclusionOur study revealed a significantly high prevalence of anticholinergic prescribing among elderly cancer patients. Nearly half of the patients were at high risk of developing serious effects related to anticholinergic activity from the drugs administered. Polypharmacy was strongly associated with increased anticholinergic burden score. Evidence-based recommendations utilizing prescribing strategies for safer alternatives and deprescribing of inappropriate medications could reduce such inappropriate prescribing.

Daptomycin Exposure as a Risk Factor for Daptomycin-Induced Eosinophilic Pneumonia and Muscular Toxicity.

High-dose daptomycin is increasingly used in patients with bone and joint infection (BJI). This raises concerns about a higher risk of adverse events (AEs), including daptomycin-induced eosinophilic pneumonia (DIEP) and myotoxicity. We aimed to examine pharmacokinetic and other potential determinants of DIEP and myotoxicity in patients with BJI receiving daptomycin. All patients receiving daptomycin for BJI were identified in a prospective cohort study. Cases were matched at a 1:3 ratio, with controls randomly selected from the same cohort. Bayesian estimation of the daptomycin daily area under the concentration-time curve over 24 hours (AUC24h) was performed with the Monolix software based on therapeutic drug monitoring (TDM) data. Demographic and biological data were also collected. Risk factors of AEs were analyzed using Cox proportional hazards model. From 1130 patients followed over 7 years, 9 with DIEP, 26 with myotoxicity, and 106 controls were included in the final analysis. Daptomycin AUC24h, C-reactive protein, and serum protein levels were associated with the risk of AEs. The adjusted hazard ratio of DIEP or myotoxicity was 3.1 (95% confidence interval [CI], 1.48-6.5; P < .001) for daptomycin AUC24h > 939 mg/h/L, 9.8 (95% CI, 3.94-24.5; P < .001) for C-reactive protein > 21.6 mg/L, and 2.4 (95% CI, 1.02-5.65; P = .04) for serum protein <72 g/L. We identified common determinants of DIEP and myotoxicity in patients with BJI. Because the risk of AEs was associated with daptomycin exposure, daptomycin TDM and model-informed precision dosing may help optimize the efficacy and safety of daptomycin treatment in this setting. A target AUC24h range of 666 to 939 mg/h/L is suggested.

Cardiovascular Risk Management for All Older Patients?

Current guidelines on cardiovascular risk management are extrapolated to all older adults. It is, however, highly debatable whether recommendations also apply for patients with dementia since previous studies have not included this specific population. Time to benefit as well as higher risk of adverse events play a crucial role in the decision process of prescribing or deprescribing. Regular monitoring is needed in older patients with dementia, in order to make individual-based treatment strategies. Cardiovascular risk management in older patients with dementia should focus on quality of life, preventing cognitive and functional deterioration, and maintaining independence.

Coronary slow flow is not an adverse prognostic factor in MINOCA patients in the 5-year follow-up

Introduction: The research aimed to compare the characteristics and outcomes of myocardial infarction with non-obstructive coronary arteries (MINOCA) patients with coronary slow flow (CSF) vs. normal coronary flow (no CSF) in a 5-year follow-up. Material and methods: Between 2010–2015 were identified 111 patients as having final MINOCA diagnosis and available calculated corrected TIMI frame count (cTFC). CSF was defined as cTFC greater than 27 frames per second in any of the three coronary arteries. The primary endpoint was the 5-year major adverse cardiovascular events rate, defined as cardiac death, myocardial infarction, or hospitalization due to angina. Results: The mean cTFC was 28.9 ± 6.1 frames per second (median: 28, IQR 24–33; min-max: 19–58). 62 (55.9%) patients had normal coronary flow, and 49 (44.1%) had CSF. Patients did not differ in sex (females no CSF vs. CSF: 58% vs. 61%, p = 0.7) or age (63 ± 15 years vs. 63 ± 13 years, p = 0.8). Patients with CSF characterized higher rates of chronic kidney disease (0 vs. 8.2%, p = 0.035). No statistically significant difference was observed for any of the analysed points. MACE rates for no CSF vs. CSF were 9.6% vs. 14.3% (HR 0.80, 95% CI 0.28–2.96, p = 0.7), respectively. Conclusions: CSF was not associated with a higher risk of adverse events among MINOCA patients at five years.

#2996 EARLY DECLINES IN KIDNEY FUNCTION AND ADVERSE OUTCOMES IN YOUNG ADULTS

Abstract Background and Aims Whether early eGFR declines (eGFR below age-expected values) in younger adults are associated with adverse outcomes is unknown. We aim to estimate the association of an early eGFR decline with adverse outcomes by age group (18-39, 40-49, 50-65 years). Methods We included 8.9 million adults (aged 18-65) with ≥1 eGFR value using linked healthcare datasets in Ontario from January 2008-March 2020. The association of eGFR categories from &amp;lt;60 to &amp;gt;120 mL/min/1.73 m2 and adverse outcomes (death, cardiovascular outcomes, end-stage kidney disease) was examined using adjusted Cox models. Comparisons were relative to age normalized measured GFR categories (100-110 mL/min for 18-39, 90-100 mL/min for 40-49, 80-90 mL/min for 50-65). Results The mean age, eGFR and median follow up were 41 years, 104 mL/min and 9.2 years, respectively. 17.3%, 18.9%, and 17.7% had an eGFR below normal for ages 18-39, 40-49, and 50-65, respectively. The risk of an adverse event increased in a stepwise manner with eGFR values below the referent and occurred at higher eGFR values in those 18 to 39 [eGFR 70-80, age 18-39: incidence 4.37 events per 1000 person-years[p-y], HR 1.54(1.46-1.61); age 40-49: incidence 9.78 per 1000 p-y, HR 1.18(1.15-1.21); age 50-65: incidence 24.0 per 1000 p-y, HR 1.11(1.10-1.12)] (see Figure 1). Results persisted for each outcome individually, and after using repeated eGFR, using a common referent, and adjusting for multiple covariates. Conclusion Young adults (18-39) with an early eGFR decline were at a higher risk of adverse events and this occurred at higher eGFR levels relative to middle-aged and older adults.

Sex Differences in Clinical Outcomes Following First-Time Acute Coronary Syndrome in New Zealand

Clinical outcomes following acute coronary syndrome (ACS) are documented to vary by sex in several studies. This study reports short- and long-term outcomes by sex in a large cohort of New Zealanders admitted to hospital for a first-time ACS. Patient profiles were linked to national hospitalisation and mortality datasets; those admitted with a first-ACS between 1 January 2010 and 31 December 2016 were included. Clinical characteristics and adverse clinical outcomes (30-day and 2-year events) were compared between men and women. The primary outcome was time from admission to first cardiovascular readmission or all-cause death. A total of 63,245 people were admitted with first-ACS (40% women). Compared with men, women were older (mean 73 vs 66 years; p<0.001) and more likely to have a history of atherosclerotic cardiovascular disease (CVD) (27% vs 24%; p<0.001) and heart failure (11% vs 7%; p<0.001). At 30 days after admission, women had higher rates of unadjusted death/cardiovascular readmission than men (women 16%, men 12%; p<0.001) and at 2 years (women 44%, men 34%; p<0.001). In an unadjusted Cox proportional hazards model, women were at higher risk of adverse events after discharge than men at 2 years (HR 1.37, 95% CI 1.34–1.41; p<0.001, Figure 1a). After multivariable adjustment (age, ethnicity, NZ deprivation index, history of atherosclerotic CVD, history of heart failure), women were at marginally lower risk of death/readmission than men (adjusted HR 0.97; 95% CI 0.94–0.99; p=0.014, Figure 1b). Women have higher short- and long-term crude rates of death/cardiovascular readmission after first-ACS. These differences appear to be explained by age, social determinants, and prior disease burden.

Evaluation of the efficacy and safety of pegloticase for the treatment of chronic refractory gout through meta-analysis.

Gout is the most common arthritis that affects more than 2% of adults in developed countries. 3% to 4% of gout is chronic refractory gout. Conventional treatments are considered invalid. A new drug, pegloticase is used to treat chronic refractory gout, and there are still many questions about efficacy and safety. We searched PubMed, web of science, and the Cochrane Library. Preprints and references of related literature were also considered. Related efficacy and safety indicators were statistically analyzed by Review Manager 5.4 to conduct meta-analysis. A total of one article and one clinical trial were included. Pegloticase is able to reduce serum uric acid and reduce tender joints, thereby improving joint function. But pegloticase has more adverse events. Pegloticase can be used to treat chronic refractory gout. However, Pegloticase has a higher risk of adverse events. Considering the efficacy and safety, the scope of clinical applications of pegloticase can be further widened in patients in good medical condition.