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BACKGROUND: We examined the real-world comparative safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs. other newer anti-glycemic medications (dipeptidyl peptidase-4 inhibitors [DPP4i], glucagon-like peptide-1 receptor agonists [GLP1a]) in patients with and without chronic kidney disease (CKD). METHODS: Among US Veterans with diabetes receiving care from the Veterans Affairs (VA) healthcare system over 2004-19, we identified incident users of SGLT2i vs. DPP4i vs. GLP1a monotherapy. In analyses stratified by CKD status, defined by estimated glomerular filtration rate and albuminuria, we examined associations of SGLT2i vs. DPP4i vs. GLP1a use with risk of infection-related (primary outcome) and genitourinary infection hospitalizations (secondary outcome) using multivariable Cox models. FINDINGS: Among 92,269 patients who met eligibility criteria, 52% did not have CKD, whereas 48% had CKD. In the overall and non-CKD cohorts, compared to DPP4i use, SGLT2i use was associated with lower infection-related hospitalization risk (HRs [95% CIs] 0.74 [0.67-0.81] and 0.77 [0.67, 0.88], respectively), whereas GLP1a use demonstrated comparable risk. However, in the CKD cohort SGLT2i and GLP1a use were each associated with lower risk (HRs [95% CIs] 0.70 [0.61, 0.81] and 0.91 [0.84, 0.99], respectively). Propensity score-matched analyses showed similar findings in the non-CKD and CKD cohorts. In the overall, non-CKD, and CKD cohorts, SGLT2i use was associated with lower genitourinary infection hospitalization risk whereas GLP1a use showed comparable risk vs. DPP4i use. INTERPRETATION: In a national cohort of Veterans with diabetes, compared with DPP4i use, SGLT2i use was associated with lower infection-related and genitourinary infection hospitalization risk. FUNDING: VA Health Services Research and Development, USA.

BackgroundE-cigarettes have emerged as popular products, especially for younger populations. However, concerns regarding health effects exist and there is a notable gap in understanding the prevalence and nature of adverse events. This study aims to examine the rate of adverse events in individuals who use e-cigarettes in a large sample.MethodsA cross-sectional survey was conducted with a sample of 4695 current and former e-cigarette users with a median age of 34 years. The survey collected data on e-cigarette use, adverse events experienced, product characteristics, related behaviors, sociodemographic factors and presence of medical comorbidities. Statistical analyses were conducted using Pearson's chi-squared tests and logistic regression.ResultsA total of 78.9% of respondents reported experiencing an adverse event within 6 h of using a vaping device, with the most common events being headache, anxiety and coughing. Product characteristics and related behaviors significantly influenced the risk of adverse events. There were also sociodemographic disparities, with Hispanic respondents and those with at least college-level education reporting higher rates of adverse events.ConclusionsOur study found a high rate of adverse events among e-cigarette users. We identified that certain e-cigarette product characteristics, behaviors and medical comorbidities significantly increased the risk of these events.

INTRODUCTION: Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Although the US prescribing information for brodalumab includes a boxed warning regarding suicidal ideation and behavior, no causal association has been demonstrated. Here, we summarize 5 years of pharmacovigilance data, from August 15, 2017, through August 14, 2022, reported to Ortho Dermatologics by US patients and healthcare providers. METHODS: Prevalence of the most common adverse events (AEs) listed in the brodalumab package insert (incidence ≥ 1%) and AEs of special interest are described. Brodalumab exposure was estimated as the time from the first to last prescription-dispensing authorization dates. Data were collected from 4744 patients in the USA, with an estimated exposure of 5815 patient-years. RESULTS: Over 5 years, 11 cases of adjudicated major adverse cardiovascular events were reported (0.23 events/100 patients), a rate lower than that experienced by patients in the international Psoriasis Longitudinal Assessment and Registry. There were 106 serious infections. No serious fungal infections were reported. There were 40 confirmed and 2 suspected COVID-19 cases, with no new COVID-19-related deaths. Of 49 reported malignancies among 42 patients, 3 were deemed possibly related to brodalumab. No completed suicides and no new suicidal attempts were reported. CONCLUSION: Five-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and previous pharmacovigilance reports, with no new safety signals.

Drug development is complex and costly. Clinical trial participants take on risks, making it essential to maximize trial efficiency and maintain participant safety. Identifying periods of excessive burden during drug development can inform trial design, ensure patient benefit and prevent harm. This study aims to examine all published clinical trials for cabozantinib to assess patient benefit and burden over time. We conducted a retrospective cross-sectional review of interventional clinical trials of cabozantinib for solid cancer treatment. We searched PubMed/MEDLINE, Embase, Cochrane (CENTRAL) and ClinicalTrials.gov. We extracted adverse event rates, median progression-free survival (PFS), median overall survival and objective response rate (ORR) for each included trial. We calculated frequencies of trial characteristics, cumulative grade 3-5 adverse event rates and cumulative ORRs. Out of 1735 studies, 54 publications were included that involved 6372 participants and 21 cancers. Of the 54 studies in our sample, 31 (57.41%) were single-arm trials and 23 (42.60%) had negative results. Trials among and within various indications had conflicting results over time. Cumulative risk to participants increased over time, and clinical benefit decreased. The findings suggest that the risk profile of cabozantinib increased from 2011 to 2016 and has remained elevated but stable while benefit has decreased over time. The use of non-randomized and single-arm trials is concerning, and more methodologically rigorous trials are needed. The results of trials for different indications are inconsistent, and empirical administration may reduce the drug's efficacy.

OBJECTIVES: To estimate the indirect economic impact of tibial fractures and their associated adverse events (AEs) in Tanzania. DESIGN: A secondary analysis of the pilot Gentamicin Open (pGO)-Tibia randomized control trial estimating the indirect economic impact of suffering an AE, defined as a fracture-related infection (FRI) and/or nonunion, after an open tibial fracture in Tanzania. SETTING: The pGO-Tibia trial was conducted from November 2019 to August 2021 at the Muhimbili Orthopaedic Institute in Dar es Salaam, Tanzania. PATIENTS/PARTICIPANTS: One hundred adults with open tibial shaft fractures participated in this study. INTERVENTION: Work hours were compared between AE groups. Cost data were analyzed using a weighted-average hourly wage and converted into purchasing power parity-adjusted USD. MAIN OUTCOME MEASUREMENTS: Indirect economic impact was analyzed from the perspective of return to work (RTW), lost productivity, and other indirect economic and household costs. RTW was analyzed using a survival analysis. RESULTS: Half of patients returned to work at 1-year follow-up, with those experiencing an AE having a significantly lower rate of RTW. Lost productivity was nearly double for those experiencing an AE. There was a significant difference in the mean outside health care costs between groups. The total mean indirect cost was $2385 with an AE, representing 92% of mean annual income and an increase of $1195 compared with no AE. There were significantly more patients with an AE who endorsed difficulty affording household expenses postinjury and who borrowed money to pay for their medical expenses. CONCLUSIONS: This study identified serious economic burden after tibial fractures, with significant differences in total indirect cost between those with and without an AE. LEVEL OF EVIDENCE: II.

3,4-Methylenedioxymethamphetamine (MDMA) is being investigated in controlled clinical trials for use as an adjunct medication treatment for post-traumatic stress disorder. MDMA is metabolized by N-demethylation, primarily by CYP2D6, to its main inactive metabolite, 4-hydroxy-3-methoxymethamphetamine. It is also metabolized to a lesser extent by CYP1A2, CYP2B6, and CYP3A4 to its active metabolite, 3,4-methylenedioxyamphetamine. Considering the extensive hepatic metabolism and excretion, MDMA use in psychiatry raises concerns over drug-induced liver injury (DILI), a rare but dangerous event. Majority of the drugs withdrawn from the market for liver injury caused death or transplantation at frequencies under 0.01%. Unfortunately, markers for liver injury were not measured in most published clinical trials. At the same time, no visible DILI-related symptoms and adverse events were observed. Idiosyncratic DILI cases are rarely registered during clinical trials due to their rare nature. In this study, we surveyed a larger, over 1,500, and a more diverse set of reports from the FDA Adverse Event Reporting System and found 23 cases of hepatic injury and hepatic failure, in which MDMA was reported to be taken in addition to one or more substances. Interestingly, 22 out of 23 cases had one or more listed drugs with a known DILI concern based on the FDA's DILIrank dataset. Furthermore, only one report had MDMA listed as the primary suspect. Considering the nearly 20 million doses of MDMA used annually, this single report is insufficient for establishing a significant association with DILI.

PURPOSE: To report our experience of performing immediate sequential bilateral cataract surgery (ISBCS) in patients with visually significant cataracts and reduced preoperative corrected distance visual acuity (CDVA). METHODS: Data of patients who underwent ISBCS for visually significant cataracts and had preoperative CDVA ≤20/32 (≤0.2 logMAR) in each eye were retrospectively reviewed. Refractive and visual outcomes were evaluated for the last available postoperative visit. Intraoperative and serious postoperative adverse events occurring within the first three months of surgery were reviewed. RESULTS: A total of 1335 patients (2670 eyes) were included in the analysis, with a mean age of 71.9 ± 9.5 years. On the last visit, 50.2% and 89.1% of eyes achieved uncorrected distance visual acuity (UDVA) ≥20/20 (0.0 logMAR) and ≥20/32 (0.2 logMAR), respectively. Of all eyes, 83.8% were within ±0.50D, and 96.4% were within ±1.00 D of emmetropia. Ten patients had postoperative bilateral ametropia of more than 1.00D in each eye, but eight of them still achieved binocular UDVA ≥20/40. Intraoperative events occurred in 14 eyes of 13 patients (per-eye incidence: 0.524% or 1 in 191 eyes). A total of 86 postoperative adverse events occurred in 80 eyes of 53 patients (per-eye incidence 2.996% or 1 in 33 eyes), of which cystoid macular edema was the most common. Only three eyes had CDVA reduced by more than two Snellen lines compared to preoperative CDVA, two of which were not related to cataract surgery. There was no patient with bilateral CDVA loss. CONCLUSION: In our cohort of patients with visually significant cataracts, ISBCS resulted in good refractive predictability and a low incidence of serious adverse events.

Study Design. Retrospective. Objective. Evaluate whether the use of vancomycin powder (VP) placed in the surgical site before wound closure prevents delayed deep surgical site infections (DDI). Summary of Background Data. DDI after posterior spinal fusion (PSF) in adolescent idiopathic scoliosis (AIS) patients remains a significant and major complication. The use of VP to prevent acute surgical site infection has been reported, but the impact on DDI is unknown. Materials and Methods. AIS patients treated over the past 20 years with PSF or instrumentation from a large multicenter registry were reviewed. Patients were divided into two groups: intraoperative vancomycin powder placed in the wound (VP) or no antibiotics placed in the wound (NVP). DDI was defined as an infection that occurred >90 days after surgery and required surgical intervention in the operating room. Patients who developed a DDI had secondary verification of VP use or not. χ² and Kaplan-Meier (KM) survivorship analyses were used to compare demographics and the incident rate of DDI between groups. Results. Totally, 4145 cases met the inclusion criteria for this study. A total of 43 DDI cases were identified (1.0%). The incidence of DDI for the VP group was 0.2% (4/2111), and 1.9% (39/2034) in the NVP group (P < 0.001). Given the difference in follow-up for the two groups, a cumulative survival and Kaplan- Meier analysis revealed the VP group had significantly better "survival" (no DDI) than the NVP group (P < 0.001). Conclusion. DDIs are significant adverse events that can greatly complicate patient recovery after PSF for AIS, including re-hospitalization. This study found that patients who received VP intraoperatively were 10 times less likely to develop a DDI than those who did not receive VP. Although other advances and changes in surgical techniques may contribute to the significant decrease in infections found in the more recent VP cohort, VP should be considered as a prophylactic measure. Level of Evidence. 4 [ABSTRACT FROM AUTHOR]

Introduction: L-Asparaginase (L-Asp) is a key drug in the treatment of acute lymphoblastic leukemia (ALL); however, it is commonly associated with the occurrence of adverse events (AE). Risk factors such as age, sex, nutritional status, and some single nucleotide variants (SNVs) in specific genes could be related to hypersensitivity reactions to L-Asp. The objective of this study was to identify the influence of individual characteristics and three SNVs in the GRIA1 and NFATC2 genes on the occurrence of the most significant adverse events caused by the use of L-Asp in Mexican children with ALL. Methods: Eighty-five children from ages 0–17 years old diagnosed with ALL were included. The patients were treated at two hospital centers in Mexico. The SNV genotypes of the GRI1A and NFATC2 genes studied were examined using real-time qPCR. The evaluation of AE was carried out according to the Common Terminology Criteria for adverse events, and the determination of anti-L-Asp antibodies was conducted using Western blot immunoassay. Results: Homozygosity (AA) of the GRIA1 rs4958351 SNV was significantly associated with the occurrence of AE with the use of L-Asp (OR = 4.05; 95% CI = 1.06 to 15.40, p = 0.04) and was strongly associated with the development of anti-L-Asp antibodies (OR = 3.4375, 95% CI = 1.04 to 11.25, p = 0.04). With this, we found a significant risk association for the SNV rs4958351 of the GRIA1 gene. On the other hand, we did not find significant risk associations for the GRIA1 rs6889909 and NFATC2 rs6021191 SNVs, although other populations have shown a significant risk. Discussion: Our study has some limitations, such as the small sample size, the heterogeneity in adverse events due to the patients' different regions of origin, and the limited ability to conduct a more detailed follow-up on pancreatitis. Additionally, since no significant associations were found between the NFATC2 rs6021191 and GRIA1 rs6889909 SNVs and the development of adverse events or the presence of antibodies due to the use of L-Asp, it is necessary to investigate new specific SNVs that may improve the efficacy and safety of treatment in Mexican children with ALL. [ABSTRACT FROM AUTHOR]

Objective: To conduct a comprehensive data analysis based on the FDA's Adverse Event Reporting System (FAERS) to mine possible adverse event (AE) signals of Capmatinib, providing valuable references for its clinical application. Methods: Capmatinib was the primary suspected drug in the search of FAERS database from the second quarter of 2020 to the fourth quarter of 2023. Data processing, screening, and classification were performed using methods such as the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Results: A total of 1,991 AE reports directly related to Capmatinib were screened, identifying 269 Preferred Terms (PTs) involving 26 System Organ Classes (SOCs). Besides the AEs recorded in the drug label (such as edema, nausea, fatigue, and dyspnea), the study unearthed other high-risk AEs not listed in the label, including Renal and urinary disorders, Vocal cord paralysis, and Ear and labyrinth disorders. Among these, renal and urinary disorders, and ear and labyrinth disorders had a higher frequency and intensity of signals, suggesting that their mechanisms of occurrence could be a future research direction. Conclusion: This study uncovered new potential AEs of Capmatinib based on the FAERS database, providing reference for its safe clinical use. Special attention should be given to the occurrence of ear and labyrinth disorders and renal and urinary disorders, primarily presenting as pseudo-acute kidney injury, during treatment. [ABSTRACT FROM AUTHOR]

Background: Inhibitors of the anaplastic lymphoma kinase (ALK) gene mutation are first-line treatments in patients with ALK-positive lung cancer. The FDA label warns of the risk of interstitial lung disease (ILD) in patients receiving ALK TKIs. However, ILD associated with ALK TKIs is not fully understood. The aim of this study was to characterize the features of ALK TKI-related ILD and to explore risk factors for ALK TKI-related ILD. Methods: FDA's Adverse Event Reporting System (FAERS) reports from 2011 Q1 to 2023 Q2 were extracted and combined. Standardized MedDRA queries (SMQs) were used to search for AEs at the preferred term (PT) level. Four algorithms were employed to quantify the signals of ILD associated with ALK TKIs. The risk of ILD was further analyzed using logistic regression. Results: A total of 20,064 reports of ALK TKIs and 640 (3.2%) reports of ILD AEs were extracted. Significant disproportionality was detected in all five ALK TKIs. Interstitial lung disease and pneumonitis were the most common lung toxicities induced by ALK TKIs. Results of further analyses revealed a different spectrum of lung toxicity among the various TKIs. The median time to onset of ILD related to ALK TKIs was 53 days (Q1:12, Q3:209), and more than 70% of AEs occurred within the first 2 months. Logistic regression analysis and risk prediction model both showed that different ALK TKIs and their combination with PPIs, amlodipine, and magnesium oxide were independent risk factors for ILD (p <0.05). Conclusion: ALK TKIs have different safety profiles regarding lung toxicity, which normally occurs within the first 2 months. Administration in combination with PPIs, amlodipine, and magnesium oxide significantly increases the risk of ILD. These results provide risk prediction for ILD related to ALK TKIs and support pharmacovigilance to promote safe prescribing in oncology. [ABSTRACT FROM AUTHOR]

Background: Lumateperone has been approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia in adults since 2019, however, there is still a lack of data report on adverse reactions in real-world settings. Conducting data mining on adverse events (AEs) associated with Lumateperone and investigating the risk factors for serious AEs can provide valuable insights for its clinical practice. Methods: AE reports in the FDA Adverse Event Reporting System (FAERS) from 2019 Q4 (FDA approval of Lumateperone) to 2024 Q1 were collected and analyzed. Disproportionality in Lumateperone-associated AEs was evaluated using the following parameters: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Univariate and multivariate logistic regression analyses were conducted to identify the risk factors for Lumateperone-induced severe AEs. Results: A total of 2,644 reports defined Lumateperone as the primary suspected drug was collected, including 739 reports classified as severe AEs and 1905 reports as non-severe AEs. The analysis revealed that 130 preferred terms (PTs) with significant disproportionality were based on the four algorithms, 67 (51.53%) of which were not included in the product labeling, affecting 6 systems and organs. In addition, dizziness (81 cases) was the most reported Lumateperone-associated severe AEs, and tardive dyskinesia showed the strongest signal (ROR = 186.24). Logistic regression analysis indicated that gender, bipolar II disorder, and concomitant drug use are independent risk factors for Lumateperone-associated severe AEs. Specifically, female patients had a 1.811-fold increased risk compared with male patients (OR = 1.811 [1.302, 2.519], p = 0.000), while patients with bipolar II disorder had a 1.695-fold increased risk compared with patients diagnosed with bipolar disorder (OR = 1.695 [1.320, 2.178], p = 0.000). Conversely, concomitant use of CYP3A4 inhibitors or drugs metabolized by CYP3A4 was associated with a decreased risk of severe AEs (OR = 0.524 [0.434, 0.633], P = 0.000). Conclusion: Collectively, this study provides critical insights into the safety profile of Lumateperone. It highlights the need for cautious use in high-risk populations, such as females and individuals with bipolar II disorder, and emphasizes the importance of monitoring for AEs, including dizziness and tardive dyskinesia. Healthcare also should remain alert to potential AEs not listed in the prescribing information to ensure medical safety. [ABSTRACT FROM AUTHOR]

Bruton tyrosine kinase (BTK) inhibitors play an important role in targeted treatment of B-cell lymphoproliferative disorders. However, adverse events may limit the proper course of treatment in many patients. The purpose of this study is to compare the risk of cardiovascular and non-cardiovascular adverse events in patients with chronic lymphocytic leukemia (CLL) or small cell lymphocytic lymphoma (SLL) treated with the first-generation BTK inhibitor ibrutinib versus second-generation acalabrutinib, using real-world data from a collaborative multinational network. We used data from the network (TriNetX), which encompasses more than 100 healthcare organizations worldwide. We queried the database for patients aged ≥ 18 years with chronic lymphocytic leukemia or small-cell lymphomas treated with ibrutinib or acalabrutinib in the past ten years before the analysis. We used propensity score matching to balance the cohorts. The 3-year cumulative incidences and hazard ratios for the following outcomes were calculated: atrial flutter or fibrillation, other arrhythmias, heart failure, ischemic stroke or peripheral embolism, acute coronary syndrome, bleeding, and sepsis. We compared 2,107 patients in each group. Atrial fibrillation or flutter occurred in 150 (7.1%) patients with acalabrutinib and 310 (14.7%) patients with ibrutinib during the 3-year follow-up (hazard ratio, 0.68, 95% CI 0.55–0.84). New-onset hypertension occurred in 342 (16.3%) patients in the acalabrutinib group and 584 (27.7%) patients in the ibrutinib group (hazard ratio 0.81, 95% CI 0.66–0.98). Sepsis was diagnosed in 136 (6.5%) patients in the acalabrutinib group versus 239 (11.3%) patients in the ibrutinib group (hazard ratio 0.77, 95 CI 0.60–0.98). The two groups had no significant differences concerning the other adverse events. In a large retrospective cohort using real-world data from electronic medical registers, patients with CLL or SLL treated with acalabrutinib had a better cardiovascular and non-cardiovascular safety profile than those treated with ibrutinib, with lower risks of atrial flutter or fibrillation, new-onset arterial hypertension, and sepsis. [ABSTRACT FROM AUTHOR]

Background: The popularity of noninvasive botulinum toxin type A (BTX‐A) injections for masseter muscle hypertrophy is increasing among Asian individuals with a square‐shaped lower face. Aims: This study aimed to analyze the adverse events (AEs) caused by BTX‐A injections into the masseter muscle. Patients/Methods: This observational study retrospectively evaluated 46 250 patients who underwent BTX‐A injections into the masseter muscle in 2022. The inclusion criteria were the diagnosis of an AE by the physician at the return visit and subsequent follow‐up of progress (n = 223). The patients who were lost to follow‐up (n = 40) were excluded from the study. Results: Among the 223 patients with AEs, the most common AE was paradoxical bulging (88.3%, n = 197/223). The average period from treatment until confirmation of improvement was 159.6 ± 113.6 days (range 13–667 days) for all AEs, all of which were temporary. The period until improvement was 166.1 days in the intervention group (n = 122) and 151.9 days in the observation group (n = 101) (p = 0.24). As the period until improvement of AEs included the period until the patients visited the clinics and the improvements were confirmed by physicians, the actual period was likely to have been shorter. Conclusions: (1) All AEs were temporary. (2) All AEs improved within 22.2 months (within 5.3 ± 3.8 months on average). (3) There was no significant difference between the intervention and observation groups in the period until the improvement of AEs. [ABSTRACT FROM AUTHOR]

Background: Postoperative mortality might be influenced by postoperative care, vigilance, and competence to rescue. This study aims to describe the course of events preceding death in a high‐risk surgical cohort. Methods: We analyzed hospital records of patients who died within 30 days after surgery in 4 high volume hospitals using (1) reflective narrative thematic approach to identify recurring themes reflecting issues with conduct of care and (2) Global Trigger Tool to describe incidence, timing, and types of adverse events (AEs) leading to harm. Results: Preoperative predicted median risk of death in the studied group was 9%/13% according to SORT/P‐POSSUM, respectively. Nine recurring themes were identified. Prominent themes were "consensus concerning aim and/or risk with planned surgery," "level of (intraoperative) competence and monitoring," and in the postoperative period "level of care and vigilance" on signs of deterioration. We found a total of 303 AEs, with only three patients (5%) having no adverse events. Most common severity category was "I," that is "contributed to patient's death" (n = 110, 36% of all AEs). Of these, 60% were classified as preventable or probably preventable. The peak incidence of AEs was seen on the day of index surgery. Most common types of AEs were "failure of vital functions" (n = 79, 26%), followed by infections (n = 45, 15%). Conclusions: A high predicted risk of death and a peak of adverse events on the day of index surgery were detected. Identified themes reflect lack of documented multi‐professional consensus on how to handle prevalent perioperative risk, vigilance, and postoperative level of care. [ABSTRACT FROM AUTHOR]

Introduction: Prone position ventilation (PPV) of patients with adult respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (V-V ECMO) may improve oxygenation and alveolar recruitment and is recommended when extensive dorsal consolidations are present, but only few data regarding adverse events (AE) related to PPV in this group of patients have been published. Methods: Nationwide retrospective analysis of 68 COVID-19 patients admitted from March 2020 – December 2021 with severe ARDS and need of V-V ECMO support. The number of patients treated with PPV, number of PPV-events, timing, the time spent in prone position, number and causes of AE are reported. Causes to stop the PPV regimen and risk factors for AE were explored. Results: 44 out of 68 patients were treated with PPV, and 220 PPV events are evaluated. AE were identified in 99 out of 220 (45%) PPV events and occurred among 31 patients (71%). 1 fatal PPV related AE was registered. Acute supination occurred in 19 events (9%). Causes to stop the PPV regimen were almost equally distributed between effect (weaned from ECMO), no effect, death (of other reasons) and AE. Frequent causes of AE were pressures sores and ulcers, hypoxia, airway related and ECMO circuit related. Most AE occurred during patients first or second PPV event. Conclusions: PPV treatment was found to carry a high incidence of PPV related AE in these patients. Causes and preventive measures to reduce occurrence of PPV related AE during V-V ECMO support need further exploration. [ABSTRACT FROM AUTHOR]

This study aimed to identify the specific vaccine strain associated with herpes zoster (HZ) in children following a series of diagnosed cases and to explore whether differences in single nucleotide polymorphisms (SNPs) among various vaccine strains are linked to an increased incidence of herpes zoster after vaccination. From February 2021 to March 2024, children <12 years old suspected of vaccine-related varicella-like rash or HZ were included. Varicella zoster virus DNA isolated from the patients were sequenced to differentiate vaccine type versus wild-type. 3D protein structures of pORF62 were simulated using open reading frame 62 sequences extracted from whole genome sequencing of vOka, MAV/06, Oka/SK vaccines, and pOka reference. A total of 27 children with a median age of 2.1 (interquartile range, 1.5–3.4) years old presented with vaccine-related varicella-like rash (n = 4/27, 14.8%) or HZ (n = 23/27, 85.2%). One patient with varicella-like rash and 34.8% (n = 8/23) with HZ had disseminated skin involvement. All were immunized with the Oka/SK strain varicella vaccine. Genotyping showed 88.2% (n = 15/17) had SNPs specific to the Oka/SK strain, and two had SNPs considered pOka type contained within the Oka/SK vaccine. Despite accumulations of SNPs in ORF 62 of Oka/SK, the translated amino acid sequence and 3D protein structure were identical to wild-type pOka's pORF62. In vOKA and MAV/06, changes in amino acids occurred at two positions, S628G and R958G, within pORF62. The predicted 3D protein structure of vOka and MAV/06's pORF62 showed that the α helical structure within region I undergoes conformational change, potentially increasing difficulties in interactions with infection-related proteins and thereby decreasing virulence. pORF62 in pOka and Oka/SK exhibited more stable structure complex of the α helical structure. Lack of structural alternations in region I of pORF62 due to the absence of critical genetic polymorphisms in open reading frame 62 could be associated with the heightened incidence of adverse events. [ABSTRACT FROM AUTHOR]

Aim: To explore how patients with hospital experience construct patient safety, from the identification of a patient safety risk to the decision to file a complaint. Background: Patients play an important role in the prevention of adverse events in hospitals, but the ability of patients to act and influence their own safety is still challenged by multiple factors. Understanding how patients perceive risk and act to prevent harm may shed light on how to enhance patients' opportunities to participate in patient safety. Design: The research design of this study is qualitative and exploratory. Methods: Twelve participants who had experienced Swedish hospital care were interviewed between June 2022 and July 2023. The method of analysis was constructivist grounded theory, focusing on social processes. The COREQ checklist for qualitative research was followed. Results: Four categories were constructed: (1) defining the boundary between one's own capacity and that of the hospital, (2) acting to minimize the impact on one's safety, (3) finding oneself in the hands of healthcare professionals and (4) exploring the boundaries between normality and abnormality of the situation. This process was captured in the core category of navigating the path of least suffering. This illustrated how the participants constructed meaning about patient safety risks and showed that they prevented multiple adverse events. Conclusions: Provided that participants were able to act independently, they avoided a multitude of adverse events. When they were dependent on healthcare professionals, their safety became more vulnerable. Failure to respond to the participants' concerns could lead to long‐term suffering. Relevance to Clinical Practice: By responding immediately to patients' concerns about their safety, healthcare professionals can help prevent avoidable suffering and exhaustive searching for someone in the healthcare system who will take their needs seriously. Patient Contribution: A member check was performed with the help of one of the participants who read the findings to confirm familiarity. [ABSTRACT FROM AUTHOR]

Propofol is an ultra-fast-acting intravenous anesthetic, which is rapidly metabolized primarily into inactive compounds in the live and then excreted in the urine. The purpose of this study is to explore the risk signals of propofol based on the US FDA Adverse Event Reporting System database. The risk signals of propofol-related adverse reactions in adverse event (AE) reports from 2004 to 2021 in the US FAERS were mined using ratio-report method (ROR) and the ratio-report ratio method (PRR) methods. We screened out 1651 pairs AE reports using propofol as primary suspect (PS) drugs. ROR, PRR, BCPNN and MGPS methods were used to calculate respectively, there are 363 positive preferred terms (PT) signals with 9549 cases. Among them, the top 3 adverse reactions associated with using propofol from the FAERS database were anaphylactic shock, hypotension and propofol infusion syndrome. The top 3 systems of the body associated with adverse reaction of propofol from the FAERS database were General disorders, Cardiac disorders and administration site conditions and Respiratory, thoracic and mediastinal disorders. The top 4 indication of using propofol from the FAERS database, including anaesthesia, induction of anaesthesia, sedation, general anaesthesia. There are many adverse reactions that are not included in the drug insert of propofol and involve a wide range of organs and/or systems. Caution should be exercised in the clinical use of propofol. [ABSTRACT FROM AUTHOR]

Antibody-drug conjugates (ADCs) are an emerging class of anticancer agents that combine targeting antibodies with potent cytotoxic agents. Their molecular configuration allows for increased therapeutic efficacy and reduced adverse-effect profiles compared to monoclonal antibodies or cytotoxic chemotherapy alone. ADCs cause off-target toxicities through several mechanisms, including premature deconjugation of the cytotoxic agent in the serum and the presence of the targeted antigen on normal tissues. Given cutaneous adverse events comprise 31.3% of all-grade adverse events in clinical trials involving ADCs, dermatologists are increasingly called upon to manage the cutaneous toxicities caused by these drugs. In this review, we summarize known cutaneous toxicities of the ADCs that have been approved for use by the US Food and Drug Administration to date. Dermatologists can play a key role in recognizing cutaneous reactions associated with ADCs, contributing to guidelines for their management, and aiding during clinical trials to generate detailed morphologic and histopathologic descriptions of cutaneous toxicities caused by ADCs. [ABSTRACT FROM AUTHOR]

New anticancer therapies have improved patient outcomes but associated dermatologic adverse events (AEs) may cause morbidity and treatment discontinuation. A comprehensive estimation of associations between cancer drugs and skin AEs is lacking. This study utilized the Food and Drug Administartion (FDA)'s Adverse Event Reporting System database (January 2013-September 2022), with 3,399,830 reports involving 3084 drugs and 16,348 AEs. A nearest neighbor matching model was employed to select 10 controls for each case report, utilizing the cosine similarity of demographic and AE severity factors to minimize false positives/negatives. There were 10,698 unique anticancer drugs (n = 212) to skin AE (n = 873) pairs, of which 676 had significant reporting odds ratios (ROR) > 1, comprising 113 drugs and 144 AEs. The minimum ROR was 1.25, and 50% of associations displayed a ROR >10. The most common were rash (51 agents) and dry skin (28 drugs). Methotrexate induced the most distinct AEs (34), then mechlorethamine (33), and vemurafenib (24). Targeted therapies accounted for 49% of pairs, cytotoxic chemotherapies for 35.9%, and immunotherapies for 11%. A total of 113 anticancer drugs were identified as significantly associated with skin AEs, most frequently rash and dry skin. Data are likely under-reported but enable quick postmarketing identification of skin toxicity signals. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective observational cohort study. Objective: En bloc resection for primary tumours of the spine is associated with a high rate of adverse events (AEs). The objective was to explore the relationship between frailty/sarcopenia and major perioperative AEs, length of stay (LOS), and unplanned reoperation following en bloc resection of primary spinal tumours. Methods: This is a unicentre study consisting of adult patients undergoing en bloc resection for a primary spine tumor. Frailty was calculated with the modified frailty index (mFI) and spine tumour frailty index (STFI). Sarcopenia was quantified with the total psoas area/vertebral body area ratio (TPA/VB) at L3 and L4. Univariable regression analysis was used to quantify the association between frailty/sarcopenia and major perioperative AEs, LOS and unplanned reoperation. Results: 95 patients met the inclusion criteria. The mFI and STFI identified a frailty prevalence of 3% and 18%. Mean CT TPA/VB ratios were 1.47 (SD ±.05) and 1.83 (SD ±.06) at L3 and L4. Inter-observer reliability was.93 and.99 for CT and MRI L3 and L4 TPA/VB ratios. Unadjusted analysis demonstrated sarcopenia and mFI did not predict perioperative AEs, LOS or unplanned reoperation. Frailty defined by an STFI score ≥2 predicted unplanned reoperation for surgical site infection (SSI) (P <.05). Conclusions: The STFI was only associated with unplanned reoperation for SSI on unadjusted analysis, while the mFI and sarcopenia were not predictive of any outcome. Further studies are needed to investigate the relationship between frailty, sarcopenia and perioperative outcomes following en bloc resection of primary spinal tumors. [ABSTRACT FROM AUTHOR]

Background: Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed agents to treat depression. Considering the growth in antidepressant prescription rates, SSRI-induced adverse events (AEs) need to be comprehensively clarified. Objective: This study was to investigate safety profiles and potential AEs associated with SSRIs using the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: A retrospective pharmacovigilance analysis was conducted using the FAERS database, with Open Vigil 2.1 used for data extraction. The study included cases from the marketing date of each SSRI (ie, citalopram, escitalopram, fluoxetine, paroxetine, fluvoxamine, and sertraline) to April 30, 2023. We employed the reporting odds ratio and Bayesian confidence propagation neural network as analytical tools to assess the association between SSRIs and AEs. The Medical Dictionary for Regulatory Activities was used to standardize the definition of AEs. AE classification was achieved using system organ classes (SOCs). Results: Overall, 427 655 AE reports were identified for the 6 SSRIs, primarily associated with 25 SOCs, including psychiatric, nervous system, congenital, familial, genetic, cardiac, and reproductive disorders. Notably, sertraline (n = 967) and fluvoxamine (n = 169) exhibited the highest and lowest signal frequencies, respectively. All SSRIs had relatively strong signals related to congenital, psychiatric, and nervous disorders. Conclusions and relevance: Most of our findings are consistent with those reported previously, but some AEs were not previously identified. However, AEs attributed to SSRIs remain ambiguous, warranting further validation. Applying data-mining methods to the FAERS database can provide additional insights that can assist in appropriately utilizing SSRIs. [ABSTRACT FROM AUTHOR]

Background The optimal cumulative activity (CA) of I-131 therapy for patients with metastatic differentiated thyroid cancer (mDTC) remains contentious. This study aimed to determine the maximum CA of I-131 that could be administered without a significant increase in adverse events (AEs) by analyzing a long-term cohort of patients. Methods Data from patients with mDTC treated with I-131 therapy and followed for at least 2 years from 1967 to 2019 were reviewed. Patients were categorized into 3 groups based on the received CA: group A (≤600 mCi), group B (>600-1000 mCi), and group C (>1000 mCi). The study assessed long-term AEs and survival outcomes. Results The study included 671 adult patients with mDTC (mean age, 48 years; range, 19-81) with a median follow-up of 122 months (interquartile range: 82-180). Group A, group B, and group C comprised 269 (40.0%), 212 (31.6%), and 190 (28.4%) patients, respectively. Ten-year survival rates were 72%, 42.7%, and 29% in groups A, B, and C, respectively. A total of 40/671 (6%) AEs were observed in 38 patients: 3 (1.1%), 12 (5.7%), and 25 (13.2%) in groups A, B, and C, respectively. Five patients developed second primary malignancy: 3 in group A and 1 each in group B and C. However, CA >1000 mCi of I-131 was associated with significant increase in bone marrow suppression, decreased pulmonary function, and xerostomia (P <.001). Conclusion The study suggests that a maximum CA of up to 1000 mCi strikes a favorable balance between keeping AEs low and benefiting a subset of patients with extensive metastases showing intense I-131 concentration. [ABSTRACT FROM AUTHOR]

Background: Adverse events in psychiatric settings present ongoing challenges for both patients and staff. Despite advances in psychiatric interventions and treatments, research on early warning scores and tools to predict patient deterioration is limited. This review provides a summary of the few tools that have been developed in a psychiatric setting, comparing machine learning (ML) and nonmachine learning/traditional methodologies. The outcomes of interest include the selected key variables that contribute to adverse events and the performance and validation measures of the predictive models. Methods: Three databases, Ovid MEDLINE, PsycINFO, and Embase, were searched between February 2023 and April 2023 to identify all relevant studies that included a combination of (and were not limited to) the following search terms: "Early warning," "Alerting tool," and "Psychiatry". Peer-reviewed primary research publications were included without imposing any date restrictions. A total of 1,193 studies were screened. A total of 9 studies met the inclusion and exclusion criteria and were included in this review. The PICOS model, the Joanna Briggs Institute (JBI) Reviewer's Manual, and PRISMA guidelines were applied. Results: This review identified nine studies that developed predictive models for adverse events in psychiatric settings. Encompassing 41,566 participants across studies that used both ML and non-ML algorithmic approaches, performance metrics, primarily AUC ROC, varied among studies between 0.62 and 0.95. The best performing model that had also been validated was the random forest (RF) ML model, with a score of 0.87 and a high sensitivity of 74% and a specificity of 88%. Conclusion: Currently, few predictive models have been developed for adverse events and patient deterioration in psychiatric settings. The findings of this review suggest that the use of ML and non-ML algorithms show moderate to good performance in predicting adverse events at the hospitals/units where the tool was developed. Understanding these models and the methodology of the studies is crucial for enhancing patient care as well as staff and patient safety research. Further research on the development and implementation of predictive tools in psychiatry should be carried out to assess the feasibility and efficacy of the tool in psychiatric patients. [ABSTRACT FROM AUTHOR]

Purpose: Although bone morphogenetic protein-2 (BMP-2) possesses potent osteoinductivity, there have been some concerns on the safety of BMP-2 and BMP-2-incorporated bone substitutes used for bone formation. On the other hand, BMP-2-loaded calcium phosphate cement (BMP-2@CPC) has been developed and used for bone regeneration in oral implantology. Therefore, this study aims to investigate this product's biocompatibility and clinical safety after being used in maxillofacial surgery. Materials and methods: A rat model was employed to assess the osteoinduction and biocompatibility of BMP-2@CPC. Further, a retrospective investigation was carried out: 110 patients who received BMP-2@CPC treatment after their maxillofacial surgery were recruited to describe relative adverse events. Results: In vivo, BMP-2@CPC showed a significantly higher mean bone volume density and osteoblasts volume density (15 ± 2% and 3 ± 1%)than those of the CPC group (p < 0.05) after being implanted in the dorsal area of rats. Regarding biocompatibility, the mean fibrous tissue volume density was significantly lower in the BMP-2@CPC group (20 ± 5% compared to 31 ± 6%, p = 0.026). The retrospective clinical study showed that only five mild/moderate adverse events were identified in four patients based on the medical records of 110 patients, including swelling, bony mass, and wound dehiscence. This adverse event occurrence was not affected by gender, age, the dose of filled materials, and operations in the study (p > 0.05). Conclusions: BMP-2-loaded CPC has osteoinductivity and more promising biocompatibility than pure CPC. However, its degradation is slower than CPC. The safety of BMP-2-loaded CPC with 0.5 or 1 mg BMP-2 is promising in oral maxillofacial surgery. Clinical implications: This study confirmed the promising safety of this BMP-2 incorporated CPC used in dental clinical practice, which can promote its reassuring application for dental implant placement in bone insufficient areas. [ABSTRACT FROM AUTHOR]

Background: Patient safety is a critical concern in dentistry. Adverse events (AEs) can harm patients, increase costs, and decrease satisfaction. Understanding AE types and frequencies is crucial for effective risk management and quality improvement. This study analyzes incident reports to identify preliminary incident patterns as a starting point for developing risk management strategies. However, under-reporting limits the ability to identify true incident patterns, highlighting the need for improved reporting systems and encouragement of incident reporting. Further research is underway to develop such a system and promote reporting to ensure sufficient data quality for effective risk management. Methods: A retrospective analysis of 1,618 incident reports from December 2018 to August 2023 was conducted. A validated classification system, developed from a 5-year retrospective analysis and approved by 14 experts, categorized patient safety incidents, aligning with Thailand's Hospital Accreditation standards. Descriptive statistics summarized AE frequency and distribution. Results: Of the reports, 752 were patient safety, 503 personnel safety, and 363 organizational safety incidents. Top patient safety incidents included medical record errors (176), accidental damage (66), post-operative complications (65), medical emergencies (64), and communication errors (53). Personnel safety incidents involved inappropriate working conditions (135) and work-related injuries with contact transmission risk (117). Organizational safety incidents mainly concerned policy and operational processes (131). Conclusions: This study reveals the preliminary patterns of adverse events (AEs) in dental settings and underscores the limitations due to under-reporting, which affect the ability to fully understand true incident patterns. To effectively manage risks, there is a critical need for improving the existing incident reporting system and encouraging a culture of comprehensive reporting among dental professionals. Future efforts should focus on enhancing reporting systems to ensure high-quality data, enabling better identification of incident trends and supporting targeted risk management strategies to improve patient safety in dentistry. [ABSTRACT FROM AUTHOR]

Simple Summary: Radioligand therapy (RLT) with the use of [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE is a subsequent line of the neuroendocrine neoplasms (NENs) treatment. A total of 127 patients with progressive NENs underwent 4 courses of RLT. Changes in laboratory parameters, adverse events (AEs), progression-free survival (PFS), and overall survival (OS) were analyzed. RLT caused changes in laboratory parameters regarding kidney and bone marrow function, as well as glucose concentration. Nevertheless, RLT appeared to be a safe method of NEN treatment with a low number of AEs and a high percentage of survival rate in a long-term observation. Background: Neuroendocrine neoplasms (NENs) are neoplastic tumors developing in every part of the body, mainly in the gastrointestinal tract and pancreas. Their treatment involves the surgical removal of the tumor and its metastasis, long-acting somatostatin analogs, chemotherapy, targeted therapy, and radioligand therapy (RLT). Materials and Methods: A total of 127 patients with progressive neuroendocrine neoplasms underwent RLT—4 courses, administered every 10 weeks—with the use of 7.4 GBq [177Lu]Lu-DOTA-TATE or tandem therapy with 1.85 GBq [177Lu]Lu-DOTA-TATE and 1.85 GBq [90Y]Y-DOTA-TATE. Assessment of short- and long-term complications, as well as the calculation of progression-free survival (PFS) and overall survival (OS) were performed. Results: RLT caused a statistically but not clinically significant decrease in blood morphology parameters during both short- and long-term observations. Glomerular filtration rate (GFR) significantly decreased only in a long-term observation after RLT; however, it was clinically acceptable. Computed predictions of progression-free survival (PFS) and overall survival (OS) indicated that five years post-RLT, there is a 74% chance of patients surviving, with only a 58.5% likelihood of disease progression. Conclusions: Computed predictions of PFS and OS confirmed treatment efficiency and good patient survival. RLT should be considered a safe and reliable line of treatment for patients with progressive NENs as it causes only a low number of low-grade adverse events. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic necessitated rapid and widespread vaccination efforts, which proved critical in reducing the severity and mortality of the virus. However, the interplay between vaccinations, pre-existing skin conditions, and other comorbidities still needs to be explored. This study investigated the occurrence and severity of adverse events following immunization (AEFIs) with COVID-19 vaccines in individuals with chronic skin diseases and comorbidities within a Central European cohort. Methods: An anonymous online survey was conducted between May 2022 and February 2023, targeting students and employees of universities in Wrocław, Poland. A total of 513 respondents were analyzed, focusing on AEFIs following the first, second, and third doses of COVID-19 vaccines and the effects of COVID-19 on conditions such as atopic dermatitis, psoriasis, vitiligo, acne vulgaris, rosacea, and various comorbidities. Results: COVID-19 vaccination effectively protected against severe disease across all doses. The analysis revealed no significant impact of either COVID-19 infection or vaccination on the course of selected skin diseases and comorbidities. The reporting of AEFIs to the Sanitary Inspection was notably low. The Moderna and Pfizer mRNA-based vaccines were associated with a higher reported number of AEFIs, particularly after the second and third doses, compared to AstraZeneca, which exhibited fewer adverse events after subsequent doses. Conclusions: COVID-19 vaccination is both safe and effective, even in patients with pre-existing skin conditions and comorbidities. Vaccine selection may benefit from considering individual health profiles, and better reporting of AEFIs is needed to enhance vaccine safety monitoring. [ABSTRACT FROM AUTHOR]

Relapsed/refractory (R/R) primary and secondary central nervous system lymphomas (PCNSL, SCNSL) are associated with short survival and represent an unmet need, requiring novel effective strategies. We retrospectively compared the safety and efficacy of CD19/22 CAR-T-cell therapy following ASCT (ASCT + CAR-T group), CD19/22 CAR-T-cell cocktail therapy (CAR-T group) and chemoimmunotherapy (CIT group) in treating R/R CNSL patients. Analysis of the differences in clinical characteristics among the three groups revealed that the median age in the CIT group was older than that in the ASCT + CAR-T group and CAR-T group, and the median number of prior lines of therapy in the CIT group was less than that in the other groups. Patients in the two CAR-T-therapy groups exhibited comparable incidences and severities of CRS and ICANS. Grade 4–5 CRS and ICANS were not observed in either CAR-T-cell therapy group. The incidence of Grade 3/4 hematological toxicity in the ASCT + CAR-T and CAR-T groups was greater than that in the CIT group. The ORR was 82.75% in the ASCT + CAR-T group, 60.00% in the CAR-T group and 58.83% in the CIT group. As of December 31, 2022, the median follow-up after therapy was 16.73 months (range, 0.67-42.00 months). The median durations of PFS and OS were not reached in the ASCT + CAR-T group. The median PFS in the CAR-T group was 4.72 months, and OS was not reached. In the CIT group, the median PFS and OS were 6.63 months and 16.77 months, respectively. The 2-year PFS rate of patients in the ASCT + CAR-T group (65.52%) was significantly greater than that of patients in the CAR-T group (30.00%, P = 0.0321) and CIT group (23.53%, P = 0.0043). Our results support the development of CAR-T-cell therapy for R/R CNSL. With the durability of remission and low toxicity, ASCT combined with CAR-T-cell therapy appears to be a more effective and safer treatment option for primary and secondary R/R CNS lymphoma. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Objective Methods Results Conclusion Aesthetic neuromodulator injections of the upper face are frequently performed to temporarily block muscular actions of the periorbital muscles to ultimately reduce skin rhytids. However, the adverse event rate in the literature for toxin‐induced blepharoptosis ranges from 0.51% to 5.4%.To identify access pathways by which injected neuromodulator product can travel from extra‐ to intra‐orbital and therefore affect the levator palpebrae superioris muscle.Nine non‐embalmed human body donors were investigated in this study with a mean age at death of 72.8 (16.1) years. The 18 supraorbital regions were injected in 28 times (14 for supratrochlear and 14 for supraorbital) with 0.5 cc, whereas eight cases (four for supratrochlear and four supraorbital) were injected with 0.1 cc of colored product. Anatomic dissections were conducted to identify structures stained by the injected color.The results of this injection‐ and dissection‐based study revealed that both the supratrochlear and the supraorbital neurovascular bundles are access pathways for injected neuromodulator products to reach the intra‐orbital space and affect the levator palpebrea superioris muscle. Out of 36 conducted injection passes, seven (19.44%) resulted in affection of the sole elevator of the eyelid of which 100% occurred only at an injection volume of 0.5 cc and not at 0.1 cc.Clinically, the results indicate that a low injection volume, a superficial injection for the supraorbital location, and angling the needle tip away from the supratrochlear foramen (toward the contralateral temple) when targeting the corrugator supercilii muscles, can increase the safety profile of an aesthetic toxin glabellar treatment. [ABSTRACT FROM AUTHOR]

Objective: To conduct a comprehensive data analysis based on the FDA's Adverse Event Reporting System (FAERS) to mine possible adverse event (AE) signals of Capmatinib, providing valuable references for its clinical application. Methods: Capmatinib was the primary suspected drug in the search of FAERS database from the second quarter of 2020 to the fourth quarter of 2023. Data processing, screening, and classification were performed using methods such as the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Results: A total of 1,991 AE reports directly related to Capmatinib were screened, identifying 269 Preferred Terms (PTs) involving 26 System Organ Classes (SOCs). Besides the AEs recorded in the drug label (such as edema, nausea, fatigue, and dyspnea), the study unearthed other high-risk AEs not listed in the label, including Renal and urinary disorders, Vocal cord paralysis, and Ear and labyrinth disorders. Among these, renal and urinary disorders, and ear and labyrinth disorders had a higher frequency and intensity of signals, suggesting that their mechanisms of occurrence could be a future research direction. Conclusion: This study uncovered new potential AEs of Capmatinib based on the FAERS database, providing reference for its safe clinical use. Special attention should be given to the occurrence of ear and labyrinth disorders and renal and urinary disorders, primarily presenting as pseudo-acute kidney injury, during treatment. [ABSTRACT FROM AUTHOR]

Background: Inhibitors of the anaplastic lymphoma kinase (ALK) gene mutation are first-line treatments in patients with ALK-positive lung cancer. The FDA label warns of the risk of interstitial lung disease (ILD) in patients receiving ALK TKIs. However, ILD associated with ALK TKIs is not fully understood. The aim of this study was to characterize the features of ALK TKI-related ILD and to explore risk factors for ALK TKI-related ILD. Methods: FDA's Adverse Event Reporting System (FAERS) reports from 2011 Q1 to 2023 Q2 were extracted and combined. Standardized MedDRA queries (SMQs) were used to search for AEs at the preferred term (PT) level. Four algorithms were employed to quantify the signals of ILD associated with ALK TKIs. The risk of ILD was further analyzed using logistic regression. Results: A total of 20,064 reports of ALK TKIs and 640 (3.2%) reports of ILD AEs were extracted. Significant disproportionality was detected in all five ALK TKIs. Interstitial lung disease and pneumonitis were the most common lung toxicities induced by ALK TKIs. Results of further analyses revealed a different spectrum of lung toxicity among the various TKIs. The median time to onset of ILD related to ALK TKIs was 53 days (Q1:12, Q3:209), and more than 70% of AEs occurred within the first 2 months. Logistic regression analysis and risk prediction model both showed that different ALK TKIs and their combination with PPIs, amlodipine, and magnesium oxide were independent risk factors for ILD (p<0.05). Conclusion: ALK TKIs have different safety profiles regarding lung toxicity, which normally occurs within the first 2 months. Administration in combination with PPIs, amlodipine, and magnesium oxide significantly increases the risk of ILD. These results provide risk prediction for ILD related to ALK TKIs and support pharmacovigilance to promote safe prescribing in oncology. [ABSTRACT FROM AUTHOR]

AbstractL-asparaginase (L-Asp) is an essential enzyme in the treatment of patients with Acute Lymphoblastic Leukemia (ALL), commonly associated with adverse events (AE). Knowing the pharmacokinetic and pharmacodynamic (PK/PD) parameters of L-Asp as well as its relationship with the development of AE is an important strategy in the search to improve the efficacy and safety of the treatment. Seventy-four children with ALL that were being treated with L-Asp, were included. One to three blood samples were randomly obtained from each patient, at times from 0 to 30 hours, until completing a total of 211 samples. The L-Asp activity and the Asparagine (Asp) concentration were quantified, in addition, the presence of anti-L-Asp antibodies (Anb) was determined. A population PK/PD model of L-Asp was developed to determine the association of covariates with PK/PD parameters. The presence of Anb was associated with the increase in L-Asp clearance (CL) and with the decrease of volume of distribution 1 (V1). On the other hand, female sex was significantly associated with the increase of V1, while the age from 1 to 6 years was significantly associated with the increase of V1. The presence of Anb as well as the female sex were related to the increase IC50 (concentration-needed to deplete-50% of Asp). Patients who presented Asp depletion before the first 24 hours after administration presented pancreatitis, this could be a risk marker. Significant results were found in this study, use of these results may contribute to the safe and effective use of L-Asp. [ABSTRACT FROM AUTHOR]

Background : Increased levels of physical activity are associated with a reduction of breast cancer mortality, especially in postmenopausal women with positive hormone receptor status. So far, previous observational case–control and cohort studies have focused on associations between overall leisure time physical activity and survival of women with breast cancer in general. Methods: In this multicenter prospective cohort study, conducted in Germany between 30th August 2012 to 29th December 2017, we investigated general physical activity in a homogenous sample of n = 1440 postmenopausal women with advanced (inoperable locally advanced or metastatic), hormone receptor-positive breast cancer receiving the same therapy (everolimus and exemestane). Self-reported physical activity was assessed using the Godin Leisure Time Exercise Questionnaire (GLTEQ) before and every 3 months during treatment. Participants were then classified into "active" and "insufficiently active" to screen their activity behavior the week prior to medical treatment. In addition, changes in physical activity patterns were assessed. Adjusted Cox regression analyses were performed for the activity categories to determine hazard ratios (HR). Besides progression-free survival (PFS), adverse events (AEs), QoL, and fatigue were assessed every 3 months until study termination. Results: Compared to "insufficiently active" patients, "active" individuals indicated a significantly longer PFS (HR: 0.84 [0.74; 0.984], p =.0295). No significant differences were observed for changes of physical activity behavior. Patients who reported to be "active" at baseline revealed significantly fewer AEs compared to "insufficiently" active patients. In detail, both severe and non-severe AEs occurred less frequently in the "active" patients group. In line with that, QoL and fatigue were better in physical "active" patients compared to their insufficient active counterparts at the last post-baseline assessment. Participants who remained or become active indicated less AEs, a higher QoL, and reduced fatigue levels. Conclusions: Physical activity behavior prior to medical treatment might have prognostic value in patients with advanced breast cancer in terms of extending the PFS. Moreover, physical activity before and during treatment may reduce treatment-related side effects and improve patients' QoL and fatigue. Trial registration: EUPAS9462. Registered 30th October 2012 "retrospectively registered." [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to comprehensively assess the safety of rimegepant administration in real-world clinical settings. Methods: Data 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. Results: A 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. Conclusion: This 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. [ABSTRACT FROM AUTHOR]

Background: Drug resistance (DR) is one of the several challenges to global tuberculosis (TB) control. The implementation of bedaquiline (BED) for DR-TB after more than 40 years was expected to improve treatment outcomes as well as microbiologic conversion and adverse events (AE) occurrence. Methods: Retrospective cohort study based on secondary data of patients with rifampicin-resistant (RR) or multidrug-resistant (MDR) TB reported to the Outpatient Clinic of Mycobacterial Diseases of the Thorax Diseases Institute – Federal University of Rio de Janeiro - Brazil, between 2016 and 2023. We aimed to evaluate microbiologic conversion, AE and TB treatment outcomes and compare them according to the treatment regimen used for RR/MDR-TB patients under routine conditions [Injectable Containing Regimens (ICR) versus BED Containing Regimens (BCR)]. Logistic regression and survival analysis using Cox regression and Kaplan Meier curve were used for statistical analysis. Results: Of the 463 DR-TB patients notified during the study period, 297 (64.1%) were included for analysis (ICR = 197 and BCR = 100). Overall AEs were more frequent (83.7 vs. 16.3%, p < 0.001) and occurred earlier in the ICR group (15 days vs. 65 days, p = 0.003). There were no cases of cardiotoxicity requiring interruption of BED treatment. None of the regimens of treatment tested were associated with smear or culture conversion on Cox regression analysis (p = 0.60 and 0.88, respectively). BED-containing regimens were also associated with favorable outcomes in multivariable logistic regression [adjusted odds ratio (aOR) = 2.63, 95% confidence interval (CI)1.36–5.07, p = 0.004], as higher years of schooling, primary drug resistance, and no previous TB treatment. In the survival analysis, BCR was inversely associated with the occurrence of AE during treatment follow-up (aHR 0.24, 95% CI 0.14–0.41, p < 0.001). In addition, TB treatment regimens with BED were also associated with favorable outcomes (aHR 2.41, 95% CI 1.62–3.57, p < 0.001), along with no illicit drug use and primary drug resistance. Conclusions: The implementation of a fully oral treatment for RR/MDR-TB in a reference center in Brazil was safe and associated with favorable outcomes under routine conditions, despite social, demographic, and behavioral factors that may influence TB treatment completion. [ABSTRACT FROM AUTHOR]

Background: Periampullary diverticulum (PAD) is commonly encountered in endoscopic retrograde cholangiopancreatography (ERCP) procedures. Objectives: We sought to determine whether PADs are associated with a lower success rate of cannulation and an increased risk of adverse events. Design: A retrospective cohort study was conducted using prospectively gathered nationwide registry data. Methods: Using the Swedish registry for gallstone surgery and ERCP, we analyzed a cohort of 66,974 prospectively registered ERCP procedures performed in 2006–2021. The presence of PAD was divided into two groups based on the PAD type: Boix type 1 (the papilla located inside the PAD) and Boix types 2–3 (the papilla located either at the edge of the PAD or immediately adjacent to the PAD). The primary outcomes were the success rate of cannulation and overall adverse events within 30 days. Results: PADs were registered in 8130 (12.1%) of ERCPs included in the study population. In total, 2114 (3.9%) patients had Boix type 1 PAD, while 5035 (8.2%) patients had Boix type 2 or 3 PAD. The chance of successful cannulation was lower in patients with type 1 PAD compared to no PAD (80.1% vs 88.7%; odds ratio: 0.42, 95% confidence interval: 0.38–0.46). No differences were seen in overall adverse events or post-ERCP pancreatitis. Adverse events occurred in 14.6% of patients with PAD type 1 and 16.0% of patients with PAD type 2 or 3, compared to 16.5% of patients without a PAD. Conclusion: Cannulation appears less successful during ERCP when the papilla is located in the PAD (i.e., type 1). Adverse events seem not to increase with the presence of a PAD, but they could theoretically be influenced by the inability to cannulate. Plain language summary: How a pouch in the duodenum affects the difficulty and complications of an endoscopic procedure investigating the bile ducts A duodenal diverticulum (pouch in the duodenum) is a common finding during endoscopic examinations. A diverticulum can make it harder to do an ERCP, which is an endoscopic procedure that examines the bile ducts. The diverticulum might make it harder to do an ERCP because it affects the opening where the bile is released into the intestine. If the bile duct opening is inside the diverticulum, it is classified as type 1. If it is on the edge or outside, it is classified as type 2-3. This study used Swedish registry data to see if these types of diverticula make ERCP harder and cause more problems after the procedure. 47,486 procedures were investigated, and 12.1% had a diverticulum. A type 1 diverticulum makes ERCP harder. There was no difference in complications between the types of diverticula and no diverticulum. This means a diverticulum does not raise the risk of complications during ERCP. However, for a type 1 diverticulum, not being able to perform ERCP may prevent complications. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Dexmedetomidine is commonly used in hospitals for sedation during procedurals. It has been considered safe even though studies have shown that it may cause bradycardia and hypotension. The aim of this study was to map the current evidence regarding potential risks of sedation of children with dexmedetomidine.Two database searches were conducted to gather all articles published through 30 January 2024 that matched the inclusion criteria. PubMed and Embase were chosen for the initial search. Search terms were chosen to create a broad systematic search that would include articles reporting adverse events during procedural sedation on children. From the included articles, data on type of sedation, administration, patient characteristics, endpoints and number of adverse events were collected.After the initial search, 357 individual papers were screened and 41 papers were included. The most common adverse event reported was bradycardia. In almost 40% of the articles that measured oxygen saturation, one or more incidents of desaturation occurred. 27% reported that interventions to prevent further harm were preformed, most of the interventions were to improve oxygenation.There is a need for further investigation regarding adverse events, especially respiratory adverse events during sedation with dexmedetomidine. [ABSTRACT FROM AUTHOR]

Oral antimicrobials remain the mainstay of long-term treatment for many infections. Meanwhile, the use of oral agents is becoming commonplace for the treatment of several pediatric infections once managed exclusively with parenteral therapies. Unfortunately, antimicrobials are associated with several laboratory toxicities, particularly when high doses or combination therapies are used, but there is a paucity of data on optimal laboratory monitoring strategies. In this ID Consultant article, we offer a summary of the 3 most common laboratory-based toxicities seen with long-term use of oral antimicrobials—drug-induced kidney injury, liver injury, and hematological toxicities—and we provide our recommended approach to monitoring. [ABSTRACT FROM AUTHOR]

The article investigates the safety of COVID-19 vaccines in the Czech Republic by analyzing adverse events (AEs) reported in connection with different vaccine batches. Data from the State Institute for Drug Control of the Czech Republic was used to compare the findings with a previous study from Denmark. The analysis revealed batch-dependent safety signals, with early vaccine batches associated with higher numbers of AE reports. The study also highlighted differences in AE reporting systems between the Czech Republic and Denmark, suggesting potential underreporting in the Czech system. [Extracted from the article]

Continuous vital sign monitoring (CVSM) with wireless sensors in general hospital wards can enhance patient care. An artificial intelligence (AI) layer is crucial to allow sensor data to be managed by clinical staff without over alerting from the sensors. With the aim of summarizing peer-reviewed evidence for AI support in CVSM sensors, we searched PubMed and Embase for studies on adult patients monitored with CVSM sensors in general wards. Peer-reviewed evidence and white papers on the official websites of CVSM solutions were also included. AI classification was based on standard definitions of simple AI, as systems with no memory or learning capabilities, and advanced AI, as systems with the ability to learn from past data to make decisions. Only studies evaluating CVSM algorithms for improving or predicting clinical outcomes (e.g., adverse events, intensive care unit admission, mortality) or optimizing alarm thresholds were included. We assessed the promised level of AI for each CVSM solution based on statements from the official product websites. In total, 467 studies were assessed; 113 were retrieved for full-text review, and 26 studies on four different CVSM solutions were included. Advanced AI levels were indicated on the websites of all four CVSM solutions. Five studies assessed algorithms with potential for applications as advanced AI algorithms in two of the CVSM solutions (50%), while 21 studies assessed algorithms with potential as simple AI in all four CVSM solutions (100%). Evidence on algorithms for advanced AI in CVSM is limited, revealing a discrepancy between promised AI levels and current algorithm capabilities. [ABSTRACT FROM AUTHOR]

Background: The treatment-free interval is a significant predictor of worse prognosis and poor response rates of the second-line treatment in patients with carboplatin and paclitaxel (PT)-pretreated, advanced, or recurrent endometrial cancer (EC). Whether lenvatinib plus pembrolizumab still confers a survival benefit compared with doxorubicin in patients with platinum-free intervals of <6 months remains unclear. Methods: This multi-institutional retrospective analysis was performed using de-identified electronic health records from the TriNetX Research Network. Patients with advanced or recurrent ECs who received lenvatinib plus pembrolizumab or doxorubicin within six months of first-line PT were identified. A 1:1 propensity score matching (PSM) was conducted to control for potential confounding variables. Overall survival (OS) and adverse event profile were the primary and secondary outcomes. Results: Between January 2018 and February 2024, 130 patients with PT-treated, advanced, or recurrent ECs who received lenvatinib plus pembrolizumab and 122 patients who received doxorubicin at a platinum-free interval of <6 months were identified across 31 healthcare organizations. In the balanced cohort following PSM with 117 patients in each group, treatment with lenvatinib plus pembrolizumab was associated with improved OS compared with treatment with doxorubicin (12.8 vs. 8.2 months, p = 0.012, hazard ratio: 0.65, 95% confidence interval: 0.46–0.91). Regarding adverse event analysis, a higher incidence of hypothyroidism and proteinuria was observed with lenvatinib plus pembrolizumab, and more hematological toxicities were observed with doxorubicin. Conclusions: in patients with treatment-free intervals of <6 months, lenvatinib plus pembrolizumab still confers improved survival compared with doxorubicin in PT-treated, advanced, or recurrent ECs. [ABSTRACT FROM AUTHOR]

Growing evidence from pharmacovigilance data and postmortem toxicology reports highlights the misuse potential of gabapentinoids. This study aimed to investigate the risk of serious adverse outcomes (drug misuse, overdose, major trauma), and their risk factors, in primary care patients who are prescribed gabapentinoids. Using the UK Clinical Practice Research Datalink, a matched cohort study calculated adverse event rates separately for gabapentinoid-exposed and unexposed cohorts. In the exposed cohort, event rates for exposure to a range of potential risk factors were calculated. Event rates were compared using Cox proportional hazards models, adjusted for age, sex, deprivation, previous mental health diagnosis, and coprescribing with potentially interacting medicines. Substance misuse (gabapentin adjusted hazard ratio [95% CI]: 2.40 [2.25-2.55]), overdose (2.99 [2.56-3.49]), and major trauma (0-2.5 years: 1.35 [1.28-1.42]; 2.5 to 10 years: 1.73 [1.56-1.95]) were more common among patients prescribed gabapentinoids than matched individuals who were not. The association with overdose was stronger for pregabalin than gabapentin. All adverse outcomes were significantly associated with smoking, history of substance misuse, overdose, or a mental health condition and prescription of opioids, benzodiazepines, antidepressants, and Z-drug hypnotics (eg, gabapentin hazard ratios for association of concurrent opioid use: misuse 1.49 [1.47-1.51]; overdose 1.87 [1.78-1.96]; major trauma 1.28 [1.26-1.30]). Our findings highlight the importance of careful patient selection when prescribing gabapentinoids and the need to educate prescribers about the risks of these drugs, particularly in combination with other central nervous system depressants. [ABSTRACT FROM AUTHOR]

Background: In the breast cancer treatment, there may be a gap between patients' information needs and physicians' perceptions. To address this issue, we conducted a comprehensive questionnaire survey aimed to assess the specific information needs of patients regarding the adverse events (AEs) associated with treatment. Methods: A web-based questionnaire survey (UMIN000049280: Registered on October 31, 2022) was conducted in patients with a history of breast cancer treatment. Responses were obtained regarding AEs experienced, AEs for which remedies were identified, AEs patients sought to prevent, and pre-treatment information on AEs patients desired to have. Results: Data from 435 breast cancer patients were analyzed. The most common AEs reported included hair loss (93.3%), malaise/fatigue (89.4%), nail changes (83.2%), dysgeusia (69.0%), leukopenia/white blood cell decreased (65.1%), neuropathy (62.3%), and nausea/vomiting (61.4%). Financial anxiety was reported in 35.2% of the participants. AEs for which a minority of patients found effective solutions included neuropathy (20.3%), financial anxiety (21.6%), edema (24.3%), joint pain (26.0%), and malaise/fatigue (26.7%). Patients expressed the greatest desire to avoid hair loss (34.7%), followed by nausea/vomiting (23.7%), interstitial lung disease/pneumonitis (5.5%), malaise/fatigue (5.1%), and dysgeusia (5.1%). The most commonly requested pre-treatment information regarding AEs was their duration, followed by prevention methods, management strategies, time to onset, and the impact on daily life. Conclusions: This survey highlights the existence of significant unmet medical needs among breast cancer patients, due to the inadequate solutions available for managing AEs associated with various therapeutic agents. In addition, the survey revealed that patients have different information needs regarding different types of AEs. [ABSTRACT FROM AUTHOR]

A phase 1b study was conducted to evaluate the safety and feasibility of ciprofloxacin and etoposide combination treatment in subjects with relapsed and refractory acute myeloid leukemia. Eleven subjects were enrolled in the study. Utilizing the standard '3 + 3' design, escalating ciprofloxacin doses (750 mg, 1000 mg) twice daily on D1-D10 in combination with a fixed dose (200 mg) of etoposide on D2-D8 were administered. Maximum tolerated dose was determined to be 1000 mg of ciprofloxacin in combination with 200 mg of etoposide. Serious adverse events occurred in 54.5% (n = 6) subjects and 91% (n = 10) subjects reported ≥ grade 3 toxicities. Nine subjects completed treatment, one had a dose-limiting toxicity, and one withdrew. One subject achieved complete remission with a duration of 111 days and one subject achieved morphologic leukemia-free state after cycle 1. While the combination demonstrated safety and an acceptable toxicity profile, only modest hematologic and clinical benefits were observed. This trial was registered at as #NCT02773732. [ABSTRACT FROM AUTHOR]

Background: The second victim phenomenon refers to the emotional trauma healthcare professionals experience following adverse events (AEs) in patient care, which can compromise their ability to provide safe care. This issue has significant implications for patient safety, with AEs leading to substantial human and economic costs. Analysis: Current evidence indicates that AEs often result from systemic failures, profoundly affecting healthcare workers. While patient safety initiatives are in place, the psychological impact on healthcare professionals remains inadequately addressed. The European Researchers' Network Working on Second Victims (ERNST) emphasizes the need to support these professionals through peer support programs, systemic changes, and a shift toward a just culture in healthcare settings. Policy Options: Key options include implementing peer support programs, revising the legal framework to decriminalize honest errors, and promoting just culture principles. These initiatives aim to mitigate the second victim phenomenon, enhance patient safety, and reduce healthcare costs. Conclusion: Addressing the second victim phenomenon is essential for ensuring patient safety. By implementing supportive policies and fostering a just culture, healthcare systems can better manage the repercussions of AEs and support the wellbeing of healthcare professionals. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is a significant concern, especially for individuals undergoing renal transplantation, as it disrupts bone health and increases the risk of fractures. Interventions for osteoporosis aim to address bonerelated challenges in patients with renal transplantation, yet concerns persist regarding both efficacy and potential adverse events. Materials and Methods: We searched PubMed/MEDLINE, EMBASE, and the Cochrane CENTRAL databases until December 15, 2023, seeking studies that evaluated the efficacy and adverse events of osteoporosis medications in patients with renal transplantation. The Cochrane tool was utilized to assess the quality of the studies. The statistical analysis was performed using Comprehensive Meta-Analysis software, version 3.0. Results: We enrolled 594 participants from 7 randomized controlled trials. Combining trial results reveals that using anti-osteoporotic agents (Ibandronate, Risedronate, and Pamidronate) reduces the risk of vertebral fractures compared to the placebo. However, the reduction was not statistically significant (OR: 0.49, CI 95%: 0.20-1.22). Additionally, lumbar spine, femoral neck, and total hip BMD showed no significant differences between anti-osteoporotic agents (Denosumab, Zoledronic acid, Ibandronate, Risedronate, and Pamidronate) and placebo. Moreover, there were no significant differences in adverse events between the interventions and placebo. Conclusion: The study suggests that anti-osteoporotic agents in renal transplantation patients may be associated with a non-significant lower risk of vertebral fractures compared to a placebo. Findings also indicate no significant differences in adverse events between interventions and placebos. Caution is advised in interpreting these results due to the absence of statistically significant differences, emphasizing the need for further research to enhance our understanding of efficacy and safety in renal transplantation. [ABSTRACT FROM AUTHOR]

BACKGROUND: About one-quarter of patients with advanced prostate cancer have alterations in homologous recombination repair (HRR) genes. In a global phase 3 study, talazoparib plus enzalutamide significantly improved progression-free survival in patients with HRR-deficient metastatic castration-resistant prostate cancer (mCRPC). OBJECTIVES: This article reviews the role of oncology nurses and advanced practice providers (APPs) in administering talazoparib plus enzalutamide in patients with mCRPC. METHODS: This review and hypothetical case study illustrate the role of oncology nurses and APPs in the administration of talazoparib plus enzalutamide and the management of adverse events to ensure safe and effective use in clinical practice. FINDINGS: Oncology nurses and APPs play an important role in the dosing and administration of talazoparib plus enzalutamide and can recognize and manage adverse events in patients with HRR-deficient mCRPC. [ABSTRACT FROM AUTHOR]