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Introduction: Propofol is an anesthetic agent commonly used in emergency department (ED) procedural sedation. It is often preferred in orthopedic procedures because of its muscle-relaxing properties. Rarely, however, it can induce agitation and muscle hypertonicity.Case Report: A 58-year-old man presented to the ED with a left ankle fracture-dislocation. Propofol was used to facilitate procedural sedation, but the patient became mildly agitated. Ketamine was used to achieve full induction, after which propofol was used again to facilitate muscle relaxation. Near the end of the procedure, the patient had opisthotonos and masseter spasm requiring bag-valve-mask ventilation and subsequent intubation. This reaction was ultimately attributed to adverse effects of the propofol.Conclusion: While propofol is generally well tolerated, it can potentially cause agitation, hypertonicity, and other side effects such as muscle spasms and seizure-like activity. Acknowledging and preparing for these risks can potentially improve patient outcomes.

Little is known about adverse events surrounding animal-assisted interventions (AAIs) since they are reluctantly reported and uncommonly discussed in the literature. Voluntarily reported adverse events occurring within an AAI program in the south-east United States over a 5-year period (2015–2019) were retrospectively reviewed. Thirteen adverse events were reported with four events resulting in injury to a human while engaged in AAI. Nine of the 13 animals involved in adverse events were reported in their first year of service. Outcomes of adverse events were based on severity of the event and likelihood of recurrence. All animal-handler teams involved in adverse events that occurred outside of the AAI setting (3/13) were retired and of the remaining 10 adverse events that occurred while engaged in AAI, three animal-handler teams returned to work, three returned to modified work, and four were retired. These findings indicate that adverse events do occur in AAI, although they are typically not severe in nature. When they do occur, retirement of the animal-handler team is not compulsory. Based on the findings of this study, recommendations are offered for potentially preventing, managing, and determining outcomes of adverse events.

We present a 44-year-old man with metastatic clear cell renal cell cancer undergoing treatment with nivolumab immunotherapy. Three months post-initiation, he developed symmetric recurrent nodules and boils in intertriginous areas, diagnosed as stage II hidradenitis suppurativa of the groin and gluteal cleft. The progressive course, lesion symmetry and location, worsening with nivolumab infusions, and biopsy findings supported the diagnosis. Hidradenitis suppurativa pathogenesis involves immune dysregulation marked by elevated IL17 and neutrophil-dominated inflammation [1]. Immune checkpoint inhibitors, including anti-PD1 agents like nivolumab, are linked to immune-related adverse events related to widespread T cell activation, potentially increasing IL17 signaling associated with HS [2,3]. Clinicians should be aware of, and observant for anti-PD1-induced HS, a rare immune-related adverse event, in patients undergoing immune checkpoint inhibitor therapy.

Leflunomide can be used in management of psoriatic disease. Leflunomide's active metabolite, teriflunomide, is used in the treatment of multiple sclerosis and has unexpectedly been rarely reported to induce pustular psoriasis. In this report, we present a patient with multiple sclerosis who developed inverse psoriasis after starting teriflunomide.

BackgroundIn randomized clinical trials (RCTs), monitoring adverse events (AEs) and serious AEs (SAEs) is critical. All Alzheimer's disease (AD) RCTs require participants to enroll with a study partner.ObjectiveWe examined AE reporting rates in mild-to-moderate AD trials and their associations with study partner type.MethodsWe estimated AE reporting rates using placebo data from seven independent RCTs conducted by the Alzheimer's Disease Cooperative Study. We assessed the heterogeneity of reporting rates as a function of visits using generalized estimating equations. In the primary analysis, we tested the hypotheses that the rates of reporting differed by study partner type and time they spent with the participant weekly using Poisson regression with robust variance estimation. In all regression models, log-transformed total patient years was included.ResultsThe estimated reporting rates were 2.83 (95% CI: 2.66, 3.02), 1.18 (95% CI: 1.09, 1.28), 0.23 (95% CI: 0.19, 0.27), and 0.28 (95% CI: 0.24, 0.33) events per participant year for grade 1-3 AEs and SAEs, respectively. We estimated that greater number of visits per year was associated with increased reporting for grade 1-2 AEs and SAEs. We did not find evidence to suggest that AE reporting differed by study partner type or by time the study partner spent with the participant.ConclusionsStudy partner type and time the study partner spent with the participant did not appear to impact AE reporting. Estimated reporting rates may be useful to evaluate safety in future studies, particularly those with no control arm and similar visit frequencies.

Background Methods Results Conclusions While the occurrence of immune‐related adverse events has been recognized as a prognostic marker in patients receiving immune checkpoint inhibitors, the prognostic significance of treatment‐related adverse events (trAEs) in patients undergoing antibody–drug conjugates such as enfortumab vedotin (EV) is controversial.We reviewed 106 patients with advanced urothelial carcinoma who were treated with EV therapy at 10 institutions between 2021 and 2023. Associations of clinical parameters with overall survival and progression‐free survival were assessed using the Cox proportional hazards model. For the assessment of trAEs, landmark analysis was conducted to minimize immortal time bias.Of 106 patients, 55 (51.9%) experienced disease progression and 44 (41.5%) died during the follow‐up period. Any grade and grade ≥3 trAEs occurred in 94 (88.7%) and 44 (41.5%) patients, respectively. Common trAEs included skin disorders (74.5%), gastrointestinal disorders (62.3%), fatigue (50.0%), peripheral neuropathy (36.8%), and hematological disorders (37.7%). One patient died of interstitial pneumonia (grade 5). According to landmark analysis using 88 patients who survived for 2 months or more, trAEs were significantly associated with longer survival. Furthermore, when trAEs were classified into “physical trAEs” such as skin disorders and “laboratory trAEs” such as hematological disorders, the former were associated with longer survival while the latter were associated with shorter survival.Physical, but not laboratory, trAEs are associated with favorable outcomes of EV therapy for advanced urothelial carcinoma. Both managing trAEs and utilizing them as prognostic markers are key points in the use of antibody–drug conjugates such as EV. [ABSTRACT FROM AUTHOR]

Background: Enzalutamide and abiraterone may differ in their immunomodulatory effects, and the prednisone coadministered with abiraterone can be immunosuppressive. This study aimed to compare the risk of different types of infection in patients with prostate cancer receiving enzalutamide or abiraterone in combination with androgen deprivation therapy. Methods: Patients with prostate cancer receiving enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between December 1999 to March 2021 were identified in this retrospective cohort study and followed up until September 2021, death, or crossover. Outcomes, including any sepsis, pneumonia, urinary tract infection, cellulitis or skin abscess, central nervous system infections, and tuberculosis, were analyzed as both time‐to‐event outcomes (multivariable Fine‐Gray regression, with mortality considered a competing event) and recurrent‐event outcomes (multivariable negative binomial regression). Results: Altogether, 1582 patients were analyzed (923 abiraterone users; 659 enzalutamide users) with a median follow‐up of 10.6 months (interquartile range: 5.3–19.9 months). Compared to abiraterone users, enzalutamide users had lower cumulative incidences of sepsis (adjusted subhazard ratio [SHR] 0.70 [0.53–0.93], p =.014), pneumonia (adjusted SHR 0.76 [0.59–0.99], p =.040), and cellulitis or skin abscess (adjusted SHR 0.55 [0.39–0.79], p =.001), but not urinary tract infection (adjusted SHR 0.91 [0.62–1.35], p =.643). Associations between exposure and central nervous system infections and tuberculosis were not assessed because of low event rates. Analyzing the outcomes as recurrent events gave similar results. Enzalutamide use may be associated with a lower risk of urinary tract infection in patients with diabetes mellitus. Conclusions: Compared to abiraterone users, enzalutamide users have significantly lower risks of sepsis, pneumonia, cellulitis, or skin abscess. This study compared the risk of infections in patients with prostate cancer taking enzalutamide versus abiraterone. The results showed that enzalutamide users had a lower risk of sepsis, pneumonia, and cellulitis or skin abscess compared to those on abiraterone. [ABSTRACT FROM AUTHOR]

Accurate, comprehensive, and consistent reporting of adverse events is of great importance for treatment decisions in clinical practice and patient safety. Aiming to evaluate the completeness and transparency of reported adverse events we conducted a retrospective analysis of completed clinical trials on glaucoma interventions registered in ClinicalTrials.gov from September 27, 2009, and updated and with results on or before November 1, 2023, as well as in corresponding journal publications. Any difference in completeness, number, or terminology/description of adverse events and all-cause mortality between ClinicalTrials.gov and the publication was categorized as inconsistent reporting of adverse events. All 79 trials with results both in the registry and a journal publication exhibited at least one inconsistency in reporting adverse events. In 19 publications (24%), the number of serious adverse events was smaller than in the registry. 69 (87%) trials reported more other adverse events in the registry than in the publication. Trials completed after the FDAA mandate for summary reporting of all-cause mortality more often reported this item in the registry but not in the publication. Trials on glaucoma interventions do not consistently report adverse events and thus introduce concerns about study credibility and potential harms of the interventions. Journals and other stakeholders in trial reporting must address this problem to ensure the safety of patients and trust in health interventions. [ABSTRACT FROM AUTHOR]

Background: Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). It is known that non-serious treatment-emergent adverse events (TEAEs) may not lead to UC drug discontinuation but can affect treatment tolerability. Objectives: This post hoc analysis evaluated the incidence of specific, common, non-serious TEAEs reported in the etrasimod UC clinical programme and the characteristics of affected patients. Design: Data included patients from the Placebo-controlled UC cohort (phase II OASIS, and phase III ELEVATE UC 52 and ELEVATE UC 12 trials) receiving QD etrasimod (2 or 1 mg) or placebo. Methods: Proportions and incidence rates (IRs; the number of patients with a TEAE divided by the total exposure in patient-years (PYs), per 100 PY) of Headache, Pyrexia, Nausea and Dizziness TEAEs were reported. Changes in heart rate among patients with Dizziness TEAEs were also evaluated. Results: Among 943 patients (etrasimod 2 mg, N = 577 (276.7 PY); etrasimod 1 mg, N = 52 (11.4 PY); placebo, N = 314 (115.1 PY)), 48, 34, 27 and 21 patients experienced events of Headache, Pyrexia, Nausea and Dizziness, respectively. All events were non-serious; one patient treated with etrasimod was discontinued due to a Pyrexia TEAE. Numerically, IRs of Headache and Dizziness TEAEs were higher, and Nausea slightly higher, with etrasimod versus placebo (13.45 vs 8.63 per 100 PY, 6.52 vs 1.69 and 7.18 vs 5.13 per 100 PY, respectively); IRs were similar for Pyrexia. The duration of most TEAEs was 1–10 days. Conclusion: In the etrasimod UC clinical programme, all Headache, Pyrexia, Nausea and Dizziness events were non-serious. Headache and Dizziness were more frequent, and Nausea slightly more frequent, among patients receiving etrasimod versus placebo. The post hoc nature of this analysis is a limitation. These results reiterate the favourable safety profile and tolerability of etrasimod. Trial registration: ClinicalTrials.gov: NCT02447302; NCT03945188; NCT03996369. [ABSTRACT FROM AUTHOR]

Janus kinase inhibitors (JAKi) are drugs that block tyrosine kinases responsible for transducing cytokine signals. The first JAKi was approved by the US Food and Drug Administration (FDA) in 2011 to treat rheumatoid arthritis in adults. A pediatric indication was not approved until 8 years later, for acute graft‐versus‐host disease. Since then, topical and oral formulations have gained FDA approval for pediatric patients with dermatologic diseases. While increasing evidence supports the safety of these medications in adults, data are limited in children. We sought to determine whether JAKi adverse events (AEs) as reported in clinical trials and via postapproval pharmacovigilance services are comparable in adult and pediatric patients. Pharmacovigilance data were extracted from the FDA's Adverse Event Reporting System and the Canada Vigilance Adverse Reaction Online Database for baricitinib, upadacitinib, abrocitinib, ruxolitinib, and tofacitinib. The pooled data were analyzed to detect the most common AEs for specific JAKi and for the drug class. We assessed 399,649 AEs from 133,216 adults and 2883 AEs from 955 patients under 18 years old and identified slightly different AE profiles for the two age groups. Both populations had increased risk for infections and gastrointestinal AEs. However, pediatric patients reported a higher proportion of blood and lymphatic disorders, while reports of nervous system and musculoskeletal/connective tissue disorders were more common in adults. The spectrum of AEs extracted from pharmacovigilance reports was similar to clinical trials. The JAKi AE profiles we observed may prove helpful in counseling patients and their parents before starting therapy and for monitoring once patients are on therapy. [ABSTRACT FROM AUTHOR]

Background: Antibody‐drug conjugates (ADC) have emerged as a highly promising systemic option in the treatment of recurrent ovarian cancer. The present study aimed to evaluate the treatment efficacy of folate receptor α (FRα)‐targeting ADCs, associated treatment‐related adverse events (TRAEs), and their impact on treatment safety. Methods: We conducted an electronic search to identify prospective trials of single‐agent ADCs targeting FRα and those combined with chemotherapy in recurrent ovarian cancer. Information regarding the objective response rate (ORR) and TRAEs was collectively analyzed, and differences in subgroups based on FRα receptor expression levels were investigated. The protocol was registered with PROSPERO (CRD42023491151). Results: Ten studies with a total of 940 patients (859 treated with Mirvetuximab soravtansine‐gynx (MIRV)), 45 with Farletuzumab Ecteribulin (MORAb‐202), and 36 with Luveltamab Tazevibulin (STRO‐002) were included in this meta‐analysis. Based on the pooled data, the ORR of the entire cohort was 37% (95% CI: 0.30–0.43), while that of the high‐FRα expression group was 34% (95% CI: 0.26–0.42). The incidence of grade ≥ 3 adverse events was 27% (95% CI: 0.19–0.36). Conclusion: FRα‐targeting ADCs, including MIRV, demonstrated definite efficacy and good safety as novel choices for second‐line and beyond treatment of advanced or recurrent ovarian cancer. Patients with high FRα expression showed ORR and PFS benefits similar to those in the overall cohort. [ABSTRACT FROM AUTHOR]

Background The use of androgen biosynthesis and second-generation androgen receptor inhibitors for advanced prostate cancer is increasing. Because these therapies alter the androgen pathway, they have been associated with cardiometabolic and neurocognitive toxicities. Although their safety profiles have been assessed in clinical trials, real-world data are limited. Methods A 20% sample of national Medicare claims was used to perform a retrospective cohort study of Medicare beneficiaries with advanced prostate cancer treated with androgen biosynthesis (ie, abiraterone) and second-generation androgen receptor inhibitors between 2012 and 2019. Outcomes were assessed after the first fill of either class of drug for the 12-month period after starting therapy. The primary outcome was a hospital admission or emergency department visit for a cardiometabolic event. Secondary outcomes included neurocognitive events and fractures. Multivariable regression was used to assess the association between the class of drug and occurrence of an adverse event. Results There were 3488 (60%) men started on an androgen biosynthesis inhibitor and 2361 (40%) started on an androgen receptor inhibitor for the first time. Cardiometabolic adverse events were more common in men managed with androgen biosynthesis inhibitor (9.2% vs 7.5%, P  = .027). No difference between androgen biosynthesis and androgen receptor inhibitors was observed for neurocognitive events (3.3% vs 3.4%, respectively; P  = .71) or fractures (4.2% vs 3.6%, respectively; P  = .26). Conclusions Men with advanced prostate cancer initiating an androgen biosynthesis inhibitor for the first time more commonly had cardiometabolic events than those started on androgen receptor inhibitors. Neurocognitive events and fractures did not differ by drug class. [ABSTRACT FROM AUTHOR]

Simple Summary: Our research explores the profile and risk factors for infections in multiple myeloma patients undergoing treatment with daratumumab, a key drug in chemotherapy regimens for this disease. The study seeks to identify which patients are at the highest risk of developing severe infections and the factors contributing to this risk, as infections are a major concern for these patients. Analysis of patient data from our facility showed that lower hemoglobin levels and poorer performance status significantly increase the risk of serious infections. Additionally, we developed predictive algorithms to identify individuals at elevated risk of developing pneumonia during treatment. The findings from our study may help healthcare providers identify high-risk patients and implement targeted strategies to prevent infections, ultimately improving patient care. Background: Daratumumab (Dara) is the first monoclonal antibody introduced into clinical practice to treat multiple myeloma (MM). It currently forms the backbone of therapy regimens in both newly diagnosed (ND) and relapsed/refractory (RR) patients. However, previous reports indicated an increased risk of infectious complications (ICs) during Dara-based treatment. In this study, we aimed to determine the profile of ICs in MM patients treated with Dara-based regimens and establish predictors of their occurrence. Methods: This retrospective, real-life study included MM patients treated with Dara-based regimens between July 2019 and March 2024 at our institution. Infectious events were evaluated using the Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: The study group consisted of a total of 139 patients, including 49 NDMM and 90 RRMM. In the RR setting, the majority (60.0%) of patients received the Dara, bortezomib, and dexamethasone (DVd) regimen, whereas ND patients were predominantly (98%) treated with the Dara, bortezomib, thalidomide, and dexamethasone (DVTd) regimen. Overall, 55 patients (39.6%) experienced ICs. The most common IC was pneumonia (37.5%), followed by upper respiratory tract infections (26.8%). Finally, twenty-five patients had severe ICs (grade ≥ 3) and required hospitalization, and eight patients died due to ICs. In the final multivariable model adjusted for setting (ND/RR) and age, hemoglobin level (OR 0.77, 95% CI: 0.61–0.96, p = 0.0037), and Eastern Cooperative Oncology Group (ECOG) >1 (OR 4.46, 95% CI: 1.63–12.26, p = 0.0037) were significant factors influencing severe IC occurrence. Additionally, we developed predictive models using the J48 decision tree, gradient boosting, and random forest algorithms. After conducting 10-fold cross-validation, these models demonstrated strong performance in predicting the occurrence of pneumonia during treatment with daratumumab-based regimens. Conclusions: Simple clinical and laboratory assessments, including hemoglobin level and ECOG scale, can be valuable in identifying patients vulnerable to infections during Dara-based regimens, facilitating personalized prophylactic strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer immunotherapies, while revolutionary in boosting the immune system to fight cancer, can also trigger serious side effects, including inflammation of the brain. We review the existing literature on encephalitis with a special focus on cancer treatment-related encephalitis, including its etiopathogenesis, differential diagnosis, and identification of optimal diagnostic approaches and treatment strategies. This review aims to help clinicians from oncology and neurology improve the diagnosis and management of this condition, help reduce complications, improve patient outcomes, and inform future therapeutic approaches. Encephalitis associated with cancer therapies is a rare but serious complication that can significantly impact patients' quality of life and it requires prompt identification and management. Over the past two decades, immunotherapy—particularly immune checkpoint inhibitors—has become a cornerstone of cancer treatment, with up to half of metastatic cancer patients in economically developed countries now receiving these therapies. The widespread adoption of immunotherapy has led to improved survival rates and long-term remissions, even in patients with advanced metastatic disease. However, as immune modulators, these therapies can trigger a range of immune-related adverse events, including a variety of novel neurological toxicities. Among these, encephalitis is of particular concern due to its potential severity, which can compromise treatment outcomes. This review aims to provide a comprehensive overview of the literature on this condition, highlighting optimal diagnostic strategies and management approaches to mitigate the risk of significant morbidity, while also comparing encephalitis induced by immunotherapy with that caused by traditional chemotherapies and targeted oncologic treatments. [ABSTRACT FROM AUTHOR]

Anti-amyloid drugs for early Alzheimer's disease, including lecanemab, are associated with adverse events (AEs), such as amyloid-related imaging abnormalities (ARIA)-edema/effusion (E), ARIA-hemorrhage, and infusion-related reactions, which can indicate allocated arms in clinical trials. Herein, we evaluated the predictive value of AEs using a meta-analysis to estimate their incidence and simulated positive predictive value (PPV). The PPV for ARIA-E was high (0.915), but that for ARIA hemorrhage was low (0.630). Infusion-related reactions had a high PPV of 0.910, but with a wide confidence interval. Our results suggest the need to ameliorate the unblinding effects of AEs, particularly ARIA-E in trials. [ABSTRACT FROM AUTHOR]

Pityriasis rosea is an acute, self‐limited exanthem that typically occurs in adolescence and young adulthood, classically featuring ovoid erythematous and scaly lesions on the trunk and proximal extremities. While its cause is not definitively known, the classic form of pityriasis rosea may result from the reactivation of latent human herpesvirus (HHV) infections (HHV‐6 and HHV‐7). Interestingly, drug eruptions that clinically and/or histopathologically resemble pityriasis rosea have also been reported. These pityriasis rosea‐like drug eruptions tend to occur at an older age and have a shorter duration than the classic type. As there are different management paradigms, the distinction between classic pityriasis rosea and the mimicking drug eruption is important to recognize. Herein, we report a case of a pityriasis rosea‐like drug eruption that occurred in association with imatinib mesylate treatment for chronic myeloid leukemia. We also review the clinicopathologic features of reported cases of pityriasis rosea‐like drug eruption, including those due to imatinib. While the clinical morphology of the cutaneous drug‐related eruption mimics the lesions seen in classic pityriasis rosea, the presence of unique histopathologic findings, including necrotic keratinocytes, interface dermatitis, and eosinophils, may aid in distinction. [ABSTRACT FROM AUTHOR]

Background/Aim: Radiotherapy is one of the most frequently used options for prostate cancer (PCa). However, adverse effects related to irradiation of surrounding normal organs are significant clinical concerns. Specifically, genitourinary toxicity can dramatically reduce the quality of life. This clinical trial investigated the efficacy of oral 5-aminolevulinic acid phosphate combined with sodium ferrous citrate (ALA-SFC) in patients treated with low-dose-rate brachytherapy (LDR-BT) using an iodine-125 seed source. Patients and Methods: The AMBER study was a prospective single-center trial involving patients with localized PCa who underwent LDR-BT without external-beam radiotherapy (jRCTs051190077). Fifty patients were included and instructed to take capsules of ALA-SFC twice a day (200 mg phosphate salt and 229.42 mg per day) for six months from the day of seed implantation (prescribed radiation dose of 160 Gy). Patient data were collected before implantation, during ALA-SFC treatment, and at 1, 3, 6, 9, and 12 months post-LDR-BT. The primary endpoint of this trial was urinary frequency at three months. Other patientreported outcomes, investigator-reported adverse events, and oncological outcomes were secondary endpoints. Results: Of 50 enrolled cases (45 in the per-protocol analysis, 49 in the safety analysis), urinary frequency and its increase from baseline did not differ from 141 historical controls at any time point, including at three months post-LDR-BT. Propensity score matched analysis confirmed no time-course differences in frequency, volume, or urinary symptom scores between groups. Biochemical failure-free and metastasis-free survival also remained similar. Conclusion: Oral supplementation of ALA-SFC to LDR-BT did not alleviate radiation-induced toxicity or improve oncological outcomes. [ABSTRACT FROM AUTHOR]

Background: Various prognosticative approaches to assist in recognizing clinical deterioration have been proposed. To date, early warning scores (EWSs) have been evaluated in hospital with limited research investigating their suitability in the prehospital setting. This study evaluated the predictive ability of established EWSs and other clinical factors for prehospital clinical deterioration. Methods: A retrospective cohort study investigating adult patients of all etiologies attended by Queensland Ambulance Service paramedics between January 1, 2018, and December 31, 2020, was conducted. With logistic regression, several models were developed to predict adverse event outcomes. The National Early Warning Score (NEWS), Modified Early Warning Score (MEWS), Queensland Adult Deterioration Detection System (Q‐ADDS), and shock index were calculated from vital signs taken by paramedics. Results: A total of 1,422,046 incidents met the inclusion criteria. NEWS, MEWS, and Q‐ADDS were found to have comparably high predictive ability with area under the receiver operating characteristic curve (AUC‐ROC) between 70% and 90%, whereas shock index had relatively low AUC‐ROC. Sensitivity was lower than specificity for all models. Although established EWSs performed well when predicting adverse events, these scores require complex calculations requiring multiple vital signs that may not be suitable for the prehospital setting. Conclusions: This study found NEWS, MEWS, and Q‐ADDS all performed well in the prehospital setting. Although a simple shock index is easier for paramedics to use in the prehospital environment, it did not perform comparably to established EWSs. Further research is required to develop suitably performing parsimonious solutions until established EWSs are integrated into technological solutions to be used by prehospital clinicians in real time. [ABSTRACT FROM AUTHOR]

Background: This single center prospective observational study was conducted to evaluate the acute toxicity of hypo-fractionated radiotherapy for Japanese breast cancer patients after surgery. Methods: This study recruited patients who were scheduled for moderately hypo-fractionated radiotherapy including supraclavicular lymph node area (Cohort M) or ultra-hypo-fractionated radiotherapy for the conserved breast (Cohort U) as postoperative treatment for breast cancer. Radiotherapy plans were generated using automated planning system. Irradiation of 42.5 Gy/16 fractions (Cohort M) or 26 Gy/5 fractions (Cohort U) was delivered, and boost irradiation of 10 Gy/5 fractions was added as needed. The primary endpoint was the proportion of grade ≥ 2 acute adverse events within 90 days. The toxicities were evaluated using CTCAE ver 5.0. Results: Between January 2023 and December 2023, 123 patients (81 in Cohort M and 42 in Cohort U) were enrolled. All the included patients were Japanese and completed their planned radiotherapy and were also able to be evaluated for acute adverse events. Grade 1/2/3–5 acute adverse events were observed in 67/12/0 for Cohort M and 31/4/0 for Cohort U. The proportion of grade ≥ 2 acute adverse events within 90 days was 15% (95% confidence interval 8–24%) for Cohort M and 10% (95% confidence interval 3–23%) for Cohort U. Conclusions: The proportion of acute toxicity of hypo-fractionated radiotherapy for Japanese breast cancer patients after surgery was shown to be acceptable in this study. [ABSTRACT FROM AUTHOR]

Background: Surveys on Patient Safety Culture™ Hospital Survey (HSOPSC) developed by the U.S. Agency for Healthcare Research and Quality (AHRQ) has been adopted worldwide. The Hospital Survey on Patient Safety Culture (HSOPSC) version 2.0 was released in 2019, but there have been no publications to date of its translation and validation for use in Malaysia. This study aimed to translate and cross-culturally adapt the revised HSOPSC 2.0 into the Malay language and determine its psychometric properties including the content, face, and construct validity, and reliability analyses. Methods: This study was conducted from April – June 2023 and divided into three stages: translation and cultural adaptation; content and face validation; and construct validation using confirmatory factor analysis and reliability testing among 319 healthcare personnel from a public university hospital in Malaysia. Results: The translated instrument demonstrated excellent content validity (I-CVI = 0.80 ~ 1.0, SCVI-average = 0.96) and face validity (I-FVI = 0.80 ~ 1.0, SFVI-average = 0.98). Reliability testing was acceptable (Cronbach's α = 0.60 ~ 0.80) but indicated that reverse-coded items were poorly perceived. Confirmatory factor analysis showed a satisfactory model fit for the translated instrument (RMSEA = 0.08, GFI = 0.80, CFI = 0.80, and χ2/df = 2.96). Six items had very low factor loadings (< 0.40), with two constructs "Staffing and Work Pace" and "Response to Error" having AVE < 0.4, but acceptable CR ≥ 0.6. No items were removed from the questionnaire despite low factor loadings following a consensus from an expert panel. Conclusion: The Malay version of the HSOPSC 2.0 containing ten domains and 32 items demonstrated satisfactory psychometric properties following expert consensus, with acceptable reliability and construct validity for measuring patient safety culture. Given factor loadings smaller than 0.40 in six items, broader validation is suggested to support the use of the translated instrument in the Malaysian healthcare setting. [ABSTRACT FROM AUTHOR]

Background: The aims of this study were to assess the presence of inverse publication bias (IPB) in adverse events, evaluate the performance of visual examination, and explore the impact of considering effect direction in statistical tests for such assessments. Methods: We conducted a cross-sectional study using the SMART Safety, the largest dataset for evidence synthesis of adverse events. The visual assessment was performed using contour-enhanced funnel plots, trim-and-fill funnel plots, and sample-size-based funnel plots. Two authors conducted visual assessments of these plots independently, and their agreements were quantified by the kappa statistics. Additionally, IPB was quantitatively assessed using both the one- and two-sided Egger's and Peters' tests. Results: In the SMART Safety dataset, we identified 277 main meta-analyses of safety outcomes with at least 10 individual estimates after dropping missing data. We found that about 13.7–16.2% of meta-analyses exhibited IPB according to the one-sided test results. The kappa statistics for the visual assessments roughly ranged from 0.3 to 0.5, indicating fair to moderate agreement. Using the one-sided Egger's test, 57 out of 72 (79.2%) meta-analyses that initially showed significant IPB in the two-sided test changed to non-significant, while the remaining 15 (20.8%) meta-analyses changed from non-significant to significant. Conclusions: Our findings provide supporting evidence of IPB in the SMART Safety dataset of adverse events. They also suggest the importance of researchers carefully accounting for the direction of statistical tests for IPB, as well as the challenges of assessing IPB using statistical methods, especially considering that the number of studies is typically small. Qualitative assessments may be a necessary supplement to gain a more comprehensive understanding of IPB. [ABSTRACT FROM AUTHOR]

Introduction: The majority of metastatic renal cell carcinoma (mRCC) patients receive one or more VEGFR TKI agents, alone or in combination with an immune-oncology (IO) agent or an mTOR inhibitor. To date, the cost of adverse events (AEs) common to VEGFR TKIs has not been quantified. This study estimated the potential impact of differences in VEGFR TKI AE profiles on treatment cost efficiency in the relapsed/refractory (R/R) setting. Methods: Patients with documented mRCC who were treated with VEGFR TKI therapies between Jan 2015 and Mar 2021 were identified using EMR. ICD-10 diagnosis codes were used to identify the first occurrence of each class effect AE. Patients were matched to 3rd party insurance claims, and costs associated to TKI AEs within 90 days of index event were captured. Average per patient AE cost data was calculated and applied to published incidence data to estimate regimen-specific AE total cost burden within a hypothetical commercial plan for mRCC patients undergoing treatment in the R/R setting. Results: The highest total cost for AE management was attributed to lenvatinib and everolimus use at $13,303, followed closely by sunitinib at $13,092. Tivozanib treatment was associated with the lowest total cost of AE management at $7,523, driven by the relatively lower incidence of certain high-cost AEs. Conclusions: The estimated costs of managing VEGFR TKI class-effect AEs were lowest with tivozanib, and highest with lenvatinib and everolimus, indicating potentially differential healthcare resource burden by TKI regimen. The use of tivozanib in the 3 L + mRCC setting suggests potential costs offsets when compared to other TKI regimens. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions Improved understanding of the deteriorating patient in the pre‐hospital setting may result in earlier recognition and response. Considering the effects of undetected deterioration are profound, it is fundamental to report the prevalence of pre‐hospital clinical deterioration to advance our understanding. The present study investigated the prevalence of pre‐hospital clinical deterioration and adverse events (AEs) within 3 days of the pre‐hospital episode of care.This retrospective cohort study was based on pre‐hospital incidents involving adult patients attended by Queensland Ambulance Service between 1 January 2018 and 31 December 2020. Due to lacking a standardised definition of pre‐hospital clinical deterioration, established early warning scores (NEWS, MEWS and Q‐ADDS) were calculated from pre‐hospital vital signs to identify clinical deterioration. Linked hospital data were used to identify the occurrence of an AE.Some degree of physiological derangement was initially observed in over half of the patients, and pre‐hospital clinical deterioration was seen in 2.7%–4% of patients. The prevalence of AEs was 3.2%. Patients that experienced an AE were more likely to be male, elderly, suffering from a medical (non‐trauma) condition, and had a greater burden of disease. Concerningly, almost 50% of patients that suffered an AE did not meet escalation thresholds of NEWS, MEWS or Q‐ADDS.The present study found the prevalence of pre‐hospital clinical deterioration and AEs subsequent to pre‐hospital episodes of care to be low. Future research should prioritise using standardised criteria to define pre‐hospital clinical deterioration and evaluate the performance of early warning scores. [ABSTRACT FROM AUTHOR]

In the treatment process of atopic dermatitis, pompholyx may occurs on palms and soles. However, there is limited knowledge about which patients are more likely to develop pompholyx and when it is expected to occur. Therefore, this study investigated the occurrence of pompholyx after the start of induction remission treatment. We collected medical information from48 AD patientswho visited Hiroshima University Hospital for the first time between January 2019 and December 2020, from the time of their first visit to 12 months later. In the initial group of 48 patients, 10 individuals developed pompholyx within 1 year after their first visit. There was no clear connection between the occurrence of pompholyx and treatment received. Most of the patients who developed pompholyx were above the age of 30. Serum thymus and activation-regulated chemokine (TARC) levels tended to be higher at the first visit in the group that later developed pompholyx compared to the group that did not. In conclusion, patients over the age of 30 with higher serum TARC levels may develop pompholyx while their AD is improving. It is crucial to provide these patients with information about the possibility of developing pompholyx during the course of their AD treatment and that it would be cured in the course of treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Previous studies have demonstrated that the occurrence of immune-related adverse events (irAEs) is significantly associated with favorable efficacy and prognosis in patients with cancers treated with immune checkpoint inhibitors (ICIs), such as anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T lymphocyte-associated antigen. However, few studies have investigated this association in patients with esophageal squamous cell carcinoma (ESCC). Herein, we evaluated the relationship of irAEs with tumor response and survival in patients with unresectable advanced or recurrent ESCC treated with second- or later-line nivolumab, an anti-PD-1 antibody, monotherapy. We observed that the occurrence of mild (grade 1/2) irAEs during the entire period, as well as within 8 weeks of nivolumab initiation, was significantly associated with tumor response and survival following nivolumab monotherapy. Thus, mild irAEs may serve as predictive markers for the response and prognosis of patients with ESCC treated with ICIs. Background: Patients across various cancers who develop immune-related adverse events (irAEs) post-immune checkpoint inhibitor (ICI) treatment tend to experience better tumor response and survival than those who do not. However, studies regarding this association in patients with esophageal squamous cell carcinoma (ESCC) are limited. Methods: We assessed the relationship of irAEs with tumor response and survival in 82 consecutive patients with unresectable advanced or recurrent ESCC treated with second- or later-line nivolumab, an anti-PD-1 antibody, monotherapy. Results: We observed irAEs in 24 (29.3%) patients, with the overall response and disease control rates in the irAE-positive group being significantly better than those in the irAE-negative group (both p < 0.0001). During the entire period and within 8 weeks of nivolumab initiation, progression-free and overall survivals (PFS and OS, respectively) were significantly better in patients with grade1/2 irAEs than in those without. Univariate and multivariate analyses indicated grade1/2 irAEs during the entire period and within 8 weeks as independent covariates for PFS (entire period: hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.16–0.49, p < 0.001; within 8 weeks: HR 0.46, 95% CI 0.23–0.93, p = 0.03) and OS (entire period: HR 0.24, 95% CI 0.13–0.44, p < 0.001; within 8 weeks: HR 0.41, 95% CI 0.18–0.92, p = 0.03). Conclusions: Grade1/2 irAEs during the entire treatment period and within 8 weeks of nivolumab initiation were significantly associated with improved tumor response and survival in patients with advanced ESCC treated with nivolumab monotherapy. Therefore, mild irAEs may be predictive markers for the response and prognosis of ESCC following ICI treatment. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusions Given the introduction of new advanced therapies for inflammatory bowel diseases (IBDs), expanded risk mitigation strategies are essential.To create a comprehensive set of statements on assessment procedures and vaccinations before starting monoclonal antibodies, Janus kinase (JAK) inhibitors or sphingosine‐1‐phosphate (S1P) modulators for IBD.We examined literature, guidelines and drug product information regarding vaccination and assessment recommendations for initiating advanced IBD therapies. Using a modified Delphi approach, delegates voted anonymously on the acceptability of these statements prior to and following consensus discussion.We developed eight statements on the domains of infectious diseases screening, vaccinations and assessments prior to commencing JAK inhibitors and S1P modulators. Six statements received agreement. Pre‐advanced therapy screening for infectious diseases was established, and the vaccination protocol was revised. Malignancy, cardiovascular and thromboembolic risk assessments are necessary before initiating JAK inhibitors. Those starting S1P modulators need cardiac and ophthalmic assessments.These consensus statements combine vaccination and assessments on the currently available advanced therapies for IBD as a single comprehensive document that may reduce IBD complications associated with use of advanced therapies. Knowledge gaps identified during the consensus process will provide further research opportunities. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusions Trial Registration The positivity thresholds of faecal immunochemical testing (FIT) in colorectal cancer (CRC) screening vary between countries.To explore the trade‐off between colonoscopies performed, adverse events and lesions detected at different FIT thresholds in a Norwegian CRC screening trial.We included first participation in biennial FIT screening for 47,265 individuals aged 50–74 years. Individuals with FIT > 15 μg Hb/g faeces were referred for colonoscopy. We estimated the number of colonoscopies, adverse events, screen‐detected CRCs, advanced adenomas and serrated lesions expected at FIT thresholds currently or recently used in other European countries ranging between 20 and 150 μg/g.At the 15 μg/g threshold (Norway), 3705 participants underwent colonoscopy, of whom 203 had CRC, 1119 advanced adenomas and 256 advanced serrated lesions. Using a 47 μg/g threshold, 1826 (49.3%) individuals would have undergone colonoscopy, and 154 (75.9%) would have been diagnosed with CRC, 702 (62.7%) with advanced adenoma and 128 (50.0%) with advanced serrated lesion compared to the 15 μg/g threshold. At 150 μg/g, the corresponding figures would have been 838 (22.6%) undergoing colonoscopy, 114 (56.2%) with CRC, 345 (30.8%) advanced adenoma and 54 (21.1%) advanced serrated lesions. The detection rate of stage I CRC was 0.22% at 15 μg/g and 0.11% at 150 μg/g. Post‐colonoscopy bleeding rates were 0.8% and 1.7%, respectively.Increasing the FIT threshold reduces colonoscopy demand, but substantially decreases lesion detection and unfavourably changes CRC stage distribution. The risk of adverse events at colonoscopy increased with FIT threshold, requiring country‐specific information on adverse events.Clinicaltrials.gov identifier: NCT01538550 [ABSTRACT FROM AUTHOR]

Background: Bone modifying agents (BMAs) have been used to prevent skeletal-related events (SRE) in cancer patients with bone metastases. In this meta-analysis, efficacy and adverse events (AEs) were studied based on a de-escalation strategy in which the BMA dosing interval was prolonged from 4 to 12 weeks. Methods: PubMed, Cochrane, ICHUSHI, and CINAHL were searched for articles on BMA dosing intervals from outcomes measured were the incidence of SRE and related various AEs. A quantitative meta-analysis was performed using a random-effects model to calculate relative risk ratios (RRs) and 95% confidence intervals (CIs). Result: The meta-analysis included three randomized controlled studies (RCTs) of Zoledronic acid hydrate (ZA) (n = 2663) and six RCTs (n = 141) on BMA other than ZA. There was no difference in the incidence of SREs when comparing the dosing frequency of 12 versus 4 weeks for BMA (RR = 1.21, 95% CI [0.82–1.78], p = 0.33). Further, AEs related to treatment discontinuation were significantly less frequent with ZA given every 12 weeks than when given every 4 weeks (RR = 0.51 [0.30–0.89], p = 0.02). In particular, renal dysfunction leading to grade ≥3 or discontinuation of treatment with ZA occurred significantly less frequently with every 12-week dosing (RR = 0.33 [0.12–0.91], p = 0.33). Conclusion: This meta-analysis showed no influence of BMA de-escalation on the incidence of SRE; nevertheless, AEs appeared to reduce with the de-escalated usage of ZA. [ABSTRACT FROM AUTHOR]

Background Falls have high socioeconomic costs. Information and communication technologies may support provision and monitoring of multisensory (MSR) physiotherapy programmes. The HOLOBalance platform used augmented reality holograms to provide patient-centred, individualised MSR. Objectives To determine the platform's safety, acceptability and feasibility, investigate functional gait and dynamic balance benefits and provide data for a definitive trial. Design and setting Single-blinded pilot randomised controlled feasibility study. Interventions were conducted at clinical sites or participants' homes in three European countries. Participants Community-dwelling older adults (median age 73 years; 64.2% female) at risk of falls were enrolled (May 2020-August 2021). Methods Participants were randomised to an 8-week clinic or home-based telerehabilitation MSR or OTAGO (control group) programme. Compliance, satisfaction, and adverse events determined feasibility. Clinical outcomes, assessed (blinded) within one-week prior to and post-intervention, included functional gait assessment (FGA), Mini BESTest and cognitive function. Results Randomisation to completion rate was 76.15% with 109 participants recruited (n = 289 screened). Drop-out rate was similar between groups. Adverse events were reported (n = 3) in the control group. Sixty-nine percent would recommend the HOLOBalance intervention. Findings were similar for the home and clinic-based arms of each intervention; data was combined for analysis. FGA (95%CI [1.63, 4.19]) and Mini-BESTest (95%CI [1.46, 3.93]) showed greater improvement in the HOLOBalance group with a clinically meaningful change of 4/30 noted for the FGA. Conclusions HOLObalance was feasible to implement and acceptable to older adults at risk of falls, with FGA and Mini-BEST improvements exceeding those for the OTAGO programme. A definitive trial is warranted. [ABSTRACT FROM AUTHOR]

OBJECTIVES Left ventricular assist device (LVAD) therapy has evolved from a short-term bridge-to-transplant strategy into a long-term and often chronic therapy due to long waiting times for heart transplantation and application as destination therapy. Consequently, patients are at risk of developing complications necessitating LVAD exchange. The aim of this study is to assess patient outcomes after LVAD exchange. METHODS Patients who underwent LVAD exchange between January 2010 and December 2022 were included. Logistic and cox regression analyses were used to identify potential risk factors for short and long-term adverse events, respectively. Survival after exchange was assessed using Kaplan–Meier estimates. RESULTS Sixty-one patients underwent a total of 80 LVAD exchanges. Most frequently observed short-term complications were pulmonary infections (16.3%) and right heart failure (16.3%). Exit-site infections (34.7%) and device malfunctions (25.3%) were the most often observed long-term complications. HeartWare ventricular assist device as index device was associated with a higher risk of right heart failure [hazard ratio 6.42, 95% confidence interval (CI) 1.80–22.90] and respiratory failure (hazard ratio 7.81, 95% CI 1.95–31.23) compared to HeartMate II and HeartMate 3. Survival was 83% (95% CI 75.5–95.3%) at 1 year and 67% (95% CI 53.9–84.7%) at 6 years after exchange. After 5 years, 25.0% was transplanted, 23.8% had undergone a re-exchange and 32.5% was alive without new intervention. CONCLUSIONS Although LVAD exchange can be performed with a relatively low mortality, other post-operative adverse events are common. Patients with the HeartWare ventricular assist device as index device may be at higher risk of developing right heart failure and respiratory failure after exchange. [ABSTRACT FROM AUTHOR]

Background: Despite recommendations to perform esophageal biopsies during esophagogastroduodenoscopy (EGD) for esophageal food impaction to evaluate for eosinophilic esophagitis (EoE), endoscopists often forgo biopsies. There are minimal data on the risks of biopsies in this setting. Aims: To determine the safety of performing biopsies during EGD for food impaction. Methods: We conducted a retrospective cohort study of patients who presented to University of North Carolina Hospitals from 2014 to 2021 with endoscopically confirmed food impaction. Data were abstracted from the medical records. Baseline clinical characteristics, procedural details, and adverse events were compared between patients who did and did not undergo biopsy. Adverse events were classified as esophageal (mucosal tear, bleeding, perforation) or extra-esophageal (aspiration, respiratory compromise, hypotension, arrhythmia). Results: Of 188 patients who underwent EGD for food impaction, 73 (39%) had biopsies taken. Older and non-White patients were less likely to be biopsied. None of the Black patients had biopsies taken. Only 2 (2.7%) of the 73 biopsied patients had an adverse event, and neither was related to the biopsies. Patients who were biopsied were less likely to experience adverse events. There were no differences in re-admission, ICU admission, or 30-day mortality between patients who were and were not biopsied. Conclusions: Esophageal biopsies remain underperformed during EGD for food impaction, especially in certain patient populations. Esophageal biopsies at the time of food impaction are unlikely to cause adverse events. Safety concerns should not preclude biopsies, and biopsies should be performed in the absence of extenuating circumstances. [ABSTRACT FROM AUTHOR]

Background Progressive disseminated histoplasmosis is a significant issue in Latin America, particularly in Brazil, contributing to high mortality rates. Objectives Our objectives were to comprehensively describe histoplasmosis treatment with various amphotericin B (AmB) formulations, including mortality rates, adverse effects and risk factors for mortality. Methods This multicentre retrospective cohort study (January 2014–December 2019) evaluated medical records of patients with proven or probable histoplasmosis treated with at least two doses of AmB in seven tertiary medical centres in Brazil. We assessed risk factors associated with death during hospitalization using univariate and multivariate analyses. Results The study included 215 patients, mostly male (n  = 158, 73%) with HIV infection (n  = 187, 87%), and a median age of 40 years. Only 11 (5%) patients initiated treatment with liposomal amphotericin B (L-AmB). Amphotericin B deoxycholate (D-AmB) was administered to 159 (74%) patients without changes in the treatment. The overall mortality during hospitalization was 23% (50/215). Variables independently associated with mortality were use of D-AmB (OR 4.93) and hospitalization in ICU (OR 9.46). There was a high incidence of anaemia (n  = 19, 90%), acute kidney injury (n  = 96, 59%), hypokalaemia (n  = 73, 55%) and infusion reactions (n  = 44, 20%) during treatment. Conclusions We found that D-AmB was the main formulation, which was also associated with a higher mortality rate. Lipid formulations of AmB have become more readily available in the public health system in Brazil. Further studies to evaluate the effectiveness of L-AmB will likely show improvements in the treatment outcomes for patients with disseminated histoplasmosis. [ABSTRACT FROM AUTHOR]

Background Antibiotic overuse leads to the emergence of antibiotic resistance that threatens immunocompromised cancer patients. Infections caused by MDR Gram-negative pathogens are difficult to treat and associated with high mortality. Hence, empirical therapy with standard-of-care (SOC) antibiotics could be suboptimal in these vulnerable patients. New antibiotics covering potential resistant pathogens may be considered. Methods We conducted a randomized non-inferiority study comparing safety and efficacy of imipenem/cilastatin/relebactam (IPM/REL), a β-lactam/β-lactamase inhibitor combination, with SOC antibiotics (cefepime, piperacillin/tazobactam or meropenem) in cancer patients with febrile neutropenia. Patients received at least 48 h of IV antibiotics and were assessed at end-of-IV (EOIV) therapy, test of cure (TOC; Days 21–28), and late follow-up (LFU; Days 35–42). Results A total of 100 patients were enrolled (49 IPM/REL and 50 SOC). Demographics and rates of documented microbiological infections were similar in both groups. In the SOC arm, 86% of antibiotics consisted of cefepime. Patients on IPM/REL had a higher favourable clinical response at EOIV than those on SOC (90% versus 74%; P  = 0.042); however, responses were similar at TOC and LFU. Microbiological eradication was comparable at all three timepoints. Study drug-related adverse events and adverse events leading to drug discontinuation were similar in both groups, with no study drug-related mortality. Conclusions Our results suggest that compared with SOC antibiotics, predominantly cefepime, IPM/REL for empirical coverage of febrile neutropenia in cancer patients is generally safe and could be associated with a better clinical outcome at EOIV. The current SOC consisting mainly of agents that do not cover for ESBL-producing and carbapenem-resistant Enterobacterales bacteria should be reconsidered. [ABSTRACT FROM AUTHOR]

The management of resistant tuberculosis (tb) can be extremely difficult, especially in case of novel unpredicted complications. In this report, we present a case of a 48-year-old patient with pre-extensively drug-resistant (XDR) tb who received a treatment regimen including pretomanid, bedaquiline, linezolid, cycloserine, and amikacin and died due to myocarditis. Acquired resistance to first- and second-line drugs developed due to previous poor adherence to medication. The clinical presentation of the patient, along with her initial ultrasonographical, electrocardiogram (ECG), and laboratory examinations, were typical for acute myocarditis; however, the patient was considered unstable, and further investigations, including magnetic resonance imaging (MRI), pericardiocentesis, and endomyocardial biopsy were not performed. To our knowledge, this is the first case of myocarditis in such a patient, the clinical features of which raised a high suspicion of drug induction that could be attributed to the treatment regimen that was administered. Clinicians who manage cases of drug-resistant tb should be aware of this newly reported, potentially lethal, adverse event. [ABSTRACT FROM AUTHOR]

Background and Aim: Delayed endoscopic sphincterotomy‐related bleeding (ES bleeding) is an unavoidable adverse event (AE) that can have serious ramifications. Intraoperative ES bleeding, which stops spontaneously in most cases, is a known risk factor for delayed bleeding. This study aimed to examine the preventive effect of a novel self‐assembling peptide (SAP) for delayed ES bleeding in patients who attained spontaneous hemostasis after intraoperative ES bleeding. Methods: A total of 1507 patients met the eligibility criteria for inclusion in this study. The rates of delayed ES bleeding and AE besides bleeding were compared between patients administered the SAP (SAP group) and those who were simply observed after spontaneous hemostasis of intraoperative ES bleeding (control group). Propensity score matching was performed to adjust for differences between the groups. Results: The rate of delayed ES bleeding was significantly lower in the SAP group than that in the control group (0.9% vs 3.8%, P = 0.044). The rates of AEs other than bleeding were 2.4% and 3.8% in the SAP and control groups, respectively, and the difference lacked statistical significance (P = 0.481). Multivariate analysis revealed that the use of SAP was significantly associated with a lower frequency of delayed ES bleeding (odds ratio, 0.35; 95% confidence interval, 0.13–0.98; P = 0.047). Conclusions: Self‐assembling peptide may be a simple, safe, and useful way to reduce the risk of delayed ES bleeding in patients who experienced intraoperative ES bleeding and obtained subsequent spontaneous hemostasis. [ABSTRACT FROM AUTHOR]

There are many opportunities for urologists to be emotionally impacted, and possibly injured, in the regular course of their work. In particular, urologists are vulnerable to become Second Victims as a result of errors, adverse events, and distressing clinical events. This article reviews best practices that individuals, training programs, hospitals, and healthcare systems can implement to intentionally and programmatically mitigate the short and long-term effects on healthcare professionals. [ABSTRACT FROM AUTHOR]

Pimavanserin, a novel 5-HT2A receptor antagonist, has been approved for the treatment of Parkinson's disease psychosis (PDP). This study aims to conduct a comprehensive analysis of the adverse events (AEs) of pimavanserin by analyzing the FDA's Adverse Event Reporting System (FAERS) database. AE reports related to pimavanserin in the FAERS database from the second quarter of 2016 to the fourth quarter of 2023 were mined. Signal detection methods, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), were employed to identify and classify AEs. The study collected 12,839,687 AE reports, with 30,997 reports primarily suspecting pimavanserin, identifying 166 Preferred Terms (PTs) across 27 System Organ Classes (SOCs). The data showed that males reported more frequently than females, with the highest reporting in patients aged 75 and above. Reports increased over time, with a significant rise in 2023 compared to 2016. Major categories of AEs included hallucination, death, product dose omission issue, and confusional state, with death being notably the second most reported issue. Strong and new potential AEs were identified, including sleep-related issues like somnolence, insomnia, and sleep talking; cognitive and behavioral issues such as alexithymia, belligerence, and aggression; dose-related issues like prescribed underdose and underdose; and other AEs like nonspecific reactions. This study reveals potential AEs of pimavanserin, including sleep disorders and cognitive changes, underscoring the importance of careful monitoring and personalized treatment in managing PDP. • Study of 12.8 million AE reports found 30,997 linked to Nuplazid. • Key AEs for Nuplazid included hallucinations, death, and dose issues. • New potential AEs like somnolence, insomnia, and cognitive changes were identified. [ABSTRACT FROM AUTHOR]

Daridorexant, a novel dual orexin receptor antagonist, was approved by the FDA in 2022 for the treatment of insomnia in adults. The aim of this study is to delve into the adverse events (AEs) of daridorexant by analyzing data from the FAERS database, to assess its safety and effectiveness in clinical applications. This study selected data from the FAERS database from the first quarter of 2022 to the third quarter of 2023. Various data analysis methods were used, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), to assess AEs related to daridorexant. The study analyzed a total of 2,624,030 AE reports, of which 1318 were related to daridorexant. It identified 59 preferred terms (PTs) involving 23 system organ classes (SOCs). Signal mining identified new potential AEs related to daridorexant, including sleep-related psychiatric symptoms (nightmare, abnormal dreams, sleep terror, etc.), emotional and perceptual abnormalities (hallucination, depression, agitation), physiological and behavioral responses (palpitations, dry mouth, energy increased, etc.), suicide risk (suicidal ideation, intentional overdose), and other special concern AEs (tachyphrenia, sleep-related eating disorder, hypersensitivity). Although some new potential AEs have been identified, these findings need further verification in broader datasets and long-term studies due to limitations in data sources and analysis methods. Future research should comprehensively assess the safety and effectiveness of daridorexant, providing more accurate guidance for medical professionals in the treatment of insomnia. • Analyzed over 2.6 million FAERS reports, including 1,318 Daridorexant-related cases. • Found new potential adverse events linked to Daridorexant. • Highlighted the need for further verification in broader datasets and long-term studies. [ABSTRACT FROM AUTHOR]

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Background A surgeon's daily performance may be affected by operating room organizational factors, potentially impacting patient outcomes. The aim of this study was to investigate the link between a surgeon's exposure to delays in starting scheduled operations and patient outcomes. Methods A prospective observational study was conducted from 1 November 2020 to 31 December 2021, across 14 surgical departments in four university hospitals, covering various surgical disciplines. All elective surgeries by 45 attending surgeons were analysed, assessing delays in starting operations and inter-procedural wait times exceeding 1 or 2 h. The primary outcome was major adverse events within 30 days post-surgery. Mixed-effect logistic regression accounted for operation clustering within surgeons, estimating adjusted relative risks and outcome rate differences using marginal standardization. Results Among 8844 elective operations, 4.0% started more than 1 h late, associated with an increased rate of adverse events (21.6% versus 14.4%, P = 0.039). Waiting time surpassing 1 h between procedures occurred in 71.4% of operations and was also associated with a higher frequency of adverse events (13.9% versus 5.3%, P < 0.001). After adjustment, delayed operations were associated with an elevated risk of major adverse events (adjusted relative risk 1.37 (95% c.i. 1.06 to 1.85)). The standardized rate of major adverse events was 12.1%, compared with 8.9% (absolute difference of 3.3% (95% c.i. 0.6% to 5.6%)), when a surgeon experienced a delay in operating room scheduling or waiting time between two procedures exceeding 1 h, as opposed to not experiencing such delays. Conclusion A surgeon's exposure to delay before starting elective procedures was associated with an increased occurrence of major adverse events. Optimizing operating room turnover to prevent delayed operations and waiting time is critical for patient safety. [ABSTRACT FROM AUTHOR]

Background Cyclin-dependent kinases (CDK) 4/6 inhibitors have significantly improved outcomes for patients with ER+/HER2− breast cancer. Nevertheless, they differ from each other in terms of chemical, biological, and pharmacological features, as well as toxicity profiles. We aim to determine whether QTc prolongation is caused by CDK4/6i in general or if it is associated with ribociclib only. Methods We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing the prevalence of QTc prolongation as an adverse event in HR+ breast cancer patients treated with CDK4/6i vs those without CDK4/6i. We pooled relative risk (RR) and mean difference (MD) with 95% confidence interval (CI) for the binary endpoint of QT prolongation. Results We included 14 RCTs comprising 16 196 patients, of whom 8576 underwent therapy with CDK4/6i. An increased risk of QTc prolongation was associated with the use of CDK4/6i (RR = 2.35, 95% CI = 1.67 to 3.29, P  < .001; I2 = 44%). Subgroup analyses revealed a significant increase in the QTc interval for the ribociclib and palbociclib cohorts. The ribociclib subgroup showed a relative risk of 3.12 (95% CI = 2.09 to 4.65, P  < .001; I2 = 12%), whereas the palbociclib subgroup had a relative risk of 1.51 (95% CI = 1.05 to 2.15, P  = .025; I2 = 0%). Conclusion Palbociclib was associated with QTc prolongation; however, the relative risk for any grade QTc was quantitively twice with ribociclib. Furthermore, grade 3 QTc prolongations were observed exclusively with ribociclib. These results are important for guiding clinical decision-making and provide reassurance regarding the overall safety profile of this drug class. [ABSTRACT FROM AUTHOR]

Background In 2022, the US experienced a significant increase in demand for minimally invasive aesthetic procedures, underscoring its rising acceptance amid an unregulated educational environment for practitioners. The absence of standardized educational pathways and quality control in aesthetic medicine, primarily provided by nonacademic institutions, highlights a critical need for establishing educational standards to ensure practitioner competence and patient safety. Objectives The aim of this study was to identify levels of competency for the aesthetic practitioner and necessary achievement milestones during the educational path from novice to expert injector. Methods A total of n = 386 international study participants responded to an online questionnaire regarding their experience in aesthetic medicine practice. The questionnaire comprised 58 questions focusing on professional data, the perceived difficulty of injection, and risk for the occurrence of adverse events for specific facial regions in soft tissue filler and toxin injections. Results Regardless of medical specialty and experience level, averages of 3.85 (1.8) years, 786.4 (2628) filler injections and 549.9 (1543) toxin injections were estimated to progress from novice to advanced injector, while averages of 6.10 (3.7) years, 1842.2 (4793) filler injections, and 1308.5 (3363) toxin injections were estimated to advance from advanced to expert injector. The nose and the perioral region have been ranked as the facial regions where it is most difficult to achieve a perfect aesthetic outcome and with the greatest risk for the occurrence of adverse events for filler and toxin injections, respectively. Conclusions In this study we establish an educational framework in aesthetic medicine by defining the progression from novice to competent and expert injector levels, suggesting 4 years of practice and over 790 filler and 550 neuromodulator injections for competence, and at least 6 years with 1840 filler and 1310 neuromodulator injections for expertise. We also identify critical facial regions for targeted treatments by different expertise levels. Level of Evidence: 4 [ABSTRACT FROM AUTHOR]

We compared the effects of capsule resection versus capsule suturing in patients treated with a dual-mobility trapeziometacarpal joint prosthesis. We included 131 patients with capsular resection and 57 patients with repair. The mean scores for pain and the brief Michigan Hand Outcomes Questionnaire were similar between the groups preoperatively and at 6 weeks and 1 year postoperatively. Mean key pinch strength was also similar in both groups before surgery and at 1 year, but higher in the capsular resection than in the suture group at 6 weeks. The incidence of complications reported throughout the 1-year postoperative period was not significantly different between the groups. One implant in the capsular resection group was revised for reasons most likely unrelated to capsule management. We conclude that the capsule can be safely resected during trapeziometacarpal joint implant arthroplasty. Level of evidence: III [ABSTRACT FROM AUTHOR]

Transmesenteric internal hernia is an uncommon cause of small bowel obstruction that occurs when small bowel loops protrude through a mesenteric defect into the abdominal cavity. Herein, we present an unexpected case of colonoscopy-induced transmesenteric internal hernia. An 81-year-old male patient presenting with intermittent hematochezia and constipation had undergone a laparoscopic left nephrectomy for ureteral cancer. A colonoscopy was performed to identify the etiology of his symptoms. He complained of severe abdominal pain 2 h after the examination despite uneventful endoscopic procedures, including cold snare polypectomy. Contrast-enhanced computed tomography revealed a strangulated small bowel obstruction with a closed-loop formation outside the descending colon. The small bowel loop was incarcerated into the left retroperitoneal space. Emergency laparotomy detected small bowel loops that prolapsed into the nephrectomy pedicle via a descending mesenteric defect, developed during the laparoscopic left nephrectomy. The incarcerated small bowel was detached from the hernia and returned to its normal position, and the mesenteric defect was closed. He demonstrated an uneventful postoperative course, with no internal hernia recurrence after discharge. This case indicates the risk of transmesenteric internal hernia through inadvertently created mesenteric defects should be borne in mind, especially when performing colonoscopies in patients who underwent laparoscopic nephrectomies. [ABSTRACT FROM AUTHOR]

Background: Sulfasalazine is a widely used anti-inflammatory medication for treating autoimmune disorders such as ulcerative colitis (UC), Crohn's disease, and rheumatoid arthritis. However, its safety profile has not been systematically evaluated in real-world settings. By analyzing the FDA Adverse Event Reporting System (FAERS) database, we identified risk signals associated with adverse reactions to sulfasalazine, offering valuable insights for clinical decisionmaking and risk management. Methods: Reports of adverse events (AEs) associated with sulfasalazine, covering the period from Q1 2004 to Q4 2023, were extracted from the FAERS database. Detailed case information was aggregated to assess demographic characteristics. The associations between sulfasalazine and adverse events were evaluated using the Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM). Results: We extracted 7,156 adverse event reports from the FAERS database where sulfasalazine was identified as the "Primary Suspect (PS)" drug. Using disproportionality analysis, we identified 101 preferred terms (PT) related to sulfasalazine across 24 organ systems. Notable adverse reactions consistent with the drug's labeling were observed, including Stevens-Johnson syndrome, agranulocytosis, eosinophilic pneumonia, and crystalluria. Additionally, novel positive signals not previously documented in the drug label were identified, including acute febrile neutrophilic dermatosis, aseptic meningitis, glomerulonephritis, and hepatosplenic T-cell lymphoma. Conclusion: Most of the adverse reaction findings in this study are consistent with previous clinical research, and we have also identified new potential AEs associated with sulfasalazine. These findings provide valuable insights for the safety monitoring and clinical application of sulfasalazine. [ABSTRACT FROM AUTHOR]

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a refractory chronic respiratory infectious disease and its prevalence is increasing globally. The standard treatment regimen for NTM-PD involves long-term multidrug therapy including macrolides. The incidence of adverse events is high given the advanced age of many NTM-PD patients. In addition, drug-drug interactions under coexisting conditions add additional complexity. Despite guidelines advocating multidrug therapy for NTM-PD, low adherence rates probably owing to the relatively frequent adverse events and drug interactions. An appropriate treatment regimen can improve the bacteriological response rates, reduce the development of macrolide resistance, and mitigate adverse events. Of particular concern are the interactions arising from new complications that develop with NTM-PD. Notably, chronic pulmonary aspergillosis occasionally co-infects NTM-PD, which can lead to poor prognosis. The primary therapeutic modality for chronic pulmonary aspergillosis is the azoles. However, the interaction with rifamycin is problematic, making it challenging to continue standard treatment for NTM-PD and requiring drug adjustments. The implications of rifamycin extend beyond chronic pulmonary aspergillosis, impacting various other diseases such as those requiring immunosuppressive agents and AIDS patients requiring antiretroviral therapy. Hence, a comprehensive consideration of drug interactions is imperative for the initiation of NTM-PD treatment. This mini-review focuses on drug-drug interactions in a multidrug regimen for NTM-PD and discusses the essential points to be considered in the treatment of NTM. [ABSTRACT FROM AUTHOR]

Background: To investigate the characteristics and trends of therapeutic errors that occur outside of healthcare facilities involving diabetes medications reported to US poison centers. Methods: National Poison Data System data from 2000 to 2021 were retrospectively analyzed. Results: There were 157,623 exposure cases of non-healthcare facility-related therapeutic errors associated with diabetes medications as the primary substance reported to US poison centers from 2000 to 2021. The rate of all therapeutic errors involving diabetes medications increased by 279.8% from 2000 to 2011, followed by a slower 15.0% increase to 2021. Half (50.1%) of the exposure cases were treated/evaluated and released and 44.1% did not receive treatment in a healthcare facility; however, 9.9% experienced a serious medical outcome, including 17 fatalities, and 1.0% were admitted to a critical care unit and 2.2% to a non-critical care unit. Insulin had the highest rates of therapeutic errors and serious medical outcomes, while sulfonylureas and insulin had the highest medical hospital admission rates. Metformin accounted for 59% (n = 10) of fatalities. Conclusions: Although most cases of therapeutic errors involving diabetes medications had no or minimal clinical consequences, an important minority were associated with a serious medical outcome or medical hospital admission. Increased efforts to prevent therapeutic errors involving diabetes medications are warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: The most common adverse events (AEs) that occurred in response to targeted therapy for hepatocellular carcinoma were appetite loss (adverse event grade 0/1/2/3 = 97/23/55/12), general fatigue (102/31/44/6), hypertension (120/6/40/17), hand-foot syndrome (HFS) (135/21/24/3), proteinuria (140/13/16/14), and hypothyroidism (148/12/23/0). Among these, appetite loss and general fatigue negatively affect overall survival (OS) and progression-free survival (PFS). Increasing AE grades of hypertension, proteinuria, and hypothyroidism were associated with better OS, whereas hypertension, HFS, and hypothyroidism were associated with better PFS. To assess the impact of adverse event (AE) severity, caused by targeted therapy, on overall survival (OS) and progression-free survival (PFS) in patients with unresectable hepatocellular carcinoma (HCC), a total of 183 patients with HCC treated with atezolizumab plus bevacizumab (40), lenvatinib (57), sorafenib (79), cabozantinib (3), ramucirumab (3), and regorafenib (1) were included in this study. Age-, AFP-, and ALBI score-adjusted hazard ratios (HRs) of AE grades 1 to 3 versus grade 0 for OS and PFS were calculated using Cox proportional hazards models. The linear trend of the HRs was assessed by calculating the p values for this trend. The most common AEs were appetite loss (AE grade 0/1/2/3 = 97/23/55/12), general fatigue (102/31/44/6), hypertension (120/6/40/17), hand-foot syndrome (HFS) (135/21/24/3), proteinuria (140/13/16/14), and hypothyroidism (148/12/23/0). The adjusted HRs for OS of these AEs were 0.532–1.450–2.361 (p for trend 0.037), 1.057–1.691–3.364 (p for trend 0.004), 1.176–0.686–0.281 (p for trend 0.002), 0.639–0.759–1.820 (p for trend 0.462), 1.030–0.959–0.147 (p for trend 0.011), and 0.697–0.609 (p for trend 0.119), respectively. Those for PFS of the corresponding AEs were 0.592–1.073–2.811 (p for trend 0.255), 1.161–1.282–4.324 (p for trend 0.03), 0.965–0.781–0.655 (p for trend 0.095), 0.737–0.623–2.147 (p for trend 0.153), 1.061–0.832–0.800 (p for trend 0.391), and 1.412–0.560 (p for trend 0.081), respectively. Appetite loss and general fatigue negatively affected clinical outcomes, whereas hypertension, HFS, proteinuria, and hypothyroidism had positive effects. [ABSTRACT FROM AUTHOR]

Simple Summary: Stereotactic ablative radiation (SAbR) is a focused, high-dose radiation technique used to treat cancers that have spread to the adrenal glands. One of the feared consequences of this therapy is causing adrenal insufficiency in patients, which is a lack of adrenal function; however, the rates and severity at which this occurs in patients are still poorly studied. We studied patients with 66 treated adrenal glands using SAbR, which demonstrated that this technique was effective at controlling cancer sites with a control rate of 75% at 1 year. The risk of patients developing adrenal insufficiency in the entire cohort was significant at 14%, with a median time of 4.3 months. There was a higher risk in patients who had both adrenal glands treated with SAbR, or who had received a prior surgical removal of their other adrenal gland prior to SAbR therapy, with 44% of these patients developing adrenal insufficiency. Background: Adrenal metastases are often treated with stereotactic ablative radiation (SAbR). We aimed to assess the incidence, timing, and factors associated with the development of primary adrenal insufficiency (PAI) following SAbR. Methods: A retrospective cohort study comprised 66 consecutive patients (73% men, median age 61 years) who underwent SAbR for adrenal metastasis. Results: The series encompassed metastases from renal cell carcinoma (41%), lung tumors (38%), colorectal adenocarcinoma (9%), melanoma (5%), and others (7%). Median follow-up was 17 months from SAbR. Nine (14%) patients developed PAI at a median of 4.3 months (range, 0.7–20.2). The incidence of PAI was 44% in patients with prior adrenalectomy receiving unilateral SAbR, 44% with bilateral SAbR, 2% with unaffected contralateral gland, and 0% with bilateral metastases treated with unilateral SAbR. PAI was associated with prior adrenalectomy (odds ratio [OR] 32) and bilateral SAbR (OR 8.2), but not age, sex, metastasis size, or biological effective dose. Post-SAbR 6-month and 1-year local control rates were 82% and 75%, respectively. Conclusions: Patients undergoing SAbR for adrenal metastasis are at high risk of developing PAI. PAI is associated with bilateral SAbR and contralateral adrenalectomy. PAI is unlikely with a remaining unaffected adrenal gland or in the setting of bilateral adrenal metastases with unilateral SAbR. [ABSTRACT FROM AUTHOR]