In recent years, there has been a growing trend in the use of immune checkpoint inhibitors (ICIs) for treating a larger patient population. However, it is important to note that immune-related adverse events (irAEs) frequently arise as a result. Therefore, precise patient monitoring becomes essential. We present the findings of a retrospective study conducted at the International University of Health and Welfare Narita Hospital (referred to as \"our hospital\") that aimed to identify risk factors linked to the occurrence of irAEs. The study focused on analyzing various factors, including therapeutic and lifestyle backgrounds, as well as laboratory values of patients who received ICI treatment and were subsequently diagnosed with irAE. The study included patients who met the eligibility criteria for ICIs (both single agent and combination therapy) as well as ICI in combination with anticancer drugs. The inclusion period for the study encompassed April 2020 to May 2022 at our hospital. The fifty patients were divided into two groups based on the severity of irAEs: the first group consisted of patients with irAE Grade 2 or lower (referred to as irAE Grade under 2), while the second group included patients with irAE Grade 3 or higher (referred to as irAE Grade over 3). Statistical analysis revealed significant differences in age (p=0.027) and CRP (C-reactive protein) levels (p=0.008) among the background factors when comparing the two groups. Additionally, statistically significant differences were observed among different ICI treatment groups in the occurrence of irAEs (p=0.035). however, it was indicated to be a relatively weak correlation. Moving forward, we shifted our focus to examine the frequency of irAEs in relation to exposure. However, we did not observe any significant correlation between exposure and irAE grade. Additionally, even when exposure was doubled through the use of ipilimumab in combination with ICIs (referred to as \"Mod exposure\"), no correlation was found. Exposure was further categorized into three groups: the PD-1 group, PD-L1 group, and PD-1 + CTLA-4 group. However, no significant correlation was observed between exposure in any of these groups and the grade of irAEs. Similarly, no significant correlation was observed between the dosage of ICI in the fixed-dose group and the weight-based dosage group with exposure and irAE Grade. Based on our study findings, there is a suggestive relationship between age and CRP levels and the occurrence of irAEs of Grade 3 or higher. These factors may play a role in contributing to the development of more severe irAEs.

OBJECTIVE: To evaluate the FeelBetter machine learning system\'s ability to accurately identify older patients with multimorbidity at Brigham and Women\'s Hospital at highest risk of medication-associated emergency department (ED) visits and hospitalizations, and to assess the system\'s ability to provide accurate medication recommendations for these patients.
METHODS: Retrospective cohort study.
METHODS: The system uses medications, demographics, diagnoses, laboratory results, health care utilization patterns, and costs to stratify patients\' risk of ED visits and hospitalizations. Patients were assigned 1 of 22 risk levels based on their system-generated risk percentile of either ED visits or hospitalizations. Logistic regression models were used to estimate the odds of ED visits and hospitalizations associated with each successive risk level compared with the 45th to 50th percentiles. After stratification, 100 high-risk (95th-100th percentiles) and 100 medium-risk (45th-55th percentiles) patients were randomly selected for generation of medication recommendations. Two clinical pharmacists reviewed the system-generated medication recommendations for these patients.
RESULTS: Logistic regression models predicting 3-month utilization showed that compared with the 45th to 50th percentiles, patients in the top 1% risk percentile had ORs of 7.9 and 17.3 for ED visits and hospitalizations, respectively. The first 5 high-priority medications on each patient\'s medication list were associated with a mean (SD) of 6.65 (4.09) warnings. Of 1290 warnings reviewed, 1151 (89.2%) were assessed as correct.
CONCLUSIONS: The FeelBetter system effectively stratifies older patients with multimorbidity at risk of ED use and hospitalizations. Medication recommendations provided by the system are largely accurate and can potentially be beneficial for patient care.

暂无摘要。

The Ad26.RSV.preF/RSV preF protein vaccine has previously demonstrated efficacyin protecting older adults against respiratory syncytial virus (RSV)-related lower respiratory tract disease in a phase 2b study. This study compared the immunogenicity of vaccine clinical trial material (CTM) representative of phase 2b clinical studies with CTM used in phase 3 clinical studies. A total of 248 adults aged 60-75 years, randomized in a 1:1 ratio, received one dose of either phase 3 CTM or phase 2b CTM. Solicited adverse events (AEs), unsolicited AEs, and serious AEs (SAEs) were assessed for 7-d, 28-d, and 6-month periods post-vaccination, respectively. RSV preF-ELISA antibody titers and RSV neutralizing titers were measured before and 14 d after vaccination. The phase 3 CTM-induced preF-ELISA response at Day 15, in terms of geometric mean titer, was shown to be non-inferior to that induced by phase 2b CTM. The RSV neutralizing antibody titers were also similar in the two groups at Day 15. The safety profile in terms of solicited AEs, unsolicited AEs, or SAEs was in general similar between the phase 3 CTM and phase 2b CTM groups, and solicited AEs were mostly mild to moderate in intensity. No related SAEs were reported, and no safety concerns were identified.

BACKGROUND: The prescription of sodium-glucose cotransporter-2 (SGLT2) inhibitors have been increasing due to their additional benefits, including weight loss, cardioprotection and renoprotection. Accordingly, there are concerns about the potential rise in severe adverse drug reactions (ADRs), such as urinary tract infections, diabetic ketoacidosis, volume depletion, and hypoglycemia. The Society has announced recommendations on the proper use of SGLT2 inhibitors. We aimed to elucidate the recent occurrence of severe ADRs which need discontinuation of SGLT2 inhibitors or hospitalization.
METHODS: In this retrospective cohort study, we identified 391 diabetic patients who were prescribed SGLT2 inhibitors upon admission to our hospital between April 2017 and March 2023. Of these, 68 patients who discontinued SGLT2 inhibitors for reasons other than ADRs were excluded. Patients were classified into the 2017 group and the 2020 group based on the treatment period of SGLT2 inhibitors, and the occurrence of ADRs and patient backgrounds were compared between the two groups.
RESULTS: A total of 323 eligible patients were identified. Discontinuations of SGLT2 inhibitors decreased in the 2020 group (p < 0.05). However, discontinuations due to frailty increased (p < 0.05). Hospitalization due to ADRs, specifically those due to urinary tract infections, diabetic ketoacidosis, or volume depletion, did not specifically decrease (p = 0.273).
CONCLUSIONS: This study indicated that there has been some improvement in the awareness of the proper use of SGLT2 inhibitors and there is still a need to continue enlightenment activities.

暂无摘要。

Mitrofanova et al.1 engineer a human colonic in vitro model capable of producing an intestinal mucus barrier, with potential applications for predicting drug-induced gastrointestinal toxicity. This improved system paves the way for more accurate and efficient drug development processes.

OBJECTIVE: The European Medicines Agency\'s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) launched a strategy to examine the public health impact of major regulatory interventions aimed at minimising risks of medicinal products. We conducted a lessons learnt analysis of impact studies completed between 2015 and 2023.
METHODS: We surveyed PRAC Sponsors and (Co-)Rapporteurs involved in the evaluation of 12 impact studies (10 commissioned by EMA and 2 conducted collaboratively by Member States) to explore how these support regulatory decision-making. Questions covered achievement of study objectives, risk minimisation effectiveness, added value for regulatory decision-making, and recommendations for future impact studies. Themes were generated using thematic content analysis.
RESULTS: Survey responses from 15 PRAC Sponsors and (Co-)Rapporteurs from 10 European Union Member States were included in the analysis. Among four cross-sectional surveys and eight drug utilisation studies, 50% achieved all objectives, the other studies partially due to limitations. Two studies concluded that risk minimisation measures were overall effective, two were effective with variation across countries, two were partially effective and four studies showed limited effectiveness. Two studies were deemed inconclusive due to limitations. The reasons for the limited effectiveness of risk minimisation may be explored using mixed-method approaches. Assessment of study feasibility and a priori discussion of effectiveness measurements is important.
CONCLUSIONS: Despite limitations, impact research adds value to regulatory decision-making by addressing knowledge gaps and providing additional information on unintended consequences of regulatory interventions. Our recommendations will help to improve planning, conducting and interpretating future impact studies.

BACKGROUND: The potentially fatal attacks experienced by porphyria carriers are triggered by various porphyrinogenic drugs. However, determining the safety of particular drugs is challenging.
METHODS: We retrospectively used the U.S. Food and Drug Administration\'s Adverse Event Reporting System (FAERS) to identify drugs associated with porphyria as an adverse event (AE) extracted from data from January 2004 to March 2022. The associated search terms included \"Porphyria,\" \"Porphyria screen,\" \"Porphyria non-acute,\" \"Porphyria acute,\" \"Acquired porphyria,\" and \"Pseudoporphyria.\" Signal mining analysis was performed to identify the association between drugs and AEs by four algorithms, namely the reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker.
RESULTS: FAERS reported 1470 cases of porphyria-related AEs, and 406 drugs were screened after combining trade and generic names. All four algorithms identified 52 drugs with signals. The characteristics of all the reports and signaling drugs were analyzed.
CONCLUSIONS: This is the first report of drug-associated porphyria that provides critical information on drug porphyrogenicity, facilitating rational and evidence-based drug prescription and improving the accuracy of porphyrogenicity prediction based on model algorithms. Moreover, this study serves a reference for clinicians to ensure that porphyrinogenic drugs are not prescribed to carriers of porphyria genetic mutations.

Systemic anticancer therapies (SACTs) are the leading cause of drug-induced interstitial lung disease (ILD). As more novel SACTs become approved, the incidence of this potentially life-threatening adverse event (AE) may increase. Early detection of SACT-related ILD allows for prompt implementation of drug-specific management recommendations, improving the likelihood of AE resolution and, in some instances, widening the patient\'s eligibility for future cancer treatment options. ILD requires a diagnosis of exclusion through collaboration with the patient\'s multidisciplinary team to rule out other possible etiologies of new or worsening respiratory signs and symptoms. At Grade 1, ILD is asymptomatic, and thus the radiologist is key to detecting the AE prior to the disease severity worsening. Planned computed tomography scans should be reviewed for the presence of ILD in addition to being assessed for tumor response to treatment, and when ILD is suspected, a high-resolution computed tomography (HRCT) scan should be requested immediately. An HRCT scan, with < 2-mm slice thickness, is the most appropriate method for detecting ILD. Multiple patterns of ILD exist, which can impact patient prognosis. The four main patterns include acute interstitial pneumonia / acute respiratory distress syndrome, organizing pneumonia, hypersensitivity pneumonitis, and non-specific interstitial pneumonia; their distinct radiological features, along with rarer patterns, are discussed here. Furthermore, HRCT is essential for following the course of ILD and might help to determine the intensity of AE management and the appropriateness of re-challenging with SACT, where indicated by drug-specific prescribing information. ILD events should be monitored closely until complete resolution. CRITICAL RELEVANCE STATEMENT: The incidence of potentially treatment-limiting and life-threatening systemic anticancer therapy-related interstitial lung disease (SACT-related ILD) events is likely increasing as more novel regimens become approved. This review provides best-practice recommendations for the early detection of SACT-related ILD by radiologists. KEY POINTS: Radiologists are crucial in detecting asymptomatic (Grade 1) ILD before severity/prognosis worsens. High-resolution computed tomography is the most appropriate method for detecting ILD. Drug-induced ILD is a diagnosis of exclusion, involving a multidisciplinary team. Familiarity with common HRCT patterns, described here, is key for prompt detection. Physicians should highlight systemic anticancer therapies (SACTs) with a known risk for interstitial lung diseases (ILD) on scan requisitions.