Adverse Events Research Articles

Infection-related adverse events comparison of Bortezomib, Carfilzomib and Ixazomib:A pharmacovigilance study based on FAERS.

Bortezomib, carfilzomib and ixazomib are the most common proteasomeinhibitors (PIs) used to treat Multiple Myeloma (MM). We conducted a pharmacovigilanceanalysis using the Food and Drug Administration Adverse Event Reporting System(FAERS), aiming to offer a reference for safe and reasonable clinical use. Adverse drug reaction (ADR) signals of bortezomib, carfilzomiband ixazomib were analyzed by statistical methods including Reporting OddsRatio (ROR), Proportional Reporting Ratios (PRR), and Multi-item Gamma-PoissonShrinker (MGPS). A total of 13,977, 8263 and13296 ADRs of bortezomib, carfilzomib andixazomib were analyzed respectively from the FAERS database. The most frequent adverse reactionsignal for bortezomib was peripheral neuropathy; for carfilzomib, it was acutekidney injury; for ixazomib, it was vomiting. Then a total of 43, 23 and 10 infection-related adverseevents of bortezomib, carfilzomib and ixazomib were analyzed. The most commoninfection-related adverse event for bortezomib was cytomegalovirus infection;for carfilzomib, it was bacteremia; and for ixazomib, it was conjunctivitis. In real-world pharmacovigilance studies, PIs are associated withinfection-related adverse events, which is crucial for the safe use of PIs inthe treatment of MM. However, further research is needed to validate thehypotheses generated in this study.

Phototherapy of granuloma annulare: a single center retrospective study.

Granuloma annulare is a chronic, benign skin condition characterized by small erythematous patches, plaques or papules in annular or disseminated order. Due to the cosmetic impact, many patients experience a significant level of distress. Nevertheless, selecting the optimal treatment method often poses a challenge due to the limited available data. A remission of skin lesions can be achieved through topical, systemic, or intralesional therapies, and various forms of phototherapy. This retrospective study included 58 patients diagnosed with granuloma annulare and evaluated a total of 73 cycles of phototherapy (UVA-1, oral-PUVA, bath-PUVA) concerning treatment response and adverse events. It was conducted at the outpatient phototherapy clinic of the University Department for Dermatology and Venereology, Medical University of Graz. The Data was collected over the period from February 2011 and February 2021. Complete response was achieved in 37.5% of the 16 bath-PUVA therapy cycles, 25.7% of the 35 oral-PUVA therapy cycles, and 35.3% of the 17 UVA-1 therapy cycles. Partial response was noted in 62.5% of the oral-PUVA therapies, 50% of the bath-PUVA therapies, and 41.2% of the UVA-1 therapies. Generally, the adverse events of phototherapy were mild, with the highest incidence of adverse events associated with oral-PUVA and the lowest with UVA-1 therapy. No significant differences in efficacy were found between UVA-1 therapy, oral-PUVA, and bath-PUVA. However, UVA-1 therapy resulted in the fewest adverse events. Given the frequent occurrence of recurrences, the risk-benefit profile of each therapy should be carefully assessed in advance.

The combined effect of nutritional status and body mass index on 90-day adverse events following long-segments fusion for adult spinal deformity: a propensity score-matched analysis.

The aim of this study was to investigate the individual and combined effects of PNI (prognostic nutritional index) and BMI (body mass index) on 90-day adverse events (AEs) following adult spinal deformity (ASD) surgery. A retrospective analysis was conducted on prospectively collected data from patients who underwent open long-segment fusion surgery for ASD. Patients were stratified into four groups based on BMI and PNI: low BMI with low PNI (LBLP), high BMI with low PNI (HBLP), low BMI with high PNI (LBHP), and high BMI with high PNI (HBHP). The primary outcome was the incidence of postoperative AEs within 90 days of ASD surgery. The LBLP group had a significantly higher risk of overall AEs (58.7% vs. 33.3%, p = 0.004) and infectious complications (20.6% vs. 7.9%, p = 0.042) compared to the LBHP group. The HBHP group exhibited a higher rate of major AEs (28.1% vs. 12.3%, p = 0.036) and infectious complications (15.6% vs. 3.5%, p = 0.026) within 90 days postoperatively than the LBHP group. Multivariate logistic regression analysis identified male, higher American Society of Anesthesiologists class, increased intraoperative blood loss, and HBHP status (compared to LBHP) as independent predictors of 90-day major AEs. In patients with low PNI, those with low BMI had a significantly higher risk of overall adverse events and infectious complications. Conversely, among patients with high PNI, those with high BMI were more prone to major adverse events and infectious complications within 90 days postoperatively.

Fidanacogene Elaparvovec for Hemophilia B — A Multiyear Follow-up Study

BackgroundTreatment with fidanacogene elaparvovec, a recombinant adeno-associated virus (AAV) vector developed for the treatment of hemophilia B, led to sustained expression of the high-activity factor IX variant (FIX-R338L, or FIX-Padua) in a phase 1–2a study. The long-term safety and efficacy of this treatment are not known.MethodsIn a 12-month study, 15 participants with severe or moderately severe hemophilia B (factor IX coagulant activity, ≤2% of the normal value) received fidanacogene elaparvovec at a dose of 5×1011 vector genomes (vg) per kilogram of body weight; thereafter, participants could enroll in a 5-year follow-up study. Safety end points included adverse events and changes in laboratory measures. Efficacy end points included the annualized rate of treated bleeding events (annualized bleeding rate) and factor IX activity.ResultsA total of 14 participants provided consent and completed at least 3 years of follow-up (median, 5.5; range 3 to 6); participation was ongoing among 8 at the data cutoff. None of the participants reported treatment-related adverse events after year 1. Throughout follow-up, nine serious adverse events were noted in 4 participants; none were thrombotic or treatment-related. No factor IX inhibitors were detected. Throughout follow-up, mean factor IX activity was in the mild hemophilia range; the mean annualized bleeding rate was less than 1, and 10 participants had no treated bleeding episodes. Surveillance liver ultrasounds obtained from year 1 onward showed no evidence of cancer but showed steatosis in 4 participants who had weight gain and elevated aminotransferase levels (maximum alanine aminotransferase level, 77 U per liter). One participant with a history of hepatitis C, hepatitis B, human immunodeficiency virus infection, and an elevated body-mass index had progression of underlying advanced liver fibrosis. A total of 13 surgical procedures were performed in 8 participants; exogenous factor IX was administered for 10 procedures, and no associated unexpected bleeding complications occurred.ConclusionsFidanacogene elaparvovec was associated with no or only low-grade adverse effects over a period of 3 to 6 years. Efficacy was maintained in the long term at 5×1011 vg per kilogram, one of the lowest intravenous doses of AAV used for any indication. (Funded by Pfizer; ClinicalTrials.gov number, NCT03307980.)

Adverse events of concomitant use of immune checkpoint inhibitors and metformin or statin: an observational, retrospective disproportionality analysis

ABSTRACT Background Preclinical investigations have indicated that the concurrent administration of ICIs with statins or metformin may enhance the anticancer properties. Nevertheless, the patterns of potential toxicity associated with this combination have yet to be elucidated. Research design and methods We utilized the Food and Drug Administration Adverse Event Reporting System (FAERS) to provide an overview of the adverse event landscape tied to the concomitant utilization of ICI and statins or metformin. Results Our study reveals significant side effects associated with combining ICIs with metformin or statins, including gastrointestinal, respiratory, hepatobiliary, and renal disorders. Amalgamated treatment of ICIs plus metformin may heighten the likelihood of bone marrow aplasia, inflammatory bowel disease, intestinal perforation, hepatic impairments, insomnia, autoimmune nephritis, and eczematous manifestations. For ICIs plus statins, colitis, pneumonitis, interstitial lung disease, hypothyroidism, adrenal insufficiency, myocarditis, myositis, hypophysitis, myasthenia gravis, and hepatitis. Importantly, a significant number of adverse events occur within the first two months of starting ICIs alongside metformin or statins, with some appearing after a year of treatment, emphasizing the need for ongoing monitoring. Conclusion The observations delineated offer pivotal insights into the refinement of the co-administration strategy for ICIs with metformin or statins, attenuating the incidence of adverse side effects.

Tecovirimat for Clade I MPXV Infection in the Democratic Republic of Congo

BackgroundTecovirimat is available for the treatment of mpox (formerly known as monkeypox) in Europe and the United States, on the basis of findings from efficacy studies in animals and safety evaluations in healthy humans. Evidence from randomized, controlled trials of safety and efficacy in patients with mpox is lacking.MethodsWe conducted a double-blind, randomized, placebo-controlled trial of tecovirimat in patients with mpox in the Democratic Republic of Congo (DRC). Patients with at least one mpox skin lesion and positive polymerase-chain-reaction results for clade I MPXV were assigned in a 1:1 ratio to receive tecovirimat or placebo. All patients received supportive care. The primary end point was resolution of mpox lesions, measured in number of days after randomization. Safety was also assessed.ResultsFrom October 7, 2022, through July 9, 2024, a total of 597 patients underwent randomization — 295 to receive tecovirimat and 302 to receive placebo. The median time from randomization to lesion resolution was 7 days with tecovirimat and 8 days with placebo; the competing-risks hazard ratio for lesion resolution was 1.13 (95% confidence interval [CI], 0.97 to 1.31; P=0.14). Results were similar whether patients began the trial regimen within 7 days after the reported onset of symptoms (competing-risks hazard ratio, 1.16; 95% CI, 0.98 to 1.37) or more than 7 days after onset (competing-risks hazard ratio, 1.00; 95% CI, 0.71 to 1.40). Overall mortality was 1.7%, which was lower than the case fatality rate of 4.6% reported in the DRC in 2023. At 14 days, the percentages of patients who had blood, lesion, and oropharyngeal samples negative for MPXV by PCR were similar in the two groups. Adverse events occurred in 72.9% of the patients in the tecovirimat group and 70.5% of those in the placebo group, and serious adverse events were reported in 5.1% and 5.0%, respectively.ConclusionsTecovirimat did not reduce the number of days to lesion resolution in patients with mpox caused by clade I MPXV. No safety concerns were identified. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM007 ClinicalTrials.gov number, NCT05559099.)

Safety and effectiveness of brolucizumab in patients with neovascular age-related macular degeneration: A phase IV study from India.

The purpose of this study is to evaluate the safety and effectiveness of brolucizumab intravitreal injections (IVI) in Indian patients with neovascular age-related macular degeneration (nAMD). This prospective, interventional, single-arm, open-label phase IV study included 105 treatment-naïve nAMD patients prescribed brolucizumab as per the local prescribing information, across ten centers. The treatment period consisted of 56 weeks, including loading doses at Weeks 0, 4, and 8, followed by disease activity assessment at Week 16, evaluating patients for 12-weekly (q12w) or 8-weekly (q8w) dosing. The primary endpoint was the incidence and characteristics of treatment-emergent adverse events (TEAEs) during 56 weeks. Secondary endpoints included changes in effectiveness variables - visual acuity, intraretinal fluid (IRF), subretinal fluid (SRF), and central subfield thickness (CST), at 16 and 56 weeks. Post-Week 16, 74 (70.5%) patients received q12w, and 27 (25.7%) patients received q8w dosing. Four TEAEs were reported in three (2.9%) patients, all ocular: vitritis in two patients who were discontinued and retinal vasculitis and uveitis in one patient who completed the study. No TEAEs were severe, and there were no serious adverse events. Best corrected visual acuity (BCVA) improved significantly by seven letters (95% CI: 5.0, 10.0) at Week 16 and by 15 letters (95% CI: 10.0, 18.0) at Week 56 (P < 0.0001 for both). All anatomical parameters also showed significant reductions over the study period. Brolucizumab 6 mg IVI, given as per the prescribing information, demonstrated a positive benefit/risk profile in Indian patients with nAMD, with no new safety signals.

Hepatobiliary disorders and direct-acting antiviral (DAA) therapies: real-world evidence and insights from the EudraVigilance database.

The introduction of Direct-Acting Antivirals (DAA) brought abouts a breakthrough in the treatment of HCV. This study aims to analyze the hepatic safety profile of Harvoni® (sofosbuvir/ledipasvir), Epclusa® (sofosbuvir/velpatasvir), and Vosevi® (sofosbuvir/velpatasvir/voxilaprevir) through a review of the Individual Case Safety reports (ICSRs) reported in EudraVigilance (EV). ICSRs with Adverse Events (AE) belonging to the System Organ Class (SOC) hepatobiliary disorders were retrieved from the EV database. A descriptive analysis was performed. Reporting Odds Ratios (ROR) were calculated to assess the reporting frequency of hepatobiliary disorders among the DAA combinations. Out of 5,552 ICSRs reported between Jan 2018 and Dec 2023, 1,942 were for Harvoni®, 3,180 for Epclusa® and 430 for Vosevi®. 339 ICSRs reported 1,616 PT within the SOC hepatobiliary disorders. Harvoni® showed a statistically significant lower frequency of reporting for the hepatobiliary disorders SOC when compared to Epclusa® and Vosevi® (ROR, 0.33; 95% CI [0.26 - 0.41], and ROR 0.31; 95% CI [0.19 - 0.48], respectively). Harvoni® showed a lower reporting frequency of hepatobiliary disorders and fewer drug ineffectiveness reports, suggesting it may be preferred over Epclusa® and Vosevi® in patients with preexisting liver or biliary conditions.

Visual rehabilitation in keratoconus by altering corneal shape using the corneal crosslinking pen: initial results.

A Phase I/II trial to evaluate the initial safety and performance of a novel corneal crosslinking device, the Corneal Crosslinking Pen in keratoconus patients. This was a prospective exploratory study with 12 months of follow up. Twenty-one eyes of 21 patients aged 14-27 years and diagnosed with progressive keratoconus were enrolled and treated unilaterally. Corneal crosslinking (CXL) following an accelerated epi-off protocol with riboflavin was done using the Corneal Crosslinking Pen. Effectiveness endpoints included changes in astigmatism, maximum keratometry (KMax), and best corrected visual acuity (BCVA) compared to baseline. Safety included adverse events and changes in pachymetry, intraocular pressure (IOP), and endothelial cell count (ECC). Astigmatism was significantly reduced at 12 months by a mean (95% CI) of 0.56 (0.10, 1.03) D. KMax was also reduced by a mean of 0.63 D, but this was not significant. BCVA improved significantly by nearly four lines of vision (- 0.38; logMAR). No corneal thinning was observed; pachymetry, IOP and ECC all remained stable across 12 months. Adverse events were infrequent and mild. These early results suggest that the Corneal Crosslinking Pen was safe and effective for CXL. Future studies will seek to confirm the large improvement seen for BCVA and elucidate a potential mechanism.

Hypnosis and mindfulness audio recordings for reducing fatigue in individuals with multiple sclerosis: A randomized controlled study.

Fatigue is a common problem in individuals with multiple sclerosis (MS). The objective was to evaluate the effects on fatigue of having 4 weeks of access to audio recordings of therapeutic hypnosis (HYP) and mindfulness meditation (MM) practices. A total of 333 individuals with MS and fatigue were randomly assigned to one of the three treatment conditions for 28 weeks: (1) access to therapeutic HYP audio recordings, (2) access to MM audio recordings, or (3) no access to recordings (treatment as usual or TAU). Fatigue impact (primary outcome) and other outcomes were assessed at 4, 16, and 28 weeks after random assignment. Participants assigned to the HYP and MM conditions reported significantly greater reductions in fatigue impact, sleep disturbance, and depressive symptom severity than participants assigned to the TAU condition after 4 weeks of access to audio recordings of these interventions. These improvements were maintained for 16 and 28 weeks following initial access and did not result in any serious adverse events. Given the ease with which audio recordings of HYP and MM could be provided to individuals with MS, the findings support the feasibility of a simple approach to have a significant beneficial impact on people with MS-related fatigue.

Comparative safety analysis of baloxavir marboxil and oseltamivir based on the FAERS database.

This study aimed to analyze adverse drug events (ADEs) of oseltamivir or baloxavir marboxil monotherapy using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, providing a valuable reference for clinical drug safety. FAERS data for oseltamivir and baloxavir marboxil from their market approval in the United States until the third quarter of 2023 were retrieved. Signal detection was performed using the reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods. ADEs were classified according to the System Organ Class (SOC) in the Medical Dictionary for Regulatory Activities (MedDRA) version 25.0. A total of 1,727 and 12,607 ADE reports were retrieved for baloxavir marboxil and oseltamivir, respectively, involving 17 and 26 SOC categories. Baloxavir marboxil demonstrated a strong association with ischemic colitis, melena, delirium febrile, enterocolitis, febrile convulsion, and altered state of consciousness. Oseltamivir exhibited a strong association with pathological personality, thinking abnormal, agitation, abnormal behavior, somnambulism, delirium febrile,and spinal cord hemorrhage. When using oseltamivir and baloxavir marboxil clinically, attention should be paid not only to common ADEs but also to those not mentioned on the drug label.

Incremental healthcare costs among patients experiencing adverse events on oral antipsychotics: a real-world analysis of U.S. Medicare beneficiaries with schizophrenia.

Continuous antipsychotic treatment is fundamental to successful management of schizophrenia. However, many oral antipsychotics are associated with adverse effects (AEs). While prior research has shown antipsychotic AEs to negatively impact patient adherence, no study has examined the incremental costs associated with AEs, especially among Medicare beneficiaries who constitute approximately half of all patients with schizophrenia in the U.S. This study aimed to compare incremental healthcare costs among Medicare beneficiaries with schizophrenia treated with oral antipsychotics who did and did not experience adverse events (AEs). All fee-for-service Medicare beneficiaries with schizophrenia who initiated a new OAP between 01/01/2017 and 12/31/2019 were included in the sample (index date = date of new OAP prescription). All-cause and schizophrenia-related costs were measured while a patient was receiving treatment and were converted into monthly measures given differential follow-up periods. Generalized linear models were used to generate adjusted cost estimates. In our final sample of 46,452 Medicare beneficiaries with schizophrenia, movement disorders such as tardive dyskinesia and extrapyramidal symptoms were observed in 10.0% of beneficiaries. Metabolic side effects included hyperlipidemia (33.6%), diabetes (33.1%), and hypotension (6.8%). Patients who experienced adverse events consistently had significantly higher all-cause monthly healthcare costs compared to patients who did not experience adverse events. This was true for beneficiaries experiencing movement disorders ($5,281 vs. $4,851, Δ = $430, p = 0.0766), hyperlipidemia ($5,123 vs. $4,768, Δ = $355, p = 0.0179), diabetes ($5,249 vs. $4,698, Δ = $551, p = 0.0049), and hypotension ($6,631 vs. $4,685, Δ = $1,946, p < 0.001). A similar pattern was observed for monthly schizophrenia-related costs. Our findings underscore the additional healthcare cost burden associated with adverse events in patients receiving oral antipsychotic treatment. Efforts should be directed towards selecting agents that minimize side effects and/or developing new therapeutic alternatives with improved tolerability profiles.

Strategies to minimize fall-related injuries in older adults at risk of falls: the Falling Safely Training (FAST) study.

Falls are the leading cause of accidental injury among older adults. Current fall prevention programs are useful but do not target the key variable for injury (i.e., impact force). An approach, which has shown promise in robust older adults, is to teach safe-falling strategies to reduce impact forces. In this single-blinded, pilot randomized controlled trial, we explored the feasibility and preliminary efficacy of a safe-falling program. Twenty-four older adults at risk of injurious falls were randomly assigned either to Falling Safely Training (FAST), a standardized progressive training of safe-falling strategies, or an active control group consisting of evidence-based balance training. Participants underwent a series of experimentally induced falls at baseline, after the 4-week intervention, and three months after the intervention. Hip and head acceleration (proxies of impact force) and the number of head impacts experienced during the falls were collected. No adverse events were reported, and eleven of 12 FAST participants completed the intervention. The FAST group had a greater reduction in the number of fall-related head impacts following the intervention (odds ratio = 0.10, 95% CI: 0.02, 0.61, p=0.012). This improvement coincided with a significant reduction in head acceleration in the FAST group compared to control (between-group mean difference = -9.54 m/sec2, p=0.028). Hip acceleration decreased significantly in both groups (p's˂0.001). Teaching older adults at risk of falls safe-falling strategies is safe and feasible and has the potential to minimize fall-related head impacts and reduce fall morbidity.

Detrimental impact of gastric acid suppressants on vascular endothelial growth factor receptor tyrosine kinase inhibitors efficacy: evidence from a systematic review and meta-analysis.

This meta-analysis evaluated theprevalence of gastric acid suppressants (GASs) in patients receiving vascularendothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) andexplored drug-drug interactions (DDIs). PubMed, Embase, and Cochrane Library were searched upto 20 October 2024. Studies comparing VEGFR-TKIs monotherapy versus VEGFR-TKIswith GASs, reporting pharmacodynamic (PD), pharmacokinetic (PK), or adverseevents (AEs), were analyzed using random-effects models. Subgroups includedcancer types and VEGFR-TKI types. 24 studies comprising 6,406 patients were included. Theprevalence of GASs use in VEGFR-TKIs users was 40% (95% CI 31-50%). GASssignificantly impaired survival, increasing mortality risk by 29% (OS HR 1.29,95% CI 1.14-1.45) and progression risk by 31% (PFS HR 1.31, 95% CI 1.06-1.61).PK analyses revealed clinically meaningful exposure reductions (AUC0-24GMR 0.78, 90% CI 0.65-0.94; Cmax GMR 0.80, 90% CI 0.70-0.91). AEincidence (except vomiting) did not differ between groups. GASs may reduce the efficacy of mosttypes of VEGFR-TKIs by decreasing their bioavailability, thereby having adetrimental effect on patient survival outcomes. It is recommended to givepriority to H2 receptor antagonists (H2RAs) and monitor blood drugconcentrations to optimize efficacy. www.crd.york.ac.uk/prospero identifier CRD42024597729.

Meta-Analysis of Cardiovascular Efficacy of Empagliflozin Versus Dapagliflozin in Type 2 Diabetes: Unveiling Key Insights.

The favorable safety profile of sodium-glucose cotransporter 2 inhibitors, notably empagliflozin and dapagliflozin, makes them a suitable treatment option for type 2 diabetes. However, the comparative cardiovascular (CV) benefits of empagliflozin versus dapagliflozin require further investigation. A comprehensive search of electronic databases was conducted from inception till November 7, 2024. Studies reporting CV outcomes of empagliflozin and dapagliflozin were included in the meta-analysis. The random-effects model was used to pool the risk ratio (RR) along with the corresponding 95% confidence intervals (CIs) for all outcomes. We pooled 8 studies with a total of 428,940 participants. The evaluation of pooled results demonstrated that empagliflozin was associated with a nonsignificant association in reducing all-cause death (RR: 0.91, 95% CI: 0.68-1.20), CV death (RR: 1.12, 95% CI: 0.81-1.55), major adverse cardiovascular events (RR: 1.03, 95% CI: 0.86-1.23), myocardial infarction (RR: 1.01, 95% CI: 0.84-1.22), stroke (RR: 0.90, 95% CI: 0.79-1.04), and heart failure-related events (RR: 1.07, 95% CI: 0.87-1.32). This study does not suggest a clear CV benefit of using empagliflozin over dapagliflozin, or vice versa, as an add-on therapy for type 2 diabetes. If both medications have similar safety profiles, differences in their costs are likely to impact their cost-effectiveness in CV risk reduction.

Intraluminal thrombus volume correlates with the crural vessel runoff in popliteal artery aneurysms upon initial presentation.

Background: Patients having emergency surgery due to ischemia caused by a popliteal artery aneurysm (PAA) have worse outcomes in all endpoints (operation time, major adverse limb events (MALE), amputation-free survival) than after elective treatment, mostly due to a limited crural vessel runoff. This study investigates the relationship between PAA diameter, volume, and luminal thrombus load in relation to the preoperative crural runoff. Patients and methods: Retrospective single-centre evaluation of surgically treated patients with PAA and semi-automated quantitative CT analysis of PAA morphologies (diameter, volume and intraluminal thrombus volume). Primary endpoints were the correlations these characteristics with the number of patent crural vessels. Results: A total of 89 PAAs (61 patients, median age 75, IQR 12; 94.4% male) were identified, of which 47.2% were symptomatic with 18 acute limb ischemia (ALI). The diameter at surgery was 33.8 ± 12.1mm and the volume 68.5 ± 13.6mm3. A median of two lower leg vessels were patent (elective 3 [1, 2, 3] vs. emergency 1 [1, 2], p=0.1) upon preoperative CTA. 77 PAAs underwent elective surgery, five PAAs (5.6%) received endovascular treatment. The surgical complication rate was 23.6% without immediate or early occlusion. The follow-up was 42.5 [39-45] months. The overall mortality rate was 11.2% and the primary patency rate 73.9%. While the total aneurysm volume correlated well with the diameter (r=0.77, p<0.01), the intraluminal thrombus volume (ILT) showed the clearest correlation with the crural runoff (r=-0.34, p=0.01). No correlation between the diameter and crural runoff was observed (r=-0.17, p=0.1). A reduced crural run-off was significantly associated with impaired amputation-free survival (p=0.01). A subgroup analysis (n=21) with sequential CTs showed a tendency towards greater increase of thrombus volume compared to plain diameter during PAA growth. The thrombus volume index (=ILT/total PAA volume) was significantly higher in emergency patients (p=0.01), while diameters tended to be smaller (p=0.57). Conclusions: The increasing intraluminal thrombus volume correlates most distinctly with a reduced crural runoff in PAAs and should therefore be considered prognostically important, especially in the presence of an increased growth rate compared to the diameter.

Subcutaneous Infliximab (CT-P13 SC) as Maintenance Therapy for Crohn's Disease and Ulcerative Colitis: 2-Year Results from Open-Label Extensions of Two Randomized Controlled Trials (LIBERTY).

In the LIBERTY Phase 3 studies in Crohn's disease (CD) or ulcerative colitis (UC), maintenance CT-P13 subcutaneous (SC) 120mg was more effective than placebo after 1 year. Here we report 2-year data from the LIBERTY open-label extensions. Two randomized, placebo-controlled, double-blind studies evaluated the efficacy and safety of CT-P13 SC maintenance in moderate-to-severe CD or UC. Responders to CT-P13 intravenous induction were randomized at Week (W) 10 to CT-P13 SC 120mg or placebo biweekly, until W54. From W22, dose adjustment to CT-P13 SC 240mg was permitted for loss of response. At W56, patients could enter an open-label extension, receiving CT-P13 SC 120mg (or 240mg if dose-adjusted), biweekly, until W102. The extension comprised 278/343 (81.0%) and 348/438 (79.5%) patients in the CD and UC studies, respectively. In those continuing on-study, efficacy (non-responder imputation) was well maintained in the CT-P13 SC group at W102: 63.5% (as-observed: 70.5%) and 49.0% (as-observed: 58.8%) of CD patients (N=192) achieved clinical remission and endoscopic response, respectively; 45.1% (as-observed: 60.1%) and 41.4% (as-observed: 52.4%) of UC patients (N=237) achieved clinical remission and endoscopic-histologic mucosal improvement, respectively. No new safety signals were identified from longer-term CT-P13 SC treatment or starting CT-P13 SC 120mg after placebo, with similar adverse event rates for patients undergoing dose adjustment to CT-P13 SC 240mg from CT-P13 SC 120mg or placebo. CT-P13 SC is an effective and well-tolerated long-term maintenance treatment in moderate-to-severe CD and UC.

Efficacy and safety of lemborexant vs placebo in treating adults with insomnia disorder: a systematic review and meta-analysis of 1976 patients.

Insomnia is a typical sleep disorder in which an individual finds it difficult to fall asleep and stay asleep resulting in poor daytime functioning and decreased health and quality of life. The orexin system, which regulates wakefulness and arousal, is often overactive in individuals with insomnia, disrupting normal sleep patterns. Lemborexant, a dual orexin receptor antagonist, works through the inhibition of the orexin system, thus facilitating increased sleep onset and maintenance of sleep. This systematic review and meta-analysis seek to determine the effectiveness and safety of lemborexant in the treatment of insomnia. A comprehensive search was conducted on PubMed, Scopus, Web of Science, and Cochrane Library, from inception to September 2024. Four randomized controlled trials (RCTs) assessing the efficacy and safety of lemborexant for patients with confirmed DSM-5 diagnosis of insomnia as compared to placebo were included. By adopting a random-effect inverse variance model, RevMan was used to pool dichotomous and continuous data. We employed the ROB2 methodology to evaluate the quality of the evidence, so ensuring the reliability of the findings obtained throughout these investigations. Four studies with a total of 1976 patients were included. Lemborexant was superior to placebo in decreasing sleep onset latency and wake after sleep onset: (MD = - 9.23min, P = 0.02 and MD = - 19.9min, P < 0.0001) with 5mg and (MD = - 12.56min, P = 0.004) and (MD = - 22.24min, P < 0.0001) with 10mg, respectively. In addition, sleep efficiency was statistically significantly higher in the lemborexant group (MD = 6.08%, P < 0.0001) and (MD = 7.46%, P < 0.0001) with 5mg and 10mg, respectively. Regarding safety analysis, Treatment emerged adverse events (TEAEs) and somnolence were statistically significantly higher in the lemborexant group (RR = 1.94, P < 0.0001) and (RR = 4.95, P < 0.0001), respectively. In accordance with this systematic review and meta-analysis, lemborexant is an effective pharmacotherapy for the treatment of insomnia as it improves sleep onset latency, wake after sleep onset, and sleep efficiency. Both formulations of 5-mg and 10-mg doses were well tolerated with no significant difference in their effect; however, somnolence was more common relative to placebo. Lemborexant appears to fill a therapeutic gap in the treatment of insomnia but should be used with caution and smaller dose (5mg) in those who are at risk of developing an excessive daytime somnolence state.

Grade 3 and Grade 4 Cutaneous toxicities in patients across multiple solid tumour types receiving checkpoint inhibitor therapy: An observational study. The experience of a single large specialist institution.

Immunotherapy has significantly advanced cancer treatment, enhancing overall survival in melanoma, lung, triple negative breast cancer and renal-cell carcinoma. However, immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), including severe cutaneous toxicity. This study aims to investigate the demographics, incidence, presentation, management, and survival outcomes of patients experiencing ESMO grade 3 and 4 cutaneous toxicities secondary to various ICI regimens across all solid tumour types at a single tertiary oncology centre. This retrospective observational study looked at 5042 adult oncology patients treated with ICIs for all solid tumours at the Royal Marsden NHS Foundation Trust over a 9-year period between April 2015 and March 2024. Patients managed with commonly used ICIs (Pembrolizumab, Nivolumab, Ipilimumab, Cemiplimab, Avelumab, Atezolizumab, and combinations) were included in the study population. A data-cross search of these patients and those supplied with moderately potent to very potent topical steroids was done, resulting in 619 patients. Electronic patient records for these 619 patients were manually examined to determine the number of patients meeting the criteria for grade 3 or 4 cutaneous toxicity as per the European Society for Medical Oncology (ESMO) guidelines, of whom 88 patients met the criteria and relevant data was manually extracted from these patients' records. Out of 5042 patients receiving ICIs, 88 (1.7%) developed grade 3 or 4 cutaneous toxicity. The most common tumor types were melanoma (42%), lung (17%), renal (14%), and breast (13%). The most frequently observed grade 3 toxicities were maculopapular eruptions (31%) and erythema (19%), with all grade 4 cases (8%) presenting as toxic epidermal necrolysis (TEN). The ICIs most associated with these toxicities were Pembrolizumab (36%) and combined Ipilimumab/Nivolumab (35%). Management involved oral corticosteroids (45%), IV methylprednisolone (23%), and topical steroids (18%). Immunotherapy was discontinued in all grade 4 cases and 64% of grade 3 cases. Overall survival rate at time of data collection with a median follow-up of 38 months was 44%. Severe cutaneous toxicities can result in discontinuation of ICI therapy. Early recognition of severe cutaneous toxicity is necessary to balance effective skin toxicity management with continued cancer control.

Using Genomics to Develop Personalized Cardiovascular Treatments.

Advances in genomic technologies have significantly enhanced our understanding of both monogenic and polygenic etiologies of cardiovascular disease. In this review, we explore how the utilization of genomic information is bringing personalized medicine approaches to the forefront of cardiovascular disease management. We discuss how genomic data can resolve diagnostic uncertainty, support cascade screening, and inform treatment strategies. The role that genome-wide association studies have had in identifying thousands of risk variants for polygenic cardiovascular diseases, and how these insights, harnessed through the development of polygenic risk scores, could advance personalized risk prediction beyond traditional clinical algorithms. We detail how pharmacogenomics approaches leverage genotype information to guide drug selection and mitigate adverse events. Finally, we present the paradigm-shifting approach of gene therapy, which holds the promise of being a curative intervention for cardiovascular conditions.