Occurrence Of Adverse Events Research Articles

Real-world application of disitamab vedotin (RC48-ADC) in patients withbreast cancer with different HER2 expression levels: efficacy and safety analysis.

Disitamab vedotin (RC48-ADC), an antibody-drug conjugate (ADC), combines specific antibody disitamab with cytotoxicity monomethyl auristatin E to effectively target the human epidermal growth factor receptor 2 (HER2) protein on tumor cells for precise elimination. Recent studies have demonstrated that RC48-ADC offers therapeutic benefits for patients with HER2-positive and HER2-low-expression breast cancer (BC). However, a thorough exploration of its efficacy and safety in real-world settings for patients with metastatic breast cancer (mBC) is currently lacking. This retrospective, multicenter, real-world study included patients with mBC who received RC48-ADC from September 2021 to March 2024. These patients include HER2-positive BC and HER2-low-expression BC. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), restricted mean survival time, objective response rate (ORR), and disease control rate (DCR). Factors affecting efficacy and the occurrence of treatment-related adverse events (TRAE) were evaluated. The study included a cohort of 89 patients with mBC, with 48 of those being identified as HER2-positive. As of March 2024, 22 deaths were recorded, with an immature median OS. Total PFS varied from 1.0 to 31.2 months, with a median of 5.5 months (95% CI, 4.368-6.632). HER2-positive patients exhibited prolonged PFS compared with HER2-low-expression patients (6.6 months vs 4.1 months, P = .023). The overall ORR stood at 25.8% (95% CI, 0.178-0.358), with higher rates observed in HER2-positive patients compared with HER2-low-expression patients (31.3% vs 19.5%). Similarly, the overall DCR was 78.7% (95% CI, 0.691-0.859), with HER2-positive patients demonstrating superior DCR compared with HER2-low-expression patients (83.3% vs 73.2%). Notably, HER2 expression emerged as the primary determinant of RC48-ADC efficacy. The most prevalent TRAE among all patients included leukopenia (21.3%) and alopecia (20.2%). RC48-ADC showcases promising efficacy and manageable safety in patients with both HER2-positive and HER2-low-expression mBC.

Therapeutic Potential of Cannabinoids in Glaucoma – Hit or Myth? - A Review

Introduction: Glaucoma is a leading cause of irreversible blindness, characterized by elevated intraocular pressure (IOP) that damages the optic nerve. Current treatments mainly focus on reducing IOP, but some patients do not respond adequately to conventional therapies. Cannabinoids, particularly Δ9-tetrahydrocannabinol (Δ9-THC), have been investigated as potential adjunctive treatments for glaucoma. Studies have shown varying effects of cannabinoids on IOP regulation, though their precise mechanisms remain unclear. Aim of Study: This study aims to evaluate the therapeutic potential of cannabinoids in the treatment of glaucoma by examining their effects on IOP, their mechanisms of action, and the risks and benefits associated with their use. Material and methods: A comprehensive literature review of studies on the therapeutic potential of cannabinoids in glaucoma was conducted using the PubMed database. Results and Conclusions: Cannabinoids, especially Δ9-THC, have demonstrated the ability to reduce IOP in both healthy individuals and glaucoma patients. However, the effect is typically short-lived, lasting only 3-4 hours. The efficacy of cannabinoids in reducing IOP is influenced by the method of administration (oral, intravenous, inhalation) and the delivery system used for topical application. Despite some promising results, the use of cannabinoids as a mainstream glaucoma treatment is limited by factors such as the short duration of action, the potential for addiction, and the occurrence of adverse effects like tachycardia, hypotension, and cognitive impairment. Although cannabinoids offer a unique approach to glaucoma management, further research is necessary to address these limitations and determine their long-term therapeutic viability.

The prognostic value of cartilage intermediate layer protein 1 (CILP1) in patients with diabetic cardiomyopathy.

To measure the plasma levels of human cartilage intermediate layer protein 1 (CILP1) in patients with diabetic cardiomyopathy (DCM), and to investigate its association with the occurrence of major adverse cardiovascular events (MACE) in DCM. A total of 336 diabetic patients were enrolled and assigned into two groups based on the presence or absence of DCM (DCM group and N-DCM group). The baseline clinical data including glutamic-pyruvic transaminase (ALT), glutamic oxaloacetic acid transferase (AST), albumin, serum creatinine, glycosylated hemoglobin (HbA1c), C-reactive protein (CRP), and N-terminal pro brain natriuretic peptide (NT-proBNP) were recorded. Subsequently, plasma levels of CILP1 at admission were detected by the enzyme linked immunosorbent assay (ELISA) method. Echocardiographic parameters were also acquired for all patients. The association of CILP1 with LVEF, LVDD and CRP was determined. In addition, the occurrence of MACE was examined during the 12-month follow-up in the DCM group. The concentration of CILP1 in the DCM group was higher than in the N-DCM group [1329.97 (1157.14, 1494.36) ng/L vs. 789.00 (665.75, 937.06) ng/L, P < 0.05], higher in the MACE group than in the non-MACE group [1777.23 (1532.83, 2341.26)ng/L vs. 885.00 (722.40, 1224.91) ng/L, P < 0.05). Correlation analysis revealed that CILP1 expression was associated with LVEF, CRP and LVDD (r = -0.58, 0.29 and 0.44, respectively, P < 0.05). Analysis of a nomogram demonstrated that CILP1, sex, age, BMI, LVEF and LVDD could predict the occurrence of MACE in DCM patients at 12months (P < 0.05). The plasma levels of CILP1 were independently associated with a stronger discriminating power for DCM. Furthermore, inclusion of CILP1 as a covariate in the model caused a significant improvement in risk estimation compared with traditional risk factors for DCM [BASIC: AUC: 0.556, 95%CI: 0.501-0.610; BASIC + CILP1: AUC: 0.913, 95%CI: 0.877-0.941, P < 0.05] and MACE [BASIC: AUC: 0.710, 95%CI: 0.616-0.792; BASIC + CILP1: AUC: 0.871, 95%CI: 0.794-0.928, P < 0.05]. The serum concentration of CILP1 was increased in DCM patients. Elevated fasting plasma CILP1 levels was a robust diagnostic marker of DCM and was independently associated with an increased risk of MACE.

Robotic minimally invasive inguinal hernia repair with the Dexter robotic system™: A prospective multicenter clinical investigation.

Robot-assisted transabdominal preperitoneal inguinal hernia repair (rTAPP) has been established with various robotic platforms. The Dexter robotic system is an open platform consisting of a sterile surgeon's console, two robotic instrument arms, and one robotic endoscope arm. This study aimed to confirm the perioperative and early postoperative safety and clinical performance of the Dexter system in patients undergoing primary transperitoneal inguinal hernia repair. The primary objectives of this multicenter study conducted at three centers in France, Germany, and Switzerland were to document the successful completion of rTAPP procedures and the occurrence of serious adverse events (Clavien-Dindo grades III-V), device-related events up to 30days post-surgery. The procedures were performed by three surgeons with varying levels of experience in robotic systems. 50 patients with a median age of 62.5years (IQR 51.0-72.0) and BMI of 25.1kg/cm2 (IQR 23.5-28.7), respectively,underwent inguinal hernia repair (33 unilateral, 17 bilateral). All surgeries were successfully completed using three standard laparoscopy trocars. There were no conversions to open surgery, intraoperative complications or device deficiencies. The median skin-to-skin operative time was 50min (IQR 45-60) for unilateral hernias and 96min (IQR 84-105) for bilateral hernias. The median console time was 30min (IQR 26-41) for unilateral and 66min (IQR 60-77) for bilateral hernias. Twenty-six patients were discharged on the day of surgery, and 22 on postoperative day 1. This study confirmed the use of the Dexter system in rTAPP was feasible and safe in multicenter cohorts, with operative times consistent with the literature on other robotic platforms. Our data demonstrated the accessibility of this new robotic approach, even when adopted by surgeons new to robotics. The Dexter system emerged as a valuable device in the hernia repair toolkit for both experienced robotic surgeons and those new to the field.

Systemic antimicrobials as an adjunct in the management of periodontitis - which drug is best?

This study is a systematic review and meta-analysis that assesses systemic antimicrobials: azithromycin (AZT) and amoxicillin/metronidazole (AMX/MTZ), as adjuvants to subgingival instrumentation in the treatment of periodontitis. The aim is to establish if one antimicrobial is superior as an adjuvant therapy in the management of periodontal disease. This systematic review and meta-analysis included randomised controlled trials (RCTs), controlled clinical trials, and prospective and retrospective human studies. Participants had to be adults (≥18 years of age) with a diagnosis of periodontitis in the categories: chronic/aggressive, stages II/III, grades B/C. All participants completed full mouth subgingival instrumentation (SI) with the use of adjunct systemic antimicrobial therapy: the intervention group: AZT and the control group: AMX/MTZ. A total of 779 studies were retrieved from the data search; following the application of selection criteria and independent review duplicated by two authors, seven studies were eligible for review. Two studies were subsequently excluded due to insufficient information. Therefore five studies were included in the review, all were self-funded and four were conducted in recognised universities. The primary outcome measure was probing pocket depth changes at 1-12 months. Secondary outcome measures were: the number of residual sites with pocket depths ≥5 mm, clinical attachment levels, bleeding on probing, plaque indices (at 1-12 months), and occurrence of adverse events. Review Manager Software (The Cochrane Collaboration, Copenhagen, Denmark) was used to conduct meta-analysis. Heterogeneity between studies was expected, therefore the random-effects model was utilised to pool results from multiple studies. Statistical heterogeneity was assessed by I2 and Cochrane's test for heterogeneity. The certainty of evidence was assessed and a summary of GRADE criteria: risk of bias, inconsistency, imprecision, indirectness and publication bias. Bias was graded for the five studies included in this meta-analysis and systematic review. Two studies were low risk, two were moderate risk and one was high risk. The study rated high for risk of bias was due to an incomplete description of blinding. Three of the studies were rated low bias for outcome measurement as they reported blinding of data assessors. No studies had deviations from the intended interventions and all outcomes were detected; therefore, all studies were rated as low bias for these domains. All five of the studies demonstrated changing in probing pocket depths at 1-3 months, however, the intervention and control cohorts showed no significant difference. One study showed a statistically significant difference in probing pocket depths at 12 months, in favour of AZT. This systematic review and meta-analysis demonstrates no statistically significant difference between the two cohorts: AZT and AMX/MTZ for mean changes in clinical attachment level, probing pocket depths or bleeding on probing at 1-3 months; when used as an adjunct to mechanical intervention in the treatment of periodontitis. It was recorded, evidence of low to moderate certainty, that for the AZT cohort: fewer adverse events were evident and fewer sites with residual probing pocket depths of ≥5 mm at 1-3 months were recorded. Based on this systematic review and meta-analysis, there is no statistically significant superior drug therapy, comparing the use of AZT versus AMX/MTZ as an adjunct in the treatment of periodontists. However, evidence of low to moderate certainty demonstrates fewer adverse events and fewer sites with residual pocket depths ≥5 mm at 1-3 months in the AZT cohort, compared to the AMX/MTZ cohort. A greater number of clinical trials and a stronger evidence base in the future will allow for authentication of current findings.

Pharmacokinetics and Bioequivalence of Two Formulations of Montelukast Sodium Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions.

Montelukast sodium is a leukotriene type 1 receptor antagonist that can be used for the prophylaxis and treatment of asthma. However, the pharmacokinetics of montelukast sodium tablets (10mg) remain unclear in healthy Chinese subjects. Here, a single-dose randomized, open-label, 2-sequence, and 2-period crossover (7-day washout period between treatments) study was performed to compare the pharmacokinetics and bioequivalence between the test products and the reference at a single dose of 10mg among healthy Chinese subjects under fasting and fed conditions. Blood samples were collected at specified time points to analyze the plasma concentrations of montelukast by a validated liquid chromatography-tandem mass spectrometry method. The results showed that the 90% confidence interval values of the geometric mean ratio of test/reference for the maximum plasma drug concentration, area under the concentration-time curve from time 0 to the end, and area under the concentration-time curve from time 0 to infinity were within the range of 80%-125%. Moreover, both the test and reference formulations were safe and well tolerated, with no occurrence of severe adverse events. These results demonstrate that both the test montelukast sodium tablets and the reference showed similar bioequivalence, safety, and tolerability among healthy Chinese subjects under fasting and fed conditions.

Ruminative thinking mediates the effects of exposure to adverse life events on psychotic-like experiences

Introduction:A growing literature has shown that exposure to adverse life events during childhood or adolescence is associated with the presence of psychotic-like experiences (PLEs), which is in turn associated with the risk of psychotic outcomes. Ruminative thinking, i.e., the tendency to dwell on particular issues or ideas, may affect the perceived aversiveness and ability to cope with adverse life events. However, the role that rumination plays in the relationship between adverse life events and the presence of PLEs remains unclear. The purpose of this study is to assess the association between adverse life events and PLEs in a longitudinal sample of young adults and adolescents, and to investigate whether this relationship is mediated by ruminative thinking.MethodsWe used a longitudinal naturalistic sample of 706 volunteers assessed at ages 18 and 22 years, within the Imagen consortium. Lifetime occurrence of adverse life events (i.e., events perceived as strongly negative by participants) was investigated using the Life Events Questionnaire. The Community Assessment of Psychic Experience (CAPE-42) served to assess the presence of PLEs, while ruminative thinking was investigated through the Ruminative Response Scale.ResultsResults showed that both frequency of PLEs and their persistence over time were associated with greater adverse life events exposure (r = 0.32, p &amp;lt; 0.001 and F1 = 9.8; p &amp;lt; 0.001, respectively) and greater ruminative response (r = 0.66, p &amp;lt; 0.001 and F1 = 94.9; p &amp;lt; 0.001, respectively). Mediation analyses showed that relationship between adverse life events and PLEs frequency was partially mediated by rumination (direct effect Z: 5.4, p &amp;lt; 0.001; indirect effect Z: 6.9, p &amp;lt; 0.001; total effect Z: 5.9, p &amp;lt; 0.001). Considering changes between the two assessment timepoints, relationship between PLEs variation between 18 and 22 years and adverse life events occurred during the same period was partially mediated by changes in rumination (direct effect Z: 2.8, p &amp;lt; 0.005; indirect effect Z: 4.3, p &amp;lt; 0.001; total effect Z: 4.3; p &amp;lt; 0.001).DiscussionOverall, our findings confirm that the presence of adverse life events may increase the risk of experiencing PLEs in healthy individuals and suggest that dysfunctional coping strategies, such as ruminative thinking, may be related to psychosis proneness. Results do not disentangle whether individuals with greater risk for psychosis tend to ruminate more or whether rumination exacerbates psychosis risk.

Abstract 4134308: Re-evaluating the safety profile of Semaglutide: An updated meta-analysis

Background: Semaglutide is increasingly used in the management of type 2 diabetes mellitus and obesity. Ensuring safety of this medication is crucial for its clinical use. This meta-analysis evaluates the safety profile of semaglutide across patient populations and treatment durations. Methods: Randomized controlled trials assessing the safety of semaglutide versus placebo, with specified treatment durations were identified. The primary outcome was occurrence of any cardiovascular adverse events. Secondary outcomes included sudden cardiac death, adverse events leading to death, adverse events, gastrointestinal side effects, occurrence of hypoglycemia and new-onset neoplasm. Results: A total of 23 studies met the inclusion criteria with a combined sample size of 57,911 participants. The meta-analysis revealed that the adverse event associated with semaglutide is gastrointestinal in nature (nausea and vomiting). No significant differences were observed between semaglutide and comparator groups. (See Figure 1) Conclusion: Semaglutide appears to have a favorable safety profile across diverse patient populations and treatment durations, supporting its continued use in the management of type 2 diabetes mellitus and obesity. It is generally well-tolerated, with a low incidence of adverse events. Clinicians should be aware of these findings and monitor patients accordingly. Further long-term studies are warranted to assess the safety of semaglutide in clinical practice.

Abstract 4138221: Ezetimibe plus statin combination vs. double dose statin for patients with dyslipidemia and ASCVD risk: A Systematic Review and Meta-Analysis

Background: Dyslipidemia is a major risk factor for Atherosclerotic Cardiovascular Disease (ASCVD). Statin is a crucial intervention to fix dyslipidemia and reduce the ASCVD risk. Still, there are several regimens to achieve blood lipid level targets, including increasing the statin dose or adding ezetimibe to the statin used. However, the best option between the two regimens is still a matter of debate. Research Question: We aim to evaluate the efficacy and safety of Ezetimibe plus any type of statin versus a double dose of the same statin in patients with ASCVD risk. Methods: A systematic review and meta-analysis based on randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and WOS till December 2023. We used the random-effects model to report dichotomous outcomes using odds ratio (OR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI). Results: Forty-seven studies with a total of 18592 patients were included. Ezetimibe plus statin was associated with a decrease in low-density lipoprotein (LDL) levels [MD: -13.69 with 95% CI (-15.64, -11.74), P &lt;0.01], and more patients achieving their targeted LDL levels [OR: 2.89 with 95% CI (2.40, 3.47), P &lt;0.01]. However, there was no significant difference between the two groups regarding any adverse events [OR: 0.98 with 95% CI (0.89, 1.08), P =0.62], and the composite endpoint of cardiovascular death, major coronary events, or nonfatal stroke [OR: 0.72 with 95% CI (0.39, 1.32), P = 0.29], although there was a trend towards better results for patients with the combination regimen. Conclusion: Ezetimibe plus statin combination led to more reduced LDL levels and more patients achieving their goal levels than double dose statin, without a significant difference in the rate of any adverse events occurrence. More RCTs are mandatory to assess the effect of both regimens on major clinical events such as stroke, coronary events, and death.

CTNI-52. EXPEDITED CHEMORADIATION AFTER LASER INTERSTITIAL THERMAL THERAPY (LITT) IS FEASIBLE AND SAFE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Abstract BACKGROUND High-grade gliomas (HGG) are incurable primary brain tumors. Laser Interstitial Thermal Therapy (LITT) has emerged as an alternative to surgery for select patients. Hyperthermia can improve the efficacy of radiation and chemotherapy. Shortening the time between LITT and chemoradiation may maximize their biological and clinical benefits. This clinical trial evaluated the safety and feasibility of expediting chemoradiation after biopsy and LITT in patients with newly-diagnosed HGG. METHODS Patients with suspected HGG were enrolled. Those with pathologic confirmation of HGG and deemed appropriate candidates for LITT and chemoradiation were considered evaluable. Participants underwent 6 weeks of adjuvant chemoradiation within seven days of LITT. Endpoints were assessed until the completion of radiation, and included the occurrence of wound dehiscence; new, treatment-refractory seizures; cerebral edema; and completion of planned radiotherapy. RESULTS Fifteen patients with suspected HGG were enrolled and ten were considered evaluable. All ten patients were diagnosed with glioblastoma (GBM, IDHwt). Five patients were deemed unevaluable: four patients with other CNS tumors and one GBM patient who developed grade 4 postoperative edema. Of ten evaluable patients, the median age was 60.2 years (IQR: 51.0, 69.4), and median preoperative KPS was 90 (IQR: 90, 80). The median time between LITT and the initiation of chemoradiation was seven days. There were no occurrences of significant protocol-related adverse events. CONCLUSIONS Accelerated initiation of chemoradiation after biopsy and LITT is safe and feasible for patients with newly diagnosed HGG. A larger study is needed to assess potential synergy of hyperthermia and chemoradiation to improve survival.

Effectiveness of Ayush Rasayana A and B on the Quality of Life of Older Adults: Protocol for a Cluster Randomized Controlled Trial.

With advancing age among older adults, the associated debilities increase, indicating a deteriorating health status as there is a gradual loss of muscle mass, strength, and functionality. Ayush Rasayana A and B are coded Ayurvedic medicines developed from herbal extracts. This study has been planned to prevent debilitating conditions and improve the quality of life (QOL) in older adults. This study aimed to assess the effectiveness of Ayush Rasayana A and B on the QOL, quality of sleep, and functionality of older adults, along with the tolerability of the intervention. This was a multicenter, open-label, cluster randomized controlled trial conducted with 720 participants aged 60 to 75 years. The participants were divided into 2 groups (intervention and control), with both receiving Ayurvedic ancillary treatment for 3 months. The intervention group additionally received 10 g of Ayush Rasayana A orally once daily at bedtime for 6 days, followed by 1.5 g of Ayush Rasayana B orally twice daily before food for the remaining 84 days. The assessment criteria included the Older People's Quality of Life Questionnaire Brief, Katz Index of Independence in Activities of Daily Living, Pittsburgh Sleep Quality Index, Five Times Sit-to-Stand Test, and shoulder and scapular movements. Any change in hematological and biochemical parameters and occurrence of treatment-emergent adverse events were also assessed during the study period. The recruitment of the participants started in December 2023, and the final follow-up was completed in April 2024. Out of the total 720 enrolled participants, 686 (95.3%) completed the study up to the last follow-up. This study may provide evidence-based data to establish preventive treatment protocols for enhancing the QOL and functionality among older adults. The study results may also be helpful for the planning of interdisciplinary health policies for improving the health conditions of different populations. DERR1-10.2196/58186.

Safety and Efficacy of Aspiration Thrombectomy With Intracoronary Tirofiban in Patients Undergoing Primary Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis

BACKGROUND: Primary percutaneous coronary intervention (PPCI) may be complicated by heavy intracoronary thrombus burden leading to decrease in myocardial perfusion and increase in infarct size. The current meta-analysis aims to investigate the clinical outcomes of aspiration thrombectomy (AT) with intracoronary tirofiban during PPCI. METHODS: A systematic search for randomized controlled trials that evaluate the safety and efficacy of AT with intracoronary tirofiban in ST-elevation myocardial infarction (STEMI) patients who underwent PPCI was done using PubMed, MEDLINE, EMBASE, Cochrane, ClinicalTrials.gov., and Herdin PH. Studies included those published between 2010 and 2023 and involved human subjects. Search terms included “aspiration thrombectomy,” “intracoronary tirofiban,” “primary percutaneous coronary intervention,” and “STEMI patients.” RESULTS: Four randomized controlled trials (n = 490 participants) were included in this metaanalysis comparing AT with intracoronary tirofiban versus AT alone in STEMI patients undergoing PPCI. The results revealed no statistically significant difference in ST-segment resolution (risk ratio [RR], 1.02; 95% confidence interval [CI], 0.97–1.08; P = 0.41, I2 = 0%), myocardial blush grade 2–3, (RR, 1.04; 95% CI, 0.97–1.12; P = 0.22, I2 = 62%), and Thrombolysis In Myocardial Infarction 3 flow (RR, &lt;1.0; 95% CI, 0.95–1.04; P = 0.87). The occurrence of major adverse cardiovascular events did not significantly differ between the two groups (RR, 0.46; 95% CI, 0.19–1.09; P = 0.08, I2 = 0%). There was no statistically significant difference in terms of bleeding when combining intracoronary tirofiban to standard medical therapy (RR, 1.35; 95% CI, 0.64–2.84; P = 0.78, four trials [490 patients]). CONCLUSION: In PPCI, major adverse cardiovascular event outcomes of AT with intracoronary tirofiban were similar to those for AT alone in terms of improving myocardial perfusion in STEMI patients without increasing the risk for bleeding. Our meta-analysis suggests that AT alone may be the more acceptable standard during PPCI when encountering heavy thrombus burden. Future validated studies may help further investigate the strategy of adding tirofiban during AT.

Efficacy of durvalumab plus tremelimumab treatment for unresectable hepatocellular carcinoma in immunotherapy era clinical practice.

Since the development of tremelimumab plus durvalumab (Dur/Tre) for unresectable hepatocellular carcinoma (uHCC), it has been used as not only an initial but also later line treatment in clinical practice. This study aimed to elucidate clinical prognostic factors for progression-free survival (PFS) in Dur/Tre treatment cases. Enrolled were 183 uHCC patients treated with Dur/Tre from 2023 to May 2024 (median age, 74years; male patients, 152; Child-Pugh class A:B, 150:33; Barcelona Clinic Liver Cancer stage B:C,59:124; initial line use, 64). Clinical factors with prognostic influence on PFS in these patients were retrospectively evaluated. The median observation period was 7.2months (interquartile range, 3.2-10.4). History of atezolizumab plus bevacizumab (Atz/Bev) treatment was the only significant prognostic factor for PFS at introduction of Dur/Tre in multivariate analysis (hazard ratio 2.040, p=0.028) (median PFS: without vs. with=5.6 vs. 2.7months, p<0.001). Although immune-mediated adverse events (imAE) occurrence was only significant in univariate analysis, when objective response and disease control rates were examined according to imAE positivity (any grade) at the time of analysis, those were noted in 14.4% and 39.2%, respectively, of patients without imAE, while in patients with imAE (any grade), they were noted in 18.2% and 56.1%, respectively (p=0.523 and p=0.038, respectively). History of Atz/Bev treatment may be an independent clinical factor for poor PFS at Dur/Tre introduction.

Effectiveness and safety of enzyme replacement therapy in the treatment of Fabry disease: a Chinese monocentric real-world study.

To assess the effectiveness and safety of enzyme replacement therapy (ERT) for treating Fabry disease in clinical practice. The clinical data of patients with Fabry disease were retrospectively collected and screened according to inclusion and exclusion criteria. The effectiveness of ERT was evaluated by analyzing the improvement in renal dysfunction (decreased estimated glomerular filtration rate (eGFR) and proteinuria), cardiac system injury (mainly increased left ventricular mass index (LVMI)), and neuropathic pain after ERT treatment. The safety of ERT was measured by summarizing the occurrence of adverse events (AE) and adverse drug reactions (ADR) before and after ERT. Sixteen patients with Fabry disease who underwent ERT treatment 2-36 times over a period of 2-89weeks were enrolled in the study. Among them, 13 received symptomatic treatment based on the involvement of various organs, 14 were treated with anti-inflammatory and anti-allergic drugs, and 16 had no AE or ADR. After ERT, there was no significant difference in (eGFR, microalbumin (mALB), 24h urinary protein quantitation (24h PRO), urinary albumin/creatinine ratio (ACR), uric acid (UA), and β2 microglobulin (β2MG) (P > 0.05), and the renal function remained stable or improved; ERT could significantly reduce left ventricular mass index (LVMI) (P = 0.043) and lactate dehydrogenase (LDH) (P = 0.031), and other cardiac function indexes had an improvement trend or remained stable, but the difference was not significant (P > 0.05). After ERT, the degree of limb pain in three of the four minor patients improved. ERT could effectively stabilize or improve renal and cardiac function and relieve neuropathic pain in patients with Fabry disease, and no AE occurred during treatment, and the clinical effectiveness and safety were satisfactory.

INTERVENÇÃO FARMACÊUTICA NA INCIDÊNCIA DE ERROS DE PRESCRIÇÃO RELACIONADA A MEDICAMENTOS

The pharmacist plays a crucial role in healthcare by helping to reduce prescription and medication errors, as well as issues related to pharmacotherapy that could harm hospitalized patients. The aim of this study was to analyze, based on the literature, the contribution of the clinical pharmacist in the hospital setting, focusing on intervention and reducing the incidence of medication-related prescription errors. By working in collaboration with the multidisciplinary team, the clinical pharmacist provides guidance to professionals on the safe and rational use of medications, which enhances the quality of patient therapy. The impact of the clinical pharmacist is significant, as they are capable of reducing the occurrence of avoidable adverse effects by 66%, which can be controlled not only through the discontinuation of medication combinations but also through dose adjustment. It is important to highlight the central role of the pharmacist in medication dispensing, emphasizing the importance of technical and clinical analysis of prescriptions and medication releases in hospital settings, thereby promoting the rational use of medications.

First-choice hormonal therapies for children with infantile epileptic spasms syndrome in South Asia: A network meta-analysis of randomized controlled trials.

Considering the peculiar challenges with infantile epileptic spasms syndrome (IESS) in South Asia and a wide variation in the usage of hormonal therapies, we compared the efficacy and safety of various hormonal therapies for children with IESS in South Asia. We searched PubMed, Embase, Scopus, and Web of Science databases from the inception until April 2024. We included only randomized clinical trials (RCTs) evaluating the efficacy and safety of hormonal therapies for IESS in the South Asian region. Complete cessation of epileptic spasms (ES), electro-clinical response, and time taken to be spasm-free at 2 or 6 weeks of therapy were efficacy outcomes, while the occurrence of adverse events was the safety outcome. Effect estimates were reported as odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CI) and Cochrane risk of bias 2.0 (ROB 2.0) used for quality assessment of each study. The surface under the cumulative ranking curve (SUCRA) was used to rank the different therapies and reported as a p-score ranging from 0 to 1. Of 747 citations, nine RCTs comprising 566 children with IESS were included. After 2-week treatment, dexamethasone (OR: 6.72; 95% CI: 1.47, 30.72), adrenocorticotropic hormone therapy (ACTH) high dose (HD) (OR: 5.30; 95% CI: 1.05, 26.91), and prednisolone HD (OR: 2.41; 95% CI:1.07, 5.46) had shown significantly greater efficacy for cessation of EScompared with ACTH low dose (LD). Similarly, for electroclinical response, dexamethasone (OR: 9.63; 95% CI: 1.99, 46.70) and prednisolone HD (OR: 3.46; 95% CI: 1.38, 8.68) had greater efficacy compared with ACTH LD. Safety outcomes revealed that hypertension was significantly less common with ACTH LD and prednisolone HD as compared with ACTH HD. This study provides quality evidence on preferred first-choice hormonal therapy for managing IESS in South Asia. ACTH HD, dexamethasone, and prednisolone HD are the most effective hormonal therapy options with dose-dependent therapeutic efficacy. PLAIN LANGUAGE SUMMARY: This study provides insights into the selection of first-line hormonal therapies among the various treatments for managing infantile epileptic spasms syndrome (IESS) in South Asia. The study findings suggested that the effectiveness of these therapies is dose-dependent, with high doses of ACTH, dexamethasone, and prednisolone being the most effective for achieving cessation of epileptic spasms.

High-risk features in non-culprit lesions and clinical outcome after NSTEMI versus STEMI.

Complete non-culprit (NC) revascularization may help reduce recurrent events after NSTEMI, especially if NC lesions would harbor high-risk plaque features similar to STEMI. The study aimed to assess differences in fractional flow reserve (FFR)-negative NC plaque morphology in patients presenting with NSTEMI versus STEMI and assess the association of high-risk plaque morphology and clinical outcome. In the prospective PECTUS-obs study, 438 patients presenting with myocardial infarction (MI) underwent optical coherence tomography (OCT) of all FFR-negative intermediate NC lesions. The primary endpoint was the occurrence of major adverse cardiovascular events (MACE, all-cause mortality, non-fatal MI or unplanned revascularization) at two-year follow-up. Four hundred and twenty patients had at least one analyzable OCT, including 203 (48.3%) with NSTEMI and 217 (51.7%) with STEMI. The prevalence of high-risk plaques (HRP), including thin-cap fibroatheromas (TCFA), plaque rupture and thrombus, was comparable between groups. MACE occurred in 29 (14.3%) NSTEMI patients and 16 (7.4%) STEMI patients (Punivariable=0.025 and Pmultivariable=0.270). Incidence of MACE was numerically higher among patients with HRP, irrespective of the clinical presentation at index (Pinteraction=0.684). Among high-risk plaque criteria, plaque rupture was associated with MACE in both NSTEMI (p<0.001) and STEMI (p=0.020). Presence of NC HRP is comparable between NSTEMI and STEMI and leads to numerically higher event rates in both. These results call for additional research on complete revascularization in NSTEMI and treatment of HRP.

Pro-Con Debate: Air or Saline for Loss-of-Resistance Technique of Interlaminar Epidural Access with Fluoroscopy-Guided Pain Medicine Procedures

In this Pro-Con commentary article, the Pro side advocates that using the loss of resistance (LOR) to air technique for interlaminar epidural access is safe as the risk of pneumocephalus is exceptionally low. They note that case reports detailing complications typically utilize at least 1 mL of air, frequently exceeding this amount. Even a 1-mL dosage surpasses the requirement, particularly when fluoroscopy is applied in the context of chronic pain management. The proponents also suggest a modified technique, where a syringe containing a drop of saline or contrast acts as a visual cue, minimizing air injection into the epidural space to a negligible quantity. Moreover, they emphasize that air facilitates the identification of any fluid as an indicator of unintended intrathecal access. The Con perspective argues against the utilization of air for epidural access and advocates for the use of LOR with saline instead. This stance is supported by evidence pointing to a greater occurrence of adverse events, such as postdural puncture headache (PDPH) and pneumocephalus, associated with LOR to air compared to LOR with saline. They also argue that saline’s physical properties enhance tactile feedback, potentially contributing to its increased safety. Both saline and air have been used for many years for epidural access via the interlaminar approach. Although both are generally accepted in practice, neither has been formally established as the standard of care. It would benefit the medical community to further delineate the pros and cons of each medium, enabling practitioners to make more informed decisions. This Pro-Con debate will provide 2 perspectives (Table) on the evidence and rationales for the use of air or saline for the LOR technique in interlaminar epidural access with fluoroscopy.

Clinical characteristics of diabetes patients complicated with COVID-19.

Patients with both diabetes and coronavirus disease 2019 (COVID-19) are more likely to experience negative outcomes. This study aimed to identify the risk factors associated with these adverse outcomes that can assist clinicians in implementing suitable treatment strategies to minimize the occurrence of severe complications. A total of 92 patients with diabetes and COVID-19 in the Endocrine Department of Zhejiang Provincial Hospital of Chinese Medicine from December 2022 to February 2023 were enrolled and divided into the recovered group and the transfer to the intensive care unit (ICU) or death group. The clinical characteristics and infection indicators were compared between the 2 groups. Additionally, the patients were further divided into the normal group and the reduction group based on their glomerular filtration rate (GFR), and their clinical characteristics and infection indicators were also analyzed. Compared with the GFR normal group, the GFR reduction group exhibited worse outcomes, higher COVID-19 severity, a higher proportion of mechanical ventilation, and a longer hospital stay. However, there were no significant differences in leukocyte, lymphocyte, and neutrophil counts between these 2 groups. Compared with the recovered group, the transfer to ICU or death group demonstrated an increase in leukocytes and neutrophils, while lymphocytes decreased (P < .05). The C-reactive protein, procalcitonin, interleukin-6, and serum amyloid A levels in the transfer to ICU or death group were significantly higher than those in the Recovered group (P < .05). In addition, C-reactive protein, procalcitonin, and serum amyloid A levels in the GFR reduction group were significantly higher than those in the normal group (P < .05), while interleukin-6 levels were only slightly higher (P > .05). In clinical treatment, it is necessary to monitor infection indicators and GFR closely and intervene in time to reduce the occurrence of adverse events.

Olaparib-associated toxicity in cancer patients: a systematic review and meta-analysis.

To investigate the characteristics of olaparib-associated adverse events (AEs) in cancer patients. Databases were searched for phase II and III randomized controlled trials (RCTs) involving olaparib treatment up to March 2024. A systematic assessment was performed. Twenty-seven RCTs involving 9542 patients were included. This meta-analysis indicates that olaparib could significantly increase the risk of developing any all-grade (RR, 1.08; 95% CI, 1.03-1.13; p = 0.001) and high-grade (RR, 1.45; 95% CI, 1.19-1.77; p = 0.0003) AEs in cancer patients. Olaparib could increase the risk of dose reduction (RR, 3.00; 95% CI, 1.59-5.70; p = 0.0007) and treatment discontinuation (RR, 2.00; 95% CI, 1.28-3.14; p = 0.002). Hematologic toxicities and gastrointestinal toxicities commonly occur in patients receiving olaparib. Anemia, nausea, and fatigue were the most frequent AEs, with olaparib increasing the risk of both all-grade and high-grade occurrences of these events. Patients with longer treatment durations tend to have a higher risk of anemia. Patients with urinary system tumors tend to have a higher risk of nausea, while those with breast cancer tend to have a higher risk of fatigue. Olaparib maintenance therapy may be associated with a higher risk of fatigue. Olaparib could increase other AEs such as diarrhea, vomiting, decreased appetite, dyspepsia, dysgeusia, dizziness, headache, back pain, urinary tract infection, dyspnea, and cough. Olaparib-containing therapy could increase the occurrence of specific AEs in patients with cancer. Clinicians should be aware of these risks and conduct regular monitoring.