Frequency Of Adverse Events Research Articles

High comorbidity burden and low incidence of adverse events in primary shoulder arthroplasty in tertiary care at a university hospital

BackgroundReducing perioperative risk is in the focus of primary arthroplasty caregivers. Primary shoulder arthroplasty patients are considered among those with the lowest perioperative risk. Nonetheless, in tertiary care centres and university settings patients with significant comorbidities are being treated. It remains unclear whether the overall comorbidity burden is truly higher and if this results in an increased frequency of adverse events (AE). As a result, we conducted a study to assess the comorbidity burden and the frequency of major perioperative adverse events and predictive factors following primary shoulder arthroplasty in the university setting. MethodsA retrospective cohort analysis was conducted on patients undergoing primary shoulder arthroplasty for a non-trauma, non-tumour indication from January 1st, 2014 through December 31st, 2018. Administrative data were recorded to assess comorbidity burden and revision surgery within the first postoperative year. Major adverse events were routinely recorded on a weekly basis by the treating physicians. Descriptive and comparative statistical analyses were performed. The cohort was compared against a large North American sample. ResultsOf 386 patients who underwent 400 primary shoulder arthroplasties 14 (3.5 %) experienced adverse events. While AE were distributed equally among anatomical and reverse shoulder arthroplasties, no adverse event was recorded in the 34 hemiarthroplasty patients. The cohort showed an increased comorbidity burden in international comparison. Peptic ulcer disease was significantly associated with AE, while mild liver disease experienced a trend towards AE. ConclusionWe found an increased comorbidity burden and a low rate of AE for primary shoulder arthroplasty in a tertiary care and university setting. The distinct role of peptic ulcer disease in this cohort and the trend in mild liver disease merit further investigation in larger samples. The findings underscore the importance of perioperative risk assessment and management. Level of evidenceIII, retrospective cohort study.

Correlation between postoperative chemotherapy regimen and survival in patients with resectable gastric adenocarcinoma accompanied with vascular cancer thrombus.

Patients with resectable gastric adenocarcinoma accompanied by vascular cancer thrombus (RGAVCT) have a poor prognosis, with a 5-year survival rate ranging from 18.42%-53.57%. These patients need a reasonable postoperative treatment plan to improve their prognosis. To determine the most effective postoperative chemotherapy regimen for patients with RGAVCT. We retrospectively collected the clinicopathological data of 530 patients who underwent radical resection for gastric cancer between January 2017 and January 2022 and who were pathologically diagnosed with gastric adenocarcinoma with a choroidal cancer embolus. Furthermore, we identified the high-risk variables that can influence the prognosis of patients with RGAVCT by assessing the clinical and pathological features of the patients who met the inclusion criteria. We also assessed the significance of survival outcomes using Mantel-Cox univariate and multivariate analyses. The subgroups of patients with stages I, II, and III disease who received single-, dual-, or triple-drug regimens following surgery were analyzed using SPSS 25.0 and the ggplot2 package in R 4.3.0. In all, 530 eligible individuals with RGAVCT were enrolled in this study. The median overall survival (OS) of patients with RGAVCT was 24 months, and the survival rates were 80.2%, 62.5%, and 42.3% at 12, 24, and 59 months, respectively. Preoperative complications, tumor size, T stage, and postoperative chemotherapy were identified as independent factors that influenced OS in patients with RGAVCT according to the Cox multivariate analysis model. A Kaplan-Meier analysis revealed that chemotherapy had no effect on OS of patients with stage I or II RGAVCT; however, chemotherapy did have an effect on OS of stage III patients. Stage III patients who were treated with chemotherapy consisting of dual- or triple-agent regimens had better survival than those treated with single-agent regimens, and no significant difference was observed in the survival of patients treated with chemotherapy consisting of dual- or triple-agent regimens. For patients with stage III RGAVCT, a dual-agent regimen of postoperative chemotherapy should be recommended rather than a triple-agent treatment, as the latter is associated with increased frequency of adverse events.

Initial clinical experience with durvalumab plus tremelimumab in patients with unresectable hepatocellular carcinoma in real‑world practice.

Although durvalumab plus tremelimumab (Dur/Tre) has been approved as first-line therapy for patients with unresectable hepatocellular carcinoma (u-HCC), its outcomes in real-world clinical practice are unclear. The present study aimed to evaluate the efficacy and safety of Dur/Tre treatment. This multicenter study was conducted between March 2023 and January 2024, and included 120 patients with u-HCC treated with Dur/Tre. Among the patients, 44 had no history of systemic treatment. Progression-free survival (PFS), therapeutic response and adverse events (AEs) were assessed. The objective response rate (ORR) and disease control rates (DCR) were 15.8 and 53.3%, respectively. The median PFS was 3.9 months. The incidence rates of AEs of any grade and those grade 3 or higher were 83.3 and 36.7%, respectively. Liver injury was the most frequent AE of any grade and grade 3 or higher. Although there was no significant difference in ORR and PFS between the first and later line groups (ORR 15.8 vs. 15.7%, P=0.986; PFS 4.5 vs. 3.6 months, P=0.213), there was a significant difference in DCR between the two groups (65.8 vs. 45.9%, P=0.034). No significant differences were noted between the first- and later-line treatment groups regarding the incidence rate of AEs. Decision tree analysis revealed that poor liver function and advanced age were significant variables for discontinuation owing to AEs. In conclusion, Dur/Tre as first-line therapy had better disease control responses compared with later-line therapy; however, this regimen should be carefully administered to patients with deteriorating hepatic function or advanced age.

Local side effects during sublingual allergen-specific immunotherapy and pathogenetically based methods for their correction (Review)

Introduction. The study of the effectiveness and safety of allergen-specific immunotherapy remains relevant due to the emergence of a personalized approach in allergology and new dosage forms. Adverse reactions during sublingual allergen-specific immunotherapy are the leading reason of treatment discontinuation. Understanding the mechanisms of side effects and knowing how to overcome them allows us to achieve better tolerability of allergen-specific immunotherapy and maintain patient compliance.The aim of the review is to combine the available literature data on the frequency, nature, and pathogenetic basis of adverse events during sublingual allergen-specific immunotherapy and to consider options for their prevention and treatment.

Target engagement and immunogenicity of an active immunotherapeutic targeting pathological α-synuclein: a phase 1 placebo-controlled trial

Investigational therapeutics that target toxic species of α-synuclein (αSyn) aim to slow down or halt disease progression in patients with Parkinson’s disease (PD). Here this 44-week, randomized, placebo-controlled, double-blind, single-center phase 1 study investigated safety, tolerability and immunogenicity of UB-312, an active immunotherapeutic targeting pathological αSyn, in patients with PD. The primary outcome measures were adverse event frequency and change in anti-αSyn antibody titers in blood and cerebrospinal fluid (CSF). Exploratory outcomes were changes in clinical scales and biomarker-based target engagement as measured by seed amplification assays. Twenty patients were randomized 7:3 (UB-312:placebo) into 300/100/100 μg or 300/300/300 μg (weeks 1, 5 and 13) intramuscular prime-boost dose groups. Safety was similar across groups; adverse events were mostly mild and transient. Two patients experienced three serious adverse events in total, one possibly treatment related; all resolved without sequalae. Anti-αSyn antibodies in serum from 12/13 and CSF from 5/13 patients who received three UB-312 doses confirmed immunogenicity. Mean serum titers (in log-dilution factor) increased from baseline by 1.398 and 1.354, and peaked at week 29 at 2.520 and 2.133, for 300/100/100 μg and 300/300/300 μg, respectively. CSF titers were 0 at baseline and were 0.182 and 0.032 at week 21, respectively. Exploratory analyses showed no statistical differences in clinical scales but a significant reduction of αSyn seeds in CSF of a subset of UB-312-treated patients. These data support further UB-312 development. ClinicalTrials.gov:NCT04075318.

Efficacy and safety of tesamorelin in people with HIV on integrase inhibitors.

Tesamorelin is the only FDA-approved therapy to treat abdominal fat accumulation in people with HIV (PWH). Phase III clinical trials were conducted prior to the introduction of integrase inhibitors (INSTIs), which are now a mainstay of HIV antiretroviral therapy. We leveraged a randomized double-blind trial of 61 PWH and metabolic dysfunction-associated steatotic liver disease to evaluate the efficacy and safety of tesamorelin 2 mg once daily vs. identical placebo among participants on INSTI-based regimens at baseline. In the parent clinical trial, visceral fat cross-sectional area, hepatic fat fraction, and trunk-to-appendicular fat ratio were quantified using magnetic resonance imaging, proton magnetic resonance spectroscopy, and dual-energy x-ray absorptiometry, respectively, at baseline and 12 months. Metabolic and safety outcomes were compared between treatment arms. Among 38 participants on INSTI-based regimens at baseline, 15 individuals on tesamorelin and 16 individuals on placebo completed the 12-month study. Tesamorelin led to significant declines in visceral fat (median [interquartile range]: -25 [-93, -2] vs. 14 [3, 41] cm 2 , P = 0.001), hepatic fat (-4.2% [-12.3%, -2.7%] vs. -0.5% [-3.9%, 2.7%], P = 0.01), and trunk-to-appendicular fat ratio (-0.1 [-0.3, 0.0] vs. 0.0 [-0.1, 0.1], P = 0.03). Tesamorelin was well tolerated with a similar frequency of adverse events, including hyperglycemia, between groups. The current analysis provides the first dedicated data on the efficacy and safety of tesamorelin among PWH on INSTI-based regimens. Despite the association of INSTI use with weight gain and adipose tissue dysfunction, tesamorelin had beneficial effects on body composition with no exacerbation of glycemic control.

LGG-39. REAL-LIFE STUDY OF THE EFFICACY AND TOLERANCE OF TRAMETINIB IN THE TREATMENT OF LOW-GRADE GLIOMAS IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1

Abstract BACKGROUND Low grade gliomas (LGG) are the most common brain tumors in children. Targeted therapies such as the MEK-inhibitor trametinib have revolutionized the management of pediatric LGGs. NF1 mutations generate misregulations in the RAS/MAP kinase pathway, but data on trametinib in type 1 neurofibromatosis (NF1)-related LGG are scarce. Efficacy and safety of trametinib in NF1 patients with LGG need to be further investigated. METHODS This retrospective study included patients with NF1 <18 years from two French centers having received trametinib for a relapsing/progressive LGG between March 2020 and July 2022. Treatment efficacy was assessed according to RAPNO criteria, and toxicities and therapeutic exposure were assessed using real-life data collected retrospectively up to July 2023. RESULTS The study enrolled 11 patients, the median age at LGG diagnosis was 3 (1-9) years. All patients previously received a median number of 2 (1-4) lines of chemotherapy. Median age at treatment initiation was 9 (4-13) years. Median duration of trametinib treatment was 9.3 (5.8-24) months. Progression-free survival was 91% at 6 months and 61% at 2 years. Median time to best response was 2.7 (1.1-9) months, including 5 stable diseases, 4 minor responses, and 2 partial responses. Median duration of response was 8.6 (3.7-36.2) months. Adverse events (AEs) occurred in all patients, and 64% of the patient had grade 3 AEs. Skin toxicities and paronychia were the most frequent AEs. Treatment interruption occurred in 55% of the patients, and 3 patients permanently discontinued trametinib due to treatment-related toxicities. Real therapeutic exposure was significantly shorter than theoretically expected (19.6% treatment reduction). CONCLUSION Trametinib showed promising efficacy in NF1 children with relapsing/progressive LGG. Trametinib toxicity remains challenging. Further prospective clinical trials stratified according to molecular alterations are needed to support these preliminary results.

Treatment of Aggressive Behavior and Agitation in an 11-Year-Old Boy with Co-Occurring Autism and ADHD: A Case Report and Literature Review on the Use of Intravenous Valproate in Emergency Psychiatry

Background: Autism spectrum disorder (ASD) is a persistent neurodevelopmental disorder frequently co-occurring with attention-deficit/hyperactivity disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage the core symptoms of ASD, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend the use of neuroleptics to reduce psychomotor agitation in patients with ASD. However, as children with ASD are often drug-resistant, alternative treatments are often justified. Reports from the literature have indicated that intravenous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with a lower frequency of adverse events compared to conventional treatments. However, as the related findings are occasionally inconsistent, IV-VPA is not yet an approved option in the context of clinical psychiatry. We aim to improve knowledge of the IV-VPA treatment option for emergency psychiatric treatment in pediatric patients. Methods: We report the case of an 11-year-old boy suffering from a complex neurodevelopmental condition who experienced a psychotic episode with severe aggressive and disruptive behaviors and was successfully treated with IV-VPA. Furthermore, we provide an updated literature review on this topic. Conclusion: In our case, first-line therapies proved to be ineffective. To the contrary, IV-VPA led to safe and prompt clinical success, which is in line with other reports. Based on our literature review, IV-VPA can be highly effective and reduces the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry.

Rituximab in the treatment of progressive interstitial lung disease associated with the antisynthetase syndrome

ObjectiveTo assess the real-world, long-term effectiveness of rituximab (RTX) as a rescue therapy in patients with antisynthetase syndrome and progressive interstitial lung disease (ASS-ILD).MethodsMulticentre observational retrospective longitudinal study of a cohort of patients with ASS-ILD that started treatment with RTX due to recurrent or ongoing progressive ILD despite therapy with glucocorticoids and immunosuppressants.ResultsTwenty-eight patients were analyzed. Examining the entire study population, before treatment with RTX the mean decline in %pFVC and %pDLCO from the ASS-ILD diagnosis to the initiation of RTX treatment (T0) was -6.44% and -14.85%, respectively. After six months of treatment, RTX reversed the decline in pulmonary function test (PFT) parameters: ∆%pFVC +6.29% (95% CI: -10.07 to 2.51; p=0.002 compared to T0) and ∆%pDLCO +6.15% (95% CI: -10.86 to -1.43; p=0.013).Twenty-four patients completed one year of therapy and 22 two years, maintaining the response in PFT: ∆%pFVC: +9.93% (95% CI: -15.61 to -4.25; p=0.002) and ∆%pDLCO: +7.66% (95% CI: -11.67 to -3.65; p<0.001). In addition, there was a significant reduction in the median dose of prednisone, and it could be suspended in 18% of cases. In 33% of patients who required oxygen therapy at the start of treatment, it could be discontinued.The frequency of adverse events reached 28.5% of cases.ConclusionBased on our results, RTX appears to be effective as rescue therapy in most patients with recurrent or progressive ASS-ILD unresponsive to conventional treatment. The use of RTX was well tolerated in the majority of patients.

Rizatriptan as an Over-the-Counter Triptan in the Treatment of Migraine Attacks.

Around 91% of migraine patients use over-the-counter medicines to treat attacks, often without further treatment or medical consultation. This therapeutic principle is established in most countries, regardless of how the healthcare system is otherwise structured or financed. Using Germany as an example, the basis for an expansion of attack therapy with rizatriptan as an over-the-counter triptan is described. To achieve the best possible tolerability and safety in the context of self-medication, the lowest possible dose should be selected to provide the most favourable tolerability and safety profile in the context of self-medication through low dosages. The lowest approved dose of rizatriptan is 5mg. This was investigated in three randomized controlled trials with 752 patients. The results show that rizatriptan at a dose of 5mg is more effective than the triptans naratriptan 2.5mg, almotriptan 12.5mg and sumatriptan 50mg, which were previously available for self-medication in Germany. There was no significant difference in the frequency of adverse events with rizatriptan 5mg compared to placebo. Rizatriptan 5mg does not have a higher side effect potential than sumatriptan 50mg, which is already exempt from the prescription requirement. The reasons given show that rizatriptan in a dose of 5mg for the treatment of acute migraine attacks fulfils the requirements for a transfer from prescription to pharmacy-only status at least as well as sumatriptan 50mg, naratriptan 2.5mg and almotriptan 12.5mg. From a clinical care perspective, it is desirable for affected patients to have other options available for self-medication. Non-responders to other substances also have a further treatment option with rizatriptan 5mg, with the same or even better risk-benefit profile, to treat migraine attacks safely, effectively and in a tolerable manner as part of self-medication.

Efficacy and safety of once daily oral administration of sodium-glucose cotransporter-2 inhibitor velagliflozin compared with twice daily insulin injection in diabetic cats.

Options for treatment of diabetes mellitus in cats are limited to insulin injections and monitoring for hypoglycemia. Once daily sodium-glucose cotransporter-2 inhibitor velagliflozin PO is noninferior to insulin injections. Client-owned diabetic cats (127 safety; 116 efficacy assessment). Prospective, randomized (1 mg/kg velagliflozin), positive controlled (titrated Caninsulin), open label, noninferiority field trial, comparing number of cats with treatment success in ≥1 clinical variable and ≥1 glycemic variable (margin Δ: 15%) on Day 45; secondary endpoints included glycemic and clinical assessments during 91 days. On Day 45, 29/54 (54%) velagliflozin-treated cats and 26/62 (42%) Caninsulin-treated cats showed treatment success, demonstrating noninferiority (difference -11.8%; upper 1-sided 97.5% confidence interval, -∞ to 6.3%). By Day 91, quality of life (QoL), polyuria, and polydipsia had improved in 81%, 54% and 61% (velagliflozin); on blood glucose (BG) curves, mean BG was <252 mg/dL in 42/54 (78%; velagliflozin) and 37/62 (60%; Caninsulin); minimum BG was <162 mg/dL in 41/54 (76%; velagliflozin) and 41/62 (66%; Caninsulin); serum fructosamine was <450 μmol/L in 41/54 (76%; velagliflozin) and 38/62 (61%; Caninsulin). Velagliflozin's most frequent adverse events were loose feces/diarrhea (n = 23/61, 38%), positive urine culture (n = 19/61, 31%), and nonclinical hypoglycemia (BG <63 mg/dL; n = 8/61, 13%); Caninsulin's: clinical and nonclinical hypoglycemia (n = 35/66, 53%), positive urine culture (n = 18/66, 27%), and loose feces/diarrhea (n = 10/66, 15%). Diabetic ketoacidosis occurred in 4/61 (7%; velagliflozin) and 0/66 (Caninsulin). Once daily oral administration of velagliflozin was noninferior to insulin injections, showed good QoL and glycemia without clinical hypoglycemia.

A potential novel treatment for cirrhosis-related ascites: Empagliflozin is safe and tolerable in advanced chronic liver disease.

Advanced chronic liver disease and advanced chronic liver disease-related ascites have a high mortality. The pharmacological treatment of ascites and fluid overload has changed little over time. Empagliflozin, a sodium-glucose cotransporter type 2 inhibitor is an untested potential novel treatment in cirrhosis, as it has survival benefits in heart failure, which has similar pathophysiological fluid overload mechanisms. Before investigating empagliflozin's potential benefit in cirrhosis, its safety must be addressed. Ten participants (five each with compensated or decompensated advanced chronic liver disease, based on Child-Pugh class) received empagliflozin 10 mg orally daily for 4 weeks with 2 weeks follow-up. Empagliflozin safety, pharmacokinetics and pharmacodynamics were investigated. In total, eight patients (80%) reported an adverse event, and three patients (30%) experienced a serious adverse event, one of which was attributed to empagliflozin. Overall, the frequency of adverse events was similar to previous phase 3 trials of gliflozins. Higher plasma empagliflozin concentrations did not significantly increase the risk of adverse events. Four-week treatment with empagliflozin was safe and well tolerated in patients with advanced chronic liver disease. These preliminary data support assessment of long-term treatment on disease-related and mortality outcomes in patients with cirrhosis through randomized control trials.

Safety and Tolerability of Rituximab in the Treatment of Systemic Sclerosis.

Rituximab (RTX) has been used for the treatment of systemic sclerosis (SSс) for a long time and has shown good efficacy for skin fibrosis and interstitial lung disease (ILD). However, data on tolerability and long-term adverse events (AEs) during RTX therapy in SSc are insufficient. The objective of this study was to assess the tolerability and safety of RTX in patients with SSс in a long-term prospective follow-up. Our open-label prospective study included 151 SSс patients who received at least one RTX infusion. The mean age of the patients was 47.9 ± 13.4 years; the majority of them were women (83%). The mean disease duration was 6.4 ± 5.8 years. The mean follow-up period after the first RTX infusion was 5.6 ± 2.6 years (845.6 patient-years (PY)). All patients received RTX in addition to ongoing therapy with prednisone and/or immunosuppressants. AEs were assessed and recorded by a doctor in the hospital immediately after RTX infusion and then by patient's reported outcome during the observation period. All causes of death were considered, regardless of treatment. A total of 85 AEs (56%) were registered, the overall incidence of AEs was 10/100 PY (95% confidence interval (CI) 8-12). The highest frequency of all AEs was observed in the first 2-6 months after the first course of RTX, however, these were mainly mild and moderate AEs (71%). The most frequent AEs were infections, they were observed in 40% of cases, with no serious opportunistic infections reported. The overall incidence of all infections was 7.1/100 PY (95% CI 5.5-9), serious infections-1.5/100 PY (95%CI 0.9-2.6). Infusion reactions occurred in 8% of patients. Other AEs were noted in 3% (0.6/100 PY, 95% CI 0.3-1.4). The overall incidence of serious AEs was 18%-3.2/100 PY (95% CI 2.2-4.6). There was a significant decrease of the immunoglobulin G (Ig G) during follow-up; however, its average values remained within normal limits. There were 17 deaths (11%) (2/100 PY, 95% CI 1.3-3.2). In most cases, patients died from the progression of the major organ failure, which arose before RTX treatment. In our study, the safety profile of RTX in SSс was assessed as favorable. It was similar to the AE profile in other autoimmune diseases treated with RTX. With an increase in the cumulative dose of RTX, no increase in AEs was observed. The mortality is comparable to the other severe autoimmune diseases in observational studies. Monitoring of IgG may be useful for patients with SSс on RTX therapy for early detection of the risk of developing infectious complications. RTX could be considered as a relatively safe drug for the complex therapy of SSс when standard therapy is ineffective or impossible.

Key results from observational studies and real-world evidence of sodium-glucose cotransporter-2 inhibitor effectiveness and safety in reducing cardio-renal risk.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, originally designed to manage blood sugar levels in individuals with type 2 diabetes (T2D), have emerged as a crucial class of drugs for managing cardio-renal diseases. These drugs work by targeting the SGLT2 protein in the kidneys, promoting the excretion of glucose and influencing metabolic pathways beyond glucose control. The relationship between cardio-renal diseases and SGLT2 inhibitors has been explored through landmark trials and real-world evidence (RWE) studies, demonstrating significant reductions in cardio-renal complications. This review discusses the importance of RWE studies alongside randomized controlled trials in understanding the real-world effectiveness and safety of SGLT2 inhibitors. It outlines the advantages and disadvantages of RWE compared to RCTs, highlighting their complementary roles in providing comprehensive insights into treatment outcomes. By examining a range of RWE studies, the review underscores the cardio-renal benefits of SGLT2 inhibitors across various patient populations. Safety assessments indicate that SGLT2 inhibitors are generally well tolerated, with severe adverse events being rare. Common issues, such as genital mycotic infections and urinary tract infections, are acknowledged, alongside less frequent but significant adverse events including diabetic ketoacidosis, lower-limb amputations, and bone fractures. In summary, SGLT2 inhibitors show promising cardio-renal protective effects in real-world scenarios across diverse populations in T2D, indicating their potential as early intervention measures. Continued research is essential for gaining a thorough understanding of their long-term effects and safety profiles.

The Effects of Intraoperative Methadone on Postoperative Pain Control in Pediatric Patients: A Scoping Review.

Inadequate perioperative pain control has deleterious effects on children's development and can lead to heightened pain experiences and the avoidance of future medical procedures. Reports of perioperative use of methadone in children are increasing, as it has a favorable pharmacodynamic profile; however, the effectiveness of methadone in reducing postoperative pain has not been established. We, therefore, aimed to provide a scoping review of the literature comparing the effect of intraoperative methadone versus other opioids on postoperative opioid consumption, pain scores, and adverse events in pediatric patients. We identified studies in PubMed, Scopus, Embase, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to January 2023. Postoperative opioid consumption, pain scores, and adverse events were extracted for analysis. We screened 1864 studies, of which 83 studies were selected for full-text review. Five studies were included in the final analysis. Postoperative opioid consumption was decreased overall in children who received methadone compared to those who did not. The majority of studies indicated that methadone was superior to other opioids in reported pain scores, while the frequency of adverse events was similar between the groups. Although the data reviewed highlight a potential benefit of intraoperative methadone in pediatric patients, 4 of the 5 studies had serious methodological concerns. Thus, we cannot make strong recommendations for the regular use of methadone in the perioperative setting at this time. Our results highlight the need for large, well-designed randomized trials to fully evaluate the safety and efficacy of intraoperative methadone in diverse pediatric surgical populations.

Cuidados de enfermería para prevenir las úlceras por presión durante la estancia hospitalaria

Introduction: pressure ulcers (PUs) are ischemic injuries which compromise the integrity of the skin and underlying tissue. They occur in 3-10% of in-patients, and the incidence rate of a new PU ranges from 7.7 and 26.9%. Objective: to describe nursing care for preventing PUs during hospital stay. Materials and methods: an integrative review of the literature based on health sciences journals and databases. Article search was conducted using DeCS and MeSH terms, screened by title, abstract and full text, and organized by levels of evidence and grades of recommendation. Critical Reading was completed using the CASPe and Strobe tools. This study was classified as non-risk according to Law 23 of 1982. Results: forty-three (43) articles were included, and seven topics were constructed including elements and interventions for PUs prevention, as frequent adverse events, as well as the obstacles and complications derived from the lack of these actions. Conclusions: in this study, care provided for PU prevention is classified as nursing care interventions and tools used, acknowledging that 95% of skin lesions are preventable through proper management. Professionals should be aware of and apply specific care interventions to prevent the development of PUs.

Bulevirtide Combined with Pegylated Interferon for Chronic Hepatitis D

BackgroundIn a phase 3 trial, bulevirtide monotherapy led to a virologic response in patients with chronic hepatitis D. Pegylated interferon (peginterferon) alfa-2a is recommended by guidelines as an off-label treatment for this disease. The role of combination therapy with bulevirtide and peginterferon alfa-2a, particularly with regard to finite treatment, is unclear.MethodsIn this phase 2b, open-label trial, we randomly assigned patients to receive peginterferon alfa-2a alone (180 μg per week) for 48 weeks; bulevirtide at a daily dose of 2 mg or 10 mg plus peginterferon alfa-2a (180 μg per week) for 48 weeks, followed by the same daily dose of bulevirtide for 48 weeks; or bulevirtide at a daily dose of 10 mg alone for 96 weeks. All the patients were followed for 48 weeks after the end of treatment. The primary end point was an undetectable level of hepatitis D virus (HDV) RNA at 24 weeks after the end of treatment. The primary comparison was between the 10-mg bulevirtide plus peginterferon alfa-2a group and the 10-mg bulevirtide monotherapy group.ResultsA total of 24 patients received peginterferon alfa-2a alone, 50 received 2 mg and 50 received 10 mg of bulevirtide plus peginterferon alfa-2a, and 50 received 10 mg of bulevirtide monotherapy. At 24 weeks after the end of treatment, HDV RNA was undetectable in 17% of the patients in the peginterferon alfa-2a group, in 32% of those in the 2-mg bulevirtide plus peginterferon alfa-2a group, in 46% of those in the 10-mg bulevirtide plus peginterferon alfa-2a group, and in 12% of those in the 10-mg bulevirtide group. For the primary comparison, the between-group difference was 34 percentage points (95% confidence interval, 15 to 50; P<0.001). At 48 weeks after the end of treatment, HDV RNA was undetectable in 25% of the patients in the peginterferon alfa-2a group, in 26% of those in the 2-mg bulevirtide plus peginterferon alfa-2a group, in 46% of those in the 10-mg bulevirtide plus peginterferon alfa-2a group, and in 12% of those in the 10-mg bulevirtide group. The most frequent adverse events were leukopenia, neutropenia, and thrombocytopenia. The majority of adverse events were of grade 1 or 2 in severity.ConclusionsThe combination of 10-mg bulevirtide plus peginterferon alfa-2a was superior to bulevirtide monotherapy with regard to an undetectable HDV RNA level at 24 weeks after the end of treatment. (Funded by Gilead Sciences; MYR 204 ClinicalTrials.gov number, NCT03852433.)

What has antifibrotic therapy changed for patients with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic interstitial lung disease of unknown cause. IPF is characterized by excessive production and deposition of extracellular matrix components, which lead to irreversible violations of the architectonics of lung tissue and loss of function. Without treatment, the average survival rate of patients after diagnosis does not exceed 3–5 years. However, published observations report improved survival over the past decade, due to the advent of antifibrotic drugs and earlier diagnosis. The benefits of antifibrotic therapy include a slower rate of reduction in forced lung capacity (FVC) and a reduction in mortality. Pirfenidone and nantedanib are the only currently approved antifibrotic drugs for the treatment of IPF. Several generic drugs with the INN pirfenidone are registered on the Russian market, including the drug PIRFASPEC® (267 mg capsules). Their efficacy and safety have been demonstrated both in randomized clinical trials and in real clinical practice studies. IPF patient registries, which have been maintained in many countries since 2010, provide additional information regarding the progression of the disease, the effectiveness of therapy, and the frequency of adverse events. Although they have a different mechanism of action and safety profile, their effectiveness in slowing the decline of FVC and reducing the risk of mortality over time is similar. However, IPF is still characterized by progressive shortness of breath and poor prognosis, as treatment can only delay the progression of IPF and cannot stop or reverse the damage. Although clinical trials of new drugs for the treatment of IPF are currently underway, no other drugs have yet been approved in the Russian Federation.

Efficacy, reactogenicity, and safety of the adjuvanted recombinant zoster vaccine for the prevention of herpes zoster in Chinese adults ≥ 50 years: A randomized, placebo-controlled trial

ABSTRACT Phase III multi-country studies (ZOE-50/70) demonstrated that the adjuvanted recombinant zoster vaccine (RZV) was well tolerated and prevented herpes zoster (HZ) in healthy ≥ 50-year-olds, with a vaccine efficacy (VE) > 90% across age groups. These pivotal trials did not enroll participants from mainland China where RZV is licensed, therefore similar clinical data are missing for this population. In this phase IV observer-blind study (NCT04869982) conducted between 2021 and 2023 in China, immunocompetent and medically stable ≥ 50-year-olds were randomized 1:1 to receive two RZV or placebo doses, 2 months apart. This study assessed the VE (overall, as confirmatory objective, and descriptively by age category [50–69-year-olds/≥ 70-year-olds]), reactogenicity, and safety of RZV in this Chinese population. Of the 6138 enrolled participants, 99.2% completed the study. During a mean follow-up period of 15.2 (±1.1) months, 31 HZ episodes were confirmed (RZV = 0; placebo = 31) for an incidence rate of 0.0 vs 8.2 per 1000 person-years and an overall VE of 100% (89.82–100). The descriptive VE was 100% (85.29–100) for 50–69-year-olds and 100% (60.90–100) for ≥ 70-year-olds. Solicited adverse events (AEs) were more frequent in the RZV vs the placebo group (median duration: 1–3 days for both groups). Pain and fatigue were the most frequent local and general AEs (RZV: 72.1% and 43.4%; placebo: 9.2% and 5.3%). The frequencies of unsolicited AEs, serious AEs, potential immune-mediated diseases, and deaths were similar between both groups. RZV is well tolerated and efficacious in preventing HZ in Chinese ≥ 50-year-olds, consistent with efficacy studies including worldwide populations with similar age and medical characteristics.

Bempegaldesleukin Plus Nivolumab Versus Sunitinib or Cabozantinib in Previously Untreated Advanced Clear Cell Renal Cell Carcinoma: A Phase III Randomized Study (PIVOT-09).

Bempegaldesleukin (BEMPEG) is a pegylated interleukin (IL)-2 cytokine prodrug engineered to provide controlled and sustained activation of the clinically validated IL-2 pathway, with the goal of preferentially activating and expanding effector CD8+ T cells and natural killer cells over immunosuppressive regulator T cells in the tumor microenvironment. The open-label, phase III randomized controlled PIVOT-09 trial investigated the efficacy and safety of BEMPEG plus nivolumab (NIVO) as first-line treatment for advanced/metastatic clear cell renal cell carcinoma (ccRCC) with intermediate-/poor-risk disease. Patients with previously untreated advanced/metastatic ccRCC were randomly assigned (1:1) to BEMPEG plus NIVO, or investigator's choice of tyrosine kinase inhibitor (TKI; sunitinib or cabozantinib). Coprimary end points were objective response rate (ORR) by blinded independent central review and overall survival (OS) in patients with International Metastatic RCC Database Consortium (IMDC) intermediate-/poor-risk disease. Overall, 623 patients were randomly assigned to BEMPEG plus NIVO (n = 311) or TKI (n = 312; sunitinib n = 225, cabozantinib n = 87), of whom 514 (82.5%) had IMDC intermediate-/poor-risk disease. In patients with IMDC intermediate-/poor-risk disease, ORR with BEMPEG plus NIVO versus TKI was 23.0% (95% CI, 18.0 to 28.7) versus 30.6% (95% CI, 25.1 to 36.6; difference, -7.7 [95% CI, -15.2 to -0.2]; P = .0489), and median OS was 29.0 months versus not estimable (hazard ratio, 0.82 [95% CI, 0.61 to 1.10]; P = .192), respectively. More frequent all-grade treatment-related adverse events (TRAEs) with BEMPEG plus NIVO versus TKI included pyrexia (32.6% v 2.0%) and pruritus (31.3% v 8.8%). Grade 3/4 TRAEs were less frequent with BEMPEG plus NIVO (25.8%) versus TKI (56.5%). First-line BEMPEG plus NIVO for advanced/metastatic ccRCC did not improve efficacy in patients with intermediate-/poor-risk disease but led to fewer grade 3/4 TRAEs versus TKI.