Incidence Of Adverse Events Research Articles

The Application of Psychological Nursing in Pediatric Clinical Nursing

Objective: To study the application effect of psychological nursing in pediatric clinical nursing. Method: 100 pediatric patients who underwent treatment in our hospital from January 2019 to December 2020 were selected as the research subjects. They were randomly divided into a control group and an observation group, with 50 cases in each group. The control group received routine nursing care, while the observation group received psychological care based on routine nursing care. The nursing compliance, incidence of adverse events, and parental satisfaction of the two groups of pediatric patients were compared and analyzed. Result: Through psychological nursing intervention, it was found that the observation group had better nursing compliance, incidence of adverse events, and parental satisfaction than the control group, P < 0.05, the differences are statistically significant. Conclusion: The application of psychological nursing in pediatric clinical nursing can improve the compliance of pediatric care, reduce the incidence of adverse events, enhance parental satisfaction, and have clinical promotion and application value.

Safety, tolerability, and pharmacokinetics of antisense oligonucleotide BIIB078 in adults with C9orf72-associated amyotrophic lateral sclerosis: a phase 1, randomised, double blinded, placebo-controlled, multiple ascending dose study

Hexanucleotide repeat expansion of C9orf72 is a common genetic cause of amyotrophic lateral sclerosis (ALS). No C9orf72-targeted treatments are available. BIIB078 is an investigational antisense oligonucleotide targeting C9orf72 sense RNA. We aimed to assess the safety, tolerability, and pharmacokinetics of BIIB078 in participants with C9orf72-associated ALS. This phase 1, randomised controlled trial was done at 22 sites in six countries (Canada, Ireland, Netherlands, Switzerland, UK, and USA). Adults with ALS and a pathogenic repeat expansion in C9orf72 were randomly assigned within six cohorts, via Interactive Response Technology in a 3:1 ratio per cohort, to receive BIIB078 (5 mg, 10 mg, 20 mg, 35 mg, 60 mg, or 90 mg in cohorts 1-6, respectively) or placebo, via an intrathecal bolus injection. The treatment period consisted of three loading doses of study treatment, administered approximately once every 2 weeks, followed by monthly maintenance doses during a treatment period of about 3 months for cohorts 1-3 and about 6 months for cohorts 4-6. Patients and investigators were masked to treatment assignment. The primary endpoint was the incidence of adverse events and serious adverse events. This trial was registered with ClinicalTrials.gov (NCT03626012) and is completed. Between Sept 10, 2018, and Nov 17, 2021, 124 patients were screened for inclusion in the study. 18 patients were excluded and 106 participants were enrolled and randomly assigned to receive 5 mg (n=6), 10 mg (n=9), 20 mg (n=9), 35 mg (n=19), 60 mg (n=18), or 90 mg (n=18) of BIIB078, or placebo (n=27). 58 (55%) of 106 patients were female. All patients received at least one dose of study treatment and were included in all analyses. All participants had at least one adverse event; most adverse events were mild or moderate in severity and did not lead to treatment discontinuation. The most common adverse events in BIIB078-treated participants were falls, procedural pain, headache, and post lumbar puncture syndrome. 14 (18%) of 79 patients who received any dose of BIIB078 reported serious adverse events, compared with nine (33%) of 27 patients who received placebo. Five participants who received BIIB078 and three participants who received placebo had fatal adverse events: respiratory failure in a participant who received 10 mg BIIB078, ALS worsening in two participants who received 35 mg BIIB078, traumatic intracerebral haemorrhage in one participant who received 35 mg BIIB078, pulmonary embolism in one participant who received 60 mg BIIB078, and respiratory failure in three participants who received placebo. All deaths were assessed as not related to the study treatment by the reporting investigator. On the basis of these phase 1 study results, including secondary and exploratory findings showing no reduction in neurofilament levels and no benefit on clinical outcomes relative to the placebo cohort, BIIB078 clinical development has been discontinued. However, these results will be informative in furthering our understanding of the complex pathobiology of C9orf72-associated ALS. Biogen.

Evaluation of the Effectiveness and Safety of One-Time Endodontics in the Treatment of Chronic Apical Periodontitis with Sinus Tract in Pediatric Deciduous Teeth

Objective: To observe the effectiveness and safety of one-time endodontics in the treatment of chronic apical periodontitis with sinus tract in pediatric deciduous teeth. Methods: 109 cases of children with chronic apical periodontitis with sinus tract in the deciduous teeth treated in our hospital from January 2022 to December 2023 were selected and grouped by the randomized numerical table method, with 54 cases in the experimental group and 55 cases in the control group. The experimental group was treated with one-time endodontics and the control group was treated with conventional endodontics. Results: After the treatment, the total effective rate of treatment was higher in the experimental group than in the control group (P < 0.05); the incidence of adverse events was lower in the experimental group than in the control group (P < 0.05); the satisfaction of the children’s family members was higher in the experimental group than in the control group (P < 0.05); the pain duration was lower in the experimental group than in the control group (P < 0.05). Conclusion: In the experimental group, children with chronic apical periodontitis with sinus tract of the deciduous teeth were given one-time endodontic treatment, and the results of its implementation were relatively good.

Association between pregnancy loss and depressive symptoms in women: a population-based study

BackgroundDepression is a common mental disorder with a much higher prevalence in women than in men. Although there has been a gradual increase in research on the association between reproductive health and depression, there is still some inconsistency in the evidence of the relationship between pregnancy loss and depression. This study aimed to investigate the relationship between pregnancy loss and depressive symptoms.MethodsWe analyzed data from the 2007–2020 National Health and Nutrition Examination Survey (NHANES), which included female participants aged 20 to 80 years. Pregnancy loss was determined based on participants’ self-reported number of pregnancies and pregnancy outcomes. Depressive symptoms were measured using the Patient Health Questionnaire (PHQ-9, score ≥ 10). Multivariate logistic regression, smoothed curve fitting, and generalized additive modeling were used to examine the association between pregnancy loss and depression. We also performed sensitivity analyses and subgroup analyses to verify the robustness and specificity of the findings.ResultsA total of 12,873 female participants were included in our study, of which 1,595 (12.39%) were categorized as depressed. Multivariate logistic regression results indicated that experiencing a pregnancy loss increased the risk of prevalence of depression in women (for 1 loss: OR = 1.31, 95% CI 1.15,1.50; for 2 or more losses: OR = 1.58, 95% CI 1.38, 1.81). When sensitivity analyses were performed, an association between pregnancy loss and depression was found in both multivariate linear regressions with PHQ-9 scores as a continuous variable and multivariate logistic regressions with a threshold of 5 PHQ-9 scores. The association between pregnancy loss and depression remained stable across subgroups.ConclusionPregnancy loss correlated with elevated PHQ-9 scores and a heightened risk of depression in adult women across the United States. Focusing on the incidence of adverse pregnancy events in the female population may help prevent or early recognize the onset of depression.

Adherence to optimal medical therapy and control of cardiovascular risk factors in patients after ST elevation myocardial infarction in Mexico.

In developing countries, there is a notable scarcity of real-world data on adherence to optimal medical therapy (OMT) and its correlation with major cardiovascular adverse events (MACEs) after ST-elevation myocardial infarction (STEMI). Our study focuses on addressing this gap by evaluating adherence to OMT, examining its influence on the risk of MACEs after STEMI, and assessing subsequent cardiovascular risk factor control in Mexico. We conducted a prospective observational study of post-STEMI patients after hospital discharge. Adherence to treatment was assessed over a median of 683 days (interquartile range: 478-833) using the Simplified Medication Adherence Questionnaire (SMAQ). Patients were followed up for 4.5 years to monitor MACEs (cardiovascular death, cardiogenic shock, recurrent myocardial infarction, and heart failure). We included 349 patients with a mean age of 58.08 years (±10.9), predominantly male (89.9%). Hypertension (42.4%), smoking (34.3%), type 2 diabetes mellitus (31.2%), obesity (22.92%), and dyslipidemia (21.4%) were highly prevalent. Adherence to OMT per SMAQ was 44.7%. The baseline clinical characteristics of adherent and non-adherent patients did not significantly differ. OMT prescription rates were as follows: acetylsalicylic acid, 91.1%; P2Y12 inhibitors, 76.5%; and high-intensity statins, 86.6%. While non-adherent patients had a numerically higher rate of MACEs (73 vs. 49 first events), there was no statistically significant difference (hazard ratio 1.30, 95% confidence interval 0.90-1.88). In this real-world study of patients after STEMI, we observed low adherence to OMT, a low proportion of global cardiovascular risk factor control, and a numerically higher incidence of recurrent major adverse cardiovascular events in non-adherent patients. Strategies to improve adherence to OMT and risk factor control are needed.

Real-World Use of Off-Label MVASI in the Treatment of Patients With Neovascular AMD and DME.

The purpose of this study was to evaluate the efficacy and safety of bevacizumab-awwb in the off-label treatment of neovascular age-related macular degeneration (n-AMD) and diabetic macular edema (DME). All patients with n-AMD and DME treated in the maintenance phase according to the "treat and extend" strategy, who underwent forced drug substitution from bevacizumab to bevacizumab-awwb from October 2022 to April 2023 at the Tor Vergata Polyclinic in Rome, were evaluated in a retrospective study. The primary outcome was changes in central retinal thickness (CRT) over time following drug substitution. The secondary outcomes were variations in drug durability, best corrected visual acuity (BCVA) and retinal fluid, and the incidence of drug-related local and systemic serious adverse events. Of 80 eyes of 76 patients with n-AMD and 55 eyes of 44 patients with DME included, before and after drug substitution, the average CRT did not statistically differ; the proportion of patients within time intervals of q8, q12, and q16 was not different; and the mean BCVA remained constant. Of a cumulative 3496 bevacizumab-awwb treatments (2154 for patients with n-AMD and 1342 for patients with DME), no local severe complications were detected. Out of a total of 544 patients (342 affected by n-AMD and 202 affected by DME), no serious adverse events were reported. In our cohort of patients with n-AMD and DME in the maintenance phase, bevacizumab-awwb seems to represent a viable and cost-effective intravitreal therapy with comparable efficacy and safety to the originator. This study provides a preliminary assessment of the efficacy and safety of intravitreal bevacizumab-awwb, which is widely used off-label in retinal vascular diseases.

Comparing intravenous lidocaine and pethidine for pain management in emergency department patients with femoral bone fracture: a randomized controlled trial

BackgroundIntravenous lidocaine has shown promise as an effective analgesic in various clinical settings, but its utility for pain management in emergency departments, especially for bone fractures, remains relatively understudied.ObjectiveThis study compared intravenous lidocaine to pethidine for femoral bone fracture pain management.MethodsThis double-blind, randomized, controlled clinical trial was conducted in the emergency department of AJA University of Medical Sciences affiliated hospitals. Patients aged 18–70 years-old with femoral bone fracture and experiencing severe pain, defined as a numerical rating scale (NRS) of pain ≥ 7, were included in the study. One group received intravenous pethidine (25 mg), while the other group received intravenous lidocaine (3 mg/kg, not exceeding 200 mg), infused with 250 ml saline over 20 min. Pain levels were evaluated before treatment administration (0 min) and at 10, 20, 30, 40, 50, and 60 min after treatment administration using the NRS.ResultsSeventy-two patients were enrolled in the study. Demographic characteristics and pain scores were similar between the two groups. The mean pain scores upon arrival for the lidocaine and pethidine groups were 8.50 ± 1 and 8.0 ± 1, respectively; after one hour, they were 4.0 ± 1 and 4.0 ± 1, respectively. While there was a statistically significant reduction in pain in both groups after one hour, there were no clinically or statistically significant differences between the two groups (p = 0.262). Pethidine had a higher incidence of adverse events, though not statistically significant. Additionally, females required more rescue analgesics.ConclusionThe administration of intravenous lidocaine is beneficial for managing pain in femoral bone fractures, suggesting that lidocaine could be a potent alternative to opioids.Trial RegistrationIRCT20231213060355N1 (https://irct.behdasht.gov.ir/trial/74624) (30/12/2023).

Comparative analysis of the safety and effectiveness of Nirmatrelvir-Ritonavir and Azvudine in older patients with COVID-19: a retrospective study from a tertiary hospital in China.

Introduction: Numerous studies have explored the treatment outcomes of Nirmatrelvir-Ritonavir and Azvudine in older patients with COVID-19. However, direct comparisons between these two drugs are still relatively limited. This study aims to compare the safety and effectiveness of these two drugs in Chinese older patients with early infection to provide strategies for clinical treatment. Methods: Older COVID-19 patients (age ≥65) hospitalized during the winter 2022 epidemic in China were included and divided into Nirmatrelvir-Ritonavir and Azvudine. Demographics, medication information, laboratory parameters, and treatment outcomes were collected. All-cause 28-day mortality, delta cycle threshold (ΔCt), nucleic acid negative conversion time, and incidence of adverse events were defined as outcomes. Propensity score matching (PSM), Kaplan-Meier, Cox proportional hazards model, subgroup analysis, and nomograms were selected to evaluate the outcomes. Results: A total of 1,508 older COVID-19 patients were screened. Based on the inclusion and exclusion criteria, 1,075 patients were eligible for the study. After PSM, the final number of older COVID-19 patients included in the study was 375, and there were no significant differences in demographic characteristics between the two groups (p > 0.05). Compared to the Azvudine group, the Nirmatrelvir-Ritonavir group showed a higher incidence of multiple adverse events (12.8% vs 5.2%, p = 0.009). The incidence of adverse events related to abnormal renal function was higher in the Nirmatrelvir-Ritonavir group compared to the Azvudine group (13.6% vs 7.2%, p = 0.045). There were no significant differences between the two groups in terms of all-cause 28-day mortality (HR = 1.020, 95% CI: 0.542 - 1.921, p = 0.951), whereas there were significant differences in nucleic acid negative conversion time (HR = 1.659, 95% CI: 1.166 - 2.360, p = 0.005) and ΔCt values (HR = 1.442, 95% CI: 1.084 - 1.918, p = 0.012). Conclusion: Azvudine and Nirmatrelvir-Ritonavir have comparable effectiveness in reducing mortality risk. Azvudine may perform better in nucleic acid negative conversion time and virus clearance and shows slightly better safety in older patients. Further studies with a larger sample size were needed to validate the result.

Impact of concomitant methotrexate on disease activity in patients with rheumatoid arthritis tapering abatacept: results from KOBIO registry.

Tapering biologic agents can be considered for patients with stable disease activity in rheumatoid arthritis (RA). However, the specific strategy for abatacept is uncertain. This study aimed to examine the impact of tapering abatacept on disease activity in RA patients and assess the potential influence of concomitant methotrexate (MTX) treatment. Using data from the KOBIO registry, we included 505 1 year intervals from 176 patients with RA that initiated abatacept with concomitant MTX at baseline. The intervals were divided into two groups based on the dose quotient (DQ) of abatacept during each period (i.e., the tapering group (DQ < 1) and control group (DQ = 1)). The primary outcome was achieving DAS28-remission at 1 year intervals. Marginal structural models (MSM) were used to minimize confounding caused by an imbalance in time-varying variables. Abatacept was tapered at 146 (28.9%) intervals, and the mean DQ was 0.68. DAS28-remission was achieved in 207 (41.8%) intervals. Tapering abatacept did not affect the odds of achieving DAS28-remission compared with the control group (OR 1.04 [0.67-1.62]). The odds remained unaffected in the subgroup that continued MTX (OR 1.42 [0.88-2.30]) but not in the subgroup that discontinued MTX (OR 0.26 [0.10-0.57]). The effects of interaction between tapering abatacept and concomitant MTX use on DAS28 and patient's functional status showed consistent results. The incidence of adverse events within a 1 year interval was comparable between the two groups. Withdrawal of MTX while tapering abatacept may compromise meeting the treatment goal for patients with RA.

Routine cardiac biomarkers for the prediction of incident major adverse cardiac events in patients with glomerulonephritis: a real-world analysis using a global federated database

Rationale & objectiveGlomerulonephritis (GN) is a leading cause of chronic kidney disease (CKD). Major adverse cardiovascular events (MACE) are prolific in CKD. The risk of MACE in GN cohorts is multifactorial. We investigated the prognostic significance of routine cardiac biomarkers, Troponin I and N-terminal pro-BNP (NT-proBNP) in predicting MACE within 5 years of GN diagnosis.Study DesignRetrospective cohort study.Setting & participantsData were obtained from TriNetX, a global federated health research network of electronic health records (EHR).Exposure or predictorBiomarker thresholds: Troponin I: 18 ng/L, NT-proBNP: 400 pg/mL.OutcomesPrimary outcome: Incidence of major adverse cardiovascular events (MACE). Secondary outcome: was the risk for each individual component of the composite outcome.Analytical Approach1:1 propensity score matching using logistic regression. Cox proportional hazard models were used to assess the association of cardiac biomarkers with the primary and secondary outcomes, reported as Hazard Ratio (HR) and 95% confidence intervals (CI). Survival analysis was performed which estimates the probability of an outcome over a 5-year follow-up from the index event.ResultsFollowing PSM, 34,974 and 18,218 patients were analysed in the Troponin I and NTproBNP cohorts, respectively. In the Troponin I all cause GN cohort, 3,222 (9%) developed composite MACE outcome HR 1.79; (95% CI, 1.70, 1.88, p < 0.0001). In the NTproBNP GN cohort, 1,686 (9%) developed composite MACE outcome HR 1.99; (95% CI, 1.86, 2.14, p < 0.0001).LimitationsThe data are derived from EHR for administrative purposes; therefore, there is the potential for data errors or missing data.ConclusionsIn GN, routinely available cardiac biomarkers can predict incident MACE. The results suggest the clinical need for cardiovascular and mortality risk profiling in glomerular disease using a combination of clinical and laboratory variables.

Sutureless Aortic Valve Replacement vs. Transcatheter Aortic Valve Implantation in Patients with Small Aortic Annulus: Clinical and Hemodynamic Outcomes from a Multi-Institutional Study.

This study aimed to compare hemodynamic performances and clinical outcomes of patients with small aortic annulus (SAA) who underwent aortic valve replacement by means of sutureless aortic valve replacement (SUAVR) or transcatheter aortic valve implantation (TAVI). From 2015 to 2020, 622 consecutive patients with SAA underwent either SUAVR or TAVI. Through a 1:1 propensity score matching analysis, two homogeneous groups of 146 patients were formed. Primary endpoint: all cause-death at 36 months. Secondary endpoints: incidence of moderate to severe patient-prosthesis mismatch (PPM) and incidence of major adverse cardiovascular and cerebrovascular events (MACCEs). All-cause death at three years was higher in the TAVI group (SUAVR 12.2% vs. TAVI 21.0%, P=0.058). Perioperatively, comparable hemodynamic performances were recorded in terms of indexed effective orifice area (SUAVR 1.12 ± 0.23 cm2/m2 vs. TAVI 1.17 ± 0.28 cm2/m2, P=0.265), mean transvalvular gradients (SUAVR 12.9 ± 5.3 mmHg vs. TAVI 12.2 ± 6.2 mmHg, P=0.332), and moderate-to-severe PPM (SUAVR 4.1% vs. TAVI 8.9%, P=0.096). TAVI group showed a higher cumulative incidence of MACCEs at 36 months (SUAVR 18.1% vs. TAVI 32.6%, P<0.001). Pacemaker implantation (PMI) and perivalvular leak ≥ 2 were significantly higher in TAVI group and identified as independent predictors of mortality (PMI: hazard ratio [HR] 3.05, 95% confidence interval [CI] 1.34-6.94, P=0.008; PPM: HR 2.72, 95% CI 1.25-5.94, P=0.012). In patients with SAA, SUAVR and TAVI showed comparable hemodynamic performances. Moreover, all-cause death and incidence of MACCEs at follow-up were significantly higher in TAVI group.

Myocardial injury and clinical outcome in octogenarians after non-ST-elevation myocardial infarction.

The aim of this study was to analyze age-associated myocardial injury and clinical outcome after non-ST-elevation myocardial infarction (NSTEMI). This prospective, multicenter study consists of 440 patients with NSTEMI enrolled at 7 centers. All patients were treated with primary percutaneous coronary intervention and underwent cardiac magnetic resonance (CMR) imaging 1-10 days after study inclusion. CMR parameters of myocardial injury and clinical outcome were evaluated by creating 2 subgroups: <80 years vs. ≥80 years. The clinical endpoint was the 1-year incidence of major adverse cardiac events (MACE) consisting of death, re-infarction and new congestive heart failure. Elderly patients ≥80 years accounted for 13.9% of the study population and showed a divergent cardiovascular risk profile compared to the subgroup of patients <80 years. CMR imaging did not reveal significant differences regarding infarct size, microvascular obstruction, left ventricular ejection fraction or multidimensional strain analysis between the study groups. At 1-year follow-up, MACE rate was significantly increased in patients ≥80 years compared to patients aged <80 years (19.7% vs. 9.6%; p = 0.019). In a multiple stepwise logistic regression model, the number of diseased vessels, aldosterone antagonist use and left ventricular global longitudinal strain were identified as independent predictors for MACE in all patients, while there was no independent predictive value of age regarding 1-year clinical outcome. This prospective, multicenter analysis shows that structural and functional myocardial damage is similar in younger and older patients with NSTEMI. Furthermore, in this heterogeneous but also clinically representative cohort with reduced sample size, age was not independently associated with 1-year clinical outcome, despite an increased event rate in patients ≥80 years.

Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication in Chinese population: A prospective, multicenter, randomized, two-stage study.

The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori) is controversial. To evaluate the efficacy of VAT in the Chinese population. This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori-infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778. In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001). VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori-infected patients in Fujian.

Effects of combined morbid insomnia and sleep apnea on long-term cardiovascular risk and all-cause mortality in elderly patients: a prospective cohort study

PurposeIt is reported that insomnia and obstructive sleep apnea (OSA) increase the incidence of adverse cardiovascular events. The aim of this study was to analyze the risk of cardiovascular disease and mortality in elderly patients with comorbid insomnia and obstructive sleep apnea (COMISA).MethodsWe included 868 elderly patients with OSA who underwent sleep monitoring at a multicenter sleep room from January 2015 to October 2017. We collected demographic data, clinical features, medical history, sleep parameters, and laboratory findings. Cox proportional hazards analysis was used to identify the relationship between COMISA and adverse cardiovascular events and all-cause mortality.ResultsThere were 181 elderly patients with COMISA. The median follow-up was 43 months, during which we observed major adverse cardiac events (MACE) in 90 patients. The Kaplan-Meier survival curve indicated a significant relationship between COMISA and MACE (Plog Rank < 0.001). Multivariate Cox regression analysis showed that COMISA increased the incidence of MACE (HR = 2.328, 95% CI: 1.349–4.018, P = 0.002), hospitalization for unstable angina (HR = 2.915, 95% CI: 1.397–6.081, P = 0.004), and the combination of all events (HR = 2.301, 95% CI: 1.393–3.803, P = 0.001). However, there were no significant differences in cardiovascular death, all-cause mortality, myocardial infarction, or hospitalized heart failure in patients with COMISA (P > 0.05). Subgroup analyses showed that among COMISA patients, male sex (HR = 2.800, 95% CI: 1.458-5.377, P = 0.002), age < 70 years (HR = 4.050, 95% CI: 2.022–8.115, P < 0.001), and overweight and obesity (HR = 2.482, 95% CI: 1.383-4.453, P = 0.002) were associated with a higher risk of MACE.ConclusionsOur results showed that COMISA increased the risk of MACE, unstable angina, and the compound occurrence of all events. Male, overweight or obese COMISA patients under 70 years of age have an increased risk of MACE.

Outcomes of same-day discharge in bariatric surgery.

Restrictions during the COVID-19 pandemic influenced a shift to same-day discharge in bariatric surgery. Current studies show conflicting findings regarding morbidity and mortality. We aim to compare outcomes for same-day discharge versus admission after bariatric surgery. Subjects included patients who underwent primary laparoscopic or robotic-assisted sleeve gastrectomy or Roux-En-Y gastric bypass at an academic center. The inpatient group included patients discharged postoperative day one, and the outpatient group included patients discharged on the day of surgery. Primary outcomes included the number of emergency room visits, reoperations, IV fluid treatments, readmissions, and mortality within 30days. Secondary outcomes were morbidity, including skin and soft tissue infection, pulmonary embolism, and acute kidney injury. 1225 patients met the inclusion criteria. In the gastric sleeve group, 852 subjects were outpatients and 227 inpatients. In the gastric bypass group, 70 subjects were outpatients, and 40 were inpatients. The mean age was 44.63 (17.38-85.31) years, and the mean preoperative BMI was 46.07 ± 8.14kg/m2. The subjects in the outpatient group had lower BMI with fewer comorbidities. The groups differed significantly in age, BMI, and presence of several chronic comorbidities. The inpatient and outpatient groups for each surgery type did not differ significantly regarding reoperations, IV fluid treatments, or 30-day mortality. The inpatient sleeve group demonstrated a significantly higher readmission percentage than the outpatient group (4.6% vs 2.1%; p = 0.02882). The inpatient bypass group showed significantly greater ER visits (21.7% vs 10%; p = 0.0108). The incidence of adverse events regarding the secondary outcomes was not statistically different. Same-day discharge after bariatric surgery is a safe and reasonable option for patients with few comorbidities.

Nrf2/FSP1/CoQ10 axis-mediated ferroptosis is involved in sodium aescinate-induced nephrotoxicity

Sodium aescinate (SA), an active compound found in horse chestnut seeds, is widely used in clinical practice. Recently, the incidence of SA-induced adverse events, particularly renal impairment, has increased. Our previous work demonstrated that SA causes severe nephrotoxicity via nephrocyte ferroptosis; however, the underlying mechanism remains to be fully elucidated. In the current study, we investigated additional molecular pathways involved in SA-induced nephrotoxicity. Our results showed that SA inhibited cell viability, disrupted cellular membrane integrity, and enhanced reactive oxygen species (ROS), ferrous iron (Fe2+), and malondialdehyde (MDA) levels, as well as lipid peroxidation in rat proximal renal tubular epithelial cell line (NRK-52E) cells. SA also depleted coenzyme Q10 (CoQ10, ubiquinone) and nicotinamide adenine dinucleotide (NADH) and reduced ferroptosis suppressor protein 1 (FSP1) and polyprenyltransferase (coenzyme Q2, COQ2) activity, triggering lipid peroxidation and ROS accumulation in mouse kidneys and NRK-52E cells. The overexpression of COQ2, FSP1, or CoQ10 (ubiquinone) supplementation effectively attenuated SA-induced ferroptosis, whereas iFSP1 or 4-formylbenzoic acid (4-CBA) pretreatment exacerbated SA-induced nephrotoxicity. Additionally, SA decreased nuclear factor-erythroid-2-related factor 2 (Nrf2) levels and inhibited Nrf2 binding to the -1170/-1180 bp ARE site in FSP1 promoter, resulting in FSP1 suppression. Overexpression of Nrf2 or its agonist dimethyl fumarate (DMF) promoted FSP1 expression, thereby improving cellular antioxidant capacity and alleviating SA-induced ferroptosis. These results suggest that SA-triggers renal injury through oxidative stress and ferroptosis, driven by the suppression of the Nrf2/FSP1/CoQ10 axis.

Mosaic HIV-1 vaccine regimen in southern African women (Imbokodo/HVTN 705/HPX2008): a randomised, double-blind, placebo-controlled, phase 2b trial

HIV type 1 (HIV-1) remains a global health concern, with the greatest burden in sub-Saharan Africa. Despite 40 years of research, no vaccine candidate has shown durable and protective efficacy against HIV-1 acquisition. Although pre-exposure prophylaxis in groups with high vulnerability can be very effective, barriers to its use, such as perceived low acquisition risk, fear of stigma, and concerns about side-effects, remain. Thus, a population-based approach, such as an HIV-1 vaccine, is needed. The current study aimed to evaluate the efficacy and safety of a heterologous HIV-1 vaccine regimen, consisting of a tetravalent mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) and aluminium phosphate-adjuvanted clade C glycoprotein (gp) 140, in young women at risk of acquiring HIV-1 in southern Africa. This randomised, double-blind, phase 2b study enrolled sexually active women without HIV-1 or HIV-2 aged 18-35 years at 23 clinical research sites in Malawi, Mozambique, South Africa, Zambia, and Zimbabwe. Participants were centrally randomly assigned (1:1) to receive intramuscular injections of vaccine or saline placebo in stratified permuted blocks via an interactive web response system. Study participants, study site personnel (except those with primary responsibility for study vaccine preparation and dispensing), and investigators were masked to treatment group allocation. The vaccine regimen consisted of Ad26.Mos4.HIV administered at months 0 and 3 followed by Ad26.Mos4.HIV administered concurrently with aluminium phosphate-adjuvanted clade C gp140 at months 6 and 12. The primary efficacy outcome was vaccine efficacy in preventing laboratory-confirmed HIV-1 acquisition diagnosed between visits at month 7 and month 24 after the first vaccination (VE[7-24]) in the per-protocol population, which included participants who had not acquired HIV-1 4 weeks after the third vaccination, received all planned vaccinations at the first three vaccination visits within the protocol-specified windows, and had no major protocol deviations that could affect vaccine efficacy. Primary safety outcomes were assessed in randomly assigned participants who received one study injection or more based on the actual injection received. The primary safety endpoints were the incidences of unsolicited adverse events (AEs), solicited local and systemic AEs, serious AEs, AEs of special interest, and AEs leading to discontinuation of vaccination. This trial is registered with ClinicalTrials.gov, NCT03060629, and is complete. Between Nov 3, 2017, and June 30, 2019, 2654 women were randomly assigned, of whom 2636 women (median age of 23 years [IQR 20-25]) were enrolled and received at least one study injection (1313 assigned vaccine, 1323 placebo; 1317 received vaccine, 1319 placebo). Analysis of the primary efficacy outcome in the per-protocol cohort included 1080 women in the vaccine group and 1108 women in the placebo group; the incidence of HIV-1 acquisition per 100 person-years over months 7-24 after the first vaccination was 3·38 (95% CI 2·54-4·41) in the vaccine group and 3·94 (3·04-5·03) in the placebo group, with an estimated VE(7-24) of 14·10% (95% CI -22·00 to 39·51; p=0·40). There were no serious unsolicited AEs, AEs of special interest, or deaths related to the study vaccine. In the vaccine group, 663 (50·3%) of 1317 participants had grade 1 or 2 solicited local AEs and ten (0·8%) of 1317 participants had grade 3 or 4 solicited local AEs. In the placebo group, 305 (23·1%) of 1319 participants had grade 1 or 2 solicited local AEs and three (0·2%) of 1319 participants had grade 3 or 4 solicited local AEs. 863 (65·5%) of 1317 participants in the vaccine group had grade 1 or 2 solicited systemic AEs and 34 (2·6%) of 1317 participants had grade 3 or 4 solicited systemic AEs. 763 (57·8%) of 1319 participants in the placebo group had grade 1 or 2 solicited systemic AEs and 20 (1·5%) of 1319 participants had grade 3 or 4 solicited systemic AEs. Overall, three (0·2%) of 1317 participants in the vaccine group and three (0·2%) of 1319 participants in the placebo group discontinued vaccination due to an unsolicited AE, and three (0·2%) of 1317 participants in the vaccine group and one (0·1%) of 1319 participants in the placebo group discontinued vaccination due to a solicited AE. The heterologous Ad26.Mos4.HIV and clade C gp140 vaccine regimen was safe and well tolerated but did not show efficacy in preventing HIV-1 acquisition in a population of young women in southern Africa at risk of HIV-1. Division of AIDS at the National Institute of Allergy and Infectious Diseases through the HIV Vaccine Trials Network, Bill & Melinda Gates Foundation, Janssen Vaccines & Prevention, US Army Medical Materiel Development Activity, and Ragon Institute.

Influence of acupuncture and moxibustion on gastrointestinal function and adverse events in gastric cancer patients after surgery and chemotherapy: a meta-analysis.

The impact of acupuncture and moxibustion on postoperative complications and adverse events (AEs) of chemotherapy in patients with gastric cancer (GC) has been investigated. Through a meta-analysis of existing randomized controlled trials (RCTs), this study sought to strengthen the evidentiary basis to help investigators further understand the effects of moxibustion and acupuncture on postoperative complications and AEs of chemotherapy among GC patients. Embase, Web of Science, PubMed, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP Database for Chinese Technical Periodicals were searched to collect RCTs on effects of acupuncture and moxibustion on gastrointestinal function and AEs among GC patients undergoing surgery and chemotherapy. Outcome measures included postoperative gastrointestinal recovery (bowel sound recovery time, time to first flatus/defecation/feeding), the incidence of AEs (nausea and vomiting, abdominal distension, and diarrhea), myelosuppression (white blood cells, hemoglobin, and platelet), and immune function indicators (CD3+ and CD4+). To assess quality, the Cochrane Risk of Bias Tool was utilized. Review Manager 5.4 was implemented to do the meta-analysis. Fifteen eligible RCTs involved 1259 patients. Meta-analysis results showed that the experimental group had a significantly shorter bowel sound recovery time (MD = - 14.57, 95% CI = [- 18.97, - 10.18], P < 0.00001), time to first flatus (MD = - 17.56, 95% CI = [- 22.23, - 12.88], P < 0.00001), time to first defecation (MD = - 17.05, 95% CI = [- 21.02, - 13.09], P < 0.00001), and time to first feeding (MD = - 23.49, 95% CI = [- 28.81, - 18.17], P < 0.00001) than the control group. There were significant decreases in the incidence of nausea and vomiting (RR = 0.46, 95% CI = [0.21, 1.02], P = 0.05) and abdominal distension (RR = 0.45, 95% CI = [0.27, 0.75], P = 0.002) observed in the experimental group in comparison with the control group. The experimental group demonstrated a significant increase in white blood cell counts in comparison with to the control group (MD = 0.89, 95% CI = [0.23, 1.55], P = 0.008). The experimental group showed significantly higher levels of CD3+ (MD = 7.30, 95% CI = [1.86, 12.74], P = 0.009) and CD4+ (MD = 2.75, 95% CI = [1.61, 3.90], P < 0.00001) than the control group. Among GC patients, acupuncture and moxibustion can aid in gastrointestinal function recovery, reduce the incidence of AEs of surgery and chemotherapy, and improve immune function.

Risankizumab versus Ustekinumab for Moderate-to-Severe Crohn’s Disease

BackgroundThe efficacy and safety of risankizumab as compared with ustekinumab in patients with Crohn’s disease are unknown.MethodsIn this phase 3b, multicenter, open-label, randomized, controlled trial with blinded assessment of end points, patients with moderate-to-severe Crohn’s disease who had had an inadequate response to anti–tumor necrosis factor (TNF) therapy or unacceptable side effects with such therapy were randomly assigned to receive risankizumab or ustekinumab at standard doses for 48 weeks. The two primary end points, which were tested sequentially, were clinical remission at week 24 (defined as a Crohn’s Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]), which was analyzed in the first 50% of patients to complete the week 24 visit, with a noninferiority margin of 10 percentage points; and endoscopic remission at week 48 (defined as a score of ≤4, a decrease of ≥2 points from baseline, and no subscore >1 in any individual variable on the Simple Endoscopic Score for Crohn’s Disease [range, 0 to 56, with higher scores indicating more severe disease]), which was analyzed for superiority in 100% of the patients. Safety was assessed in all patients who received at least one dose of risankizumab or ustekinumab.ResultsIn the full intention-to-treat population for the efficacy analysis, 230 of 255 patients (90.2%) who received risankizumab and 193 of 265 patients (72.8%) who received ustekinumab completed all the assigned treatments. Both primary end points were met; risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 (58.6% vs. 39.5%; adjusted difference, 18.4 percentage points; 95% confidence interval [CI], 6.6 to 30.3) and superior to ustekinumab with respect to endoscopic remission at week 48 (31.8% vs. 16.2%; adjusted difference, 15.6 percentage points; 95% CI, 8.4 to 22.9; P<0.001). The incidence of adverse events appeared to be similar in the two groups.ConclusionsIn this head-to-head clinical trial of risankizumab and ustekinumab involving patients with moderate-to-severe Crohn’s disease who had had unacceptable side effects with anti-TNF therapy or an inadequate response to such therapy, risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 and superior with respect to endoscopic remission at week 48. (Funded by AbbVie; ClinicalTrials.gov number, NCT04524611.)

Oral Nirmatrelvir–Ritonavir as Postexposure Prophylaxis for Covid-19

BackgroundClinical trials of treatments for coronavirus disease 2019 (Covid-19) have not shown a significant benefit of postexposure prophylaxis.MethodsWe conducted a phase 2–3 double-blind trial to assess the efficacy and safety of nirmatrelvir–ritonavir in asymptomatic, rapid antigen test–negative adults who had been exposed to a household contact with Covid-19 within 96 hours before randomization. The participants were randomly assigned in a 1:1:1 ratio to receive nirmatrelvir–ritonavir (300 mg of nirmatrelvir and 100 mg of ritonavir) every 12 hours for 5 days or for 10 days or matching placebo for 5 or 10 days. The primary end point was the development of symptomatic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, confirmed on reverse-transcriptase–polymerase-chain-reaction (RT-PCR) or rapid antigen testing, through 14 days in participants who had a negative RT-PCR test at baseline.ResultsA total of 2736 participants were randomly assigned to a trial group — 921 to the 5-day nirmatrelvir–ritonavir group, 917 to the 10-day nirmatrelvir–ritonavir group, and 898 to the placebo group. Symptomatic, confirmed SARS-CoV-2 infection developed by day 14 in 2.6% of the participants in the 5-day nirmatrelvir–ritonavir group, 2.4% of those in the 10-day nirmatrelvir–ritonavir group, and 3.9% of those in the placebo group. In each nirmatrelvir–ritonavir group, the percentage of participants in whom symptomatic, confirmed SARS-CoV-2 infection developed did not differ significantly from that in the placebo group, with risk reductions relative to placebo of 29.8% (95% confidence interval [CI], –16.7 to 57.8; P=0.17) in the 5-day nirmatrelvir–ritonavir group and 35.5% (95% CI, –11.5 to 62.7; P=0.12) in the 10-day nirmatrelvir–ritonavir group. The incidence of adverse events was similar across the trial groups, with dysgeusia being the most frequently reported adverse event (in 5.9% and 6.8% of the participants in the 5-day and 10-day nirmatrelvir–ritonavir groups, respectively, and in 0.7% of those in the placebo group).ConclusionsIn this placebo-controlled trial, postexposure prophylaxis with nirmatrelvir–ritonavir for 5 or 10 days did not significantly reduce the risk of symptomatic SARS-CoV-2 infection. (Funded by Pfizer; ClinicalTrials.gov number, NCT05047601.)