Higher Incidence Of Adverse Events Research Articles

Efficacy and safety of PD-1/PD-L1 immune checkpoint inhibitors in the treatment of recurrent ovarian cancer: A systematic review and meta-analysis.

Recurrent ovarian cancer (OC) presents a significant therapeutic challenge with limited treatment success. Programmed cell death protein 1 (PD-1/PD-L1) immune checkpoint inhibitors have emerged as a potential treatment avenue, necessitating a systematic review and meta-analysis to evaluate their efficacy and safety. Adhering to preferred reporting items for systematic reviews and meta-analyses guidelines, we conducted a comprehensive literature search across PubMed, Embase, Web of Science, and Cochrane Library, culminating in the inclusion of studies focusing on the treatment of recurrent OC with PD-1/PD-L1 inhibitors. Studies were evaluated using the Newcastle-Ottawa Scale and analyzed using fixed or random effects models depending on heterogeneity levels. Our search yielded 1215 articles, with 6 meeting the inclusion criteria for final analysis. Studies varied in size and reported median age, overall survival (OS), progression-free survival (PFS), and adverse events. The meta-analysis showed improved Objective Response Rates (ORR), Disease Control Rate (DCR), and PFS in patients treated with PD-1/PD-L1 inhibitors. The overall adverse event rate was 17.9%, indicating a need for careful patient selection and monitoring. No significant publication bias was detected, enhancing the reliability of our findings. PD-1/PD-L1 inhibitors offer a promising treatment option for recurrent OC, improving ORR, DCR, and PFS. However, the higher incidence of adverse events necessitates a cautious approach to their use. Future research should focus on long-term outcomes, biomarker identification, and optimal combination therapies.

Comparative efficacy and safety of weekly dulaglutide versus weekly insulin in type 2 diabetes: A network meta-analysis of randomized clinical trials

BackgroundAdvancements in type 2 diabetes mellitus (T2DM) therapy, notably with weekly agents like glucagon-like peptide-1 receptor agonists (GLP-RAs) such as dulaglutide, offer promising outcomes in clinical practice. The emergence of once-weekly insulin adds to this therapeutic arsenal. This research aims to explore and compare the efficacy and safety profiles of these agents in diabetes management, facilitating informed decision-making for optimizing their utilization in clinical practice. MethodsA systematic search of PubMed, Scopus, Cochrane, and Web of Science databases was conducted. The research protocol was registered at OSF registries (https://osf.io/gd67x). The primary outcome of interest was the change in hemoglobin A1C (HbA1c), with secondary outcomes including the change in fasting plasma glucose, body weight, prevalence of hypoglycemia, and treatment discontinuation due to adverse events. The evaluation of bias risk was conducted utilizing the RoB2 tool developed by the Cochrane Collaboration. Statistical analysis was performed using RStudio version 4.3.2 with the meta package version 7.0–0 and the netmeta package version 2.9–0. Confidence in network meta-analysis estimates was evaluated using the CINeMA (Confidence In Network Meta-Analysis). Heterogeneity was assessed by comparing the magnitude of the common between-study variance (τ2) for each outcome with empirical distributions of heterogeneity variances. ResultsDulaglutide 1.5 mg (mg) weekly demonstrated superior reduction in hemoglobin A1C (HbA1c) compared to insulin, with a mean difference (MD) of −0.35 (95 % CI: −0.51 to −0.19). Additionally, Dulaglutide 1.5 mg exhibited greater weight loss, with an MD of −3.12 (95 % CI: −3.55 to −2.68). However, it also showed a higher rate of adverse events, with an odds ratio (OR) of 1.40 (95 % CI: 1.12 to 1.75) compared to insulin. Both doses of Dulaglutide (1.5 mg and 0.75 mg) had lower prevalence of hypoglycemia compared to insulin, with ORs of 0.60 (95 % CI: 0.41 to 0.87) and 0.59 (95 % CI: 0.41 to 0.86), respectively. There was no significant difference in treatment discontinuation among the treatment groups. ConclusionDulaglutide, particularly at higher doses, demonstrates superior efficacy in lowering hemoglobin A1C and reducing hypoglycemia risk compared to Icodec insulin in type 2 diabetes management. However, its use is also associated with a higher incidence of adverse events. Clinicians should carefully consider these factors when selecting optimal treatment strategies for patients with type 2 diabetes mellitus.

Efficacy and safety of laparoscopic vaginoplasty with peritoneal flaps and cervicoplasty in patients with congenital cervical and complete vaginal atresia: a pilot study.

Hysterectomy places a considerable physical and mental burden on young female patients with congenital cervical and complete vaginal atresia. Thus, it is necessary to develop a method to detach the obstruction and simultaneously preserve the vagina and uterus in these patients. This study sought to evaluate the efficacy and safety of laparoscopic vaginoplasty using peritoneal flaps and cervicoplasty in patients with congenital cervical and complete vaginal atresia. Between April 2013 and June 2022, nine patients with congenital cervical and complete vaginal atresia at Henan Provincial People's Hospital were enrolled in this prospective study. All patients were treated with laparoscopic vaginoplasty using peritoneal flaps and cervicoplasty. Baseline clinical data (e.g., age and uterus size) were collected. The surgical success rate and adverse events were assessed. The nine enrolled patients had a median age of 15.0 [interquartile range (IQR), 14.0-18.0] years, and five of these patients had pelvic adhesions. The surgeries were successful in all (9/9) patients, with the vagina, uterus, and a normal menstrual cycle being preserved. After a median follow-up duration of 48 months, the neovaginas had a median length of 7.5 cm. Postoperative complications occurred in three of patients and were cured with the appropriate treatment. The five married patients reported being satisfied with their sex life. The study preliminarily demonstrated the efficacy of laparoscopic vaginoplasty using peritoneal flaps and cervicoplasty in patients with congenital cervical and complete vaginal atresia. However, due to the small sample size, lack of a control group, and relatively high incidence of adverse events, further studies are still needed to verify these results. Regardless, our findings establish an approach for preserving both the vagina and uterus for patients with congenital cervical and complete vaginal atresia.

Atezolizumab plus modified docetaxel, cisplatin, and fluorouracil as first-line treatment for advanced anal cancer (SCARCE C17-02 PRODIGE 60): a randomised, non-comparative, phase 2 study

The modified docetaxel, cisplatin, and fluorouracil (mDCF) regimen has shown efficacy and safety as first-line treatment for advanced squamous cell carcinoma of the anus, making it a standard regimen. Inhibitors of programmed cell death protein 1 and its ligand, such as pembrolizumab, nivolumab, retifanlimab, avelumab, and atezolizumab, have shown some antitumour activity as monotherapy in advanced squamous cell carcinoma of the anus that is refractory to chemotherapy. This phase 2 study evaluated the combination of mDCF and atezolizumab as first-line treatment in advanced squamous cell carcinoma of the anus. In this randomised, open-label, non-comparative, phase 2 study, participants from 21 centres (academic, private, and community hospitals and cancer research centres) across France with chemo-naive, metastatic, or unresectable locally advanced recurrent squamous cell carcinoma of the anus, aged 18 years or older, and with an Eastern Cooperative Oncology Group performance status of 0 or 1, were randomly allocated (2:1) to receive either atezolizumab (800 mg intravenously every 2 weeks up to 1 year) plus mDCF (eight cycles of 40 mg per m2 docetaxel and 40 mg per m2 cisplatin on day 1 and 1200 mg per m2 per day of fluorouracil for 2 days, every 2 weeks intravenously; group A) or mDCF alone (group B). Randomisation was done centrally using a minimisation technique and was stratified by age (<65 years vs ≥65 years) and disease status. The primary endpoint was investigator-assessed 12-month progression-free survival in the modified intention-to-treat population in group A (35% for the null hypothesis and 50% for the alternative hypothesis). This trial is registered with ClinicalTrials.gov, NCT03519295, and is closed to new participants. 97 evaluable participants (64 in group A and 33 in group B) were enrolled between July 3, 2018, and Aug 19, 2020. The median follow-up was 26·5 months (95% CI 24·8-28·4). The median age of participants was 64·1 years (IQR 56·2-71·6), and 71 (73%) were female. 12-month progression-free survival was 45% (90% CI 35-55) in group A and 43% (29-58) in group B. In participants with a PD-L1 combined positive score of 5 or greater, 12-month progression-free survival was 70% (95% CI 47-100) in group A and 40% (19-85) in group B (interaction p=0·051) Both groups showed high compliance. Adverse events of grade 3 or higher were observed in 39 (61%) participants in group A and 14 (42%) in group B. The most common grade 3-4 adverse events were neutropenia (nine [14%] participants in group A vs five [15%] in group B), anaemia (nine [14%] vs one [3%]), fatigue (three [5%] vs four [12%]), and diarrhoea (seven [11%] vs one [3%]). Serious adverse events occurred in 16 (25%) participants in group A and four (12%) in group B, and these were mDCF-related in seven (11%) participants in group A and four (12%) in group B. Atezolizumab-related serious adverse events occurred in nine (14%) participants in group A, including grade 2 infusion-related reaction in three (5%), grade 3 infection in two (3%), and grade 2 colitis, grade 3 acute kidney injury, grade 3 sarcoidosis, and a grade 4 platelet count decrease each in one participant (2%). There were no treatment-related deaths. Despite a higher incidence of adverse events, combining atezolizumab with mDCF is feasible, with similar dose intensity in both groups, although the primary efficacy endpoint was not met. The predictive value of a PD-L1 combined positive score of 5 or greater now needs to be confirmed in future studies. GERCOR, Roche.

Impact of age and cardiovascular risk factors on the incidence of adverse events in patients with rheumatoid arthritis treated with Janus Kinase inhibitors: data from a real-life multicentric cohort

Inhibiting Janus Kinases (JAK) is a crucial therapeutic strategy in rheumatoid arthritis (RA). However, the use of JAK inhibitors has recently raised serious safety concerns. The study aims to evaluate the safety profile of JAKi in patients with RA and identify potential risk factors (RFs) for adverse events (AEs). Data of RA patients treated with JAKi in three Italian centers from January 2017 to December 2022 were retrospectively analyzed. 182 subjects (F:117, 64.3%) underwent 193 treatment courses. 78.6% had at least one RF, including age ≥ 65 years, obesity, smoking habit, hypertension, dyslipidemia, hyperuricemia, diabetes, previous VTE or cancer, and severe mobility impairment. We identified 70 AEs (28/100 patients/year), among which 15 were serious (6/100 patients/year). A high disease activity was associated with AEs occurrence (p = 0.03 for CDAI at T0 and T6; p = 0.04 for SDAI at T0 and T6; p = 0.01 and p = 0.04 for DAS28ESR at T6 and T12, respectively). No significant differences in AEs occurrence were observed after stratification by JAKi molecules (p = 0.44), age groups (p = 0.08) nor presence of RFs (p > 0.05 for all of them). Neither the presence of any RFs, nor the cumulative number of RFs shown by the patient, nor age ≥ 65 did predict AEs occurrence. Although limited by the small sample size and the limited number of cardiovascular events, our data do not support the correlation between cardiovascular RFs—including age—and a higher incidence of AEs during JAKi therapy. The role of uncontrolled disease activity in AEs occurrence should by emphasized.

Feasibility and safety of a novel plastic stent designed specifically for endoscopic ultrasound-guided pancreatic duct drainage: a case series

Background/study aim: Endoscopic ultrasound-guided pancreatic duct drainage (EUS-PD) is emerging as an effective alternative treatment for obstructive pancreatitis after unsuccessful endoscopic retrograde pancreatography (ERP). However, the high incidence of adverse events associated with EUS-PD (approximately 20%) remains an issue. Recently, we developed a novel plastic stent for EUS-PD, with a radiopaque marker positioned at approximately one-third of the length from the distal end of the stent and side holes positioned exclusively distal to the marker. This study aimed to evaluate the feasibility and safety of using this stent in EUS-PD. Patients/materials and methods: We retrospectively reviewed data from 10 patients who underwent EUS-PD with the novel plastic stent at the National Cancer Center Hospital between March 2021 and October 2023. Technical and clinical success, procedure times, adverse events, recurrent pancreatic duct obstruction (RPO), and time to RPO were assessed. Results: Of the ten patients, five had postoperative benign pancreaticojejunal anastomotic strictures and five had malignant pancreatic duct obstruction. The technical and clinical success rates were both 100% (10/10). An adverse event (self-limited abdominal pain) occurred in one (10.0%) patient. Two (20.0%) patients died of their primary disease during the follow-up period (median, 44 days; range, 25–272 days). The incidence of RPO was 10.0% (1/10), and the 3-month non-RPO rate was 83.3%. Conclusion: The novel plastic stent shows potential as a useful and safe tool in EUS-PD.

Efficacy and safety of trigeminal parasympathetic pathway stimulation for dry eye: A systematic review and meta-analysis.

This study aimed to investigate the efficacy and safety of trigeminal parasympathetic pathway (TPP) stimulation in the treatment of dry eye. A comprehensive search for randomized clinical trials was performed in seven databases (MEDLINE, Embase, CENTRAL, etc.) up to 28 February 2023. After screening the suitable studies, the data were extracted and transformed as necessary. Data synthesis and analysis were performed using Review Manager 5.4, and the risk of bias and quality of evidence were evaluated with the recommended tools. Fourteen studies enrolling 1714 patients with two methods (electrical and chemical) of TPP stimulation were included. Overall findings indicate that TPP stimulation was effective in reducing subjective symptom score (standardized mean difference [SMD], -0.45; 95% confidence interval [CI], -0.63 to -0.28), corneal fluorescence staining (mean difference [MD], -0.78; 95% CI, -1.39 to -0.18), goblet cell area (MD, -32.10; 95% CI, -54.58 to -9.62) and perimeter (MD, -5.90; 95% CI, -10.27 to -1.53), and increasing Schirmer's test score (SMD, 0.98; 95% CI, 0.65 to 1.31) and tear film break-up time (SMD, 0.57; 95% CI, 0.19 to 0.95). Compared to inactive or low-activity stimulation controls, it has a higher incidence of adverse events. Therefore, TPP stimulation may be an effective treatment for dry eye, whether electrical or chemical. Adverse events are relatively mild and tolerable. Due to the high heterogeneity and low level of evidence, the current conclusions require to be further verified.

Comparison of the analgesic effects of different bupivacaine concentrations in continuous femoral block after total knee arthroplasty surgery

Aim: In regional anesthesia practice, anesthesists’ goal must be to use the lowest effective concentration of local anesthetics to provide sufficient pain relief while minimizing side effects and complications. This study was designed to compare the analgesic efficacy of two different concentrations of bupivacaine (0.125% and 0.1%) in continuous femoral block for postoperative analgesia.Method: In this study, fifty patients were enrolled, all of whom underwent femoral nerve block catheterization. The block procedure involved the administration of 30ml of bupivacaine solution at a concentration of 0.25%. Following a thirty-minute interval post-block application, patients underwent knee surgery under general anesthesia. During the closure of subcutaneous tissues, an additional 10ml of bupivacaine solution was injected through the catheter. Two groups were formed based on the concentration of the solution administered: Group(0.125%) received bupivacaine at a concentration of 0.125%, while Group(0.1%) received it at a concentration of 0.1%. Subsequently, upon arrival at the postoperative care unit, infusion through the catheter commenced at a rate of 10ml/h-1, maintaining the same concentrations for both groups. In addition to the nerve block, all patients were provided with intravenous Patient Controlled Analgesia (PCA) devices containing morphine for pain management. Throughout the postoperative period, sensory and motor block levels, Numerical Rating Scale (NRS) values for static and dynamic pain assessment, total morphine consumption, morphine demand, as well as any observed side effects and complications, were meticulously recorded for analysis.Results: Postoperatively the NRSstatic values at 24th and 48th hours and NRSdynamic values at the 24th hour were higher in Group(0.1%) and it was statistically significant(p&lt;0,007). And at 48th hour, morphine consumption was significantly higher in Group(0.1%) (p&lt;0,05).Conclusions: In our study, all patients across both experimental groups initially experienced satisfactory analgesia. However, within the 24-hour postoperative period, Group(0.1%) exhibited a decline in the quality of analgesia, necessitating increased utilization of rescue analgesics. This escalation in rescue analgesic use was associated with a higher incidence of adverse effects and reduced patient comfort levels within this group. Consequently, our findings indicate that the 0.125% concentration of bupivacaine yielded superior efficacy compared to the 0.1% concentration in the context of continuous femoral block administration.

Utility and optimal management of planned drug holidays during lenvatinib treatment in patients with unresectable differentiated thyroid cancer: a real-world multi-center study.

Lenvatinib achieves favorable therapeutic outcomes for patients with radioactive iodine therapy refractory differentiated thyroid cancer (DTC); however, its use is associated with a high incidence of adverse events. To avoid severe adverse events, planned drug holidays (PDH) have been proposed. This study aimed to evaluate treatment effects, identify prognostic factors, and investigate the usefulness of PDH in patients with unresectable DTC who received lenvatinib across the multi-institutions. Fifty-one patients with unresectable DTC treated with lenvatinib were evaluated retrospectively. Overall survival (OS) and progression-free survival (PFS) were calculated, and prognostic factors were assessed. OS, PFS, and time to treatment failure (TTF) were compared between patients with and without PDH. Lenvatinib administration schedule was evaluated in PDH. The 3-year OS and PFS rate were 53.5% and 42.1%, respectively. Multivariate analysis revealed that presence of maximum size of lung metastasis ≥10 mm was independent prognostic factor for poorer OS and PFS, and histology other than papillary thyroid carcinoma was the independent prognostic factor for poorer PFS. Twenty-five patients (49%) treated with PDH. There were significant differences in OS, PFS, and TTF between patients with and without PDH. Various schedules were used in PDH. Eight (32%) patients required switch to the different administration schedule. Our results suggest that PDHs may extend OS, PFS, and TTF. In patients with PDH, various schedules used for lenvatinib administration highlight the difficulty in determining a uniform administration schedule. Therefore, it is crucial to consider the optimal lenvatinib administration schedule on a case-by-case basis.

Pediatric sedation for emergency, imaging and endoscopic procedures: a worldwide review from the last five years

Introduction: Anatomical, physiological, pharmacokinetic, pharmaco dynamic and behavioral particularities relevant to the pediatric population make its sedation challenging for quick and low-complexity procedures. Robust evidence on this subject is still scarce, and the variety of drugs available, with their multiple routes of administration and dosage schemes, makes it difficult for providers to make a decision. Methods: Through research in four databases, we found 170 articles that addressed pediatric sedation and, after applying the exclusion criteria, we selected 32 articles for analysis. Results: In sedation for invasive or painful procedures, Esketamine in monotherapy was effective, despite the significant incidence of adverse effects. Satisfactory responses were also obtained with associations between Esketamine and Propofol and Fentanyl with Propofol or Midazolam. To perform imaging tests, continuous infusions of Propofol or Dexmedetomidine were sufficient, with associations with Esketamine or opioids associated with a higher incidence of adverse effects. Endoscopic procedures have been successfully performed after administration of continuous infusion of Propofol or Dexmedetomidine, associated with Remifentanil infusion or Fentanyl bolus. Esketamine in monotherapy was also effective. Discussion: The drugs studied have an adverse effect profile compatible with safe pediatric sedation, whether administered by a specialist or not. However, alternative administration routes and dosages still need further studies before being routinely applied. Conclusion: Sedation in pediatrics is still an open field for research in our country.

Tyrosine kinase inhibitors for radioiodine refractory differentiated thyroid cancer: A systematic review and meta-analysis.

The poor overall prognosis of radioiodine refractory thyroid cancer is an inevitable challenge in managing this disease. A series of trials have demonstrated the antitumor activity of tyrosine kinase inhibitors (TKIs)in radioiodine refractory differentiated thyroid cancer (RAIR-DTC).However, the available evidence cannot determine the optimal choice of TKI in RAIR-DTC. This study searched PubMed, EMBASE, Cochrane databases, and the ClinicalTrials website. The Cochrane bias risk tool was used to assess the risk of bias, and to evaluate randomized clinical trials (RCT)of RAIR-DTCpatients treated with the TKI system. Outcomes, including progression-free survival (PFS),overall survival (OS),and adverse events (AEs)were reported. Seven studies involving 1310 patients with RAIR-DTCwas conducted to compare the PFS and OS of various TKImonotherapies with placebo. The results showed that all TKI monotherapies had a statistically significant benefit in terms of PFS compared with placebo, with lenvatinib demonstrating the greatest benefit (hazard ratio [HR]0.19, 95% credible interval [CrI] 0.14-0.25). In terms of OS, only apatinib (HR 0.42, 95% CrI 0.18-0.97) and anlotinib (HR0.36, 95% CrI 0.18-0.73) showed statistically significant benefits compared with placebo. TKIs also had a higher incidence of AEs of grade 3 or higher compared with placebo. The findings suggest that lenvatinib may be the preferred TKI for the treatment of RAIR-DTC,although its high incidence of AEs should be considered. The results also indicate that TKI treatment may be similarly effective in RAIR-DTCpatients with BRAF or RAS mutations and in those with papillary or follicular subtypes of the disease, regardless of prior TKI treatment. The results of this meta-analysis suggest that targeted therapy with TKIs may be beneficial for patients with radioiodine-refractory advanced or metastatic differentiated thyroid cancer. Among the TKIs analyzed, lenvatinib appeared to be the most effective at improving PFS, although it also had the highest incidence of AEs. Further research through direct randomized controlled trials is needed to determine the optimal choice of TKI for treating patients with RAIR-DTC.This study is beneficial for formulating patients' treatment plans and guides clinicians' decision-making.

Stress hyperglycemia ratio as a prognostic indicator for long-term adverse outcomes in heart failure with preserved ejection fraction

BackgroundRecent studies highlighted that stress hyperglycemia ratio (SHR) is a potential predictor for future risk in heart failure (HF) patients. However, its implications specifically in HF with preserved ejection fraction (HFpEF) are not yet fully elucidated. We aimed to investigate the association between SHR and long-term clinical outcomes in HFpEF patients.MethodsHFpEF patients enrolled between 2015 and 2023, were followed (mean 41 months) for a composite outcome of all-cause, cardiovascular mortality, and HF rehospitalization. SHR was established as the ratio of acute-chronic glycemia from admission blood glucose and glycated hemoglobin. The optimal cut-off for SHR to predict outcomes based on event prediction was determined through ROC analysis, and the cutoff was identified at 0.99. The effect of SHR on adverse risk was examined through the Cox hazards and Kaplan-Meier survival methods. A Pearson correlation analysis was conducted to assess the relationship between SHR and the severity of HF, as indicated by N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Furthermore, the incremental prognostic value of SHR was further assessed by the integrated discrimination improvement (IDI) and the net reclassification improvement (NRI).ResultsAmong the 400 enrolled patients, 190 individuals (47.5%) encountered composite events over the 41-month follow-up period. SHR was significantly elevated in patients with events compared with those without (p < 0.001). All patients were stratified into high SHR (n = 124) and low SHR (n = 276) groups based on the SHR cutoff. The high SHR group had a significantly higher incidence of adverse events than the low SHR group (log-rank; p < 0.001). Additional analysis indicated a poorer prognosis in patients with low left ventricular EF (LVEF) levels (50 < LVEF < 60) and high SHR (SHR > 0.99) in comparison to the other groups (log-rank p < 0.001). In adjusted analysis, after accounting for age, sex, diabetes, and NT-proBNP, elevated SHR remained independently predictive of adverse outcomes (adjusted HR: 2.34, 95% CI 1.49–3.67; p < 0.001). Furthermore, adding SHR to a model with MAGGIC score provided an incremental improvement in predicting adverse events. Additionally, SHR displayed a slight correlation with NT-proBNP.ConclusionElevated SHR was independently associated with an increased risk for composite events of all-cause, cardiovascular mortality, and HF readmission than those with lower SHR. SHR is a valuable tool for predicting and stratifying long-term adverse risks among HFpEF patients.

Comparative efficacy and tolerability of different anesthetics in electroconvulsive therapy for major depressive disorder: A systematic review and network meta-analysis

Electroconvulsive therapy (ECT) is one of the most effective treatments for major depressive disorder. Modern ECT is conducted with anesthesia, however, the optimal anesthetic agent for ECT is yet to be understood. This study is aimed to compare the effects of different anesthetic agents on antidepressant efficacy and tolerability in depressed individuals undergoing ECT. We searched MEDLINE, EMBASE, the CENTRAL and PsycINFO for randomized controlled trials from database inception until Nov 13, 2022 (PROSPERO: CRD42022375407). Global and local inconsistencies, heterogeneity and publication bias were assessed. Rankings were calculated with the surface under the cumulative ranking curve. A total of 33 studies involving 1898 patients were enrolled. Remission rates were higher for ketamine anesthesia as compared to adjunctive ketamine and propofol. In terms of ranking, ketamine was found to be first in terms of response/remission rates and depressive scores after the 1st, 3rd and 6th ECT and at the end of ECT session, while a higher incidence of adverse events was also observed. No significant advantage of any anesthetic was revealed for the cognitive function after ECT. In summary, based on current evidence, no specific anesthetic is recommended for ECT anesthesia. However, despite more side effects, ketamine monoanesthesia seems to reveal a potential benefit in improving antidepressant efficacy of ECT, and further studies are needed to investigate the relationship between anesthetic agents and the therapeutic effect of ECT.

Prevalence and factors associated with medication adherence in children with central precocious puberty: a cross-sectional study.

Objectives: This study aimed to investigate the prevalence and influencing factors of medication adherence in children with central precocious puberty (CPP), and provide references for clinical practice. Methods: Children under 12years of age with CPP and their caregivers at a women's and children's hospital were selected for a cross-sectional study from February to May 2023, and a questionnaire was used to collect basic characteristics of pediatric patients and their caregivers, information of medication, cognition of medication, and medication adherence. The 8-item Morisky Medication Adherence Scale (MMAS-8) was adopted to assess medication adherence, and the potential influencing factors were explored by univariate and multivariate analyses. Results: A total of 125 valid questionnaires were collected. The medication adherence rate of children with CPP reported by caregivers was 76.0%. The univariate analysis showed that the percentage of parental caregivers (p = 0.027), the age of caregivers (p = 0.029), the education level of caregivers (p = 0.001), the financial burden (p < 0.000), the incidence of adverse effects (p = 0.008), and the cognition of medication including the importance of medication (p = 0.002), the dosage of medication (p = 0.002), the adverse effects of medication (p = 0.007), the harm of non-compliance with medication (p < 0.000), and the evaluation of the price of medication (p = 0.003) in the poor adherence group were significantly inferior to those in the better adherence group. The multivariate analysis showed that the higher incidence of adverse effects (p = 0.20), not understanding the harm of non-compliance with medication (p = 0.004), and evaluation of the price of medication as expensive (p = 0.043) were independent risk factors for poor medication adherence. Conclusion: Medication adherence in children with CPP is relatively better, and the factors leading to poor medication adherence are mainly on the caregivers of pediatric patients. It is recommended to increase the health education among caregivers of children with CPP to enhance the cognition of the condition and medication, and further improve the therapeutic efficacy for CPP.

Different doses of nalmefene combined with hydromorphone hydrochloride for postoperative analgesia after colorectal surgery: a randomized controlled study

BackgroundHydromorphone hydrochloride has a satisfactory postoperative analgesic effect for patients with colorectal cancer but is accompanied by a relatively high incidence of adverse events. Low-doses of naloxone combined with opioids for patient-controlled analgesia can reduce the incidence of drug-related adverse events. Nalmefene is a more selective opioid receptor antagonist than naloxone. The aim of this study was to determine the impact of low-doses of nalmefene on the analgesic effect and incidence of adverse events of patients with hydromorphone patient-controlled analgesia (PCA) undergoing colorectal radical surgery.MethodsNinety-nine patients undergoing elective laparoscopic or hand-assisted laparoscopic radical surgery under general anaesthesia were randomly divided into three groups. Group N1 received hydromorphone hydrochloride 0.15 mg/kg + nalmefene 2 µg/kg; Group N2 received hydromorphone hydrochloride 0.15 mg/kg + nalmefene 0.5 µg/kg; and the control group (Group C) received hydromorphone hydrochloride 0.15 mg/kg. All medications were diluted to 100 ml with normal saline. The primary outcome was pain intensity at 12 h after surgery; the secondary outcomes were the occurrence of nausea, vomiting and pruritus and the total analgesic consumption of the PCA pump at 1 h, 6 h, 12 h, 24 and 48 h after surgery.ResultsThe NRS scores of Group N1 (2 µg/kg) were significantly lower than those of Group C (P = 0.025), and no difference was found between group N2 and group C (P > 0.05). Among the three groups, the NRS scores of Group N1 (2 µg/kg) were significantly lower than those of Group C at 12 h (P = 0.01) and 48 h (P = 0.01) postoperatively. Compared with 12 h postoperatively, the NRS scores were lower at 24 h postoperatively in Group N1 and Group C (P < 0.05) and significantly lower at 48 h postoperatively in all three groups (P < 0.001). There was a significant difference in the incidence of pruritus among the three groups (P = 0.036).ConclusionsNalmefene at a dosage of 2 µg/kg enhances the postoperative analgesic effect of hydromorphone hydrochloride and reduces the occurrence of postoperative pruritus.Trial RegistrationThe trial was registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR2000033520, date: 03/06/2020).

GABAPENTINOIDS IN THE SYMPTOMATIC MANAGEMENT OF CANAL STENOSIS: A COMPARATIVE STUDY ON PAIN RELIEF, AMBULATION, AND SAFETY PROFILE

The multimodal management of canal stenosis is increasing, and inhibitors of central sensitization are playing a crucial role in central sensitization processes. Pregabalin and gabapentin are antiepileptic drugs that reduce presynaptic excitability. The objective of this study was to investigate whether the use of pregabalin and gabapentin is effective in the symptomatic management of canal stenosis.A literature search was conducted in four databases. The inclusion criteria were studies that compared pregabalin or gabapentin with a control group in lumbar canal stenosis. Randomized clinical trials and a comparative retrospective cohort study were included. The main clinical endpoints were VAS/NRS, ODI, and RDQ (Roland Morris Disability Questionnaire) at 2, 4, 8 weeks, and 3 months, adverse events, and walking distance were also collected. Data were combined using Review Manager 5.4 software.Six studies and 392 patients were included. The mean age was 60.25. No significant differences were observed in VAS at 2, 4, and 8 weeks: (MD: 0.23; 95% CI: −0.63-1.09), (MD: −0.04; 95% CI: −0.64 to −0.57), and (MD: −0.6; 95% CI: −1.22 to 0.02). Significant differences were observed in favor of pregabalin with respect to VAS at three months: (MD: −2.97; 95% CI: −3.43 to −2.51). No significant differences were observed in ODI (MD: −3.47; 95% CI: −7.15 to −0.21). Adverse events were significantly higher in the pregabalin/gabapentin group (OR 5.88, 95%CI 1.28-27.05). Walking distance and RDQ could not be compared, although the results were controversial.Gabapentinoids have not been shown to be superior to other drugs used in the treatment of LSS or to placebo. However, they have shown a higher incidence of adverse effects, improved results in VAS at 3 months, and a slight improvement in ambulation at 4 months in combination with NSAIDs compared to NSAIDs in monotherapy.

A Novel Dry Simulator Model for Learning Comprehensive Endoscopic Retrograde Cholangiopancreatography/Endoscopic Sphincterotomy Procedures while Minimizing Adverse Bleeding Events (with Video).

Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST) are essential skills for performing endoscopic cholangiopancreatic procedures. However, these procedures have a high incidence of adverse events, and current training predominantly relies on patient-based approaches. Herein, we aimed to develop an ERCP/EST simulator model to address the need for safer training alternatives, especially for learners with limited ERCP experience. The model was designed to facilitate the use of actual endoscopic devices, supporting learning objectives that align with the components of the validated Bethesda ERCP Skill Assessment Tool (BESAT). BESAT focuses on skills, such as papillary alignment, maintenance of duodenoscope position, gentle and efficient cannulation, controlled sphincterotomy in the correct trajectory, and guidewire manipulation. Thirty gastroenterology trainees used the simulator between May 2022 and March 2023, and their satisfaction was assessed using a visual analog scale (VAS) and pre- and post-training questionnaires. The novel simulator model comprised a disposable duodenal papillary section, suitable for incision with an electrosurgical knife, alongside washable upper gastrointestinal tract and bile duct sections for repeated use. The duodenal papillary section enabled reproduction of a realistic endoscope position and the adverse bleeding events due to improper incisions. The bile duct section allowed for the reproduction of fluoroscopic-like images, enabling learners to practice guidewire guidance and insertion of other devices. Following training, the median VAS score reflecting the expectation for model learning significantly increased from 69.5 (interquartile range [IQR]: 55.5-76.5) to 85.5 (IQR: 78.0-92.0) (p &lt; 0.01). All participants expressed a desire for repeated simulator training sessions. This innovative simulator could serve as a practical educational tool, particularly beneficial for novices in ERCP. It could facilitate hands-on practice with actual devices, enhancing procedural fluency and understanding of precise incisions to minimize the risk of bleeding complications during EST.

A Phase 1b Clinical Trial of Neoadjuvant Radio-immunotherapy for Esophageal Squamous Cell Cancer

BackgroundNeoadjuvant chemoradiotherapy is the recommended treatment for patients with resectable esophageal cancer; however, it is associated with a higher incidence of adverse effects. Given the efficacy of immunotherapy, we propose a chemotherapy-free regimen of neoadjuvant radio-immunotherapy (NRIT) to balance therapeutic efficacy and potential side effects or overtreatment. MethodsIn this phase Ib clinical trial, we assessed the safety and efficacy of NRIT in esophageal squamous cell cancer (ESCC). The enrolled patients received 41.4 Gy of radiation and four cycles of 240 mg of Toripalimab injection before surgery. The primary endpoint was treatment-related adverse events (TRAEs), and the secondary endpoints included pathological complete response (pCR) and major pathological response (MPR). Immunohistochemistry and multiplex immunofluorescence staining were utilized to evaluate the tumor microenvironments before and after neoadjuvant treatment. FindingsOut of the 22 patients enrolled, 19 underwent R0 surgery. One patient discontinued neoadjuvant immune therapy due to grade 3 TRAEs, and three patients did not undergo surgery due to tumor progression or side effects. Another three patients experienced serious complications shortly after surgery. Upon pathological evaluation, the pCR and MPR rates were 47.4% and 68.4%, respectively. ConclusionThe NRIT regimen is safe and feasible for patients with ESCC.

Statins Ticagrelor and Rhabdomyolysis: A Coincidence or a Drug Interaction?

Statins play a key role in the management of atherosclerotic cardiovascular disease for both primary and secondary prevention. However, their increasing usage has correspondingly led to a higher incidence of adverse effects, with muscle symptoms being the most common. An intriguing drug interaction exists between ticagrelor and high-intensity statins, which may exacerbate the adverse effects of statin-induced rhabdomyolysis, leading to significant consequences. This study was conducted to examine the profile of patients who have experienced statin-induced rhabdomyolysis while undergoing percutaneous transluminal coronary angioplasty (PTCA). This was an observational study that included 1,862 patients who underwent PTCA at our institute over the course of 1 year. Over a 1-year period, we encountered four patients who were being treated with high-intensity statin therapy following acute coronary syndrome. These patients presented with muscle weakness and kidney injury. A notable commonality among all patients was the co-prescription of ticagrelor. Two patients died, while the other 2 were successfully managed through hydration, electrolyte balance, dialysis, and alternative lipid management drugs. The concomitant use of ticagrelor and high-intensity statins should be carefully considered due to the additional risk of rhabdomyolysis and kidney injury. Future pharmacokinetic studies are needed to establish a causal relationship and predict potential drug interactions, which, if not avoided, could be fatal.

Efficacy and safety of steroids for chronic subdural hematoma: A systematic review and meta-analysis

Background: Chronic subdural hematoma (CSDH) is a condition characterized by the accumulation of fluid, blood, and blood breakdown products between the brain’s arachnoid and dura mater coverings. While steroids have been explored as a potential treatment option, their efficacy and safety remain uncertain. This meta-analysis and systematic review aimed to assess the impact of steroids on CSDH management, including mortality, recurrence, complications, and functional outcomes. Methods: We conducted a comprehensive literature search in major electronic databases up to June 2023, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Cochrane Handbook for Systematic Reviews and Interventions. Inclusion criteria encompassed adult patients with CSDH, the use of steroids as monotherapy or adjuvant therapy, and clearly defined outcomes. Randomized controlled trials and cohort studies meeting these criteria were included in the study. Results: The initial search yielded 4315 articles, with 12 studies meeting the inclusion criteria. Our findings indicate a non-significant trend toward reduced mortality with steroids in combination with standard care (Odds ratios [OR] = 0.66, 95% confidence interval [CI] 0.20–2.18). However, substantial heterogeneity was observed (I2 = 70%). Sensitivity analysis, excluding influential studies, suggested a potential increased mortality risk associated with steroids (OR = 1.47, 95% CI 0.87–2.48). Steroids showed a possible benefit in reducing the recurrence of CSDH (OR = 0.58, 95% CI 0.20–1.67), but with significant heterogeneity (I2 = 89%). No clear advantage of steroids was observed in terms of functional outcomes at three months (modified Rankin scale scores). Furthermore, steroids were associated with a significantly higher incidence of adverse effects and complications (OR = 2.17, 95% CI 1.48–3.17). Conclusion: Steroids may have a potential role in reducing CSDH recurrence but do not appear to confer significant advantages in terms of mortality or functional outcomes. However, their use is associated with a higher risk of adverse effects and complications. Given the limitations of existing studies, further research is needed to refine the role of steroids in CSDH management, considering patient-specific factors and treatment protocols.