Total Number Of Adverse Events Research Articles

Measuring the Overall Development of Patient Safety in a New Hospital Using Trigger Tools.

The new building of the Hospital in Lichtenfels (Germany) was put into operation in mid-July 2018. Neither the medical personnel nor medical departments have been changed. We want to evaluate how "safe" or "insecure" the new hospital or department in the beginning might have been. Our objective is to investigate if safety decreases at the beginning in a new hospital, despite modern environments and conditions. Adverse events associated with treatment were included to evaluate the total number of adverse events resulting from medical care and medications. Patients records had to be closed and completed, the length of stay had to be at least 24 hours, the patient had to have been formally admitted to the hospital (Institute for Healthcare Improvement IHI GTT "Global Trigger Tool" recommendation). The identified adverse events were grouped into 27 categories of the Institute for Healthcare Improvement "Global Trigger Tool." We randomly reviewed 40 patient records per month 6 months before and 6 months after moving to the new hospital. Statistical analysis showed that there was no significant difference in individual adverse events. The sum of adverse events was statistically higher after moving into a new hospital. Complete number of harms did reach statistical significance (χ2=6.62; df=1; p<.05; Cramer's V=0.12), indicating that new environments "triggers" significantly more potential errors (50%) in comparison to the old environments (38.33%). According to our results, the new hospital is slightly insecure in the first period (6 months) after its founding.

Randomized controlled trial of intermittent hypoxia in Parkinson’s disease: study rationale and protocol

BackgroundParkinson’s disease (PD) is a neurodegenerative disease for which no disease-modifying therapies exist. Preclinical and clinical evidence suggest that repeated exposure to intermittent hypoxia might have short- and long-term benefits in PD. In a previous exploratory phase I trial, we demonstrated that in-clinic intermittent hypoxia exposure is safe and feasible with short-term symptomatic effects on PD symptoms. The current study aims to explore the safety, tolerability, feasibility, and net symptomatic effects of a four-week intermittent hypoxia protocol, administered at home, in individuals with PD.Methods/Design: This is a two-armed double-blinded randomized controlled trial involving 40 individuals with mild to moderate PD. Participants will receive 45 min of normobaric intermittent hypoxia (fraction of inspired oxygen 0.16 for 5 min interspersed with 5 min normoxia), 3 times a week for 4 weeks. Co-primary endpoints include nature and total number of adverse events, and a feasibility-tolerability questionnaire. Secondary endpoints include Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part II and III scores, gait tests and biomarkers indicative of hypoxic dose and neuroprotective pathway induction.DiscussionThis trial builds on the previous phase I trial and aims to investigate the safety, tolerability, feasibility, and net symptomatic effects of intermittent hypoxia in individuals with PD. Additionally, the study aims to explore induction of relevant neuroprotective pathways as measured in plasma. The results of this trial could provide further insight into the potential of hypoxia-based therapy as a novel treatment approach for PD.Trial registrationClinicalTrials.gov Identifier: NCT05948761 (registered June 20th, 2023).

A transdiagnostic group exercise intervention for mental health outpatients in Germany (ImPuls): results of a pragmatic, multisite, block-randomised, phase 3 controlled trial

Globally, mental health conditions pose a substantial burden of disease. Despite the availability of evidence-based pharmacological and psychological treatments, the symptoms of a substantial subgroup of patients do not respond to these interventions, and only a minority of patients have access to them. This study aimed to assess the efficacy of ImPuls, a 6-month transdiagnostic group exercise intervention, plus treatment-as-usual, compared with treatment-as-usual alone in outpatients with various mental disorders. In this pragmatic, two-arm, multisite, randomised controlled trial in Germany, ten outpatient rehabilitative and medical care facilities were involved as study sites. Participants were outpatients diagnosed according to ICD-10 with one or more of the following disorders based on structured clinical interviews: moderate or severe depression, primary insomnia, post-traumatic stress disorder (PTSD), panic disorder, or agoraphobia. Participants were required to be aged between 18 years and 65 years, insured by the health insurers Allgemeine Ortskrankenkasse Baden-Württemberg or Techniker Krankenkasse, fluent in German, and without medical contraindications for exercise. Blocks of six participants were randomly allocated to ImPuls plus treatment-as-usual or treatment-as-usual alone (allocation ratio: 1:1), stratified by study site. The randomisation sequence was generated by an external data manager. The team responsible for data collection and management was masked to the randomisation sequence. The ImPuls intervention comprised evidence-based outdoor exercises lasting 30 min, and aimed at achieving at least moderate intensity. It also incorporated behavioural change techniques targeting motivational and volitional determinants of exercise behaviour. Treatment-as-usual was representative of typical outpatient health care in Germany, allowing patients access to any standard treatments. The primary outcome was global symptom severity at 6 months after randomisation, measured using self-report on the Brief Symptom Inventory (BSI-18) and analysed in the intention-to-treat sample. No individuals with lived experience of mental illness were involved in conducting the study or writing the final publication. Safety was assessed in all participants. The trial was registered with the German Clinical Trials Register (DRKS00024152) with a completion date of June 30, 2024. 600 patients provided informed consent, were recruited to the study, and underwent a diagnostic interview between Jan 1, 2021, and May 31, 2022. Following this, 199 were excluded on the basis of inclusion and exclusion criteria and one withdrew consent during the baseline assessment. Of the 400 eligible participants, 284 (71%) self-identified as female, 106 (27%) self-identified as male, and nine (2%) self-identified as other. The mean age was 42·20 years (SD 13·23; range 19-65). Ethnicity data were not assessed. 287 (72%) participants met the criteria for moderate or severe depression, 81 (20%) for primary insomnia, 37 (9%) for agoraphobia, 46 (12%) for panic disorder, and 72 (18%) for PTSD. 199 participants were allocated to the intervention group of ImPuls plus treatment-as-usual and 201 to the control group of treatment-as-usual alone. 38 (19%) participants did not receive the minimum ImPuls intervention dose. ImPuls plus treatment-as-usual demonstrated superior efficacy to treatment-as-usual alone in reducing global symptom severity, with an adjusted difference on BSI-18 of 4·11 (95% CI 1·74-6·48; d=0·35 [95% CI 0·14-0·56]; p=0·0007) at 6 months. There were no significant differences in the total number of adverse events or serious adverse events between the two groups. There was one serious adverse event (male, torn ligament) related to the intervention. ImPuls is an efficacious transdiagnostic adjunctive treatment in outpatient mental health care. Our findings suggest that exercise therapy should be implemented in outpatient mental health care as an adjunctive transdiagnostic treatment for mental disorders such as depression, insomnia, panic disorder, agoraphobia, and PTSD. Transdiagnostic group exercise interventions might ameliorate the existing disparity in care provision between the many individuals in need of evidence-based treatment and the few who are receiving it. The German Innovation Fund of the Federal Joint Committee of Germany.

Challenges and adverse events in pediatric hypoglossal nerve stimulation

IntroductionHypoglossal nerve stimulation was recently FDA approved for use in children with Down Syndrome and persistent obstructive sleep apnea. Although there is a robust experience in hypoglossal nerve stimulation in adults, we observed several challenges that are unique to providing this therapy to a complex pediatric population with a high rate of sensory processing disorders. We sought to review the adverse events and challenges to inform clinicians as hypoglossal nerve stimulation becomes a more accessible option for this complex population. MethodsRetrospective case series of children with Down Syndrome and persistent OSA who underwent hypoglossal nerve stimulation. Inclusion and exclusion criteria included Down Syndrome, age 10–22 years, persistent severe OSA after adenotonsillectomy (AHI>10 with <25 % central or mixed events), inability to tolerate positive airway pressure, and absence of concentric palatal collapse on sleep endoscopy. Patients were identified and their charts were reviewed. Adverse events and their subsequent management were recorded. The major outcome variable was the total number of adverse events. ResultsA total of 53 patients underwent implantation of a hypoglossal nerve stimulator; 35 (66 %) patients were male and the average age at implantation was 15.1 years (standard deviation 3.0y). A total of 30 adverse events were noted, including 17 nonserious and 13 serious. The most common nonserious complications included temporary tongue discomfort, rash at the surgical site, and cellulitis. Serious complications included readmission (for cellulitis, pain, and device extrusion), reoperation (most commonly for battery depletion) and pressure ulcer formation. ConclusionHypoglossal nerve stimulation provides a much-needed therapy for children with DS and persistent OSA after adenotonsillectomy. Although there is a robust experience in providing this treatment to adults, many considerations must be made when adapting this technology to a pediatric population with a high rate of sensory processing disorders.

Application of checklist-based nursing care process in patients undergoing intervention for coronary chronic total occlusions: a quasi-randomized study

BackgroundCoronary chronic total occlusion (CTO) interventions are more complex than general percutaneous coronary intervention (PCI) procedures. However, only a few nursing methods are specifically applied to patients undergoing CTO interventions. And the conventional nursing effect is not ideal, urgent need to explore more effective nursing methods. The checklist is a simple and effective tool for error management and performance improvement that has been widely used in many fields. But there have been no reports of the checklist being used to improve care for CTO patients.ObjectiveThis study aimed to investigate the effectiveness of a checklist-based nursing care process in patients undergoing Coronary chronic total occlusion (CTO) interventions, including duration of care, patient anxiety, improved patient satisfaction, and occurrence of adverse events.MethodsA total of 120 CTO patients undergoing percutaneous coronary intervention (PCI) were selected at our hospital and divided into an intervention group (n = 60, adopted the checklist-based nursing care process for patient care) and a control group (n = 60, adopted nursing care according to the existing workflow) according to different nursing interventions. After surgery, the nurse in charge of the patient completed the nursing according to the “List of postoperative care for CTO patients” filled in by the patient within 24 h after surgery, conducted a doctor satisfaction survey, recorded adverse events, and completed the postoperative Self-Rating Anxiety Scale (SAS) score and patient satisfaction survey before the patient was discharged. Subsequently, the Qc team checks the completion of the patient’s checklist for safety and the completion of the questionnaire. Finally, the differences between the two groups in preoperative nursing time, incidence of adverse events caused by nurses’ omission or inadequate guidance, patient anxiety, and doctor and patient satisfaction were compared.ResultsThe intervention grouphad significantly shorter preoperative nursing care time and significantly lower the total number of adverse events than the control group (P < 0.05).The postoperative Self-Rating Anxiety Scale (SAS) score of the intervention group was significantly lower than that of the control group (P < 0.05).The satisfaction of doctors and patients in the intervention groupwas significantly higher than that in the control group (P < 0.05).ConclusionThe application of the checklist-based nursing care process in patients with CTO intervention can significantly reduce the preoperative nursing care time, reduce patient anxiety, improve patients’ and doctors’ satisfaction with nursing care, and effectively reduce the occurrence of adverse events caused by nurses’ omissions or inadequate instructions.Trial registrationThe protocol of the trial was registered retrospectively of Chinese Clinical Trial Registry (registration number ChiCTR2200056804, reg date17/02/2022).

The Effectiveness of Early Food Introduction in Preventing Childhood Allergic Diseases: Protocol for a Systematic Review and Meta-Analysis.

Allergic diseases affect around 40% of the pediatric population worldwide. The coexistence of asthma, allergic rhinitis, eczema, and food allergy renders allergy treatment and prevention challenging. Infant feeding strategies recommend avoiding allergenic foods to prevent allergy development and anaphylaxis. However, recent evidence suggests that early consumption of food allergens during weaning in infants aged 4-6 months could result in food tolerance, thus reducing the risk of developing allergies. The aim of this study is to systematically review and carry out a meta-analysis of evidence on the outcome of early food introduction for preventing childhood allergic diseases. We will conduct a systematic review of interventions through a comprehensive search of various databases including PubMed, Embase, Scopus, CENTRAL, PsycINFO, CINAHL, and Google Scholar to identify potential studies. The search will be performed for any eligible articles from the earliest published articles up to the latest available studies in 2023. We will include randomized controlled trials (RCTs), cluster RCTs, non-RCTs, and other observational studies that assess the effect of early food introduction to prevent childhood allergic diseases. Primary outcomes will include measures related to the effect of childhood allergic diseases (ie, asthma, allergic rhinitis, eczema, and food allergy). PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines will be followed for study selection. All data will be extracted using a standardized data extraction form and the quality of the studies will be assessed using the Cochrane Risk of Bias tool. A summary of findings table will be generated for the following outcomes: (1) total number of allergic diseases, (2) rate of sensitization, (3) total number of adverse events, (4) improvement of health-related quality of life, and (5) all-cause mortality. Descriptive and meta-analyses will be performed using a random-effects model in Review Manager (Cochrane). Heterogeneity among selected studies will be assessed using the I2 statistic and explored through meta-regression and subgroup analyses. Data collection is expected to start in June 2023. The results acquired from this study will contribute to the existing literature and harmonize recommendations for infant feeding with regard to the prevention of childhood allergic diseases. PROSPERO CRD42021256776; https://tinyurl.com/4j272y8a. PRR1-10.2196/46816.

Evaluation of Scores to Reflect Toxicity Impact on Quality of Life of Patients With Platinum-Resistant Ovarian Cancer: AURELIA Substudy.

Current standards for toxicity reporting do not fully capture the impact of adverse events (AEs) on patients' quality of life (QoL). This study aimed to evaluate the association between toxicity and QoL by using toxicity scores that take into account CTCAE grade grouping and AE duration and cumulation. Analyses were performed on the AURELIA trial dataset, including 361 patients with platinum-resistant ovarian cancer treated with chemotherapy alone or with bevacizumab. Global and physical functioning QoL were issued from the EORTC QoL Questionnaire-Core 30 (QLQ-C30), collected at baseline and 8/9 and 16/18 weeks after treatment initiation. Four toxicity scores were computed: the total number of AEs, multiplied by their grade and not, and the cumulative duration of AEs, weighted by their grade and not. Each score included all AEs or only grade 3/4 nonlaboratory or treatment-related AEs. The relationship between toxicity scores and QoL was assessed through linear mixed regression. We found that 171 (47.5%) and 43 (11.9%) patients experienced at least one grade 3 or 4 AE, respectively, whereas 113 (31.4%) experienced grade 2 AEs only. Physical QoL was negatively associated with all toxicity scores when computed with all grades of AEs (all P<.01), with a weaker association when treatment-related AEs were considered. Global QoL was negatively associated with toxicity scores computed with nonlaboratory all-grade AEs only (β, -3.42 to -3.13; all P<.01). Degrees of association were lower when considering the AE duration. In this analysis of patients with platinum-resistant ovarian cancer, toxicity scores based on the cumulative number of AEs, modulated or not by grade, were more effective at predicting QoL changes than those based on AE duration. Toxicity impact on QoL was better reflected when grade 2 AEs were taken into account together with grade 3/4 AEs, whatever their treatment imputability, and when laboratory AEs were excluded.

Efficacy and Safety of 6-Weekly versus 12-Weekly Intravenous Methylprednisolone in Moderate-to-Severe Active Thyroid-Associated Ophthalmopathy.

To compare the efficacy and safety of 6-weekly and 12-weekly intravenous methylprednisolone (IVMP) regimens in moderate-to-severe, active thyroid-associated orbitopathy (TAO) patients. Retrospective comparative study of patients who received IVMP between January 2011 and July 2021 at the Thyroid Eye Clinic, the Chinese University of Hong Kong. Outcome measures included the 7-item clinical activity score (CAS), exophthalmos, extraocular muscle motility (EOMy), marginal reflex distance (MRD), best corrected visual acuity (BCVA), intraocular pressure (IOP), the requirement of additional treatment, and complications. A total of 65 (63% (41/65) females) moderate-to-severe, active TAO patients aged 50 ± 13 (25-74) years received 6-weekly (n = 22) or 12-weekly (n = 43) IVMP. Sex, age, smoking status, and Graves' disease status were comparable in the two groups (all p > 0.05). CAS at week 6 (p = 0.0279), 12 (p = 0.00228), and 52 (p = 0.0228) were lower at each time for the 12-weekly group. Exophthalmos improved more at week 6 (p = 0.0453) and 12 (p = 0.0347) in the 12-weekly group. The improvement of diplopia, MRD1, MRD2, and EOMy were comparable between the two groups. More patients in the 6-weekly group (p = 0.00169) required additional treatments including IVMP+/-ORT. Patients in the 6-weekly group who did not require additional treatment had a lower presenting CAS (p = 0.0193) than those who required additional treatment. The total numbers of adverse events were comparable between the two groups.

Efficacy and Safety Profile of Berberine Treatment in Improving Risk Factors for Cardiovascular Disease: A Systematic Review and Meta-analysis of Randomized, Double-blind Trials

Objective: This systematic review and meta-analysis aimed to evaluate the efficacy of berberine treatment in improving blood glucose, blood lipids, and blood pressure as well as the associated safety profile. Methods: PubMed, Embase, Cochrane Library, WanFang Data, and the China National Knowledge Infrastructure database were searched from the establishment of the database to December 31, 2021, to identify randomized, double-blind trials that examined the effect of berberine alone or as add-on treatment on blood glucose, blood lipids, and blood pressure with an intervention period of at least 3 months. Two researchers independently screened articles, extracted data, and assessed the quality of each study according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The efficacy outcomes included fasting blood glucose (FPG), 2-hour post-prandial glucose (2hPG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP). The safety outcome was the incidence of the total number of adverse events. Results: A total of 17 articles enrolling 1,485 participants were included in the meta-analysis. The intervention duration ranged from 12 to 24 weeks. Sixteen trials reported results for blood glucose, 14 trials reported results for blood lipids, and 7 reported results for blood pressure. Compared with placebo or baseline treatment, berberine alone or as add-on therapy significantly reduced FPG (by 0.35 mmol/L; 95% confidence interval (CI): 0.13–0.58 mmol/L; P = 0.002; I 2 = 89.0%, n = 16), 2hPG (by 1.50 mmol/L; 95% CI: 0.50–2.49 mmol/L, P = 0.003, I 2 = 84.1%, n = 4), HbA1c (by 0.45%, 95% CI: 0.24%–0.65%, P &lt; 0.001, I 2 = 82.8%, n = 9), TC (by 0.48 mmol/L; 95% CI: 0.36–0.60 mmol/L, P &lt; 0.001, I 2 = 72.3%, n = 13), TG (by 0.22 mmol/L; 95% CI: 0.13–0.31 mmol/L, P &lt; 0.001, I 2 = 57.1%, n = 14), and LDL-C (by 0.41 mmol/L; 95% CI: 0.34–0.48 mmol/L, P &lt; 0.001, I 2 = 35.0%, n = 12). The effect on blood glucose and blood lipids remained consistent when confined to high-quality trials. There is no significant effect of berberine treatment on HDL-C, SBP, and DBP. The incidence of the total number of adverse events was similar between the berberine group and the control group (risk ratio (RR) = 1.00, 95% CI: 0.84–1.19, P = 0.961). Gastrointestinal disorder was the most common adverse event in the berberine group and most adverse events were alleviated or disappeared as the dose was decreased or the intervention time was prolonged. Conclusions: Short-term berberine treatment significantly improved blood glucose and blood lipid profiles without raising safety concerns. A rigorously designed randomized controlled trial could be considered to examine the feasibility of the long-term application of berberine treatment in the prevention of cardiovascular disease.

Outpatient management of patients with peripheral artery disease by cardiologists or surgeons: influence on the prognosis and prevalence of surgical interventions

Highlights. The study shows for the first time that during the three-year follow-up of patients with diseases of the arteries of the lower extremities in the observation groups of a general surgeon and a cardiologist, adverse events (myocardial infarction, stroke, amputation, disability) and deaths occurred more often in a surgeon than a cardiologist. The study proves the correctness and real benefit of such an approach with the involvement of a cardiologist to the outpatient stage of management of a complex cohort of patients with atherosclerosis of the vessels of the lower extremities.Aim. To study the effect the outpatient observation of patients with peripheral arteries disease (PAD) by cardiologists and surgeons has on timing and prevalence of reconstructive surgery and the prognosis of patients. Methods We analyzed the data on 585 PAD patients who underwent outpatient observation from 2010 to 2017, dividing them into 2 groups. The first group (131 patients) managed by an surgeon; the second (454 patients) managed by a cardiologist. Since the groups were not comparable in terms of the initial parameters, the comparability of patients in the groups (observation by a surgeon or by a cardiologist) was achieved using pseudorandomization. The follow-up period was three years; we assessed the incidence of deaths, adverse events, and the prevalence of reconstructive operations.Results. During a three-year follow-up the 1st group, compared with the 2nd, had more deaths in general (p&lt;0.001), death from cardiac causes (p = 0.045), from stroke (p&gt;&lt;0.001), as well as the total number of adverse events (p&gt;&lt;0.001) and disability (p = 0.065). Indications for reconstructive surgery on the lower extremities arteries (LEA), and operations frequency were comparatible in groups. Amputation history, taking diuretics, presence of rhythm disturbances, and management by a surgeon increased the risk of adverse outcomes. Management by a cardiologist, reconstructive LEA surgeries, female sex improved the prognosis of patients. Conclusion Observation of PAD patients by a cardiologist contributes to a higher frequency of optimal drug therapy by patients and can reduce the number of adverse events in patients and improve their survival without affecting the timing and frequency of reconstructive LEA surgeries. Keywords Peripheral atherosclerosis • Outpatient follow-up • Optimal drug therapy • Reconstructive surgery&gt;˂ 0.001), death from cardiac causes (p = 0.045), from stroke (p˂ 0.001), as well as the total number of adverse events (p˂ 0.001) and disability (p = 0.065). Indications for reconstructive surgery on the lower extremities arteries (LEA), and operations frequency were comparatible in groups. Amputation history, taking diuretics, presence of rhythm disturbances, and management by a surgeon increased the risk of adverse outcomes. Management by a cardiologist, reconstructive LEA surgeries, female sex improved the prognosis of patients.Conclusion. Observation of PAD patients by a cardiologist contributes to a higher frequency of optimal drug therapy by patients and can reduce the number of adverse events in patients and improve their survival without affecting the timing and frequency of reconstructive LEA surgeries.

Phase 2 open label study of durvalumab with neoadjuvant chemotherapy in variant histology bladder cancer.

524 Background: The immune-responsive nature of bladder cancer has made it an active area of interest for novel applications of immune checkpoint inhibitors (ICIs), with multiple ICI agents approved in the metastatic setting and ongoing perioperative trials. Variant histology urothelial carcinoma is a rare, heterogenous, and aggressive disease category associated with poor prognosis and response to standard therapies. This investigator-initiated phase 2 trial explored the addition of durvalumab to neoadjuvant chemotherapy (NAC) in the setting of variant histology MIBC. Methods: Patients with cT2-T4a, N0-N1, M0 histologically-confirmed bladder cancer of variant histology who were candidates for platinum-based NAC and radical cystectomy were eligible for the study. Enrolled patients received durvalumab with each cycle of investigator’s choice of platinum NAC (ddMVAC, cisplatin/gemcitabine, or carboplatin/gemcitabine). The primary objective was to determine the safety and tolerability of each study treatment as assessed by the total number of adverse events of grade 3 or higher, judged by the investigator as probably or definitely related to durvalumab. Secondary objective was to determine the percent of subjects post neoadjuvant chemo immunotherapy who achieve tumor stage of pT2N0M0 or better at cystectomy. Target accrual was 24 patients. Results: Six patients were enrolled (the study closed early due to low accrual). Median age was 72 years, 17% were women, 67% were white, 33% were Asian. 50% received ddMVAC and 50% received carboplatin/gemcitabine. All patients completed the planned cycles of NAC and durvalumab (4 cycles) and 5/6 proceeded to radical cystectomy (one patient declined cystectomy). Three patients experienced a Grade 3 AE that was assessed by the investigator to be related to treatment (table). One patient with sarcomatoid and glandular histology had pathological complete response and one patient with papillary and 10% squamous had pT2N0 at cystectomy. Conclusions: The addition of durvalumab to platinum NAC for patients with variant-histology muscle invasive bladder cancer demonstrates a reasonable safety and tolerability profile. Further investigation into this combination is warranted in larger scale trials. Clinical trial information: NCT03912818 . [Table: see text]

Endoscopic removal of common bile duct stones in nonagenarians: a tertiary centre experience.

There are few studies assessed the efficacy and mortality of endoscopic retrograde cholangiopancreatography (ERCP) for the removal of common bile duct (CBD) stones in the elderly aged ≥90 years. We aimed to assess the safety and efficacy of endoscopic removal of CBD stones in nonagenarians. We retrospectively reviewed ERCP reports for CBD stone removal. The endoscopic and therapeutic outcomes were collected. The length of stay (LOS), the total number of adverse events, and mortality rate were compared between groups. A total of 125 nonagenarians were compared with 1,370 controls (65-89 years old individuals). The mean LOS for nonagenarians was significantly higher than in controls (13.6 days vs. 6.5 days). Completed intended treatment was similar in the nonagenarians and controls (89.8% and 89.5%, respectively). The overall complication rate did not differ between the groups. However, nonagenarians had a higher incidence of post-ERCP pneumonia (3.9%). None of the nonagenarians were readmitted to the hospital within 7 days. Four nonagenarians (3.2%) and 25 (1.8%) controls died within 30 days. Advanced age alone did not affect the decision to perform the procedure. However, prompt diagnosis and treatment of post-ERCP pneumonia in nonagenarians could improve the outcomes and reduce mortality.

The Influence of the Rapid Increase in the Number of Adverse Event Reports for COVID-19 Vaccine on the Disproportionality Analysis Using JADER.

The COVID-19 prophylactic vaccine for the prevention of coronavirus infection was approved in Japan on February 14, 2021. Adverse event reports for the vaccine were collected from the Japan Adverse Drug Event Relief (JADER) database, similar to those for drugs. Reported odds ratios (RORs) and proportional reporting ratios (PRRs) are commonly used in disproportionality analysis to detect safety signals. Therefore, adverse event reports from the vaccinated population may affect the detection of safety signals for the registered drugs. This study determined the impact of adverse event reports on the detection of safety signals for a COVID-19 prophylactic vaccine by analyzing the JADER database using disproportionality analysis. We extracted data from the JADER dataset, in which the COVID-19 vaccine was reported as a suspected drug, and selected the top 10 adverse events in terms of the number of reports. We then extracted the top 30 drugs by the amount of information in the selected 10 adverse events and compared the changes in the number of signal detections with and without the COVID-19 vaccine report data. The total number of adverse events reported in the JADER database during the study period was 2,002,564. Of the total number of reports, 85,489 (4.3%) reported adverse events related to the COVID-19 vaccine. Of the top 30 drugs reported in the 10 selected adverse events, the ROR and PRR were found to be lower with the inclusion of COVID-19 vaccine data than without. Detection by ROR excluded 23 out of 245 drugs, and detection by PRR excluded 34 out of 204 drugs. The rapid increase in the number of adverse event reports for the COVID-19 vaccine in JADER may affect the detection of safety signals by disproportionality analysis.

Adverse events in the postoperative period of cardiac surgery in a pediatric intensive care unit: the contribution of the VIS score and the RACHS-1.

To evaluate the occurrence of adverse events in the postoperative period of cardiac surgery in a pediatric intensive care unit and to find any patient characteristics that can predict such events. This was a historical cohort study of patients recovering in the pediatric intensive care unit for the first 7 days after cardiac surgery between April and December 2019, by reviewing the medical records. The following were reviewed: demographic, clinical, and laboratory characteristics; patient severity scores; and selected adverse events, grouped into device-related, surgical, and nonsurgical. A total of 238 medical records were included. At least one adverse event occurred in 110 postoperative patients (46.2%). The total number of adverse events was 193 (81%). Vascular catheters were the most common cause, followed by cardiac arrest, bleeding, and surgical reexploration. In the univariate analysis, the vasoactive-inotropic score (VIS), Risk Adjustment in Congenital Heart Surgery (RACHS-1) score, age, Pediatric Index of Mortality (PIM-2), cardiopulmonary bypass and aortic clamping duration were significantly associated with adverse events. In the multivariate analysis, VIS ≥ 20 (OR 2.90; p = 0.004) and RACHS-1 ≥ 3 (OR 2.11; p = 0.019) were significant predictors, while age and delayed sternal closure showed only trends toward significance. To predict the occurrence of adverse events from VIS and RACHS-1, the area under the curve was 0.73 (95%CI 0.66 - 0.79). Adverse events were quite frequent in children after cardiac surgery, especially those related to devices. The VIS and RACHS-1, used together, predicted the occurrence of adverse events well in this pediatric sample.

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis

Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated as a novel neuromodulation tool. Although taVNS is generally considered safe with only mild and transient adverse effects (AEs), those specifically caused by taVNS have not yet been investigated. This systematic review and meta-analysis on taVNS aimed to (1) systematically analyze study characteristics and AE assessment, (2) characterize and analyze possible AEs and their incidence, (3) search for predictable risk factors, (4) analyze the severity of AE, and (5) suggest an evidence-based taVNS adverse events questionnaire for safety monitoring. The articles searched were published through April 7, 2022, in Medline, Embase, Web of Science, Cochrane, and Lilacs databases. In general, we evaluated 177 studies that assessed 6322 subjects. From these, 55.37% of studies did not mention the presence or absence of any AEs; only 24.86% of the studies described that at least one adverse event occurred. In the 35 studies reporting the number of subjects with at least one adverse event, a meta-analytic approach to calculate the risk differences of developing an adverse event between active taVNS and controls was used. The meta-analytic overall adverse events incidence rate was calculated for the total number of adverse events reported on a 100,000 person-minutes-days scale. There were no differences in risk of developing an adverse event between active taVNS and controls. The incidence of AE, in general, was 12.84/100,000 person-minutes-days of stimulation, and the most frequently reported were ear pain, headache, and tingling. Almost half of the studies did not report the presence or absence of any AEs. We attribute this to the absence of AE in those studies. There was no causal relationship between taVNS and severe adverse events. This is the first systematic review and meta-analysis of transcutaneous auricular stimulation safety. Overall, taVNS is a safe and feasible option for clinical intervention.

The relationship between study partner type and rate of AE reporting in mild‐to‐moderate AD clinical trials

AbstractBackgroundIn randomized clinical trials (RCTs), monitoring adverse events (AE) and serious AE (SAE) is critical to maximize patient safety and trial integrity. There are, however, instances where the propensity to report AEs may differ by participant characteristics, thereby altering the observed safety profile of interventions and the generalizability of safety results. All Alzheimer’s disease (AD) clinical trials require participants to enroll with a study partner (SP), who ensures trial compliance and serves as a source of study data, including data on AEs. We examined AE reporting patterns among AD trial participants by SP type with the hypothesis that the rates of reported AEs and SAEs differ by SP type.MethodWe conducted a retrospective analysis of combined placebo data from seven independent RCTs conducted by the AD Cooperative Study (ADCS) (Docosahexaenoic Acid, Vitamin B, Huperzine A, Rofecoxib or Naproxen, Resveratrol, Simvastatin, and Valproate). Together, these seven trials provide data on 934 patients with mild‐to‐moderate AD. SP of each participant was categorized as spouse, adult child, or other. The total number of AEs by severity and SAEs were recorded for all individuals in the trial (Table 1). We also considered subject‐level reporting rates where we computed the number of unique participants reporting such events (Table 2). Chi‐squared tests were performed to determine if the rate of reporting AEs and SAEs by participants varied across SP type.ResultA total of 608 (65%) participants enrolled with spousal, 254 (27%) enrolled with adult child, and 72 (8%) enrolled with other SP. Overall, 854 (91%) participants reported at least one AE. There were 5430 AEs (66% grade 1, 28% grade 2, 6% grade 3, and 0% of grade 4 or 5) recorded. Chi‐squared tests comparing the rate of reporting by SP type yielded p‐values of 0.16 and 0.13 for AEs and SAEs, respectively.ConclusionWe observed that the reporting rate of AEs and SAEs did not substantially vary by SP type. This relationship was consistent across AE severity grades. Our results indicate little evidence that the reported safety profile in mild‐to‐moderate AD trials differs by SP type.

Valve-Related Complications in TAVI Leading to Emergent Cardiac Surgery.

Transcatheter aortic valve implantation (TAVI) is now a standard procedure for the treatment of symptomatic aortic valve stenosis in many patients. In Germany, according to the annual reports from the German Institute for Quality Assurance and Transparency in Healthcare (Institut für Qualitätssicherung und Transparenz im Gesundheitswesen), the rate of serious intraprocedural complications, such as valve malpositioning or embolization, coronary obstruction, aortic dissection, annular rupture, pericardial tamponade, or severe aortic regurgitation requiring emergency cardiac surgery has decreased markedly in recent years from more than 5.5% in 2012 to 2.0% in 2019. However, with increased use, the total number of adverse events remains about 500 per year, about 100 of which require conversion to sternotomy. These, sometimes, fatal events can occur at any time and are still challenging. Therefore, the interdisciplinary TAVI heart team should be prepared and aware of possible rescue strategies.

Telehealth utilization in gynecologic oncology clinical trials (295)

<b>Objectives:</b> In light of the COVID-19 pandemic, the Society of Gynecologic Oncology (SGO), National Cancer Institute, and Food and Drug Administration published clinical practice statements encouraging the use of telemedicine in clinical trials, which had previously been prohibited. Our study aimed to assess the feasibility and safety of telehealth utilization in clinical trials for gynecologic malignancies. <b>Methods:</b> A retrospective cohort study was performed. Patients who were enrolled in a gynecologic oncology clinical trial at the University of Pennsylvania Health System from March 16, 2020, to August 30, 2020, were included. Receipt of care during the telehealth period (March 16, 2020, to August 30, 2020) was compared to the pre-telehealth period (September 30, 2019, to March 15, 2020). Pairwise comparisons of clinical trial outcomes were performed between the two time periods, using paired t-test, Wilcoxon signed-rank test, simple linear regression, Chi-square, and ANOVA. <b>Results:</b> Thirty-one patients met the inclusion criteria. The mean age was 63.7 years (SD 10.3); 84% were non-Hispanic White. The median distance from home zip code to study center was 25.2 miles (IQR: 16-46, range: 1.9-170). Most patients had high-grade serous ovarian carcinoma (84%) and had the disease at an advanced stage (Stage III 48%, Stage IV 38.7%). Trial drugs included 22.6% (<i>n</i>=7) intravenous only, 29% (<i>n</i>=9) oral only, and 48.4% (<i>n</i>=15) combination oral/intravenous therapies. The median duration of enrollment was similar between pre-telehealth (5.2 months, IQR: 3.2-5.6) and telehealth periods (5.6 months, IQR: 3.8-5.6), (p=0.682). During the TELEHEALTH period, significantly more virtual provider visits (p <0.001) and remote laboratory testing (p=0.015) occurred, with similar rates of remote imaging (p=0.551). Delayed provider visits (p = 0.965), laboratory testing (p = 0.989) and imaging (p = 0.999) occurred infrequently in both timeframes. The number of patient touchpoints (portal messages and phone calls) per month did not increase (p = 0.147). Patients who lived farther from the study center were more likely to use remote imaging (p = 0.013); however, the distance was not associated with the use of virtual provider visits (p = 0.309) or remote laboratory testing (p = 0.821). Number of dose reductions (p = 0.112) and toxicity-related treatment delays (p = 0.888) were similar. Increased need for extra imaging was noted in the telehealth period (p=0.007) and was not associated with disease progression (p=0.614). Extra provider visits, emergency department visits, and hospital admissions were infrequent and similar in both timeframes (Table 1). The total number of deviations was increased (p=0.010); however, when adjusted for minor deviations documenting telehealth use or deferment of research-related laboratory testing given the pandemic precautions, there was no difference between timeframes (p = 0.468). The total number of adverse events and severe adverse events did not increase in the telehealth period (p=0.494 and p=0.601, respectively). <b>Conclusions:</b> Utilizing telehealth in clinical trials for gynecologic oncology patients did not increase clinical workload or adverse patient outcomes. Documentation of telehealth use and pause of research-related laboratory collections resulted in a higher number of protocol deviations during the telehealth period. Telehealth should be incorporated into future clinical trials as it appears safe and feasible and may facilitate access for remote, rural, and under-served populations.

EVALUATION OF WEIGHT REDUCTION EFFICACY AND SAFETY OF SIBUTRAMIN-CONTAINING DRUGS IN PATIENTS WITH ALIMENTARY OBESITY

The article presents clinical study results of the efficacy and safety of combination therapy with sibutramine and metformin (fixed combination) in comparison with sibutramine therapy with microcrystalline cellulose in patients with alimentary obesity.The aim is to evaluate the efficacy and safety of using the sibutramine+metformin fixed dose combination (Reduxin® Forte) and compare it with the sibutramine + microcrystalline cellulose combination (Reduxin®) in patients with alimentary obesity in the course of the obesity therapy.Materials and methods. Male and female patients (240 people) aged 18 to 65 years inclusive with alimentary obesity, meeting the inclusion criteria and not meeting the non-inclusion criteria, were randomized into 2 groups in a 1:1 ratio. One group (n=120) received sibutramine+ metformin p. o., 1 tablet (850 mg + 10 mg) once per day, the second group (n=120) received sibutramine+ microcrystalline cellulose (MCC) p. o., 1 capsule (10 mg + 158.5 mg) once per day in the morning. On day 30 ± 1, in the absence of a 2 kg weight loss compared to the first visit, the dose was increased in accordance with the medical instruction. The therapy period was 180 days. The randomization list was generated by the factory method of random numbers. The efficacy and safety were assessed by anthropometric, clinical and laboratory parameters and the SF-36 questionnaire. The proportion of patients who achieved a decrease in body weight by more than 5% in 6 months, the magnitude and dynamics of changes in body weight and body mass index, waist and hip measurements, their ratios, changes in lipid profile, blood pressure, as well as the total number of adverse events, their frequency and nature of occurrence were analyzed.Results. The both drugs have demonstrated efficacy in all parameters of the obesity therapy. At the same time, in a comparative analysis, a statistically significant advantage of therapy with sibutramine + metformin was demonstrated in relation to the proportion of patients who had achieved more than 5% weight loss (body weight dynamics). Significant benefits were shown in terms of the magnitude of the change in body mass index (BMI); there was a statistically significant increase in the proportion of the patients who had switched from one category of BMI to another. By the end of the study, the vast majority of patients had no longer met the criteria for the diagnosis of “Obesity”. There was also a statistically significant benefit of sibutramine + metformin in terms of lowering triglycerides and low-density lipoprotein levels. The analysis of the safety parameters of sibutramine + metformin confirms a high safety profile of the drug, a comparative statistical analysis of adverse events in terms of their presence, severity, causal relationship with therapy and outcome have not revealed intergroup differences. Adverse events were transient and did not require discontinuation of therapy.Conclusion. The results of the study showed that therapy with Reduxin® and Reduxin® Forte provides a pronounced decrease in body weight. However, the use of a fixed combination has a more effective positive effect on the lipid profile and patients’ quality of life, which, combined with a high safety profile, proves the possibility and expediency of using Reduxin® Forte for the treatment of obesity and restoring metabolic health, even in patients without additional carbohydrate metabolism disorders.

Analysis of adverse drug events in pulmonary Mycobacterium avium complex disease using spontaneous reporting system

BackgroundIn Japan, Mycobacterium avium complex lung disease (MAC-LD) is the most common in nontuberculous mycobacterial lung disease. Patients often experience adverse events, resulting in the discontinuation of treatment, which causes treatment failure. The JADER (Japanese Adverse Drug Event Report) database is a database of adverse events that allows us to collect real-world data on adverse events. We can collect large-scale data cost-effectively and detect signals of potential adverse events such as reporting odds ratio (ROR) by using spontaneous reporting systems. In this study, we aimed to elucidate the adverse events of clarithromycin (CAM), ethambutol (EB), and rifampicin (RFP) using the JADER database.MethodsWe included cases of MAC-LD between April 2004 and June 2017. We investigated sex, age, and medications that may have caused the adverse events, outcomes, and time of onset. We calculated the safety signal index as the ROR. Time-to-event analysis was performed using the Weibull distribution.ResultsThe total number of adverse events of CAM, EB, and RFP was 2780, with 806 patients. In the overall adverse events, hematologic and lymphatic disorders were the most common adverse events, with 17.3%, followed by eye disorders (16.6%), and hepatobiliary disorders (14.0%). The outcomes were as follows: recovery, 40.0%; remission, 27.1%; non-recovery, 11.2%; and death, 7.1%. Regarding the most common onset time of CAM, EB, and RFP was within 120 days at 40%, 181–300 days at 43.6%, and within 120 days at 88.5%. For CAM, the RORs of infections and infestations, hepatobiliary system disorders, and immune system disorders were 4.13 (95% confidence interval [CI], 2.3–7.44), 2.61 (95% CI, 1.39–4.91), and 2.38 (95% CI, 1.04–5.44). For EB, the ROR of eye disorders was 215.79 (95% CI, 132.62–351.12). For RFP, the RORs of renal and urinary tract disorders and investigations were 7.03 (95% CI, 3.35–14.77) and 6.99 (95% CI, 3.22–15.18). The β value of EB was 2.07 (95% CI, 1.48–2.76), which was classified as a wear-out failure type.ConclusionsFor MAC-LD, the adverse event which has the highest ROR is infections and infestations in CAM, eye disorders in EB, renal and urinary tract disorders in RFP. Adverse events of EB occur after 180 days, whereas the adverse events of CAM and RFP occur early in the course of treatment.