BACKGROUND: The potential association between bivalent COVID-19 vaccination and ischemic stroke remains uncertain, despite several studies conducted thus far.
OBJECTIVE: This study aimed to evaluate the risk of ischemic stroke following bivalent COVID-19 vaccination during the 2022-2023 season.
METHODS: A self-controlled case series study was conducted among members aged 12 years and older who experienced ischemic stroke between September 1, 2022, and March 31, 2023, in a large health care system. Ischemic strokes were identified using International Classification of Diseases, Tenth Revision codes in emergency departments and inpatient settings. Exposures were Pfizer-BioNTech or Moderna bivalent COVID-19 vaccination. Risk intervals were prespecified as 1-21 days and 1-42 days after bivalent vaccination; all non-risk-interval person-time served as the control interval. The incidence of ischemic stroke was compared in the risk interval and control interval using conditional Poisson regression. We conducted overall and subgroup analyses by age, history of SARS-CoV-2 infection, and coadministration of influenza vaccine. When an elevated risk was detected, we performed a chart review of ischemic strokes and analyzed the risk of chart-confirmed ischemic stroke.
RESULTS: With 4933 ischemic stroke events, we found no increased risk within the 21-day risk interval for the 2 vaccines and by subgroups. However, risk of ischemic stroke was elevated within the 42-day risk interval among individuals aged younger than 65 years with coadministration of Pfizer-BioNTech bivalent and influenza vaccines on the same day; the relative incidence (RI) was 2.13 (95% CI 1.01-4.46). Among those who also had a history of SARS-CoV-2 infection, the RI was 3.94 (95% CI 1.10-14.16). After chart review, the RIs were 2.34 (95% CI 0.97-5.65) and 4.27 (95% CI 0.97-18.85), respectively. Among individuals aged younger than 65 years who received Moderna bivalent vaccine and had a history of SARS-CoV-2 infection, the RI was 2.62 (95% CI 1.13-6.03) before chart review and 2.24 (95% CI 0.78-6.47) after chart review. Stratified analyses by sex did not show a significantly increased risk of ischemic stroke after bivalent vaccination.
CONCLUSIONS: While the point estimate for the risk of chart-confirmed ischemic stroke was elevated in a risk interval of 1-42 days among individuals younger than 65 years with coadministration of Pfizer-BioNTech bivalent and influenza vaccines on the same day and among individuals younger than 65 years who received Moderna bivalent vaccine and had a history of SARS-CoV-2 infection, the risk was not statistically significant. The potential association between bivalent vaccination and ischemic stroke in the 1-42-day analysis warrants further investigation among individuals younger than 65 years with influenza vaccine coadministration and prior SARS-CoV-2 infection. Furthermore, the findings on ischemic stroke risk after bivalent COVID-19 vaccination underscore the need to evaluate monovalent COVID-19 vaccine safety during the 2023-2024 season.

BACKGROUND: The dissolution of dental calculus, safely and at home, is among the more challenging issues facing the over-the-counter healthcare industry. Pontis Biologics, Inc. has developed novel model of calculus development and structure and has formulated a dentifrice (Tartarase™) using digestive enzymes as active ingredients that is shown to dissolve dental calculus in this Proof of Principle clinical trial.
METHODS: This investigation was designed to evaluate the safety and efficacy of a novel enzyme formulation to remove existing calculus deposits in 4 weeks, measured using the Volpe-Manhold Index (V-MI) on lingual surfaces of 6 lower anterior teeth. The test formulation was compared to Crest Cavity Protection, as a control dentifrice. A total of 40 randomized test subjects began the study with 20 assigned to the control dentifrice and 20 assigned to the Tartarase groups (ten each, one brushing with Tartarase twice daily and one brushed with Tartarase and wore a dental tray filled with Tartarase for 30 min then brushed again with Tartarase, once daily).
RESULTS: The Crest group experienced a 12% increase in calculus, in contrast to the results of both Tartarase groups that experienced a 40% reduction in calculus in 4 weeks of unsupervised at home use of the Tartarase toothpaste formulation.
CONCLUSIONS: This proof of principle study demonstrates that a dentifrice, formulated along the lines of the Tartarase material, is capable of combating calculus accumulation using the same oral hygiene habits that are common worldwide.
BACKGROUND: This trial was registered retrospectively at clinicaltrials.gov and has the Unique Identification Number: NCT06139835, 14/11/2023.

BACKGROUND: The evaluation of electronic patient-reported outcomes (ePROs) is increasingly being used in clinical studies of patients with cancer and enables structured and standardized data collection in patients\' everyday lives. So far, few studies or analyses have focused on the medical benefit of ePROs for patients.
OBJECTIVE: The current exploratory analysis aimed to obtain an initial indication of whether the use of the Consilium Care app (recently renamed medidux; mobile Health AG) for structured and regular self-assessment of side effects by ePROs had a recognizable effect on incidences of unplanned consultations and hospitalizations of patients with cancer compared to a control group in a real-world care setting without app use. To analyze this, the incidences of unplanned consultations and hospitalizations of patients with cancer using the Consilium Care app that were recorded by the treating physicians as part of the patient reported outcome (PRO) study were compared retrospectively to corresponding data from a comparable population of patients with cancer collected at 2 Swiss oncology centers during standard-of-care treatment.
METHODS: Patients with cancer in the PRO study (178 included in this analysis) receiving systemic therapy in a neoadjuvant or noncurative setting performed a self-assessment of side effects via the Consilium Care app over an observational period of 90 days. In this period, unplanned (emergency) consultations and hospitalizations were documented by the participating physicians. The incidence of these events was compared with retrospective data obtained from 2 Swiss tumor centers for a matched cohort of patients with cancer.
RESULTS: Both patient groups were comparable in terms of age and gender ratio, as well as the distribution of cancer entities and Joint Committee on Cancer stages. In total, 139 patients from each group were treated with chemotherapy and 39 with other therapies. Looking at all patients, no significant difference in events per patient was found between the Consilium group and the control group (odds ratio 0.742, 90% CI 0.455-1.206). However, a multivariate regression model revealed that the interaction term between the Consilium group and the factor \"chemotherapy\" was significant at the 5% level (P=.048). This motivated a corresponding subgroup analysis that indicated a relevant reduction of the risk for the intervention group in the subgroup of patients who underwent chemotherapy. The corresponding odds ratio of 0.53, 90% CI 0.288-0.957 is equivalent to a halving of the risk for patients in the Consilium group and suggests a clinically relevant effect that is significant at a 2-sided 10% level (P=.08, Fisher exact test).
CONCLUSIONS: A comparison of unplanned consultations and hospitalizations from the PRO study with retrospective data from a comparable cohort of patients with cancer suggests a positive effect of regular app-based ePROs for patients receiving chemotherapy. These data are to be verified in the ongoing randomized PRO2 study (registered on ClinicalTrials.gov; NCT05425550).
BACKGROUND: ClinicalTrials.gov NCT03578731; https://www.clinicaltrials.gov/ct2/show/NCT03578731.
UNASSIGNED: RR2-10.2196/29271.

BACKGROUND: Robust adverse drug event (ADE) reporting systems are crucial to monitor and identify drug safety signals, but the quantity and type of ADEs captured may vary by system characteristics.
OBJECTIVE: We compared ADEs reported in 2 different reporting systems in the same jurisdictions, the Patient Safety and Learning System-Adverse Drug Reaction (PSLS-ADR) and ActionADE, to understand report variation.
METHODS: This retrospective observational study analyzed reports entered into PSLS-ADR and ActionADE systems between December 1, 2019, and December 31, 2022. We conducted a comprehensive analysis including all events from both reporting systems to examine coverage and usage and understand the types of events captured in both systems. We calculated descriptive statistics for reporting facility type, patient demographics, serious events, and most reported drugs. We conducted a subanalysis focused on adverse drug reactions to enable direct comparisons between systems in terms of the volume and events reported. We stratified results by reporting system.
RESULTS: We performed the comprehensive analysis on 3248 ADE reports, of which 12.4% (375/3035) were reported in PSLS-ADR and 87.6% (2660/3035) were reported in ActionADE. Distribution of all events and serious events varied slightly between the 2 systems. Iohexol, gadobutrol, and empagliflozin were the most common culprit drugs (173/375, 46.2%) in PSLS-ADR, while hydrochlorothiazide, apixaban, and ramipril (308/2660, 11.6%) were common in ActionADE. We included 2728 reports in the subanalysis of adverse drug reactions, of which 12.9% (353/2728) were reported in PSLS-ADR and 86.4% (2357/2728) were reported in ActionADE. ActionADE captured 4- to 6-fold more comparable events than PSLS-ADR over this study\'s period.
CONCLUSIONS: User-friendly and robust reporting systems are vital for pharmacovigilance and patient safety. This study highlights substantial differences in ADE data that were generated by different reporting systems. Understanding system factors that lead to varying reporting patterns can enhance ADE monitoring and should be taken into account when evaluating drug safety signals.

BACKGROUND: Growing evidence suggests that Latina immigrant survivors of adverse childhood experiences (ACEs) are at increased risk for developing and remaining with either depression or anxiety or both symptoms. This study examined the feasibility and acceptability of a telehealth intervention-Cuidándome (quee-DAN-doh-meh, \"taking care of myself\"). Cuidándome is a 10-week, patient-centered, trauma-informed intervention delivered by a trained facilitator that promotes self-management of depression and anxiety symptoms through improved problem-solving skills and strategies.
OBJECTIVE: The aim of this study was to examine the feasibility and acceptability of Cuidándome delivered remotely (via Zoom) with Latina immigrant ACE survivors with either depression or anxiety or both symptoms. We also estimated the effect sizes associated with the intervention on decreasing depression and anxiety symptoms and improving social problem-solving styles.
METHODS: We evaluated Cuidándome using a randomized controlled trial design. Latina immigrants (N=47) who had experienced at least 1 ACE and had at least mild depression or anxiety symptoms were randomized to Cuidándome or a comparison group delivered by trained facilitators. We assessed for changes in depression and anxiety symptoms as well as social problem-solving styles at baseline, post intervention, and 3- and 6-month follow-up.
RESULTS: Analyses indicated significant decreases over time within both Cuidándome and comparison groups for depression and anxiety symptoms and maladaptive problem-solving. The intervention effect was largest for anxiety; at 6-month follow-up, Cuidándome participants had significantly lower anxiety scores than the comparison group. In addition, we observed a greater average point reduction in depression symptoms at 6 months among Cuidándome participants (5.7 points) than in the comparison group (3.7 points).
CONCLUSIONS: A mental health program delivered via Zoom by a trained facilitator was feasible and acceptable to Latina immigrant women and can be beneficial for reducing anxiety and depression symptoms. More research is needed to assess the effectiveness of Cuidándome among a powered sample size of Latina immigrants.
BACKGROUND: ISRCTN Registry ISRCTN16668518; https://www.isrctn.com/ISRCTN16668518.

frailty screening facilitates the stratification of older adults at most risk of adverse events for urgent assessment and subsequent intervention. We assessed the validity of the Identification of Seniors at Risk (ISAR), Clinical Frailty Scale (CFS), Programme on Research for Integrating Services for the Maintenance of Autonomy seven item questionnaire (PRISMA-7) and InterRAI-ED at predicting adverse outcomes at 30 days and 6 months amongst older adults presenting to the Emergency Department (ED).
a prospective cohort study of adults ≥65 years who presented to the ED was conducted. The ISAR, CFS, PRISMA-7 and InterRAI-ED were assessed. Blinded follow-up telephone interviews were completed at 30 days and 6 months to assess the incidence of mortality, ED re-attendance, hospital readmission, functional decline and nursing home admission. The sensitivity, specificity, negative predictive value and positive predictive value of the screening tools were calculated using 2 × 2 tables.
a total of 419 patients were recruited; 47% female with a mean age of 76.9 (Standard deviation = 7.2). The prevalence of frailty varied across the tools (CFS 57% versus InterRAI-ED 70%). At 30 days, the mortality rate was 5.1%, ED re-attendance 18.1%, hospital readmission 14%, functional decline 47.6% and nursing home admission 7.1%. All tools had a high sensitivity and positive predictive value for predicting adverse outcomes.
older adults who screened positive for frailty were at significantly increased risk of experiencing an adverse outcome at 30 days with the ISAR being the most sensitive tool. We would recommend the implementation of the ISAR in the ED setting to support clinicians in identifying older adults most likely to benefit from specialised geriatric assessment and intervention.

Study objective: The objective of the study was to evaluate the safety and efficacy of remimazolam besylate versus propofol injection in patients undergoing colonoscopy. Design: A multicenter, randomized, non-inferiority, single-blind, parallel-controlled clinical trial. Setting: Operating room. Patients: Patients aged 18-65 years (American Society of Anesthesiologists [ASA] classification I-III) undergoing a diagnostic or therapeutic colonoscopy. Interventions: Patients were administered intravenous injection of remimazolam besylate or propofol (active comparator) for sedation. Measurements: Modified Observer\'s Assessment of Alertness/Sedation [MOAA/S] scores of the included patients were assessed before dosing, 1, 1.5, 2, 2.5, and 3 min after the start of dosing, and then every 1 min until the MOAA/S score reached 5 on three consecutive occasions. Main Results: A total of 360 patients received remimazolam and 120 patients received propofol. The incidence of adverse events (67.8% vs. 84.2%, p = 0.001) was significantly lower in patients administered remimazolam compared to propofol. There was no significant difference in sedation success rates (full analysis set [FAS]: 98.9% vs. 99.2%; remimazolam vs. propofol). Remimazolam had a significantly longer onset of action, but the difference was not considered clinically significant (1.45 min vs. 1.24 min, remimazolam vs. propofol). Propofol achieved a deeper level of sedation (mean MOAA/S score 0.5 vs. 0.2; remimazolam vs. propofol). Mean time to discharge after the end of the last administration of study drug (20.3 vs. 21.8 min, p = 0.020) and incidence of injection pain was significantly lower in patients administered remimazolam (2.3% vs. 35.3%, p < 0.0001). Incidence of oxygen desaturation was significantly higher in patients administered propofol compared to patients administered remimazolam (6.7% vs. 1.1%, p = 0.001). Similarly, incidence of hypotension was more frequent in patients administered propofol compared to patients administered remimazolam (29.2% vs. 10.6%, p < 0.0001). Conclusion: Remimazolam besylate had a better safety and tolerability profile and similar sedative efficacy to propofol in patients undergoing a diagnostic or therapeutic colonoscopy in China, suggesting that remimazolam besylate has potential as a sedative agent for colonoscopy.

Gestational diabetes mellitus is a type of glucose intolerance that first manifests itself during pregnancy. A pregnant woman and her unborn child are at an increased risk of pregnancy complications and poor neonatal outcomes. Pregnancy diabetes affects one out of every 200 women. Therefore, this study aims to identify the determinants of gestational diabetes mellitus among pregnant women attending an antenatal care service in Gedeo Zone, Ethiopia.
A facility-based case-control study design was employed from 25 January 2020 through 25 April 2020. The study included 80 cases and 240 control groups of pregnant women. Face-to-face interviews with structured questionnaires were used to collect data. For analyses, data was entered into Epidata version 3.1 and exported to the Statistical Package for the Social Sciences (SPSS) version 23.0. Variables with p .25 or lower in bivariate analysis were fitted to multivariable analysis. A multivariable logistic regression model with a 95% confidence interval and a p-Value of .05 was used.
Family history of diabetes mellitus [AOR 1.837; 95% CI (1.06-3.18)], history of spontaneous abortion [AOR 2.39; 95% CI 1.33-4.31), history of still birth [AOR 2.240 (1.222-4.105)], and history of delivery of a macrocosmic baby in the previous pregnancy [AOR 1.99 (1.157-3.43)] were found to be predictors of GDM.
Previous adverse pregnancy outcomes were found to be the main predictors of GDM. Women with gestational diabetes mellitus should be followed after delivery in order to monitor hyper-glycemic status.

BACKGROUND: Cancer risk associated with topical calcineurin inhibitors (TCIs) remains unclear.
OBJECTIVE: To evaluate the association between TCIs and cancer among patients with atopic and endogenous eczema.
METHODS: Incident cancers were identified from the National Cancer Registry. Data were analyzed using the Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals.
RESULTS: 880 unique cases of cancer developed in 66 176 patients from 2004 to 2012. The adjusted HRs for overall malignancy were 0.82 (95%CI 0.44-1.39) for tacrolimus-exposed and 1.30 (95%CI 0.59-2.45) for pimecrolimus-exposed. The only significant cancer association observed was lymphoid leukemia among the tacrolimus-exposed: HR 7.58 (95%CI 1.64-25.8). All affected patients had young-onset B-cell leukemia. Subgroup analysis of pediatric patients (≤16 years) showed significant association between tacrolimus use and B-cell leukemia: HR 26.4 (95%CI 4.77-146).
CONCLUSIONS: In this first Asian study on the risk of TCIs and malignancies, we do not find an association between use of tacrolimus and pimecrolimus in atopic and endogenous eczema and the overall development of malignancies. However, the use of topical tacrolimus was found to be associated with the development of B-cell acute lymphoid leukemia in pediatric eczema patients; further studies are required to investigate if a true association indeed occurs.