Met Eligibility Criteria Research Articles

Health Experiences of LGBTQ+ People Living With Dementia and Their Care Partners: A Scoping Review of Research and Policy

Objectives This scoping review aimed to synthesize research on the health experiences of LGBTQ+ people living with dementia (PLWD) and their caregivers, and the impact of health policies on this population. Methods Six databases were searched for research studies and policy literature. Titles, abstracts, and full texts were reviewed by a three-member team. Data was extracted and thematically analyzed. Feedback from 7 LGBTQ+ adults was collected through a community consultation session. Results A total of 9257 unique research and 945 policy citations were identified, of which 60 research and 19 policy papers were reviewed. Nine research studies and ten policy papers met eligibility criteria. Themes emerged through the analysis of research findings, the community listening session, and policy findings. Discussion Future work needs to disentangle the impact of policies on the health experiences of this population. Dementia-specific and LGBTQ+ inclusive services and policies are needed to address growing health disparities.

Applying an osteopathic intervention to improve mild to moderate mental health symptoms: a mixed-methods feasibility randomised trial.

The increasing prevalence of mental health disorders in the United Kingdom necessitates the exploration of novel treatment modalities. This study aimed to assess the feasibility and acceptability of conducting a randomised controlled trial (RCT) evaluating the efficacy of four osteopathic interventions on psychophysiological and mental health outcomes. A mixed-methods feasibility study with an explanatory sequential design was implemented. The quantitative phase involved randomising 42 participants into four intervention groups: (1) high-velocity and articulation techniques (HVAT), (2) soft-tissue massage (STM), (3) craniosacral therapy (CST), and (4) a combination approach. Primary outcome measures encompassed recruitment rate, assessment duration, questionnaire completion, intervention attrition, and adverse events. Secondary outcomes included validated assessments of depression, anxiety, stress, psychological flexibility, heart rate variability (HRV), and interoception, administered pre- and post-intervention. Analysis of variance (ANOVA) was employed to evaluate pre-post intervention changes. The qualitative phase comprised semi-structured interviews analysed using thematic analysis. The study achieved a recruitment rate of 21 eligible participants per month, with 54.8% of respondents meeting eligibility criteria. All 33 participants who completed the study underwent interventions and assessments within the allocated one-hour timeframe, with full questionnaire completion. The attrition rate was 21%. No adverse events were reported. Qualitative analysis revealed positive participant experiences, with themes highlighting good practitioner communication, intervention accessibility, and increased bodily awareness. Some participants found the questionnaire battery burdensome. Exploratory quantitative analyses showed variations in effects across interventions for heart rate variability, interoceptive accuracy, and mental health measures, but these results should be interpreted cautiously due to the small sample size. This study provides evidence supporting the feasibility and acceptability of a larger-scale RCT investigating osteopathic interventions for individuals presenting with mild psychological symptoms. The preliminary findings suggest potential efficacy in improving mental health outcomes, warranting further investigation. Trial registration NCT05674071, registered 06/01/2023.

Use of commercially available wearable devices for physical rehabilitation in healthcare: a systematic review

ObjectivesTo evaluate whether commercially available ‘off-the-shelf’ wearable technology can improve patient rehabilitation outcomes, and to categorise all wearables currently being used to augment rehabilitation, including the disciplines and conditions under...

Violence Against Children in Sub-Saharan Africa: A Scoping Review of Literature on the Victim-Perpetrator Relationship.

Violence against children affects children in every region, nation, and community in the world. Despite a significant body of literature about the victims of such violence, there has been little empirical research, particularly in Sub-Saharan Africa, focused on perpetrators, their relationship to victims, and interventions that might alter their behavior. This scoping review sought to identify and summarize the scholarly literature on perpetrators of violence against children in Sub-Saharan Africa and their relationship with victims. Using a keyword search of academic databases, we included peer-reviewed studies published from January 2013 to June 2023 that focused on physical, sexual, or emotional violence against children in Sub-Saharan Africa and included prevalence data about victim-perpetrator relationships. Eighteen of the 42 studies that met eligibility criteria shared one or more primary data sources with other studies included in this review, most frequently using data from Violence Against Children Surveys (10), the Uganda Good Schools Project (7), and the National Child Homicide Study (3). The most common classifications of perpetrators, in order of frequency, were caregivers/family members, intimate partners, peers, teachers/school staff and strangers, and the most common settings in which research took place were schools. Wide variability in the taxonomies used to define and report frequencies for age, victim, perpetrator, and type of violence obscures our ability to form a complete picture of victim-perpetrator relationships. Research emphasis on victims of violence may lead to missed opportunities to disrupt the perpetration of violence against children through interventions that specifically target its source.

The effect of Vitamin K antagonists as anticoagulants on bleeding in patients post-dental procedures

Background: Individuals undergoing continuous treatment and taking vitamin K antagonist (VKA) and other anticoagulant medications are at a higher risk of experiencing bleeding complications during and after dental surgery procedures. Objective: To determine the effect of vitamin K antagonists in post-dental procedure patients by exploring existing literature on managing patients on vitamin K antagonist therapy as anticoagulants. Methods: This research utilized a literature review based on a database search of studies published between 2019-2024. The literature search used strategies with the terms “Tooth extraction bleeding,” “Odontectomy bleeding,” “Vitamin K Antagonist,” and “Anticoagulant,” utilizing databases such as PubMed, Science Direct, and SCOPUS related to the research topic and meeting eligibility criteria. The studies were then reviewed, summarized, and conclusions were drawn using tables to reveal all data regarding study characteristics and results. Results: Patients using anticoagulants are categorized as high risk for bleeding when undergoing invasive dentistry procedures. VKA is the most commonly used anticoagulant to prevent blood clotting. The consumption of VKA does not significantly affect bleeding post-procedure. Dental procedures can be performed on patients taking anticoagulants without discontinuing the therapy. Conclusion: Based on several studies from various literature sources, it can be concluded that dental procedures in patients taking vitamin K antagonist anticoagulants can still be performed without the risk of bleeding complications with proper local hemostatic measures and perioperative management.

Exploring methodologies and frameworks for best practice transfer at the primary care level

Abstract Background In Feb 2023, the EU’s Joint Action on the transfer of best praCtices In pRimary CarE (CIRCE-JA) was launched with the objective of effectively transferring and implementing six best practices (BPs) among Member States (MS). Transferability from one primary care (PC) setting to another can be challenging given organizational, legal, cultural, social, economic, and environmental factors, requiring robust a methodological framework to guide the transfer process. A scoping review was conducted to identify conceptual models and methodological frameworks for context-relevant and evidence-informed BP transfer in PC settings. Methods The study aimed to identify models or frameworks to guide BP transfer in PC settings, whilst maximizing transferability. The JBI methodology was used, and an extensive search was conducted in PubMed (time limit: Jan ‘13-May ‘23). All publications of original research, systematic reviews, and text and opinion papers in English were eligible for inclusion. Key exclusion criteria were set, i.e., intervention type, level of care and reporting quality. The search was supplemented by gray literature review. Results From a total of 369 publications, 9 met eligibility criteria, reporting on 10 conceptual and methodological models/framework largely varying. These included transfer models applicable to all BPs as well as elements specific to some BPs, i.e., addressing integration, patient-centered care, care coordination, and health promotion. Strengths and weaknesses were identified for all. Conclusions Transferability of health interventions is complex, requiring systematic consideration of setting and intervention characteristics to inform and support local adaptation, implementation, and decision-making. Key elements identified can support the CIRCE-JA BP transfer and are largely relevant for further BP transfer across PC settings in EU MS, incl. for local adaptation, stakeholder engagement and effective implementation monitoring. Key messages • Innovative BPs are successfully deployed in many EU MS. To best support transformation for strong EU primary care and resilient health systems, it is important to ensure evidence-informed BP transfer. • This review reports on the selection of appropriate frameworks and models, and key elements thereof, to allow successful transfer of CIRCE-JA BPs and other BP transfer across PC settings in Europe.

Transcatheter aortic valve implantation in failed bioprosthetic or native valves: a systematic review and meta analysis

Abstract Background and purpose Currently, there is no comparative assessment of pooled clinical outcomes between valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) for either failed transcatheter or surgical bioprosthetic aortic valves (TAV or SAV) and native aortic valve TAVI (NV-TAVI) for aortic stenosis. Thus, this systematic review investigated the clinical outcomes of ViV-TAVI compared with NV-TAVI. Methods A meta-analysis was conducted according to Cochrane Handbook and the PRISMA statement. A systematic literature search was performed, using EMBASE and MEDLINE from inspection to December 25, 2023, to explore the comparative outcomes between ViV-TAVI and NV-TAVI. RStudio software was used to calculate pooled odds ratio (OR) with 95% confidence intervals (CI). Random-effects model was used to allow a more conservative assessment. Results Eighteen cohort studies (n=65,350) met eligibility criteria. Studies were categorized into 2 groups according to initially implanted bioprosthetic valve: TAV-in-TAV (5 studies, n=14490) and TAV-in-SAV implantation (13 studies, n=50860). Each ViV-TAVI group was compared with NV-TAVI. TAV-in-TAV implantation: There were no significant differences in all-cause mortality or stroke rates at ≥ 12 months between groups. The follow-up period was 12 months in all studies except in one (i.e., 24 months). Sensitivity analyses, by removing that study, did not show difference for both outcomes [(OR=1.25, 95%CI: 0.72-2.18) and (OR=1.14, 95%CI: 0.59-2.20), respectively]. TAV-in-TAV implantation was associated with higher rates of permanent pacemaker (PPM) insertion (OR=1.78, 95%CI: 1.10-2.88) within 30-day of follow-up. PPM insertion rate remained higher by 34% (OR=1.34, 95%CI: 1.02-1.76) even after removing the study that reported PPM insertion during index admission. Early conversion to open heart surgery and coronary occlusion (OR=3.75, 95%CI: 0.99-1417) did not differ between groups. TAV-in-SAV implantation: TAV-in-SAV implantation did not significantly reduce the risk of all-cause mortality, but stroke risk was reduced by 19% at ≥ 12 months follow-up. Sensitivity analyses by removing the studies with 24 months follow-up yielded comparable results [(OR=0.88, 95%CI: 0.64-1.21) and (OR=0.81, 95%CI: 0.70-0.94), respectively]. TAV-in-SAV implantation was associated with lower rates of PPM insertion compared with NV-TAVI (OR=0.33, 95%CI: 0.17-0.62) within 30-day of follow-up. The risk remained significantly lower by 69% (OR=0.31, 95%CI: 0.10-0.92) upon removing the studies that reported PPM insertion during the index admission. Early conversion to open heart surgery and coronary occlusion (OR=1.88, 95%CI: 0.82-4.32) did not differ between groups. Conclusion In comparison with NV-TAVI, TAV-in-TAV implantation was associated with higher PPM insertion rates, whereas, TAV-in-SAV implantation was associated with lower stroke and PPM insertion rates without an impact on mortality.

Scoping Review of Health Literacy Interventions among Migrant Communities in Europe

Abstract Background The increase in migration trends in Europe has brought attention to the significant health disparities between migrant and native populations, which are largely rooted in social determinants of health such as economic difficulties, language barriers, and limited access to services. Tailored health literacy (HL) interventions can serve as an intermediate factor between social determinants of health and health outcome, thereby holding great potential for addressing these disparities. Despite a growing body of research on migrant health, there remains a gap in our understanding of effective HL interventions for this population. Methods A scoping review was conducted following the Joanna Briggs Institute (JBI) updated guidelines and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. Electronic searches were carried out across five databases (PubMed, SCOPUS, Web of Science, PsychINFO, and CINHAL) and supplemented by a manual search. We included European studies on migrant HL interventions, conducted between 2011 and 2023, and published in English or Portuguese language. Results Out of 1018 records, 7 studies met eligibility criteria. Predominantly situated in Northern and Western Europe (85.5%), interventions primarily targeted female migrants (71.4%) through in-person courses (42.9%). Identified intervention strengths included culturally adapted content, migrant engagement, and access to written materials. Gaps included mental health interventions and community outreach. Conclusions This scoping review provides a comprehensive overview of HL interventions targeting migrant populations, highlighting their characteristics, strengths, and gaps. These findings serve as a foundational step towards developing guidelines for effective HL interventions within migrant communities. Key messages • Most European health literacy interventions for migrants target women and are conducted in North or West Europe. • Cultural adaptation and community engagement are key strengths of migrant health literacy interventions, yet gaps remain in mental health support and community outreach efforts.

A study to assess the ability of the HFA-ICOS risk stratification tool to predict cancer therapy-related cardiac dysfunction for patients receiving anthracycline chemotherapy

Abstract Introduction The use of anthracycline chemotherapy is complicated by the risk of developing cancer therapy-related cardiac dysfunction (CTRCD). The Heart Failure Association (HFA) and International Cardio-Oncology Society (ICOS) have jointly published a novel cardiovascular risk stratification tool for patients receiving anthracycline chemotherapy which categorises patients according to their risk of CTRCD (1). The risk tool has not yet been validated for use in the United Kingdom. Purpose In this study, we test the ability of the HFA-ICOS risk stratification tool to predict CTRCD for patients receiving anthracycline chemotherapy. Methods A retrospective study of patients ≥18 years who received anthracycline chemotherapy between January 2019 to January 2023 at two cardio-oncology centres in the United Kingdom. Patients were eligible if they had ≥1 follow up echocardiogram after the end of anthracycline treatment. Patients receiving HER-2 targeted therapies were excluded. Patients were classified into low/medium/high/very-high risk categories using the HFA/ICOS tool. The prevalence of CTRCD was assessed during the follow up period; a minimum of 6 months after the end of chemotherapy. Results 288 patients met eligibility criteria for the study. 59 patients (20%) were treated for leukaemia, 104 (36%) lymphoma, 63 (22%) sarcoma and 49 (17%) breast cancer. The mean age was 49±18yrs, with 56% females. The mean cumulative dose of doxorubicin (or equivalent) was 235±104mg/m2. Using the HFA/ICOS tool, 50% of patients were deemed low risk, 31% medium risk, 16% high risk and 3% very high risk at baseline. Using guideline recommended CTRCD definitions, there was an overall incidence of 9% of symptomatic CTRCD and 22% of asymptomatic CTRCD (Table 1). The incidence of symptomatic CTRCD significantly increased as the baseline risk of CTRCD increased. 20% of patients deemed high or very-high risk at baseline subsequently developed symptomatic CTRCD (Fig 1). Furthermore, patients at high or very-high risk were 4.4 times more likely to develop symptomatic CTRCD than patients who were low risk (OR 4.4, 95% CI 1.7-11.6, p=0.003). There was no association with baseline risk and the development of asymptomatic CTRCD. The incidence of mild asymptomatic CTRCD may be underestimated due to the lack of routine surveillance with cardiac biomarkers and left ventricular global longitudinal strain (LV GLS) imaging for asymptomatic disease during the study period. Conclusion The novel HFA/ICOS risk stratification tool is useful in predicting patients who will develop symptomatic CTRCD in a contemporary UK setting.

Evaluation of orphan maintained biological medicinal products in the European Union between 2018 to 2023: a regulatory perspective

ABSTRACT Objectives Orphan medicinal products (OMPs) authorized in the European Union (EU) benefit from market exclusivity, fee waivers, and national incentives. Maintaining orphan status during the marketing authorization application (MAA) requires meeting eligibility criteria, especially demonstrating significant benefit (SB), which is challenging. This study identifies key features linked to successful orphan status maintenance for biological OMPs approved in the EU between 2018 and 2023. Methods Data from European public assessment reports and orphan maintenance assessment reports were analyzed. Results Among the 50 biological OMPs granted orphan designation, 68.0% had to demonstrate SB over existing treatments, with 91.2% leveraging the clinically relevant advantage area, utilizing better clinical efficacy (83.8%) and subpopulation (38.7%) sub-domains. However, 32% did not need to demonstrate SB due to a lack of alternative treatments, most of which were ultra-orphan drugs. Advanced therapy medicinal products and monoclonal antibodies were the most numerous OMP categories, whereas oncology and immunomodulation were the preferred therapeutic areas. Conclusion The Orphan Regulation plays a critical role in advancing treatments for rare diseases, fostering innovation while addressing unmet medical needs. Nonetheless, the insufficient return on investment criterion remains underused, whereas refining major contribution to patient care guidelines and incorporating real-world evidence may enhance regulatory evaluations.

Effect of four hemoglobin transfusion threshold strategies in patients with acute myocardial infarction and anemia: a target trial emulation using MINT trial data

Abstract Background The hemoglobin (Hgb) threshold at which red blood cell transfusion affords greatest benefit, without increasing transfusion-associated risks, is uncertain for patients with acute myocardial infarction (MI). The Myocardial Ischemia and Transfusion (MINT) trial recently showed a restrictive transfusion strategy (Hgb threshold <7-8g/dL) resulted in a 15% increased risk of 30-day all-cause death or recurrent MI (death/MI) compared with a liberal strategy (Hgb threshold <10g/dL) in 3,504 adults with acute MI and anemia. However, the transfusion effect at different Hgb thresholds remains uncertain. Purpose To better understand the gradient of effects from Hgb threshold transfusion triggers between 7g/dL and 10g/dL. We estimated the effects of four Hgb transfusion thresholds on 30-day death/MI and death in patients with acute MI and anemia. Methods We used data from the MINT trial and applied an innovative causal inference method, target trial emulation, to assess four Hgb thresholds. We emulated a hypothetical, 4-arm target trial of <10g/dL, <9g/dL, <8g/dL, and <7g/dL transfusion strategies in adults with acute MI and Hgb <10g/dL using a "cloning" procedure. The target trial protocol closely mirrored that of the MINT trial. We conducted a per-protocol analysis of the emulated target trial using censoring and inverse probability (IP) weighting; we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) by fitting pooled logistic regression models with a time-dependent intercept for time free of the outcomes. We estimated IP weighted Kaplan-Meier cumulative incidence curves under each strategy for 30-day outcomes. Results Of the MINT trial participants, 3,492 (99.7%) met eligibility criteria for the hypothetical target trial of four transfusion strategies. The unadjusted rate of 30-day death/MI was lowest in the <10g/dL strategy and highest in the <9g/dL strategy, and the rate of transfusions decreased monotonically as Hgb thresholds decreased. Relative to the <10g/dL strategy, the estimated HRs (95% CI) from the IP weighted model of 30-day death/MI were 1.07 (0.77-1.50) for the <9g/dL strategy, 1.14 (0.84-1.55) for the <8g/dL strategy, and 1.44 (0.99-2.09) for the <7g/dL strategy (Figure). A log-linear estimate over strategy thresholds between 7-10g/dL estimated a 1.12 (95% CI 1.00-1.27) times greater average risk of death/MI and a 1.12 (95% CI 0.92, 1.37) times greater average risk of death over 30 days for each 1g/dL decrease in the Hgb threshold. The IP weighted cumulative incidence curves showed similar increase in risk of death/MI as transfusion thresholds decreased throughout 30 days post-randomization. Conclusions Relative to a <10g/dL transfusion strategy, we estimated a progressively greater risk of 30-day death/MI as transfusion Hgb thresholds decreased within the range of 7-10g/dL. Targeting a Hgb concentration of 10g/dL in patients with a recent acute MI may avoid serious risks associated with anemia.Hazard ratios for 30-day death/MI

Applicability of VICTORION-1 PREVENT Criteria to the US Population

Abstract Background VICTORION-1 PREVENT (V-1P) is an ongoing randomized clinical trial comparing inclisiran sodium 300mg every six months with placebo for primary prevention in patients with high cardiovascular (CV) risk. Purpose We evaluated the generalizability of V-1P trial enrollment criteria to the US population to understand the demographic and CV health characteristics of the trial target population. Methods We included data from the National Health and Nutrition Examination Survey (N=25,531, 2015-March 2020), a nationally representative sample of the US population. Enrollment criteria similar to V-1P were applied. Nonpregnant adults 40-79 years with low-density lipoprotein cholesterol (LDL-C) of 70-189 mg/dL were included. 10-year risk for CV disease was determined using the American Heart Association race-free 10-year PREVENT risk equations. Individuals with 10-year risk >20% or 7.5%-19.9% with two risk enhancing factors at baseline were included. Risk enhancing factors included elevated high sensitivity C-reactive protein (≥2 mg/L), inflammatory arthritis, estimated glomerular filtration rate <60 ml/min/1.73 m2, metabolic syndrome, or early family history of CV disease. Patients with history of atherosclerotic CV disease or liver disease were excluded. Estimates of demographics and health characteristics were nationally representative using survey weights. Results Among US adults, 21,576,506 (standard error [SE]: ±1,258,255) meet eligibility criteria for V-1P (weighted estimate). This represents 8.8% of all US adults or 15.1% of US adults 30-79 years. The V-1P eligible population had a mean age of 65.3 years (SE: ±0.5 years), and 55.0% (SE: ±2.5%) were female. Compared with the US adult population (≥18 years), V-1P eligible population had a higher mean body mass index (32.6 ± 0.3 kg/m2 vs 29.5 ± 0.2 kg/m2) and higher rates of obesity (61.0% ± 2.1% vs 40.0% ± 1.1%) (Table). V-1P eligible population also had higher mean systolic blood pressure (133.9 ± 1.0 mmHg vs 121.7 ± 0.3 mmHg), similar mean diastolic blood pressure (72.6 ± 0.8 mmHg vs 71.8 ± 0.2 mmHg), and higher rates of hypertension (85.8% ± 2.0% vs 45.9% ± 1.1%). Mean hemoglobin A1c percent (6.3 ± 0.1 vs 5.7 ± 0.02), fasting blood sugar (127.7 ± 1.9 mg/dL vs 109.2 ± 0.6 mg/dL), and diabetes rates (39.7% ± 2.6% vs 13.1% ± 0.7%) were higher in the V-1P eligible population. Mean low-density lipoprotein cholesterol (115.8 ± 1.5 mg/dL vs 110.2 ± 0.8 mg/dL) and fasting triglycerides (137.6 ± 5.0 mg/dL vs 110.4 ± 1.7 mg/dL) were higher, while mean high-density lipoprotein cholesterol was lower (49.9 ± 0.8 mg/dL vs 54.8 ± 0.4 mg/dL). The distribution of key CV risk factors is shown in the Figure. Conclusion V-1P enrollment criteria apply to many patients. These patients have significant cardiometabolic risk factor burden, and effective preventive therapies could have substantial health impact.

Anti–Programmed Death Ligand 1 Plus Targeted Therapy in Anaplastic Thyroid Carcinoma

Anaplastic thyroid carcinoma (ATC) is a rare and lethal cancer. Although progress has been made in recent years in patients with mutated BRAF tumors, those who respond initially eventually die of their disease; furthermore, there are no approved therapies for non-BRAF mutated tumors. To determine whether treatment with matched-targeted therapy plus immune checkpoint inhibitors were associated with improved overall survival (OS). A phase 2 trial at a single center, tertiary institution with parallel cohorts, assigning treatment with targeted therapy according to the tumor mutation status. Patients with mutated BRAF V600E tumors received vemurafenib/cobimetinib plus atezolizumab (cohort 1); those with mutated RAS (NRAS, KRAS, or HRAS) or NF1/2 tumors received cobimetinib plus atezolizumab (cohort 2). Patients without any of these variants were assigned to receive bevacizumab plus atezolizumab (cohort 3). Patients were enrolled from August 3, 2017, to July 7, 2021. All consecutive, systemic therapy-naive patients with ATC with active disease and who met eligibility criteria were considered for participation. The analysis was conducted in September 2023. Patients were assigned to targeted therapy based on the driver mutation as follow: BRAF V600E (cohort 1, vemurafenib plus cobimetinib), RAS/NF (cohort 2, cobimetinib), or non-BRAF/RAS/NF (cohort 3, bevacizumab). All received atezolizumab. The primary outcome of the study was median OS of the entire targeted therapy cohort, compared with historical median OS of 5 months. Forty-three patients with ATC were enrolled in the targeted therapy cohorts, of which 42 were included in the primary analysis. The median OS in patients across these 3 cohorts was 19 months (95% CI, 7.79-43.24). Median OS and progression-free survival per cohort were as follows: cohort 1: 43 months (95% CI, 16-not estimable [NE]), 13.9 months (6.6-64.1); cohort 2: 8.7 months (95% CI, 5.1-37.0) and 4.8 months (1.8-14.7); cohort 3 (vascular endothelial growth factor inhibitor group): 6.21 months (4.1-NE) and 1.3 months (1.3-NE), respectively. In this nonrandomized clinical trial, atezolizumab combined with targeted therapy resulted in a longer median OS than historical landmark, achieving the study's primary end point, with cohort 1 achieving the longest OS. ClinicalTrials.gov Identifier: NCT03181100.

A Scoping Review of GLP-1 Receptor Agonists: Are They Associated with Increased Gastric Contents, Regurgitation, and Aspiration Events?

Background: The increased popularity and ubiquitous use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the treatment of diabetes, heart failure, and obesity has led to significant concern for increased risk for perioperative aspiration, given their effects on delayed gastric emptying. This concern is highlighted by many major societies that have published varying guidance on the perioperative management of these medications, given limited data. We conducted a scoping review of the available literature regarding the aspiration risk and aspiration/regurgitant events related to GLP-1 RAs. Methods: A librarian-assisted search was performed using five electronic medical databases (PubMed, Embase, and Web of Science Platform Databases, including Web of Science Core Collection, KCI Korean Journal Database, MEDLINE, and Preprint Citation Index) from inception through March 2024 for articles that reported endoscopic, ultrasound, and nasogastric evaluation for increased residual gastric volume retained food contents, as well as incidences of regurgitation and aspiration events. Two reviewers independently screened titles, abstracts, and full text of articles to determine eligibility. Data extraction was performed using customized fields established a priori within a systematic review software system. Results: Of the 3712 citations identified, 24 studies met eligibility criteria. Studies included four prospective, six retrospective, five case series, and nine case reports. The GLP-1 RAs reported in the studies included semaglutide, liraglutide, lixisenatide, dulaglutide, tirzepatide, and exenatide. All studies, except one case report, reported patients with confounding factors for retained gastric contents and aspiration, such as a history of diabetes, cirrhosis, hypothyroidism, psychiatric disorders, gastric reflux, Barrett’s esophagus, Parkinson’s disease, dysphagia, obstructive sleep apnea, gastric polyps, prior abdominal surgeries, autoimmune diseases, pain, ASA physical status classification, procedural factors (i.e., thyroid surgery associated with risk for nausea, ketamine associated with nausea and secretions), and/or medications associated with delayed gastric emptying (opioids, anticholinergics, antidepressants, beta-blockers, calcium channel blockers, DPP-IV inhibitors, and antacids). Of the eight studies (three prospective and five retrospective) that evaluated residual contents in both GLP-1 users and non-users, seven studies (n = 7/8) reported a significant increase in residual gastric contents in GLP-1 users compared to non-users (19–56% vs. 5–20%). In the three retrospective studies that evaluated for aspiration events, there was no significant difference in aspiration events, with one study reporting aspiration rates of 4.8 cases per 10,000 in GLP-1 RA users compared to 4.6 cases per 10,000 in nonusers and the remaining two studies reporting one aspiration event in the GLP-1 RA user group and none in the non-user group. In one study that evaluated for regurgitation or reflux by esophageal manometry and pH, there was no significant difference in reflux episodes but a reduction in gastric acidity in the GLP-1 RA user group compared to the non-user group. Conclusions: There is significant variability in the findings reported in the studies, and most of these studies include confounding factors that may influence the association between GLP-1 RAs and an increased risk of aspiration and related events. While GLP-1 RAs do increase residual gastric contents in line with their mechanism of action, the currently available data do not suggest a significant increase in aspiration and regurgitation events associated with their use and the withholding of GLP-1 RAs to reduce aspiration and regurgitation events, as is currently recommended by many major societal guidelines. Large randomized controlled trials (RCTs) may be helpful in further elucidating the impact of GLP-1 RAs on perioperative aspiration risk.

Accuracy of pre-operative tumor size assessment compared to final pathology and frequency of adjuvant treatment in patients with FIGO 2018 stage IB2 cervical cancer

ObjectiveThe primary aim of our study was to compare tumor size assessment by pre-operative evaluation (physical examination and/or imaging) with tumor size on final pathology. As a secondary outcome, we...

20 Co-occurring behaviours of concern and sleep problems in children with neurodevelopmental disorders

Abstract Background Many children with neurodevelopmental disorders (NDDs) have behaviours of concern (BoC). These behaviours, such as aggression and self-injury, can impair functioning, cause distress to the child and caregivers, and threaten physical safety. This population also commonly experiences chronic and frequent sleep problems including issues falling asleep and staying asleep. Studies in sub-populations of NDDs suggest insufficient sleep is related to worsening BoC. Therefore, sleep may be a modifiable risk factor in children with NDDs and BoC. However, no studies have systematically characterized co-occurring behaviour and sleep problems in the general NDD population. To our knowledge this is the first study to take a transdiagnostic approach in assessing the co-occurrence of sleep problems and BoC in children with NDDs, and systematically characterizing BoC and sleep problems by their type and severity. Objectives To assess the co-occurrence of BoC and sleep problems in a population of children with diverse NDDs and systematically characterize both BoC and sleep problems. Design/Methods A literature review and clinical experience informed the creation of a REDCap database. Medical information, the nature, frequency, and severity of BoC and sleep problems, and other relevant information (e.g., demographics, medications) were included. Charts from children ages 2-18 years who visited the Child Development Centre for consultation from May – October 2022 and had confirmation of an NDD diagnosis were manually reviewed. Results 241 children met eligibility criteria. Of children with data available for both sleep and behaviour, 55% had co-occurring behaviour and sleep problems. These children displayed aggression (75%) and self-injury (49%) more frequently than children who had behaviours but no sleep problems (66% and 34%, respectively). Children with co-occurring behaviours and sleep problems were more likely to have severe BoC, including severe aggression (48%) and self-injury (45%), compared to children who had behavioural concerns but no sleep problems (21% and 20%, respectively). Conclusion The majority of children with NDDs have co-occurring BoC and sleep problems. This co-occurrence was related to increased frequency and severity of BoC in children with NDDs. Addressing sleep problems may represent a previously underrecognized therapeutic target to address BoC in this population.

HIV Prevention Product Acceptability and Preference Among Women in Sub-Saharan Africa to Inform Novel Biomedical Options in Development: A Systematic Review.

The availability of several HIV prevention options may allow women to choose a product that suits their lifestyle and preferences. Product attributes and contextual factors influence product acceptability, which affects uptake and effective use. We conducted a systematic review of acceptability and preference for biomedical HIV prevention products among women in sub-Saharan Africa (SSA) to inform the development of novel products. We used a comprehensive strategy to search three databases for peer-reviewed literature from SSA published between January 2015 and December 2023. A two-stage review process assessed references against eligibility criteria. Data were abstracted using a standardized spreadsheet, then organized by constructs from two theoretical frameworks of acceptability. Results were synthesized based on product classes defined by route of administration. We identified 408 unique references; 100 references met eligibility criteria. References assessed oral PrEP (n = 65), vaginal ring (n = 44), long-acting systemic products (injectable, implant, microarray patch) (n = 28), and other vaginal products (film, insert, gel) (n = 20). Over two-thirds reported qualitative or mixed-methods data, primarily from adolescent girls and young women. Frequent dosing, especially noted for daily oral PrEP, and perceived/experienced side effects were notably negative influences. Most end-users preferred long-acting products (systemically or vaginally delivered), though on-demand products offering user control were also valued. Influencing factors, especially partners, shaped end-user perceptions of product attributes and acceptability. All products were linked to at least some barriers to uptake and/or use, highlighting the need to provide end-users with a range of options and assist them in identifying one that best suits their circumstances and needs. Biomedical HIV prevention development should advance products that address gaps in available options while optimizing favorable product attributes to achieve high acceptability that ultimately supports adoption and use.

Characteristics of patients with liver tumors deemed ineligible for enrollment on Children's Oncology Group trial AHEP1531: An opportunity to expand inclusion criteria and improve outcome.

Specific patients with hepatoblastoma (HB) and hepatocellular carcinoma (HCC) do not meet eligibility criteria for Children's Oncology Group (COG) trials, limiting an understanding of how comorbidities affect the outcome. We define such a population for future-focused care improvements. A questionnaire was sent to COG institutional principal investigators to obtain anonymized data regarding patients with a liver tumor diagnosis not enrolled on AHEP1531 due to ineligibility by trial criteria or other reasons (excluding parent/patient preference). Responses received for 55 patients (38 HB, 4 HCC, and 13 not reported) included 12 excluded from further analysis due to various factors, including lack of additional information. Five patients were eligible but not enrolled due to pandemic-related staffing issues (n=1) or the best interest of the patient (physician preference, n=1; risk for poor tolerance of chemotherapy, n=1; not specified, n=2). The remaining 38 patients included 1 ineligible due to a prior malignancy, 9 due to performance status, and 4 due to timing requirements. Thirty-five of 38 patients were ineligible due to organ function criteria (pulmonary/oxygen requirement, n=25; renal, n=10; liver, n=4; cardiac, n=3). Seven patients were ineligible due to two or more organ function criteria. Twenty-five of 38 patients were reported to have a preexisting condition including 4 patients with trisomy 18. Patients with HB, and potentially HCC, who are ineligible for COG trials are primarily patients with an oxygen requirement and/or renal insufficiency, often associated with preexisting congenital conditions. Such patients would benefit from future studies to improve outcomes.

Clinical Characteristics, Management, and Outcomes of Bacteremia in Children with Cancer: A Retrospective Study

Abstract Background Bacteremia is a common infectious complication among pediatric oncology patients, yet management practices are not standardized. Antibiotic treatment courses as short as seven days are supported by literature and could improve patient quality of life and resource use. However, it is not known if short courses are associated with greater treatment failure in immunocompromised patients. Methods We conducted a retrospective study at St. Jude Children’s Research Hospital, including patients with a laboratory confirmed bloodstream bacterial infection between April 1, 2022, and March 31, 2023. Clinical characteristics such as age, gender, type of malignancy, phase of treatment, underlying chronic conditions, and clinical sites of infection were collected. Antibiotics used, duration of therapy, and route of administration were also gathered to examine clinical management. Clinical outcomes were measured by documenting ICU admission, oxygen, fluid and vasopressor requirements, date of hospital discharge, bacteremia recurrence, and mortality. Results 86 patients contributed 112 bacteremia episodes that met eligibility criteria. Severe neutropenia was present at onset in 68% of all episodes and 32% of patients did not have neutrophil recovery over 500 cells/ml during the episode. Gram-negative organisms accounted for 52% of isolated organisms, with the most common organisms isolated overall being Escherichia coli (19%), followed by Klebsiella pneumoniae (14%), and Viridans group streptococcus (14%). The median length of antibiotic treatment was 12 days. Treatment duration was not associated with oncologic diagnosis or Gram-negative versus Gram-positive infection. Conclusion Bacteremia occurs more frequently in patients who are neutropenic, especially those who are severely neutropenic with an absolute neutrophil count less than 500 cells/mL. Treatment duration is not associated with primary cancer diagnosis or type of bacteremia. In this single high resource setting, bloodstream infections resulted in significant morbidity, resource use, and a mortality rate of 8%, highlighting opportunities for investigation to improve clinical practices.

Understanding Pediatric Experiences With Symptomatic Varicoceles: Mixed Methods Study of an Online Varicocele Community.

Varicoceles affect up to 30% of postpubertal adolescent males. Studying this population remains difficult due to this topic's sensitive nature. Using the popularity of social media in this cohort and natural language processing (NLP) techniques, our aim was to identify perceptions of adolescent males on an internet varicocele forum to inform how physicians may better evaluate and counsel this pediatric population. We aimed to characterize themes of discussion and specific concerns expressed by adolescents using a mixed methods approach involving quantitative NLP and qualitative annotation of an online varicocele community. We extracted posts from the Reddit community "r/varicocele" (5100 members) with criteria of discussant age ≤21 years and word count >20. We used qualitative thematic analysis and the validated constant comparative method, as well as an NLP technique called the meaning extraction method with principal component analysis (MEM/PCA), to identify discussion themes. Two investigators independently interrogated 150 randomly selected posts to further characterize content based on NLP-identified themes and calculated the Kaiser-Meyer-Olkin (KMO) statistic and the Bartlett test. Both quantitative and qualitative approaches were then compared to identify key themes of discussion. A total of 1103 posts met eligibility criteria from July 2015 to June 2022. Among the 150 randomly selected posts, MEM/PCA and qualitative thematic analysis separately revealed key themes: an overview of varicocele (40/150, 27%), management (29/150, 19%), postprocedural experience (28/150, 19%), seeking community (26/150, 17%) and second opinions after visiting a physician (27/150, 18%). Quantitative analysis also identified "hypogonadism" and "semen analysis" as concerns when discussing their condition. The KMO statistic was >0.60 and the Bartlett test was <0.01, indicating the appropriateness of MEM/PCA. The mean age was 17.5 (SD 2.2; range 14-21) years, and there were trends toward higher-grade (40/45, 89% had a grade of ≥2) and left-sided varicoceles. Urologists were the topic of over 50% (53/82) of discussions among discussants, and varicocelectomy remained the intervention receiving the most interest. A total of 60% (90/150) of discussants described symptomatic varicoceles, with 62 of 90 reporting pain, 24 of 90 reporting hypogonadism symptoms, and 45 of 90 reporting aesthetics as the primary concern. We applied a mixed methods approach to identify uncensored concerns of adolescents with varicoceles. Both qualitative and quantitative approaches identified that adolescents often turned to social media as an adjunct to doctors' visits and to seek peer support. This population prioritized symptom control, with an emphasis on pain, aesthetics, sexual function, and hypogonadism. These data highlight how each adolescent may approach varicoceles uniquely, informing urologists how to better interface with this pediatric population. Additionally, these data may highlight the key drivers of decision-making when electing for procedural management of varicoceles.