Primary Study Research Articles

Incidence of diarrhoeal disease among children aged less than five years in low- and middle-income countries: a systematic review.

Diarrhoea was the second leading cause of death among children aged <5 years in 2019. Most of these deaths occurred in low- and middle-income countries (LMICs). Summarising the available up-to-date evidence on the incidence of diarrhoeal disease among children could help track the effectiveness of diarrhoea prevention and control efforts. We summarised available evidence on the incidence of diarrhoea among children aged <5 years in LMICs. We included cross-sectional or cohort studies that reported diarrhoeal incidence among children aged <5 years in LMICs that were published between 2010-22 in English. Two authors searched, reviewed the quality of the selected articles, and extracted the data. We searched Medline/Pubmed, Web of Science, Scopus, CINHAL, EMBASE, WorldCat, OpenGrey, dissertations/theses, reports, and Google Scholar. We screened articles by title, abstract, and full text. We included 15 articles that met the inclusion criteria in the analysis. Four studies were from Africa, seven were from Asia, two were from Brazil, and two were from Nicaragua. Seven studies were conducted in urban settings, six in rural settings, and two in urban and rural areas. The highest incidence of diarrhoea was 5200 episodes of diarrhoea per 1000 child-years, and the lowest was 60.4 episodes of diarrhoea per 1000 child-years. There is limited evidence on the incidence of diarrhoea among children aged <5 years in LMICs. The available studies identified major differences in the incidence of diarrhoea by country, 60.4 in China, and 5200 episodes of diarrhoea per 1000 infants. We recommend more up-to-date primary studies on the incidence of diarrhoea among children aged <5 years in LMICs to monitor and evaluate the effectiveness of diarrhoea control and prevention policies and interventions. PROSPERO: CRD42022290180.

Microbial metabolites associated in stool and left ventricle of heart failure patients revealed by meta-analysis

Heart Failure (HF) impacts approximately 64 million people globally. While overall incidence of HF is relatively stable across countries, the overall number of HF patients is increasing due to aging populations. Many articles examine the microbiome in HF, however, studies from humans have not been analyzed systematically. The aim of this meta-analysis is to bridge this gap by analyzing previously published data on human HF patients with untargeted metabolomics to understand whether microbially-mediated metabolites are consistently important for HF status. A systematic survey of the literature identified 708 articles discussing HF, the microbiome, and metabolomics. Of these, 82 were primary studies of HF patients, 61 studied human adults, 23 included an untargeted metabolomics measure, and 3 studies had data that was usable and publicly accessible. These studies include a GCMS study from stool, NMR of saliva and exhaled breath condensate, and LCMS from left ventricle of HF patients undergoing transplantation and unused donor hearts. Significant differences were observed from PCA between HF and controls for stool and left ventricle, but not saliva or EBC samples. OPLS-DA was conducted for stool and ventricle samples, and further revealed significant group differences. Univariate testing with FDR correction revealed 8 significant microbially-relevant metabolites (p < 0.005 after correction), most notably asparagine from left ventricle and 2-methylbutyryl carnitine from stool. Though there is much discussion of the microbiome in health outcomes in HF, there is limited research from human populations. Some microbial co-metabolites from both stool and heart were significantly associated with HF.

Real-time ultrasound-guided laryngeal mask assisted percutaneous dilatational tracheostomy versus bronchoscopy-guided percutaneous dilatational tracheostomy in critically ill patients: a randomized controlled trial

BackgroundPercutaneous dilatational tracheostomy (PDT) is a common procedure for mechanically ventilated patients in the intensive care unit (ICU). This study compared the real-time ultrasound-guided PDT using a laryngeal mask airway (LMA) with the standard bronchoscopy-guided PDT technique in ICU patients requiring elective tracheostomy.MethodsThis randomized controlled study was conducted at Ain Shams University Hospital’s Critical Care Department from December 4th, 2021, to December 3rd, 2022. The study population included 60 critically ill patients admitted to the ICU. Thirty patients were randomly assigned to the real-time ultrasound-guided LMA-assisted group, and 30 patients were randomly assigned to the bronchoscopy-guided technique. The primary study outcome was the procedure time, and the secondary outcomes included procedure-related complications rate and cost-effectiveness.ResultsThe real-time ultrasound-guided LMA-assisted group had significantly shorter procedure time (median 17 [IQR: 15–20] min vs. 35 [IQR: 28–39] min, p < 0.001) and lower equipment damage (0% vs. 20%, p = 0.024) during the procedure compared to the bronchoscopy-guided group. Additionally, the cost of tracheostomy was significantly lower in the real-time ultrasound-guided LMA-assisted group (median: 300 vs. 800 USD, p < 0.001). The real-time ultrasound-guided LMA group had a lower major complications rate than the bronchoscopy-guided group (36.7%) vs. 3.3%, p = 0.002).ConclusionsThe study demonstrated that real-time ultrasound-guided LMA-assisted PDT had shorter procedure time, reduced equipment damage, lower costs, and was associated with lower complications when compared to the bronchoscopy-guided technique. These findings suggest that ultrasound guidance can enhance the efficiency and cost-effectiveness of PDT procedures.

Prognostic Factors in Oral Squamous Cell Carcinoma: Systematic Review and Meta-Analysis.

To evaluate current evidence on prognostic factors in oral squamous cell carcinomas (OSCCs), through a comprehensive meta-analysis of a total of 255 primary-level studies (63,114 patients). MEDLINE, Embase, Web of Science, and Scopus were searched before January 2024. The risk of bias was analyzed using the Quality in Prognosis Studies tool. Among the main influential parameters have been lymph node involvement in any of the measured forms, cN (overall survival: HR = 2.20, 95% CI = 1.98-2.45, p < 0.001; disease-specific survival: HR = 1.95, 95% CI = 1.44-2.65, p < 0.05; disease-free survival: HR = 2.13, 95% CI = 1.77-2.56, p < 0.001), pN (overall survival: HR = 2.04, 95% CI = 1.64-2.54, p < 0.001; disease-specific survival: HR = 2.83, 95% CI = 1.68-4.77, p < 0.001; disease-free survival: HR = 2.73, 95% CI = 1.96-3.81, p < 0.001) and extracapsular spread (overall survival: HR = 2.12, 95% CI = 1.81-2.47, p < 0.001; disease-specific survival: HR = 2.08, 95% CI = 1.43-3.03, p < 0.001; disease-free survival: HR = 2.27, 95% CI = 1.92-2.69, p < 0.001). In relation to the T-parameter, invasion depth greater than 5 mm strongly influenced mortality (overall survival: HR = 3.19, 95% CI = 1.74-5.84, p < 0.001; disease-free survival: HR = 1.97, 95% CI = 1.22-3.20, p = 0.006). The M parameter has been the most relevant negative prognostic factor-although with less robust results due to the lack of primary level studies: cM (overall survival: HR = 2.95, 95% CI = 2.09-4.17, p < 0.001; disease-specific survival: HR = 6.26, 95% CI = 1.54-25.42, p = 0.01; disease-free survival: HR = 2.78, 95% CI = 1.57-4.93, p < 0.001); pM (overall survival: HR = 5.19, 95% CI = 1.94-13.90, p = 0.01). The risk of death and recurrence is increased if the diagnosis is achieved when the neck nodes are affected, the tumor is large, or has given rise to distant metastases, which points to the imperative need to implement measures for improving the early diagnosis of the disease by acting on all the actors responsible for the diagnostic delay of OSCC.

How to Peer Review a Systematic Review: A Peer-Reviewer's Guide to Reviewing Reviews.

Systematic reviews hold significant academic weight, but poor execution can render them misleading and unreliable. To help improve the quality of systematic reviews, the peer review process plays a crucial role. Peer reviewing systematic reviews requires a distinct skill set compared to reviewing primary research studies. Systematic reviews differ in their methodology and reporting standards, necessitating a structured approach to evaluation. This commentary offers guidance on best practice when peer reviewing systematic reviews, with an emphasis on synthesis of quantitative data from clinical trials. In this article, nine key topics are covered, namely correct classification of review type, adherence to systematic methods, pre-registration, methodological and reporting quality, search strategy evaluation, risk of bias assessment, evidence synthesis methods, data and code availability, and use of standardized assessment tools. By helping to ensure best practice is followed for each of these topics, peer reviewers can play a crucial role in upholding the methodological integrity of systematic reviews, ensuring they contribute reliable and meaningful evidence to the scientific literature.

The Social Vulnerability Index and Incidence of Alzheimer Disease in a Population-Based Sample of Older Adults.

The primary study objective was to examine the association between Social Vulnerability index (SVI) and risk of incident Alzheimer disease (AD) and rate of cognitive decline. This is a secondary analysis of data from the Chicago Health and Aging Project, a population-based cohort study. Participants were recruited through door visits, were at least 65 years of age at enrollment, and lived in one of 4 Chicago communities representing 24 US census tracts. The association of SVI with clinically diagnosed incident AD was examined using a logistic regression model and global cognitive decline using a linear mixed-effects model. A total of 6,781 participants were in this study, with a mean age of 72 years, representing over 60% Black participants and over 60% female participants, and with a mean of 12 years of education. Over 90% of Black participants were in tracts above 50% or higher SVI, and approximately 87% of White participants were in tracts with SVI 50% or less. Participants in tracts with SVI above 50th to 75th percentiles had OR = 2.23 (95% CI 1.23-4.05) for clinical AD, and participants in tracts greater than the 75th percentile had OR = 2.04 (95% CI 1.03-4.04). Participants in more vulnerable tracts had greater incident AD risk than participants in less vulnerable tracts. The annual rate of global cognitive decline was 0.055 SD units (SDU) for participants below the 25th SVI percentile. The annual rate of global cognitive decline was faster by 0.010 SDU (approximately 18% faster, p = 0.025) in those above the 50th-75th percentile and by 0.014 SDU (approximately 25% faster, p = 0.005) in participants above the 75th percentile than in participants below the 25th SVI percentile. Most Black participants who lived in areas with higher SVI that had over twice the risk of incident AD than most White participants who lived in areas with lower SVI, showing a higher social burden in Black older adults. There was no statistically significant race difference in incident AD after adjusting for SVI. SVI should be accounted for when examining race differences in AD.

Prevalence of Olfactory Dysfunction among Postpartum Women and Impact of SARS-CoV-2 Infection During Pregnancy.

Olfactory dysfunction resulting from COVID-19 has imparted a lasting impact on olfaction among the general public, including pregnant women contracting SARS-CoV-2 infection. While olfactory dysfunction can impact physical, mental, and psychosocial well-being, there has been little research on olfaction during pregnancy and postpartum, nor the impact of SARS-CoV-2 infection on olfaction while pregnant. Therefore, the primary study aims are to evaluate olfaction in the postpartum period and determine the impact of antecedent SARS-CoV-2 infection. We recruited two cohorts of postpartum women, those with a history of SARS-CoV-2 infection before or during pregnancy (COVID cohort; n = 109) and those without (non-COVID cohort; n = 226), and evaluated their olfaction during the postpartum period by administering the University of Pennsylvania Smell Identification Test. Participants were queried about demographics, past SARS-CoV-2 infections, self-reported sense of smell (both in overall ability to smell and for the presence of qualitative smell issues such as parosmia and phantosmia), and perceived cause of smell loss, if any. We found significantly fewer postpartum women with normosmia capabilities in both COVID (27%) and non-COVID (46%) cohorts compared to normative data for aged-matched (30-39 years) women (83%). Women in the non-COVID cohort had significantly higher UPSIT scores and mean subjective olfaction ratings than those in the COVID cohort (95% CI [0.77,2.41] and 95% CI [-0.83,7.34], respectively). This study reflects the largest published cohort of postpartum women evaluated for olfactory function with standardized psychophysical testing. Our findings suggest both postpartum and SARS-CoV-2 infection are associated with diminished smell function.

Addressing data management and analysis challenges in viral genomics: The Swiss HIV cohort study viral next generation sequencing database.

Numerous HIV related outcomes can be determined on the viral genome, for example, resistance associated mutations, population transmission dynamics, viral heritability traits, or time since infection. Viral sequences of people with HIV (PWH) are therefore essential for therapeutic and research purposes. While in the first three decades of the HIV pandemic viral genomes were mainly sequenced using Sanger sequencing, the last decade has seen a shift towards next-generation sequencing (NGS) as the preferred method. NGS can achieve near full length genome sequence coverage and simultaneously, it accurately encapsulates the within-host diversity by characterizing HIV subpopulations. NGS opens new avenues for HIV research, but it also presents challenges concerning data management and analysis. We therefore set up the Swiss HIV Cohort Study Viral NGS Database (SHCND) to address key issues in the handling of NGS data including high loads of raw- and processed NGS data, data storage solutions, downstream application of sophisticated bioinformatic tools, high-performance computing resources, and reproducibility. The database is nested within the Swiss HIV Cohort Study (SHCS) and the Zurich Primary HIV Infection Cohort Study (ZPHI), which together enrolled 21,876 PWH since 1988 and include a biobank dating back to the early nineties. Since its initiation in 2018, the SHCND accumulated NGS sequences (plasma and proviral origin) of 5,178 unique PWH. We here describe the design, set-up, and use of this NGS database. Overall, the SHCND has contributed to several research projects on HIV pathogenesis, treatment, drug resistance, and molecular epidemiology, and has thereby become a central part of HIV-genomics research in Switzerland.

Abstract 6193: Population-level interventions to prevent alcohol-related cancers: A scoping review

Alcohol use and misuse are associated with at least eight types of alcohol-related cancers, namely cancers of the oral cavity, pharynx, larynx, esophagus (squamous cell carcinoma only), stomach, colon, liver (hepatocellular carcinoma only), and breast in females. Population-level interventions that reduce alcohol use may mitigate this cancer burden. This scoping review examines and synthesizes evidence on the effectiveness of these interventions on cancer-related outcomes. We followed the PRISMA-ScR guidelines and searched MEDLINE and Web of Science for English-language articles (1987 onwards) using keywords and terms related to interventions, alcohol use, and cancer in titles and abstracts. Only original quantitative research articles evaluating population-level interventions’ impact on cancer outcomes were included. Initial data extraction was conducted using Elicit, an AI-based research tool, which was reviewed by the research team for accuracy. Out of 1,531 studies, 68 full-texts were assessed for eligibility, and 35 were included in the final qualitative synthesis. Most studies were focused on Europe (N=17), Asia and Oceania (N=11), and North America (N=4). Study designs included randomized controlled trials (N=6), observational studies (N=18), and simulation models (N=11). The most common cancer-related outcome was cancer incidence (N=19), followed by cancer mortality (N=11) and knowledge/awareness of alcohol as a carcinogen (N=10). Primary prevention studies (N=31) focused on reducing alcohol-related cancers through educational or media initiatives (N= 13), adherence to clinical guidelines (N=11), and alcohol pricing policies (N=6) like alcohol taxes and minimum unit pricing. Five studies addressed secondary prevention via educational and clinical interventions like screening, health assessment, and treatment of alcohol misuse. No tertiary prevention studies were identified. This scoping review identified several gaps in our understanding of population-level interventions for alcohol-related cancers. Given the number of ever and current drinkers globally, additional studies are needed on secondary and tertiary prevention strategies. Few studies evaluated alcohol pricing policies despite the long-standing evidence supporting its effectiveness in reducing alcohol use. Meeting cancer prevention guidelines may reduce cancer incidence and mortality, and future research should focus on the most effective and cost-effective ways of translating recommendations into interventions in real-world contexts. Citation Format: Priyanka Basu, Jovan Julien, Sangeeta Goswami, Anton L.V. Avanceña. Population-level interventions to prevent alcohol-related cancers: A scoping review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6193.

Dietary practice and associated factors among patients with type 2 diabetes mellitus in the horn of Africa: a systematic review and meta-analysis

BackgroundDietary practices have a valuable impact on lowering the risk of complications associated with diabetes mellitus. The countries in the horns of Africa do not follow properly the approaches of dietary recommendation to prevent diet related complications among patients with type-2 diabetes mellitus. Numerous primary observational studies on the relationship between diabetes mellitus and dietary practices have been conducted in the horns of Africa up to this point. Inconsistent and variable findings across different countries in the Horn of Africa hinder the establishment of suitable intervention designs. To address this issue, this systematic review and meta-analysis was conducted.MethodWe searched PubMed, Medline, EMBASE, Google Scholar, and Google for studies that had been conducted in the Horn of Africa. Searches were using the English language. A preferred reporting item for systematic reviews and meta-analysis (PRISMA) checklist was used. Two authors independently reviewed the studies. The effect size of the meta-analysis was dietary practices and the adjusted odds ratio (AOR) of the associated factors. Studies were summarized on the use of dietary practices quantitatively and qualitatively. A random-effects model was conducted to obtain the pooled estimates.ResultA total of twenty-one observational studies with 5,117 study participants were included 5,117 in this review. The pooled proportion of good dietary practices among patients with type 2 diabetes mellitus in the Horn of Africa was 44.0% (95% CI: 36.0–51.0). The pooled odds ratio showed that a significant association was found between educational status (AOR = 2.57; 95% CI: 1.79–3.70). Age of the patient (AOR = 2.59; 95% CI: 2.16–3.11), Wealth index status (AOR = 3.64; 95% CI: 2.71–4.89), nutrition education (AOR = 3.35; 95% CI: 2.50–4.49), knowledge about diabetes mellitus (AOR = 2.59; 95% CI: 1.18–3.59) and patients’ attitude about diabetes mellitus (AOR = 2.64; 95% CI: 1.64–4.29).ConclusionThe overall pooled proportion of good dietary practices among patients with type-2 diabetes mellitus was below half. Educational status wealth index, nutrition education, dietary knowledge and attitude about diabetes mellitus were significantly associated with good dietary practices. Therefore, establishing strategy to promote nutrition education at the health care facilities and raising awareness about the significance of healthy eating habits through various platforms can improve patients’ eating behaviors.

Cognitive Biases and Heuristics in Surgical Settings: A Systematic Review.

This systematic review aimed to identify cognitive biases and heuristics experienced by surgeons in operative settings and the impact these biases and heuristics have on patient care. Cognitive biases and heuristics are systematic errors in thinking that can affect clinical decisions. Both are noted in surgical settings and are a risk to patient safety. This review was conducted in accordance with PRISMA guidelines and PROSPERO registered (CRD42023432099). Five major databases were searched from inception to 28th August 2022, with an updated search on 27th January 2024. Original primary research studies in English were included, with relevant risk of bias tools employed for each study. 21 papers were included. 38 biases were identified across six experiments, five analyses, and ten survey studies. Confirmation bias, anchoring, risk aversion, and overconfidence bias were the most represented. Risk of bias was moderate across most studies. Cognitive biases and heuristics were found to influence surgical outcomes and six studies cited a negative impact on patient care, with one associating biases with fatal outcomes. Biases and heuristics contribute to surgical errors and never events, and will continue to do so until they are recognised and addressed. Implementing debiasing strategies, such as mindfulness training and deliberate reflection, was found to reduce surgical errors in two studies. This review highlights the need for experimental studies, which are essential for understanding how and why biases lead to negative outcomes and for evaluating further debiasing interventions. We propose directions for future research and system changes.

Non-home discharge in the octogenarian and nonagenarian colorectal cancer population: a retrospective cohort study

PurposeThis study aims to determine the rate of non-home discharge (NHD) and identify factors associated with non-home discharge in a colorectal cancer (CRC) population of adults aged 80 years and older. This is the first study looking specifically at NHD as an outcome in the ≥ 80 years colorectal cancer cohort.MethodsThis is a single-centre retrospective exploratory observational study from a high-volume colorectal cancer unit. Patients aged ≥ 80 years from a prospectively collected CRC database from 2013 to 2020 were included. Electronic medical records were assessed to obtain demographic, clinical, functional and discharge data. Univariable and multivariable logistic regression analyses were performed to identify factors associated with NHD the primary study outcome. Secondary outcomes included discharge disposition and functional decline.ResultsTwo hundred forty-two patients aged ≥ 80 years underwent CRC resection. Alo, 234 patients and 221 patients were included in the overall and subgroup non-home discharge analysis. The non-home discharge rate was 19.9% in the cohort that pre-operatively were from home. On multivariable logistic regression, after adjusting for other significant variables, frailty (odds ratio (OR) 2.91, 95% CI 1.25–6.75, p = 0.013), severe complications (OR 3.92, 95% CI 1.40–10.97, p = 0.009) and an open operation (OR 3.93, 95% CI 1.87–8.24, p < 0.001) were associated with a significantly higher rate of NHD. The incidence of functional decline from those at home was 72.4% in the non-home discharge group and 16.7% in those who returned home (p < 0.001).ConclusionThis is the first paper describing the overall rate and identifying factors associated with non-home discharge specifically in the ≥ 80 years CRC population. Prospective studies are required to investigate causality and interventions to reduce non-home discharge rates.

Abstract 5876: ctDNA as predictor for systemic therapy response in patients with colorectal cancer: A systematic review and meta-analysis

Abstract Background: The response to systemic therapy against metastatic colorectal cancer (mCRC) is currently assessed by radiologic imaging. However, an increasing number of studies have shown that circulating tumor DNA (ctDNA) as liquid biopsy can be used as an alternative method to assess therapy efficacy. We conducted a systematic review with subsequent meta-analysis of primary studies to assess the predictive value of sequential liquid biopsies in patients with colorectal cancer treated with systemic therapy. Methods: Randomized, non-randomized, as well as prospective observational studies, reporting on the change in ctDNA concentration in total cell-free DNA over the course of systemic therapy of patients treated for metastatic colorectal cancer to predict treatment response according to RECIST criteria were included. Results: Forty-one studies involving 4546 evaluable patients with metastatic colorectal cancer were included in the meta-analysis. ctDNA increase during systemic therapy as compared to baseline was significantly associated with progression-free survival (HR: 2.47, 95%CI: 1.97-3.10) and overall survival (HR: 2.18, 95%CI: 1.66-2.86), which were reported in 31 and 22 studies, respectively. Conclusion: Longitudinal plasma-based ctDNA liquid biopsy has prognostic value and may help to identify those patients that benefit of continuing therapy or therapy switch. Although further standardization and randomized controlled clinical trials are required, based on the available data, we recommend longitudinal ctDNA measurements to be included in clinical practice and inclusion in the RECIST criteria. Protocol registration: The protocol for this review was registered on PROSPERO (CRD42023420012). Citation Format: Anja Holz, Bidisha Paul, Antonia Zapf, Klaus Pantel, Simon A. Joosse. ctDNA as predictor for systemic therapy response in patients with colorectal cancer: A systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5876.

Abstract 3817: Using gene-environment interactions to explore pathways for colorectal cancer risk

Abstract Colorectal cancer (CRC) is a major public health concern, with incidence rates increasing over the past decades particularly among younger adults. The identification of novel intervention targets for CRC prevention becomes imperative. In the present study we explored patterns of genes and pathways underlying the observed associations using estimates from genome-wide interaction studies (GWIS) of 15 exposures with established or putative CRC risk. GWIS estimates were derived from a pool of 36 primary studies including up to 38, 578 CRC cases and 49, 658 controls. The 15 risk factors included body mass index (BMI), height, physical activity, smoking, type 2 diabetes, hormone replacement therapy (HRT), and intake of non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin, alcohol, calcium, fiber, folate, fruits, processed meat, red meat, and vegetables. We conducted pathway-environment interaction analysis for CRC risk to identify associated pathways using the adaptive combination of Bayes Factors (ADABF) framework. The pathway findings were further investigated by exploring the relevance of the enriched genes for CRC using publicly available resources [hallmarks of cancer, Open Targets Platform (OTP)]. Using the ADABF, a total of 1, 973 pathways were enriched out of the 2, 950 analyzed for at least one exposure. Additionally, within the enriched pathways, 1, 227 genes showed evidence of interaction with at least one exposure. A high overlap of associated genes was observed between the three exposures with higher number of associated genes: BMI (n=768), followed by smoking (n=223) and NSAIDs (n=173), while for remaining exposures the number of enriched genes ranged from 3 to 27. Data were available for 811/1, 227 genes in the OTP, of which an overall association score &amp;gt;0.05 was found for 241 coding genes. Fifty percent of the genes (617/1, 227) mapped to at least one hallmark of cancer, most of which (388/617) pertained to the Sustaining Proliferative Signaling hallmark. Our findings reflect previously established pathways for CRC risk, such as mitogen-activated protein kinase (MAPK), Notch, PI3K/AKT, transforming growth factor-β (TGF-β), Wnt, and participating genes, for BMI, NSAIDs, and smoking, and highlight the emerging importance of several less studied genes (such as argonaute RISC component, UDP-glucuronosyltransferase, and taste receptor coding genes). Common pathways were found for several combinations of exposures (mostly for BMI, NSAIDs, and smoking), potentially suggesting common underlying mechanisms. The results of the present analysis can be used in future investigations, and, if confirmed, may aid in elucidating the etiological associations and inform personalized CRC prevention strategies. Citation Format: Emmanouil Bouras, Ren Yu, Andre E. Kim, Georgios Markozannes, Neil Murphy, Demetrius Albanes, Laura N. Anderson, Elizabeth L. Barry, Hermann Brenner, Peter T. Campbell, Robert Carreras-Torres, Andrew T. Chan, Jenny Chang-Claude, Iona Cheng, Matthew A. Devall, Niki Dimou, David A. Drew, Stephen B. Gruber, Andrea Gsur, Li Hsu, Jeroen R. Huyghe, Temitope O. Keku, Anshul Kundaje, Loïc Le Marchand, Li Li, Brigid M. Lynch, Victor Moreno, John Morrison, Christina C. Newton, Nikos Papadimitriou, Andrew J. Pellatt, Anita R. Peoples, Paul D. Pharoah, Elizabeth A. Platz, Conghui Qu, Joel Sanchez Mendez, Robert E. Schoen, Mariana C. Stern, Claire E. Thomas, Caroline Y. Um, Pavel Vodicka, Veronika Vymetalkova, Emily White, Alicja Wolk, Anna H. Wu, Marc J. Gunter, W. James Gauderman, Ulrike Peters, Marina Evangelou, Konstantinos K. Tsilidis. Using gene-environment interactions to explore pathways for colorectal cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3817.

Cybersickness and discomfort from head-mounted displays delivering fully immersive virtual reality: A systematic review.

To synthesize existing knowledge on the phenomenon of cybersickness and discomfort associated with the use of HMDs in delivering fully immersive VR experiences within educational contexts. Virtual reality (VR) plays an increasingly important role in education; however, head-mounted displays (HMDs) may trigger cybersickness and discomfort. A systematic review (PROSPERO: CRD42024583656) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed, CINAHL, Cochrane Library and Scopus databases were searched to identify primary studies in English or Italian, published from 2013 to 2024. Twenty-five studies were included. Ad hoc questionnaires followed by the Simulator Sickness Questionnaire and the Motion Sickness Assessment Questionnaire were mainly used to detect cybersickness. In 12 studies, inconsistent or very low scores of cybersickness were reported. Oculomotor disturbances were the most frequently documented negative effects, followed by disorientation. Discomfort was assessed in eight studies, mainly with ad hoc questionnaires, with five of them reporting inconsistent or minimal discomfort. Students and professionals should be informed about the possibility of some adverse effects, especially if they undertake daily activities after the educational sessions (e.g. oculomotor issues and driving).

Mineralocorticoid receptor antagonist (MRA) use in UK heart failure care: a national primary care cohort study

Background and aimsMineralocorticoid receptor antagonists (MRAs) reduce mortality and hospitalisation in heart failure with reduced ejection fraction (HFrEF) but are underused, despite recommendation in key guidelines. Identifying the factors contributing...

Breastfeeding and Health Outcomes for Infants and Children: A Systematic Review.

Our understanding of the benefits of breastfeeding and the consumption of human milk for specific infant outcomes and the magnitude of those benefits continues to evolve. Review the evidence on the association between breastfeeding and child health outcomes. Systematic literature searches in MEDLINE, Embase and CINAHL for English-language articles published from 2006 to August 14, 2024. Existing systematic reviews (ESRs) and primary studies comparing various breastfeeding exposures and child health outcomes among term infants in developed countries. Abstracted data on study design, demographics, breastfeeding exposures and referents, and outcomes. Results of ESRs were synthesized alongside those of newer primary studies. Twenty-nine ESRs and 145 primary studies were included. An association indicating a reduced risk from more versus less breastfeeding was apparent for moderate-to-severe respiratory and gastrointestinal infections, otitis media, allergic rhinitis, asthma, malocclusion, inflammatory bowel disease, type 1 diabetes, rapid weight gain and growth, obesity, systolic blood pressure, childhood leukemia, and infant mortality. There was no clear threshold of breastfeeding duration that appeared to be most beneficial for any outcome. There was little data on any associations varied by mode of breastfeeding or source of breastmilk. Observational studies with risks of bias related to confounding, missing data and a lack of consistency in measurement and reporting of breastfeeding exposures. Breastfeeding is associated with beneficial effects for several infant and child outcomes. Further research that addresses the limitations of existing studies is needed to continue to inform national initiatives.

Overtreatment of Older People Near End of Life: A Qualitative Scoping Review of Modalities, Drivers, and Solutions.

This study aimed to understand the drivers better to help minimise further risks of overtreatment for older people near the end of life (dysthanasia). A systematic scoping review of any publication types released in Medline, Embase, and Cochrane databases from January 2002 to January 2023 were used. Deductive thematic analysis was conducted independently and concurrently by paired reviewers. Risk of bias assessed for primary studies only using a modified version of the COREQ checklist. Twenty-one studies met the inclusion criteria. Determinants included healthcare system factors, patient-centered care, family and caregiver, and clinician perspectives. This review confirms that despite almost two decades of recognition of the potential harms of overtreatment near the end of life, society, patients, and health systems have a role to play in reducing and addressing the determinants. We offer a range of solutions for clinicians, health service managers, and members of the public to consider.

Genital bleeding in prepubertal girls: a systematic review

IntroductionThis systematic review aims to collate evidence of the causes of genital bleeding, other than child sexual abuse and accidental injuries, presenting in prepubertal girls. It provides an update to...

Role of Glucagon-Like Peptide-1 on Amyloid, Tau, and α-Synuclein: Target Engagement and Rationale for the Development in Neurodegenerative Disorders.

Glucagon-like Peptide-1 (GLP-1) and Glucagon-Like Peptide-1 receptor agonist (GLP-1 RA) administration has been associated with neuroprotective effects in neurodegenerative disorders. We conducted a comprehensive synthesis of known effects of GLP-1 and GLP-1 RAs on the cognitive, cellular, and molecular changes in neurodegenerative diseases. We examined preclinical and clinical paradigms that investigated changes in neurodegenerative disease pathology following administration of GLP-1 and GLP-1 RAs. Relevant articles were retrieved through OVID (MedLine, Embase, AMED, PsychINFO, JBI EBP Database), PubMed, and Web of Science from database inception to September 27th, 2024. Primary studies investigating the aforementioned changes following GLP-1 and GLP-1 RA administration were retrieved for analysis (n = 62). GLP-1 and GLP-1 RAs (i.e. dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, and tirzepatide) improved cognitive and motor function in neurodegenerative diseases in preclinical and clinical paradigms. Additionally, GLP-1 and GLP-1 RAs were associated with modulating changes in neuroinflammation, oxidative stress, and proliferative pathways. We observed that GLP-1 and GLP-1 RAs modulate molecular and cellular changes known to govern the phenomenology of neurodegenerative diseases. Future research should examine the interaction between signaling molecules, neuronal subpopulations, and cognitive effects affected by GLP-1 and GLP-1 RA administration.