Search

Background: Routine epidemiological data are essential for monitoring the effectiveness of preventive chemotherapy (PC), optimizing resource allocation, and addressing the evolving needs in the elimination of soil-transmitted helminthiasis (STH). This study assesses the prevalence, intensity, and associated risk factors of STH following five rounds of albendazole-based PC in three implementation units (IUs) in Ondo State, Nigeria., Methodology: Fresh stool samples were collected from 2,093 children aged 5-14 years across 45 systematically selected schools in three IUs: Ese-Odo, Irele, and Ile-Oluji. The samples were analyzed using the Kato-Katz technique. Additionally, standardized questionnaires were administered to gather data on demographics and access to water, sanitation, and hygiene (WASH) resources. Data analysis was conducted using R software version 4.3.2, with a 95% confidence interval., Principal Findings/conclusions: The parasitological data indicated a significant decline in the aggregated prevalence of STH across the three IUs. In Ese-Odo, the prevalence decreased to 25.8% (95% CI: 23.0-29.0) from 39% at baseline (d = -34%, p = 0.00). In Irele, prevalence dropped to 9.7% (95% CI: 7.6-12.0) from 51.3% at baseline (d = -81%, p = 0.00), and in Ile-Oluji, prevalence was reduced to 6.4% (95% CI: 4.6-8.7) from 23% at baseline (d = -72.2%, p = 0.00). The most prevalent STH species was Ascaris lumbricoides, with infection rates of 25.5%, 9.4%, and 6.4% in Ese-Odo, Irele, and Ile-Oluji, respectively, followed by Trichuris trichiura in Ese-Odo (2.7%) and Irele (0.4%), while hookworm infections were detected only in Irele (0.7%). The majority of infections were of low intensity in Ese-Odo (91.0%), Irele (96.8%), and Ile-Oluji (100%). Access to improved sanitation (17.7%, 54.9%, and 58.2%), improved water sources (24.5%, 66.1%, and 69.8%), and handwashing facilities (9.0%, 39.6%, and 25.4%) was suboptimal and significantly varied across Ese-Odo, Irele, and Ile-Oluji, respectively (p < 0.05). Open defecation rates were high in Ese-Odo (54.2%), Irele (36.3%), and Ile-Oluji (34.3%). In Ese-Odo, significant risk factors for STH infection included the use of hand-pump boreholes (AOR: 2.44, 95% CI: 1.23-4.88, p = 0.01), unprotected dug wells (AOR: 3.25, 95% CI: 0.96-11.36, p = 0.06), ventilated improved pit latrines (AOR: 3.95, 95% CI: 1.13-16.1, p = 0.04), pit latrines without a slab (AOR: 2.19, 95% CI: 1.27-3.8, p = 0.01), and failure to use soap after defecation, both when soap was available (AOR: 12.09, 95% CI: 1.86-112.97, p = 0.01) and when soap was unavailable (AOR: 8.19, 95% CI: 1.73-76.65, p = 0.04). In Irele, access to protected dug wells was marginally significant (AOR: 1.79, 95% CI: 0.96-3.21, p = 0.06), while in Ile-Oluji, access to river water emerged as a significant risk factor (AOR: 7.97, 95% CI: 1.81-58.58, p = 0.02). The use of rainwater was found to be protective across all three IUs. These findings demonstrate significant progress in reducing STH prevalence across the three IUs following PC interventions. However, the data underscores the need for enhanced efforts to improve access to and use of WASH facilities to achieve STH elimination., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Mogaji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We performed a clinical trial in patients with non-muscle-invasive (NMI) urothelial cancer randomized (2:1) to the EGFR tyrosine kinase inhibitor erlotinib or placebo (either orally once weekly × 3 doses prior to scheduled surgery) to assess for a difference in EGFR phosphorylation in tumor-adjacent normal urothelium <24 hours post-study dose and tolerance of weekly erlotinib therapy. Thirty-seven volunteers (6 female/31 male; mean age 70; 35 White/2 non-White) with confirmed or suspected NMI urothelial cancer were enrolled into either erlotinib (n = 24; 900 mg-13, 600 mg-11) or placebo (n = 13). IHC assessment of phosphorylated and total EGFR in tumor-adjacent normal urothelium (20 erlotinib and 9 placebo subjects) or tumor (21 erlotinib and 11 placebo subjects) at study end showed no significant difference between those receiving erlotinib or placebo. This was also true for other assessed tissue biomarkers (phosphorylated ERK, ERK, E-cadherin, p53, and Ki67). Adverse events were more common, in a dose-related fashion, in participants receiving erlotinib, e.g., 38% experienced grade 1 with rare grade 2 diarrhea and skin toxicity versus 8% in placebo. Clinically insignificant but statistically significant (P = 0.001) elevations in serum total bilirubin and creatinine were observed in participants receiving erlotinib. Serum erlotinib and metabolite concentrations (OSI-420) confirmed compliance in all subjects receiving erlotinib and did not significantly differ between the 600 and 900 mg doses. Despite compelling preclinical and clinical data for targeted EGFR inhibition in bladder cancer prevention, these data do not support the use of weekly erlotinib therapy to prevent progression of NMI bladder cancer. Prevention Relevance: We evaluated the potential of erlotinib in preventing cancer by performing a randomized, double-blind, placebo-controlled trial of weekly erlotinib therapy in participants undergoing surgical removal of suspected noninvasive bladder neoplasia. Weekly erlotinib therapy was tolerated with common grade 1 to 2 toxicities but without evidence of beneficial effect upon urothelial tissue. See related Spotlight, p. 7., (©2024 American Association for Cancer Research.)

Despite rapid advances in the field of HIV prevention and treatment, unacceptably high global HIV incidence rates highlight the ongoing need for effective HIV prevention interventions for populations at risk for HIV acquisition. This article provides an updated review of the current data surrounding HIV prevention strategies, including treatment as prevention (TasP), preexposure prophylaxis (PrEP), and postexposure prophylaxis (PEP), as well as advances in sexually transmitted infection biomedical prevention. This review provides an overview of the multiple PrEP modalities that are available globally, such as oral PrEP, injectable cabotegravir, and the dapivirine vaginal ring, and describes their respective clinical trials, efficacies, and regulatory approvals. We also discuss ongoing research into novel PrEP agents, such as broadly neutralizing antibodies, and efforts toward HIV vaccine development.

Objectives: To evaluate the effectiveness and cost-effectiveness of integrating seasonal malaria chemoprevention (SMC) with mass drug administration for helminth control among school-aged children living in communities where the burden of malaria and helminths is high in Ghana, West Africa., Methods: This cluster randomised controlled trial will enrol 1200 children aged 5-10 years. Eligible children randomised to intervention clusters will receive SMC drugs (sulphadoxine-pyrimethamine plus amodiaquine) and anthelminthic drugs for soil-transmitted helminths-(albendazole), and for schistosomiasis (praziquantel), while children randomised to control clusters will receive SMC drugs alone. Pre- and post-intervention blood, urine and stool samples will be collected from children in both clusters. The effectiveness of the concomitant delivery will be determined by checking whether the combination of SMC and anthelminthic drugs prevents anaemia in the children randomised to the intervention clusters compared to the children in the control clusters. Cost analysis and cost-effectiveness of this integrated delivery approach will be determined by estimating the incremental costs and effects of co-administration of SMC drugs with mass drug administration of anthelminthic drugs compared to SMC alone, including cost savings due to cases of moderate and severe anaemia averted., Expected Findings: The findings of this study will provide evidence to inform public health recommendations for an integrated control of malaria and helminths among children living in the poorest countries of the world., (© 2024 The Author(s). Tropical Medicine & International Health published by John Wiley & Sons Ltd.)

Purpose of Review: The purpose of this review is to summarize the most recent evidence on surgical management, strategies to reduce tumor recurrence, and surveillance regimens in patients diagnosed with upper tract urothelial carcinoma (UTUC) and elected for radical treatment., Recent Findings: Minimally invasive surgery is gaining momentum in the surgical management of UTUC. Chemoprophylaxis is still the gold standard to reduce intravesical recurrence after radical nephroureterectomy (RNU). Novel surveillance strategies have been proposed to adapt follow-up regimens to patients' characteristics., Summary: Minimally invasive surgery has been associated with comparable oncological outcomes to the open approach while improving postoperative morbidity. In these cases, bladder cuff excision (BCE) is mostly performed by an extravesical approach, that demonstrates a noninferiority compared to the intravesical one in terms of oncological outcomes. Although lymphadenectomy is recommended in patients with high-risk tumors, its benefits are still unclear. Currently, there is a lack of recent prospective trials on chemoprophylaxis to reduce intravesical recurrence post RNU, making single-dose postoperative chemotherapy instillation the standard treatment. Although novel risk stratification models were released by international urological guidelines, their validity is mainly nonevidence-based. Risk-adapted follow-up strategies incorporating cystoscopy and cross-sectional imaging accounting for individual patient factors should be implemented., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Implemented in 17 countries to date, seasonal malaria chemoprevention (SMC) is a recommended strategy to prevent childhood malaria in areas with seasonal transmission of P. falciparum through monthly administration of antimalarial medicines. Understanding the costs and resource requirements of SMC delivery is necessary for effective planning and resource allocation. This systematic literature review aims to assess the evidence on the cost and cost-effectiveness of SMC delivery., Methods: Following PRISMA guidelines, five databases were systematically reviewed to identify evidence on SMC costs and cost-effectiveness published between 2012 and 2023. Studies with defined costing methodologies and cost output measures were included, excluding those relying solely on mathematical modeling. Two reviewers assessed each study for eligibility and extracted cost data, which were adjusted for inflation. Quality assessment was completed using the CHEERS checklist., Results: Six costing studies were identified spanning nine countries. Four studies examined costs during an SMC pilot or introduction, one during scale-up, and one costed newly established SMC campaigns through a multi-country project. Costs were examined at country level with the financial costs per child receiving a full course of SMC ranging from $1.71 to $12.46, while economic costs per child ranged from $2.11 to $29.06. Four studies included a cost effectiveness analysis with incremental cost-effectiveness ratios (ICERs) per clinical malaria case averted ranging from $5.41 to $138.03; ICER per disability-adjusted life year (DALY) averted from $24.51 to $182.88; and ICER per death averted from $688.86 to $18,418.81. Differences in cost estimates stemmed from different factors including variations in cost ingredients, scale of the intervention, and study perspectives., Discussion: The level of detail for reporting SMC costs and cost categories varied greatly by study as did the scale of intervention, limiting comparability as well as an understanding of the complete costs and resource requirements for SMC implementation. Cost evidence is not from mature programs but from pilots or relatively new campaigns. Costs incurred by households and costs of the integrated delivery of SMC with other health interventions were often overlooked. Adopting a standardized costing approach for mature SMC programmes could provide a better understanding of resource requirements and costs while enhancing study comparability across settings, better informing future resource allocation and improving efficiency., Competing Interests: Declarations. Ethics approval and consent to participate: Not Applicable. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Raquel González and colleagues discuss the drugs available to HIV-exposed children to prevent malaria infection and the urgent need to evaluate alternative agents., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 González et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Gastric adenocarcinoma (GAC) is the fourth leading global cause of cancer mortality and leading infection-associated cancer. High-incidence regions of GAC include Latin America and Eastern Asia. Immigrants from high-incidence regions maintain their GAC risk. GAC is a major U.S. cancer disparity, and its incidence rates are 2 to 10 times higher in non-White populations. Emerging guidelines recommend 3-year surveillance endoscopy for patients with high-risk gastric premalignant conditions (GPMC). Clinical trials of GPMC chemoprevention agents are lacking. We conducted a NCI Division of Cancer Prevention-funded, phase II placebo-controlled chemoprevention trial in patients with GPMCs (atrophic gastritis and intestinal metaplasia) with a highly bioavailable preparation of curcuminoids (Meriva). The trial sites in Puerto Rico and rural Honduras had important characteristics: (i) representative Caribbean and Mesoamerican populations, linked to large U.S. immigrant populations; (ii) high prevalence of Helicobacter pylori infection and GPMCs; (iii) the absence of turmeric and curcuminoids in local diets; and (iv) proven bidirectional collaboration with U.S. academic institutions. H. pylori-negative patients with GPMCs were randomized to the study drug (500 mg po bid) or placebo for 180 days (NCT02782949), with primary outcomes based upon histologic parameters. Principal study challenges included (i) an international regulatory environment; (ii) research infrastructure strengthening, particularly in Central America; (iii) participant recruitment in Honduras, wherein only 10% to 15% are H. pylori negative; (iv) the COVID-19 pandemic; and (v) natural disasters (three hurricanes). There were no losses to follow-up related to the pandemic or natural disasters. In conclusion, the south-south partnership provides a model for chemoprevention and translational studies in Latino populations with prevalent cancers, such as GAC., (©2024 American Association for Cancer Research.)

Introduction: Oral cancer is considered the sixth most common form of cancer worldwide. It causes significant morbidity and mortality, especially in low socioeconomic status groups. However, Cancer chemoprevention encompasses the use of specific compounds to suppress the growth of tumours or inhibit carcinogenesis. Natural products have been identified as one of the most significant sources of anti-cancer agents. Meanwhile, several synthetic drugs exhibit potential cytotoxicity and can induce a wide range of degenerative diseases., Aim of the Review: This review aims to determine the various plants, vegetables, and fruits possessing natural chemotherapeutic agents against oral cancer cells., Materials and Methods: A comprehensive review of findings reported in articles retrieved from searches of computerised databases, hand searches, and authoritative texts. Inclusion databases include PubMed, Medline, Web of Science, Scopus, and Scientific. Exclusion Computerised databases: Wikipedia or unknown sources., Results: Natural products have fewer side effects, high selectivity, low toxicity, and eliminate cancer cells. Thus, the application of natural products as alternative oral and other cancer therapies has recently demonstrated remarkable progress., Conclusion: Natural products have been widely used in developing oral anti-cancer drugs. Most of these natural products present bioactive chemical agents and novel mechanisms of action, such as the inhibition of tumour cell growth, the induction of apoptosis, DNA damage, and the inhibition of topoisomerases I and II. In future, the successful integration of natural products in oral cancer chemoprevention field depends on the advancement of molecular targeting, personalised approaches, and the exploration of novel drug delivery systems. Furthermore, integration of preclinical findings in clinical trials will be important for translating research into impactful interventions.

Background: Use of chemoprophylaxis for prevention of venous thromboembolism (VTE) after bariatric surgery is a generally accepted principle; however, the optimal strategy in terms of medication type and pre- and postoperative dosing is uncertain. In our healthcare system, four hospitals performed bariatric surgery and utilized differing protocols for VTE prophylaxis. The analysis sought to evaluate the association of differing prophylaxis strategies on bleeding and VTE occurrence., Methods: Adult patients who underwent laparoscopic sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) from 2018 to 2021 at four hospitals were studied. Patients were grouped by whether or not they received preoperative chemoprophylaxis. The primary outcome was postoperative bleeding, defined as requiring a blood transfusion or reoperation for bleeding within 30 days. Bivariate analyses were performed with Chi-square and Wilcoxon Rank tests where applicable. Multivariate logistic regression was performed for the outcome of postoperative bleeding., Results: A total of 2145 bariatric surgeries were evaluated (33.6% RYGB, 66.4% SG). Among 1712 patients who underwent surgery at Hospitals A, B, and C, 93.1% received preoperative VTE prophylaxis, compared with 1 patient (0.1%) among 433 patients operated on at Hospital D. Postoperative bleeding occurred more frequently in patients who received preoperative VTE prophylaxis versus those who did not (3.7% vs 1.1%; p < 0.01). After multivariable regression analysis, only RYGB (OR 3.59; p < 0.01) and preoperative VTE prophylaxis (OR 3.54; p = 0.02) were significantly associated with postoperative bleeding. Rates of VTE for patients receiving preoperative VTE prophylaxis or no prophylaxis were not significantly different (0.6% vs. 0.2%; p = 0.26)., Discussion: Preoperative VTE prophylaxis prior to bariatric surgery was associated with postoperative bleeding without differences in VTE occurrence. These results call into question the routine use of VTE chemoprophylaxis for all patients undergoing bariatric surgery and favor selective usage., Competing Interests: Declaration. Disclosure: Joseph E. Sanchez, Audra Reiter, Catherine S. Valukas, Whitney N Jones, Dominic J Vitello, Joanne Prinz, Yan Li, Eric S. Hungness, and Ezra N. Teitelbaum have no conflicts of interest or financial ties to disclose., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Keratinocyte carcinomas such as basal cell carcinomas and squamous cell carcinomas are a major burden affecting morbidity and mortality in solid organ transplant recipients (SOTRs). Best treatment includes frequent skin checks for early detection and surgery for high incidence of skin cancers. Sirolimus is an immunosuppressive drug which may reduce the burden of skin cancer but may be poorly tolerated when given orally. Topical sirolimus has been proven effective at reducing the burden of skin cancers in animal models, and its safety has long been established in children with tuberous sclerosis. A recent 12-week phase II trial of topical sirolimus suggested it was safe and effective at reducing the early signs of skin cancer in the absence of major side effects. The aim of the SiroSkin trial is to determine whether topical sirolimus can fill a major gap in current therapies by reducing the onset and number of new skin cancers thus reducing burden of disease and cost-effectiveness., Methods: Protocol for a multi-centred phase III, participant- and clinician assessor-blinded, placebo-controlled randomised trial in SOTRs. A minimum 146 participants randomised 1:1 will be treated with 1% topical sirolimus versus placebo applied to the face on a regular basis for 24 weeks. Participation is 24 months in total-24 weeks of treatment and 18 months of follow-up. Outcomes include the number of keratinocyte carcinomas at 24 weeks of treatment compared to placebo and then at 12 and 24 months after initiation of treatment. Analysis will be as per protocol and intention to treat., Discussion: The results of this trial will inform management strategies for skin cancers in SOTRs and provide evidence for cost-effectiveness., Trial Registration: Clinicaltrials.gov NCT05860881. Registered on June 15, 2023, and on anzctr.org.au (registration number NCT05860881)., Competing Interests: Declarations. Ethics approval and consent to participate {24}: The study was approved by Metro South Human Research Ethics Committee on 18 April 2023 (HREC/2023/QMS/95325). All participants will have to provide written informed consent before participation. Consent for publication {32}: This is not applicable. No identifying images or other personal or clinical details of participants are presented here or will be presented in reports of the trial results. The participant information materials and informed consent form are available from the corresponding author on request. All authors listed above meet the authorship criteria according to the latest guidelines of the International Committee of Medical Journal Editors, and all authors agree with the manuscript. Competing interests {28}: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Asymptomatic carriers of Plasmodium falciparum represent important parasite reservoirs maintaining malaria transmission in the community. This study aimed on the one hand to screen the other household members living with children under seasonal malaria chemoprevention (SMC) coverage in order to determine the level of malaria infection in this population and on the other hand to determine the appropriate type of rapid diagnostic test (RDT) for this screening to detect these asymptomatic carriers in the community. During the 2022 SMC campaign (July to October), a cross-sectional survey was carried out in 745 participants who were screened by ultrasensitive rapid diagnostic test (usRDT), standard rapid diagnostic test (rRDT) and microscopy. Out of them, 395 had microscopy results available and were included in the data analysis. The prevalence of asymptomatic carriers of asexual forms of Plasmodium falciparum was 26.58% (105/395) while sexual forms were found in 5.32% (21/395) of the study population. Children from 5 to 15 years had the highest prevalence of P. falciparum asexual forms 35.76% (59/165) compared with older participants. Malaria positivity rate for rRDT and usRDT was 29.40% (219/745) and 40.49% (305/745) respectively. The usRDT had a higher sensitivity than the rRDT (72.38% (95% CI 62.8-80.66) vs. 60.95% (95% CI 50.94-70.33)). In terms of specificity, rRDT had a higher specificity 82.41% (95% CI 77.53-86.62) versus 69.66% (95% CI 64.01-74.89) for usRDT. This study reports a high prevalence of parasite carriers in household members of children under SMC coverage in Nanoro, Burkina Faso. In conclusion, usRDT seems more appropriate for strategies based on detection and treatment of parasite carriers within the community., Competing Interests: Declarations Ethics approval and consent to participate This study was an ancillary to a larger study entitled “Boosting the impact of seasonal malaria chemoprevention (SMC) through simultaneous screening and treatment of household members of children receiving SMC in Burkina Faso” acronym SMC-RST which has been approved by the Ethics Committee for Health Research of Burkina Faso (Deliberation No.: 2021–03-059 of 10 March 2021). A signed informed consent was obtained from participants or their parents/guardians (if they are minors) before enrollment. An impartial, literate witness (not a member of the study staff) was presented in case the parents/guardians were illiterate. The parent(s)/guardian(s) and, if applicable, the witness signed the informed consent. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Schistosomiasis is a major human disease of public health importance. Freshwater snails serving as intermediary hosts and human interaction with surface water tainted by feces or urine are both necessary components of the transmission cycle. Schistosoma haematobium, Schistosoma mansoni, and Schistosoma japonicum are the primary pathogen species. Over 250 million individuals are infected globally, according to the World Health Organization, causing significant morbidity and an estimated loss of 1.9 million disability-adjusted life years, a number that is probably underestimated. Immunological protection is slowly built up through complex immunological systems, although innate factors also play a role. Chronic schistosomiasis affects mainly individuals residing in poor rural area. Vaccination is considered as one of the most sustainable options for the control of any pathogen, but schistosomiasis vaccine for humans or animals is not available till now despite the discovery of numerous potentially promising schistosome vaccine antigens., Objective: To provide an overview of the schistosomiasis chemotherapy, chemoprevention, and vaccines history and progress., Design: Review article., Data Sources: PubMed, ISI Web of Science, Science Direct, and the World Health Organization database., Conclusion: Favorably praziquantel (PZQ) is a medication with excellent chemopreventive treatment compliance. Due to the extensive usage of PZQ, there is a great deal of debate surrounding the emergence of drug resistance. PZQ is effective against all species of schistosomes, schistosomiasis prevalence has remained largely unaffected, due to reinfection in high transmission areas and growing juvenile worms that were not affected by the drug, even though the need for a schistosomiasis vaccine is even more pressing., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: After cardiovascular disease, cancer is one of the leading causes of death due to uncontrolled cell growth. Breast cancer is among the most prevalent types of cancer. Zingiber officinale Roscoe. rich in phenolic compounds, which can stimulate and function as endogenous antioxidants., Purpose: Investigation of the in vivo chemopreventive has the potential of nano Z. officinale Roscoe (Zo-NPs) in breast cancer., Study Design: Using female Mus musculus Balb/c induced with benzo[α]pyrene, the chemopreventive action of Z. officinale Roscoe. nanoencapsulated using κ-carrageenan was assessed., Results: Z. officinale Roscoe Extract. contains 58 compounds, with the main component being [6]-gingerol with [6]-gingerol content being 697.65 ± 8.52 mg/g extract. Nanoencapsulation of Z. officinale Roscoe. has been successfully prepared with a particle size of 483.30 ± 11.23 nm. Zo-NPs are generally resistant to pH, temperature, and salt content variations. Compared to group C 1 , which underwent ductular dilatation, the administration of Zo-NPs (group T 2 ) to female Mus musculus Balb/c, induced by benzo[α]pyrene, revealed no histological alterations in breast tissue. Moreover, administering Zo-NPs can raise blood serum levels of CAT, GSH, and SOD. In addition, it showed a greater ability to lower TNF-α levels than the T 1 group, which received Z. officinale Roscoe extract. (Zo)., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Wardana et al.)

Gene expression appears altered in apparently normal tissue surrounding tumor tissue. The observed biological alterations in the tumor microenvironment play a crucial role in cancer development and are named the cancer field effect (FE). A robust set of overexpressed FE genes in tissue surrounding colorectal cancer (CRC) tumor were identified in previous studies. Our study aimed to investigate the influence of common medication intake and modifiable risk factors on FE gene expression using a colonic mucosa sample dataset of healthy individuals (BarcUVa-Seq). We applied expression enrichment analysis of the FE genes for each studied medication and factor. Both observational and instrumental (Mendelian randomization) analysis were conducted, and the results were validated using independent datasets. The findings from the observational and instrumental analyses consistently showed that medication intake, especially metformin, considerably downregulated the FE genes. Chemopreventive effects were also noted for antihypertensive drugs targeting the renin-angiotensin system. Conversely, benzodiazepines usage might upregulate FE genes, thus fostering a tumor-promoting microenvironment. In contrast, the findings from the observational and instrumental analyses on modifiable risk factors showed some discrepancies. The instrumental results indicated that obesity and smoking might promote a tumor-favorable microenvironment. These findings offer insights into the biological mechanisms through which risk factors might influence CRC development and highlight the potential chemopreventive roles of metformin and antihypertensive drugs in CRC risk.

Malaria is preventable, but the burden of disease remains high with over 249 million cases and 608,000 deaths reported in 2022. Historically, the most important protective interventions have been vector control and chemopreventive medicines with over 50 million children receiving seasonal malaria chemoprevention in the year 2023. Two vaccines are approved and starting to be deployed, bringing additional protection for children up to 36 months. However, the impact of these currently available tools is somewhat limited on various fronts. Vaccines exhibit partial efficacy, are relatively costly, and not accessible in all settings. The challenges encountered with chemoprevention are barriers to acceptability and feasibility, including frequency of dosing, and the lack of options in the first trimester of pregnancy and for women living with HIV. Also, the emergence of resistance against chemopreventive medicines is concerning. To address these limitations, a target product profile (TPP) is proposed as a road map to guide innovation and to boost the quest for novel chemopreventive alternatives. This TPP describes the ideal product attributes, while acknowledging potential trade-offs that may be needed. Critically, it considers the target populations most at risk; primarily infants, children, and pregnant women. Malaria control and elimination requires appropriate chemoprevention, not only in areas of high endemicity and transmission, but also in lower transmission areas where immunity is declining, as well as for travellers from areas where malaria has been eliminated. New medicines should show acceptable safety and tolerability, with high and long protective efficacy. Formulations and costs need to support operational adherence, access, and effectiveness. Next generation long-acting oral and injectable drugs are likely to constitute the backbone of malaria prevention. Therefore, the perspectives of front-line experts in malaria prevention, researchers, and those involved in drug development are captured in the TPP. This inclusive approach aims at concentrating efforts and aligning responses across the community to develop new and transformative medicines., (© 2024. The Author(s).)

Purpose: Individuals with Lynch syndrome (LS) are at a high lifetime risk of colorectal cancer (CRC) and other cancers. Aspirin (ASA), a nonsteroidal anti-inflammatory drug (NSAID), has proven chemopreventive benefits in LS, with the CAPP2 randomized double-blind placebo-controlled trial demonstrating a 60% relative risk reduction for CRC among participants who adhered to ASA for 2 years or more. This study sought to characterize uptake of ASA/NSAIDs among individuals with LS and to understand factors associated with use., Methods: Individuals with LS were invited (June 2020-August 2022) to complete a one-time electronic survey about LS screening behaviors, uptake of ASA/NSAIDs, and current/emerging cancer prevention options. Participants were recruited from the Fox Chase Cancer Center (FCCC) Risk Assessment Program Registry and through a research invitation posted to two patient-facing LS advocacy websites., Results: Two hundred and ninety-six participants completed the survey including 116 (39.2%) from FCCC and 180 (60.8%) recruited via the Internet, including 14.9% non-US based individuals. Uptake of regular ASA or NSAIDs was modest at 34.8% and was even lower (25.7%) when focusing on individuals taking ASA or NSAIDs solely for chemoprevention of LS. More than half (55%) were taking <100 mg ASA daily. In multivariable modeling, lower perceived threat of LS (odds ratio [OR], 0.84 [95% CI, 0.72 to 0.98]), lower concern for side effects (OR, 0.86 [95% CI, 0.76 to 0.99]), and higher likelihood of recommending ASA/NSAIDs to family or a friend were all associated with ASA/NSAIDs use (OR, 1.70 [95% CI, 1.37 to 2.10])., Conclusion: Uptake of ASA/NSAIDs chemoprevention is modest among individuals with LS. Patient perceptions of the pros and cons of ASA, more so than demographic and disease-related factors, were associated with chemoprevention uptake.

Objective: To assess the safety of preoperative chemoprophylaxis (PEC) in head and neck cancer (HNC) patients undergoing oncologic procedures., Study Design: Retrospective cohort study., Setting: Tertiary academic center., Methods: HNC patients with Caprini risk score (CRS) ≥5 who underwent inpatient surgery ≥3 hours between 2015 and 2020 were included. Patients were divided into 2 cohorts, PEC and control, based on whether or not they received a single dose of low molecular weight heparin or unfractionated heparin prior to surgery. The primary endpoint was the 30-day rate of major bleeding events., Results: A total of 539 patients were included; 427 patients received PEC prior to surgery. The rate of major bleeding was 6.7%. The PEC cohort was more likely to have received concurrent aspirin or ketorolac (225 of 427 patients vs 36 of 112 patients; P = .0002), greater duration of chemoprophylaxis (7.8 vs 5.0 days; P < .0001), have higher CRS (7.2 vs 6.6; P < .0001), longer operative times (596 vs 512 minutes; P < .0001), higher blood loss (265 vs 214 ml; P = .02), and higher bleeding rates when compared to the control (34 of 427 patients; P = .03). On multivariate analysis, only PEC was associated with bleeding (odds ratio, 8.74; 95% confidence interval, 1.15-66.5). The rate of VTE was 1.3% and was not significantly different between cohorts., Conclusion: PEC was associated with an increase in bleeding and did not result in lower rates of VTE in patients with HNC. This study highlights the need to determine the optimal regimen of chemoprophylaxis in this patient cohort., (© 2024 The Author(s). Otolaryngology–Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: Bariatric surgery has gained popularity in recent decades as an effective treatment for obesity. Abdominoplasty is one of the most often performed aesthetic procedures all over the world. In post-bariatric patients undergoing abdominoplasty, the diameter size and number of the abdominal wall perforators increase proportionally with increased body weight. Postoperative complications that may occur are haematoma, and venous thromboembolism (VTE). In plastic surgery procedures VTE prophylaxis grades vary due to the lack of consensus and clear guidelines. The aim of this study was to explore the frequency of postoperative bleeding and VTE in patients undergoing abdominoplasty and to explore the risk factors associated with major bleeding., Methods: A retrospective single-centre study of adult patients who were operated on by abdominoplasty between 2011 and 2020. Chemoprophylaxis including low molecular weight heparin (LMHW) was recommended when the operating time exceeded 2 h., Results: A total of 102 patients were included. There were no patients with VTE. Eight patients were re-operated for major haematoma. The weight loss (peak weight to weight before the abdominoplasty) was 14.4 kg larger in the re-operation group (p = 0.03). Eighty-eight percent in the re-operation group and 67% in the other group were treated with LMWH (p = 0.43). Multivariable logistic regression showed that with each decrease from the peak in BMI kg/m 2 the risk of re-operation for major haematoma was increased by 22% (p = 0.02)., Conclusion: Abdominoplasty in patients after massive weight loss has a higher risk of postoperative bleeding. Having a clear protocol for chemoprophylaxis should be considered., Level of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. The Author(s).)

In this comprehensive review we tried to reassess the role of phytochemicals in cancer chemoprevention. The exploration of the "synergistic effect" concept, advocating combined chemopreventive agents, faces challenges like low bioavailability. The review incorporates personal, occasionally controversial, viewpoints on natural compounds' cancer preventive capabilities, delving into mechanisms. Prioritizing significant contributions within the vast research domain, we aim stimulating discussion to provide a comprehensive insight into the evolving role of phytochemicals in cancer prevention. While early years downplayed the role of phytochemicals, the late nineties witnessed a shift, with leaders exploring their potential alongside synthetic compounds. Challenges faced by chemoprevention, such as limited pharmaceutical interest and cost-effectiveness issues, persist despite successful drugs. Recent studies, including the EPIC study, provide nuanced insights, indicating a modest risk reduction for increased fruit and vegetable intake. Phytochemicals, once attributed to antioxidant effects, face scrutiny due to low bioavailability and conflicting evidence. The Nrf2-EpRE signaling pathway and microbiota-mediated metabolism emerge as potential mechanisms, highlighting the complexity of understanding phytochemical mechanisms in cancer chemoprevention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Venous thromboembolism (VTE) remains a leading cause of preventable harm among hospitalized patients. Pharmacologic VTE prophylaxis reduces the rate of in-hospital VTE by 60%, but medication administration is often missed for various reasons. Electronic medical record (EMR) prompts may be a useful tool to decrease withholding of critical VTE chemoprophylaxis medications. Methods: In August 2021, an EMR prompt was implemented at a tertiary referral academic medical center mandating nursing staff to contact a provider for approval before withholding VTE chemoprophylaxis. A pre-intervention group from August 2020 to August 2021 was compared to a post-intervention group from August 2021 to August 2022. Rates of VTE chemoprophylaxis withholding were compared between the groups with a P < .01 considered significant. Results: A total of 16,395 patients prescribed VTE chemoprophylaxis were reviewed, with 13,395 (81.7%) receiving low molecular weight heparin. Of the 16,395 patients included, 10,701 (65.3%) were medical and 5694 (34.7%) were surgical. Patients in the pre-intervention cohort (n = 8803) and post-intervention cohort (n = 7592) were similar in hospital length of stay and duration of DVT prophylaxis. In the post-intervention group, the frequency of surgical patients with at least one missed dose had increased by 4.2% ( P = .002), with the trauma and acute care surgery (TACS) show an increase of 6.6% ( P < .001). However, the frequency of medical patients and non-TACS patients with missed doses decreased by 3.1% ( P = .002) and 1.0% (<.001), respectively. Conclusions: EMR prompts appear to be a low-cost intervention that increases the rate of VTE prophylaxis administration among medical and elective surgery patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Malaria-elimination interventions aim to extinguish hotspots and prevent transmission to nearby areas. Here, we re-analyzed a cluster-randomized trial of reactive, focal interventions (chemoprevention using artemether-lumefantrine and/or indoor residual spraying with pirimiphos-methyl) delivered within 500 m of confirmed malaria index cases in Namibia to measure direct effects (among intervention recipients within 500 m) and spillover effects (among non-intervention recipients within 3 km) on incidence, prevalence and seroprevalence. There was no or weak evidence of direct effects, but the sample size of intervention recipients was small, limiting statistical power. There was the strongest evidence of spillover effects of combined chemoprevention and indoor residual spraying. Among non-recipients within 1 km of index cases, the combined intervention reduced malaria incidence by 43% (95% confidence interval, 20-59%). In analyses among non-recipients within 3 km of interventions, the combined intervention reduced infection prevalence by 79% (6-95%) and seroprevalence, which captures recent infections and has higher statistical power, by 34% (20-45%). Accounting for spillover effects increased the cost-effectiveness of the combined intervention by 42%. Targeting hotspots with combined chemoprevention and vector-control interventions can indirectly benefit non-recipients up to 3 km away., (© 2024. The Author(s).)

Head and neck squamous cell carcinoma (HNSCC) is a spectrum of heterogeneous malignancies. A variety of genetic, environmental, and lifestyle factors contribute to the development of HNSCC. Carcinogenesis is a multistep process in which cell proliferation-associated oncogenes and cell-cycle regulation-associated tumor suppressor genes are dysregulated, resulting in premalignant lesions. Immune evasion is a critical step in the progression of benign lesions to advanced cancer. This review discusses the advances that have been made in chemoprevention strategies for HNSCC. The rationale for the use of chemopreventive agents to inhibit head and neck cancer development is highlighted by the positive outcomes of several clinical trials. We discuss the potential of some of the commonly studied agents including vitamin A analogs, EGFR inhibitors, COX-2 inhibitors, metabolic modulators, and natural compounds such as green tea, as well as immunotherapy and photodynamic therapy to prevent HNSCC. Our review provides insight into the potential benefits of these agents and the gaps that remain to be addressed. The published results reaffirm the promise of chemoprevention in head and neck cancer and suggest that continued exploration is needed to overcome the limitations. Because the current focus on chemopreventive agents is limited, major efforts in precision oncology approaches and substantial increase in funding will promote research into chemoprevention, which will eventually decrease the incidence of HNSCC., (©2024 American Association for Cancer Research.)

Mounting evidence from preclinical and clinical studies suggests that persistent inflammation functions as a driving force in the journey to cancer. Cyclooxygenase-2 (COX-2) is a key enzyme involved in inflammatory signaling. While being transiently upregulated upon inflammatory stimuli, COX-2 has been found to be consistently overexpressed in human colorectal cancer and several other malignancies. The association between chronic inflammation and cancer has been revisited: cancer can arise when inflammation fails to resolve. Besides its proinflammatory functions, COX-2 also catalyzes the production of pro-resolving as well as anti-inflammatory metabolites from polyunsaturated fatty acids. This may account for the side effects caused by long term use of some COX-2 inhibitory drugs during the cancer chemopreventive trials. This review summarizes the latest findings highlighting the dual functions of COX-2 in the context of its implications in the development, maintenance, and progression of cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The World Health Organization 2022 malaria chemoprevention guidelines recommend providing a full course of antimalarial treatment at pre-defined intervals, regardless of malaria status to prevent illness among children resident in moderate to high perennial malaria transmission settings as perennial malaria chemoprevention (PMC) with sulfadoxine-pyrimethamine (SP). The dhps I431V mutation circulating in West Africa has unknown effect on SP protective efficacy., Methods: This protocol is for a three-arm, parallel, double-blinded, placebo-controlled, randomised trial in Cameroon among children randomly assigned to one of three directly-observed treatment groups: (i) Group 1 (n = 450) receives daily artesunate (AS) placebo on days - 7 to -1, then active SP plus placebo amodiaquine (AQ) on day 0, and placebo AQ on days 1 and 2; (ii) Group 2 (n = 250) receives placebo AS on days - 7 to -1, then active SP and AQ on day 0, and active AQ on days 1 and 2; and (iii) Group 3 (n = 200) receives active AS on days - 7 to -1, then placebo SP on day 0 and placebo AQ on days 0 to 2. On days 0, 2, 5, 7, and thereafter weekly until day 28, children provide blood for thick smear slides. Dried blood spots are collected on the same days and weekly from day 28 to day 63 for quantitative polymerase chain reaction (qPCR) and genotype analyses., Discussion: Our aim is to quantify the chemopreventive efficacy of SP, and SP plus AQ, and measure the effect of the parasite genotypes associated with SP resistance on parasite clearance and protection from infection when exposed to SP chemoprevention. We will report unblinded results including: (i) time-to-parasite clearance among SP and SP plus AQ recipients who were positive on day 0 by qPCR and followed to day 63; (ii) mean duration of SP and SP plus AQ protection against infection, and (iii) mean duration of symptom-free status among SP and SP plus AQ recipients who were parasite free on day 0 by qPCR. Our study is designed to compare the 28-day follow-up of the new WHO malaria chemoprevention efficacy study protocol with extended follow-up to day 63., Trial Registration: ClinicalTrials.gov NCT06173206; 15/12/2023., (© 2024. The Author(s).)

Background: Post-discharge malaria chemoprevention (PDMC) is an intervention aimed at reducing morbidity and mortality in patients hospitalized with severe anaemia, with its effectiveness established in several clinical trials. The aim of this study was to better understand factors that would influence the scale up of this intervention, and to identify preferences for two delivery mechanisms, facility-based or community-based., Methods: Forty-six qualitative individual interviews were conducted in five sub-Saharan countries amongst malaria key opinion leaders and national decision makers. Findings were analysed following a thematic inductive approach., Results: Half of participants were familiar with PDMC, with a satisfactory understanding of the intervention. Although PDMC was perceived as beneficial by most respondents, there was some unclarity on the target population. Both delivery approaches were perceived as valuable and potentially complementary. From an adoption perspective, relevant evidence generation, favorable policy environment, and committed funding were identified as key elements for the scale up of PDMC., Conclusions: The findings suggest that although PDMC was perceived as a relevant tool to prevent malaria, further clarification was needed in terms of the relevant patient population, delivery mechanisms, and more evidence should be generated from implementation research to ensure policy adoption and funding., (© 2024. The Author(s).)

Abstract: The immune revolution that swept the field of oncology in the mid-2010s with the advent of checkpoint inhibitors has led to a paradigm shift in approaches toward adapting new cancer prevention modalities. Cancer vaccines have emerged from this era with astounding potential as a durable intervention to prevent cancers especially for patients with hereditary susceptibilities such as Lynch syndrome carriers. This review covers new insights in the immunoprevention landscape for patients living with Lynch syndrome including highlights ranging from clinical trials exploring the use of chemoprevention agents to boost immune cellularity to investigative studies using novel vaccine approaches to induce long-term antitumor immunity., Competing Interests: Conflicts of Interest and Source of Funding: E.V. had a consulting or advisory role with Janssen Research and Development, Recursion Pharma, Guardant Health, Rising Tide Foundation, and Nouscom, s.r.l. He has received research support from Janssen Research and Development. This work was supported by grants CA260761 and CA257375 (US National Institutes of Health/National Cancer Institute) to E.V. For the remaining authors none were declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: "Cancer chemoprevention" is a term referring to the slowing or reversal of this disease, using nontoxic natural or synthetic compounds. For about 50 years, there has been a strong scientific interest in discovering plant-derived compounds to prevent cancer, and strategies for this purpose using a concerted series of in vitro, ex vivo, and in vivo laboratory bioassays have been developed. Five examples of the more thoroughly investigated agents of this type are described herein, which are each supported by detailed literature reports, inclusive of ellagic acid, isoliquiritigenin, lycopene, trans-resveratrol, and sulforaphane. In addition, extracts of the plants avocado (Persea americana), noni (Morinda citrifolia), açai (Euterpe oleracea), and mangosteen (Garcinia mangostana) have all shown inhibitory activity in an in vivo or ex vivo bioassay using a carcinogen and germane to cancer chemoprevention, and selected in vitro-active constituents are described for each of these 4 species., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. This study was funded by Project T32 CA229114-05 (Training Program for Cancer Prevention and Control), National Cancer Institute, National Institutes of Health, Bethesda, MD., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Autologous breast reconstruction is considered high-risk for deep vein thrombosis (DVT) and thromboembolism (PE). It is therefore recommended to treat patients undergoing these complex and lengthy procedures with DVT chemoprophylaxis. The optimal anticoagulation protocol is still not established. The objective of our study was to evaluate the need of a prolonged anticoagulation in patients undergoing microsurgical breast reconstruction., Methods: This retrospective cohort study compares our former anticoagulation protocol, which was given during the in-hospital stay, with our new protocol consisting of extended anticoagulation until postoperative day 25, in terms of DVT/PE risk reduction. A logistic regression was used to evaluate the risk of DVT/PE between the two groups, while adjusting for several covariates., Results: Our cohort consisted of 205 patients in the short-term anticoagulation group and 219 in the extended protocol group. Five patients (2.4%) in the short-term anticoagulation group had a DVT/PE event versus 4 patients (1.8%) in the extended protocol group. Logistic regression revealed no difference in the incidence of DVT/PE between the two groups. Similarly, there was no differences in terms of hematoma and infection rate between the two groups. Finally, we found an increased risk of DVT/PE in patients with a Caprini score equal or greater than 8., Conclusion: In our experience, short-term anticoagulation during the hospital stay is equivalent to extended thromboprophylaxis in terms of DVT/PE prevention., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objectives: Upper extremity deep vein thrombosis (UEDVT) is associated with pulmonary embolism and other complications, but there are no recommendations for UEDVT prophylaxis. The purpose of this study was to establish incidence and risk factors for UEDVT and to determine efficacy of pharmacologic prophylaxis for UEDVT prevention., Methods: For this retrospective cohort study, we identified medical patients aged 18 years and older admitted to 13 Cleveland Clinic hospitals from January 2011 to December 2019. Patients with venous thromboembolism (VTE) on admission, length of stay <1 day, and who received therapeutic anticoagulation were excluded. The potential risk factors included demographics, comorbidities, and medical procedures. Comorbidities were identified via International Classification of Diseases codes, (ICD9 and ICD10), procedures from flowsheets, and prophylaxis from medications administered in the electronic medical record. DVT events were identified by a combination of International Classification of Diseases codes and confirmed by chart review. We performed multivariable logistic regression to identify independent risk factors and the association between VTE prophylaxis and UEDVT. The model's C statistic was obtained using 1000 bootstrap runs., Results: Of 194,809 patients, 496 (0.25% of cohort, 36.8% of all VTE) developed UEDVT by 14 days. In the logistic regression model (bias-corrected C statistic 0.87), 11 risk factors predicted UEDVT, the strongest being peripherally inserted central catheter (odds ratio [OR] 4.62, 95% confidence interval [CI] 3.81-5.60) and central venous catheter (OR 3.57, 95% CI 2.91-4.37). The predicted risk among individuals ranged from 0.02% to 23.4%. Prophylaxis was negatively associated with the development of UEDVT (OR 0.72, 95% CI 0.60-0.87)., Conclusions: UEDVT is rare but some patients are high risk. Therefore, UEDVT risk factors should be added to VTE risk assessment models, and patients at high risk for UEDVT should receive chemoprophylaxis.

Background: The Republic of Guinea, where malaria represents the leading cause of morbidity and mortality among children, the seasonal malaria chemoprevention (SMC) is deployed only in areas with very seasonal modes of transmission. It should target children at the highest risk of serious illness. The objective of the study was to prevent uncomplicated and serious cases of malaria in the target population. This study aimed to analyse the monthly trends in malaria-related morbidity among children under the age of 5 in Guinea., Methods: This was a quasi-experimental study with routine data from the National Health Information System (SNIS). The two districts Mamou (the SMC intervention site) and Kindia (the control site) were selected to compare the monthly trends in malaria cases among children under the age of 5, from July to October, covering the years from 2015 to 2020. The statistical analysis used interrupted time series to estimate the effects of the SMC., Results: The SMC programme contributed to a significant average reduction in the number of malaria cases of 225 cases per month in the intervention district (95% CI - 362 to - 88; p = 0.002), compared to the control district. However, the study also revealed that the effect of SMC varied between cycles, presenting different monthly malaria cases., Conclusion: The SMC contributed to a significant reduction in malaria cases among children under the age of 5 in the health district of Mamou from 2018 to 2020. However, this reduction varied by monthly SMC cycle. This study suggests extending the SMC in other areas with high perennial seasonal transmission respecting the World Health Organization SMC eligibility criteria, as a strategy in the dynamic of reducing malaria cases in children under the age of 5 in Guinea., (© 2024. The Author(s).)

Background and Objectives : This study aimed to evaluate the potential chemopreventive effect of antidiabetic medications, specifically metformin and pioglitazone, on lung cancer in patients with type 2 diabetes mellitus (T2DM). Additionally, the potential dose-response relationship for metformin use was analyzed. Methods : We conducted a retrospective cohort study utilizing comprehensive national health insurance and cancer registry databases to gather a large cohort of T2DM patients. Cox proportional hazards regression models were used to assess the risk of lung cancer across different antidiabetic medication groups, adjusting for potential confounders such as age and gender. A dose-response analysis was conducted for metformin users. Results : Our results indicated that metformin users had a significantly lower lung cancer risk than the reference group (HR = 0.69, 95% CI [0.55-0.86], p = 0.001). The risk reduction increased with higher cumulative metformin doses: a metformin cumulative dose between 1,370,000 and 2,976,000 had an HR of 0.61 (95% CI [0.49-0.75], p < 0.001) vs. cumulative metformin dose >2,976,000 which had an HR of 0.35 (95% CI [0.21-0.59], p < 0.001). No significant association between pioglitazone use and the risk of lung cancer was found (HR = 1.00, 95% CI [0.25-4.02]). Conclusions : This study shows that metformin may have a dose-dependent chemopreventive effect against lung cancer in T2DM, while the impact of pioglitazone remains unclear and requires further investigation.

Background: Seasonal malaria chemoprevention using sulfadoxine-pyrimethamine plus amodiaquine (sulfadoxine-pyrimethamine plus amodiaquine on Day 1 and amodiaquine on both Day 2 and Day 3) is delivered to children aged 3-59 months in areas of highly season malaria transmission. While the overall population-level impact of seasonal malaria chemoprevention on malaria control has been documented in various countries and time periods, there is no clear evidence regarding seasonal malaria chemoprevention impact based on the number of medicine doses children receive in one cycle in routine programmatic conditions., Methods: Data were extracted from Nigeria's routinely collected seasonal malaria chemoprevention end-of-round coverage surveys (2021, 2022). We matched seasonal malaria chemoprevention-targeted children who received specific numbers of seasonal malaria chemoprevention medicines with those who did not receive any doses of seasonal malaria chemoprevention medicines (non-sulfadoxine-pyrimethamine plus amodiaquine) using multiple sets of propensity score matches. We performed multilevel logistic regression for each matched group to evaluate the association between the number of doses of seasonal malaria chemoprevention medicines and monthly confirmed malaria cases (caregiver-reported malaria infection diagnosed by rapid diagnostic test at a health facility following the penultimate cycle of seasonal malaria chemoprevention)., Results: Among 21,621 SMC-targeted children, 9.7% received non-sulfadoxine-pyrimethamine plus amodiaquine, 0.5% received only Day 1 sulfadoxine-pyrimethamine plus amodiaquine, 1.0% received Day 1 sulfadoxine-pyrimethamine plus amodiaquine and either Day 2 amodiaquine or Day 3 amodiaquine (sulfadoxine-pyrimethamine plus amodiaquine + amodiaquine), and 88.8% received Day 1 sulfadoxine-pyrimethamine plus amodiaquine and both Day 2 and Day 3 amodiaquine (sulfadoxine-pyrimethamine plus amodiaquine + amodiaquine + amodiaquine). Children receiving only Day 1 sulfadoxine-pyrimethamine plus amodiaquine did not have significant lower odds of rapid diagnostic tests-confirmed malaria than those receiving non-sulfadoxine-pyrimethamine plus amodiaquine (OR 0.77, 0.42-1.42). However, children receiving sulfadoxine-pyrimethamine plus amodiaquine + amodiaquine had significantly lower odds of rapid diagnostic tests-confirmed malaria than those receiving non-sulfadoxine-pyrimethamine plus amodiaquine (OR 0.42, 95% CI 0.28-0.63). Similarly, children receiving sulfadoxine-pyrimethamine plus amodiaquine + amodiaquine + amodiaquine also had significantly lower odds of rapid diagnostic test-confirmed malaria than those receiving non-sulfadoxine-pyrimethamine plus amodiaquine (OR 0.54, 95% CI 0.47-0.62)., Conclusion: Adherence to at least one daily dose of amodiaquine administration following receipt of Day 1 sulfadoxine-pyrimethamine plus amodiaquine by eligible children is crucial to ensure the effectiveness of seasonal malaria chemoprevention. This demonstrates the importance of enhancing caregiver awareness regarding the importance of amodiaquine and identifying barriers toward amodiaquine administration at the community level., (© 2024 The Author(s). Tropical Medicine & International Health published by John Wiley & Sons Ltd.)

Background: Australian guidelines recommend that people aged 50-70 years consider taking low-dose aspirin to reduce their risk of colorectal cancer (CRC)., Aim: To determine the effect of a consultation with a researcher before an appointment in general practice using a decision aid presenting the benefits and harms of taking low-dose aspirin compared with a general CRC prevention brochure on patients' informed decision making and low-dose aspirin use., Design and Setting: Individually randomised controlled trial in six general practices in Victoria, Australia, from October 2020 to March 2021., Method: Participants were recruited from a consecutive sample of patients aged 50-70 years attending a GP. The intervention was a consultation using a decision aid to discuss taking aspirin to reduce CRC risk while control consultations discussed reducing CRC risk generally. Self-reported co-primary outcomes were the proportion of individuals making informed choices about taking aspirin at 1 month and on low-dose aspirin uptake at 6 months, respectively. The intervention effect was estimated using a generalised linear model and reported with Bonferroni-adjusted 95% confidence intervals (CIs) and P -values., Results: A total of 261 participants (86% of eligible patients) were randomised into trial arms ( n = 129 intervention; n = 132 control). Of these participants, 17.7% ( n = 20/113) in the intervention group and 7.6% ( n = 9/118) in the control group reported making an informed choice about taking aspirin at 1 month, an estimated 9.1% (95% CI = 0.29 to 18.5) between-arm difference in proportions (odds ratio [OR] 2.47, 97.5% CI = 0.94 to 6.52, P = 0.074). The proportions of individuals who reported taking aspirin at 6 months were 10.2% ( n = 12/118) of the intervention group versus 13.8% ( n = 16/116) of the control group, an estimated between-arm difference of -4.0% (95% CI = -13.5 to 5.5; OR 0.68 [97.5% CI = 0.27 to 1.70, P = 0.692])., Conclusion: The decision aid improved informed decision making but this did not translate into long-term regular use of aspirin to reduce CRC risk. In future research, decision aids should be delivered alongside various implementation strategies., (© The Authors.)

Objective: We developed the Healthy Families-PrEP intervention to support HIV-prevention during periconception and pregnancy. We evaluated preexposure prophylaxis (PrEP) use with three objective measures., Design: This single-arm intervention study enrolled women in KwaZulu-Natal, South Africa, who were HIV-uninfected, not pregnant, in a relationship with a partner with HIV or unknown-serostatus, and with pregnancy plans. PrEP was offered as part of a comprehensive HIV prevention intervention. Participants were followed for 12 months., Methods: We evaluated periconception PrEP uptake and adherence using quarterly plasma tenofovir concentrations. We modeled factors associated with PrEP uptake and high plasma tenofovir (past day dosing). Patterns of use were analyzed using electronic pillcap data. Dried blood spots to measure intracellular tenofovir product (past 2 months dosing) were analyzed for a subset of women., Results: Three hundred thirty women with median age 24 (IQR: 22-27) years enrolled. Partner HIV-serostatus was unknown by 96% ( N  = 316); 60% (195) initiated PrEP. High plasma tenofovir concentrations were seen in 35, 25, 22, and 20% of samples at 3, 6, 9, and 12 months, respectively. Similar adherence was measured by pillcap and dried blood spots. In adjusted models, lower income, alcohol use, and higher HIV stigma were associated with high plasma tenofovir. Eleven HIV-seroconversions were observed (incidence rate: 4.04/100 person-years [95% confidence interval: 2.24-7.30]). None had detectable plasma tenofovir., Conclusion: The Healthy Families-PrEP intervention supported women in PrEP use. We observed high interest in periconception PrEP and over one-third adhered to PrEP in the first quarter; one-fifth were adherent over a year. High HIV incidence highlights the importance of strategies to reduce HIV incidence among periconception women., Clinical Trial Number: NCT03194308., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Plants from the Fabaceae family are widely distributed around the world, especially in Europe, Asia and North America. They are a rich source of isoflavones, compounds with estrogen-like activity, which are suspected of having a chemopreventive effect against hormone-dependent cancers. Following the PRISMA guidelines, we conducted a systematic review aimed at assessing the impact of Fabaceae plant extracts on hormone-dependent cancer cells and the content of active compounds in plant raw materials. We analyzed the results of 63 articles from in vitro and in vivo studies describing the effect of plant extracts containing isoflavones on cancer cells, along with their anti-inflammatory and antioxidant potential. In the process, we determined the research limitations and future research directions. The collected results indicate the plant species with potentially high contents of phytoestrogens and anti-inflammatory, antioxidant and cytotoxic properties. They point to the potential use of plants in the diet as a source of compounds offering cancer prevention.

Background: Pharmacokinetic data of rifampin, when used for tuberculosis preventive treatment (TPT) are not available. We aimed to describe the pharmacokinetics of rifampin used for TPT, at standard and higher doses, and to assess predictors of rifampin exposure., Methods: A pharmacokinetic sub-study was performed in Bandung, Indonesia among participants in the 2R 2 randomized trial, which compared TPT regimens of 2 months of high-dose rifampin at 20 mg/kg/day (2R 20 ) and 30 mg/kg/day (2R 30 ), with 4 months of standard-dose rifampin at 10 mg/kg/day (4R 10 ) in adolescents and adults. Intensive pharmacokinetic sampling was performed after 2-8 weeks of treatment. Pharmacokinetic parameters were assessed non-compartmentally. Total exposure (AUC 0-24 ) and peak concentration (C max ) between arms were compared using one-way ANOVA and Tukey's post-hoc tests. Multivariable linear regression analyses were used to assess predictors of AUC 0-24 and C max ., Results: We enrolled 51 participants in this study. In the 4R 10 , 2R 20, and 2R 30 arms, the geometric mean AUC 0-24 was 68.0, 186.8, and 289.9 h⋅mg/L, and C max was 18.4, 36.7, and 54.4 mg/L, respectively; high interindividual variabilities were observed. Compared with the 4R 10 arm, AUC 0-24 and C max were significantly higher in the 2R 20 and 2R 30 arms (P < 0.001). Drug doses, body weight, and female sex were predictors of higher rifampin AUC 0-24 and C max (P < 0.05). AUC 0-24 and C max values were much higher than those previously reported in persons with TB disease., Conclusions: Doubling and tripling the rifampin dose led to three- and four-fold higher exposure compared to standard dose. Pharmacokinetic/pharmacodynamic modelling and simulations are warranted to support trials of shortening the duration of TPT regimens with high-dose rifampin., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The vitamin E family contains α-tocopherol (αT), βT, γT, and δT and α-tocotrienol (TE), βTE, γTE, and δTE. Research has revealed distinct roles of these vitamin E forms in prostate cancer (PCa). The ATBC trial showed that αT at a modest dose significantly decreased PCa mortality among heavy smokers. However, other randomized controlled trials including the Selenium and Vitamin E Cancer Prevention Trial (SELECT) indicate that supplementation of high-dose αT (≥400 IU) does not prevent PCa among nonsmokers. Preclinical cell and animal studies also do not support chemopreventive roles of high-dose αT and offer explanations for increased incidence of early-stage PCa reported in the SELECT. In contrast, accumulating animal studies have demonstrated that γT, δT, γTE, and δTE appear to be effective for preventing early-stage PCa from progression to adenocarcinoma in various PCa models. Existing evidence also support therapeutic roles of γTE and its related combinations against advanced PCa. Mechanistic and cell-based studies show that different forms of vitamin E display varied efficacy, that is, δTE ≥ γTE > δT ≥ γT >> αT, in inhibiting cancer hallmarks and enabling characteristics, including uncontrolled cell proliferation, angiogenesis, and inflammation possibly via blocking 5-lipoxygenase, nuclear factor κB, hypoxia-inducible factor-1α, modulating sphingolipids, and targeting PCa stem cells. Overall, existing evidence suggests that modest αT supplement may be beneficial to smokers and γT, δT, γTE, and δTE are promising agents for PCa prevention for modest-risk to relatively high-risk population. Despite encouraging preclinical evidence, clinical research testing γT, δT, γTE, and δTE for PCa prevention is sparse and should be considered., Competing Interests: Conflict of interest The author reports no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) have a significantly increased risk of breast cancer, which can be substantially reduced with antiestrogen therapy for chemoprevention. However, antiestrogen therapy for breast cancer risk reduction remains underutilized. Improving knowledge about breast cancer risk and chemoprevention among high-risk patients and their healthcare providers may enhance informed decision-making about this critical breast cancer risk reduction strategy., Methods/design: We are conducting a cluster randomized controlled trial to evaluate the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. We have cluster randomized 26 sites across the U.S. through the SWOG Cancer Research Network. A total of 415 patients and 200 healthcare providers are being recruited. They are assigned to standard educational materials alone or combined with the web-based decision support tools. Patient-reported and clinical outcomes are assessed at baseline, after a follow-up visit at 6 months, and yearly for 5 years. The primary outcome is chemoprevention informed choice after the follow-up visit. Secondary endpoints include other patient-reported outcomes, such as chemoprevention knowledge, decision conflict and regret, and self-reported chemoprevention usage. Barriers and facilitators to implementing decision support into clinic workflow are assessed through patient and provider interviews at baseline and mid-implementation., Results/discussion: With this hybrid effectiveness/implementation study, we seek to evaluate if a multi-level intervention effectively promotes informed decision-making about chemoprevention and provide valuable insights on how the intervention is implemented in U.S., Trial Registration: NCT04496739., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Breast cancer is the most common tumor in women. Chemotherapy is the gold standard for cancer treatment; however, severe side effects and tumor resistance are the major obstacles to chemotherapy success. Numerous dietary components and phytochemicals have been found to inhibit the molecular and signaling pathways associated with different stages of breast cancer development. In particular, this review is focused on the antitumor effects of PUFAs, dietary enzymes, and glucosinolates against breast cancer. The major databases were consulted to search in vitro and preclinical studies; only those with solid scientific evidence and reporting protective effects on breast cancer treatment were included. A consistent number of studies highlighted that dietary components and phytochemicals can have remarkable therapeutic effects as single agents or in combination with other anticancer agents, administered at different concentrations and via different routes of administration. These provide a natural strategy for chemoprevention, reduce the risk of breast cancer recurrence, impair cell proliferation and viability, and induce apoptosis. Some of these bioactive compounds of dietary origin, however, show poor solubility and low bioavailability; hence, encapsulation in nanoformulations are promising tools able to increase clinical efficiency.

Oral squamous cell carcinoma (OSCC) is worldwide health problem associated with high morbidity and mortality. From both the patient and socioeconomic perspectives, prevention of progression of premalignant oral intraepithelial neoplasia (OIN) to OSCC is clearly the preferable outcome. Optimal OSCC chemopreventives possess a variety of attributes including high tolerability, bioavailability, efficacy and preservation of an intact surface epithelium. Terminal differentiation, which directs oral keratinocytes leave the proliferative pool to form protective cornified envelopes, preserves the protective epithelial barrier while concurrently eliminating growth-aberrant keratinocytes. This study employed human premalignant oral keratinocytes and an OSCC cell line to evaluate the differentiation-inducing capacity of the synthetic retinoid, fenretinide (4HPR). Full-thickness oral mucosal explants were evaluated for proof of concept differentiation studies. Results of this study characterize the ability of 4HPR to fulfill all requisite components for keratinocyte differentiation, i.e. nuclear import via binding to cellular RA binding protein-II (molecular modeling), binding to and subsequent activation of retinoic acid nuclear receptors (receptor activation assays), increased expression and translation of genes associated with keratinocyte differentiation [Reverse transcription polymerase chain reaction (RT-PCR), immunoblotting] upregulation of a transglutaminase enzyme essential for cornified envelope formation (transglutaminase 3, functional assay) and augmentation of terminal differentiation in human oral epithelial explants (image-analyses quantified corneocyte desquamation). These data build upon the chemoprevention repertoire of 4HPR that includes function as a small molecule kinase inhibitor and inhibition of essential mechanisms necessary for basement membrane invasion. An upcoming clinical trial, which will assess whether a 4HPR-releasing mucoadhesive patch induces histologic, clinical and molecular regression in OIN lesions, will provide essential clinical insights., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Rising melanoma rates have spurred interest in preventive strategies. Nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, show potential in reducing cancer risks. NSAIDs act on cyclooxygenase (COX) enzymes, impacting COX-2 associated with inflammation and cancer progression. This paper explores aspirin's role in cutaneous melanoma prevention, elucidating its mechanisms and acknowledging varying literature outcomes. Rather than providing conclusive recommendations, the review emphasizes the influence of individual factors, contributing to the ongoing dialogue on aspirin's complexities in melanoma prevention. A PubMed search using "Aspirin" AND "Cutaneous melanoma" yielded relevant English-language, peer-reviewed studies. Selection criteria focused exclusively on skin cancers, specifically cutaneous melanoma. Exclusions included studies covering various cancers, some non-dermatologic, and those not evaluating aspirin use independently but in conjunction with NSAIDs. The potential chemopreventive effects of aspirin and NSAIDs against melanoma have gained attention due to their association with a reduced risk of various cancers including gastric, colorectal, and breast. By inhibiting COX enzymes and the NF-κB pathway, these agents theoretically slow malignant cell activities, presenting a prospect for cancer prevention. Aspirin exhibits noteworthy effects, depleting growth-stimulating hormones, generating reactive oxygen species harmful to cancerous cells, and inhibiting COX-2 linked to cancer progression. Limited literature suggests survival benefits with aspirin use in stage II and III melanoma, possibly due to slowing disease progression, evident in smaller Breslow depths. Gender-specific responses to aspirin are notable, with some studies reporting a stronger chemopreventive correlation in females. It's crucial to note that geographic disparities, demographic cohorts, and individual-specific factors are confounding variables that may contribute to conflicting findings regarding aspirin's impact on melanoma. The association between aspirin use and melanoma risk is complex, with conflicting findings across diverse populations. Although it appears that more studies suggest a protective role for aspirin rather than not, evidence lacks consistency. Factors such as gender, geography, race, sun exposure, and health conditions play a role in shaping these varied outcomes, necessitating large-scale, prospective studies research and standardized parameters for more conclusive insights that may help guide tailored clinical strategies for melanoma prevention., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Venous thromboembolism (VTE), including Portomesenteric vein thrombosis (PMVT), is a major complication of sleeve gastrectomy (SG). We changed our practice in July 2021 to routinely discharge all SG patients postoperatively with extended chemoprophylaxis for 30 days., Objectives: Evaluate the efficacy and safety of routine extended chemoprophylaxis compared to 2 prior timeframes using selective extended chemoprophylaxis., Setting: University Hospital., Methods: Between 2012-2018, SG patients were discharged on extended chemoprophylaxis for patients deemed "high-risk" for VTE, including patients with body mass index (BMI) >50, and previous VTE. Between 2018-2021, extended chemoprophylaxis was broadened to include patients with positive preoperative thrombophilia panels (including Factor VIII). After 2021, all SG were routinely discharged on extended chemoprophylaxis. The typical regimen was 30 days Lovenox BID (40-mg twice daily for BMI> 40, 60-mg twice daily for BMI >60). Outcomes evaluated were rate of VTE/PMVT and postoperative bleed, including delayed bleed., Results: A total of 8864 patients underwent SG. Average age and BMI were 37.5 years and 43.0 kg/m 2 , respectively. The overall incidence of PMVT was 33/8864 (.37%). Converting from selective extended chemoprophylaxis (Group 1) to routine extended chemoprophylaxis (Group 3) decreased the rate of PMVT from .55% to .21% (P = .13). There was a significantly higher overall bleeding rate (.85%), including delayed bleeds (.34%) in the routine extended chemoprophylaxis patients (P < .05). These bleeds were mainly managed nonoperatively., Conclusions: Routine extended (30 day) chemoprophylaxis for all SG may reduce PMVT rate but lead to a higher bleeding rate post-operatively. The vast majority of the increased bleeds are delayed and can be managed non-operatively., (Copyright © 2023 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Ovarian cancer is the seventh most common cancer in women in the world, with an estimated worldwide mortality of over 207'000 women every year. This cancer, due to the current lack of adequate screening techniques, is commonly diagnosed late and has a poor prognosis. The oral contraceptive pill is considered the most effective prevention strategy for ovarian cancer in the general population, being associated with a decreased incidence while also having a substantial positive impact on the mortality rate, which is reduced by up to 50%. BRCA1 and BRCA2 germline mutated women have an augmented risk of ovary and breast cancer: despite international guidelines that consider prophylactic surgery as the gold standard for ovarian cancer prevention, there are currently no effective non-invasive preventive methods. In BRCA1\2 mutated patients, clinicians should weigh the benefits of contraceptive pills against the risk of long-term thromboembolic side effects and hormonal malignancies such as breast and cervical cancer. A multidisciplinary team should counsel patients on the most appropriate risk-reduction strategy tailored to their needs and expectations, proposing the oral contraceptive pill to selected patients after balancing the risks of adverse effects and the benefits on both contraception and chemoprevention., (© 2023. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

Background: Perennial malaria chemoprevention (PMC) aims to protect children at risk from severe malaria by the administration of anti-malarial drugs to children of defined ages throughout the year. Sulfadoxine-pyrimethamine (SP) has been widely used for chemoprevention in Africa and a child-friendly dispersible tablet formulation has recently become available., Methods: This qualitative non-interventional observational study was conducted in Benin, Côte d'Ivoire, and Mozambique between February and June 2022. Prototype blister packs, dispensing boxes and job aids designed to support dispersible SP deployment for PMC were evaluated using focus group discussions (FGD) and semi-structured in-depth individual interviews (IDI) with health authorities, health personnel, community health workers (CHWs) and caregivers. The aim was to evaluate knowledge and perceptions of malaria and chemoprevention, test understanding of the tools and identify gaps in understanding, satisfaction, user-friendliness and acceptability, and assess the potential role of CHWs in PMC implementation. Interviews were transcribed and imported to ATLAS.ti for encoding and categorization. Thematic content analysis used deductive and inductive coding with cross-referencing of findings between countries and participants to enrich data interpretation. Continuous comparison across the IDI and FGD permitted iterative, collaborative development of materials., Results: Overall, 106 participants completed IDIs and 70 contributed to FGDs. Malaria was widely recognised as the most common disease affecting children, and PMC was viewed as a positive intervention to support child health. The role of CHWs was perceived differently by the target groups, with caregivers appreciating their trusted status in the community, whereas health authorities preferred clinic-based deployment of PMC by health professionals. Empirical testing of the prototype blister packs, dispensing boxes and job aids highlighted the context-specific expectations of respondents, such as familiar situations and equipment, and identified areas of confusion or low acceptance. A key finding was the need for a clear product identity reflecting malaria., Conclusion: Simple modifications profoundly affected the perception of PMC and influenced acceptability. Iterative quantitative investigation resulted in PMC-specific materials suited to the local context and socio-cultural norms of the target population with the aim of increasing access to chemoprevention in children most at risk of severe malaria., (© 2024. The Author(s).)

Background: Antiviral chemoprophylaxis is recommended for use during influenza outbreaks in nursing homes to prevent transmission and severe disease among non-ill residents. Centers for Disease Control and Prevention (CDC) guidance recommends prophylaxis be initiated for all non-ill residents once an influenza outbreak is detected and be continued for at least 14 days and until 7 days after the last laboratory-confirmed influenza case is identified. However, not all facilities strictly adhere to this guidance and the impact of such partial adherence is not fully understood., Methods: We developed a stochastic compartmental framework to model influenza transmission within an average-sized US nursing home. We compared the number of symptomatic illnesses and hospitalizations under varying prophylaxis implementation strategies, in addition to different levels of prophylaxis uptake and adherence by residents and healthcare personnel (HCP)., Results: Prophylaxis implemented according to current guidance reduced total symptomatic illnesses and hospitalizations among residents by a median of 12% and 36%, respectively, compared with no prophylaxis. We did not find evidence that alternative implementations of prophylaxis were more effective: compared to full adoption of current guidance, partial adoption resulted in increased symptomatic illnesses and/or hospitalizations, and longer or earlier adoption offered no additional improvements. In addition, increasing uptake and adherence among nursing home residents was effective in reducing resident illnesses and hospitalizations, but increasing HCP uptake had minimal indirect impacts for residents., Conclusions: The greatest benefits of influenza prophylaxis during nursing home outbreaks will likely be achieved through increasing uptake and adherence among residents and following current CDC guidance., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)