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.

BACKGROUND: Perennial malaria chemoprevention (PMC) is a chemoprevention strategy endorsed by the World Health Organization (WHO) and is increasingly being adopted by National Malaria Programmes. PMC aims to reduce morbidity and mortality caused by malaria and anaemia in in young children through provision of antimalarial drugs at routine contact points with the local health system. This study aims to evaluate the impact of the programmatically-implemented country-tailored PMC programmes targeting children up to two years of age using sulfadoxine-pyrimethamine (SP) on the incidence of malaria and anaemia in children in Cameroon and Côte d\'Ivoire.
METHODS: We will assess the impact of PMC using passive and active monitoring of a prospective observational cohort of children up to 36 months of age at recruitment in selected study sites in Cameroon and Côte d\'Ivoire. The primary and secondary outcomes include malaria, anaemia and malnutrition incidence. We will also conduct a time-series analysis of passively detected malaria and anaemia cases comparing the periods before and after PMC introduction. This study is powered to detect a 30% and 40% reduction of malaria incidence compared to the standard of care in Cameroon and Côte d\'Ivoire, respectively.
CONCLUSIONS: This multi-country study aims to provide evidence of the effectiveness of PMC targeting children in the first two years of life on malaria and anaemia and will provide important information to inform optimal operationalization and evaluation of this strategy.
BACKGROUND: Cameroon - NCT05889052; Côte d\'Ivoire - NCT05856357.

OBJECTIVE: 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.

Resveratrol (RSV), the primary polyphenol found in grapes, has been revealed to have anti-inflammatory properties by reducing the capacity of the peripheral blood mononuclear cells to produce pro-inflammatory cytokines, including IL-1β, IL-6, IL-1ra and TNFα. Considering the close association between chronic inflammation and cancer development, RSV\'s immunomodulatory properties are one way by which the polyphenol may inhibit cancer initiation, proliferation, neovascularization, and migration. Resveratrol influences the generation of microtumor environment which is one of the key factors in cancer progress. In addition to immunomodulation, RSV inhibits cancer development by expressing anti-oxidant effects, causing cell cycle arrest, stimulating the function of certain enzymes, and activating cell signaling pathways. The end outcome is one of the various forms of cell death, including apoptosis, pyroptosis, necroptosis, and more, as it has been observed in vitro. RSV has been shown to act against cancer in practically every organ, while its effects on colon cancer have been documented more frequently. It is remarkable that longer-term clinical studies that may have established the potential for this natural substance to serve as a therapeutic adjuvant to traditional anti-cancer medications were not prompted by the encouraging outcomes seen with cancer cells treated with non-toxic doses of resveratrol. The current review aims to assess the recent findings about the immunological and anti-cancer characteristics of RSV, with a particular emphasis on cancers of the digestive tract, as a challenge for future clinical research that may contribute to the better prognosis of cancer.

Sorghum is considered a promising food security crop and remarkable rich source of bioactive components including phenolic acids, flavonoids, and tannins. Sorghum phenolics exhibited numerous protective effects against multiple chronic diseases. However, there is no review of the effects of sorghum phenolics on gastrointestinal (GI) health. Specifically, recent studies have highly suggested that sorghum phenolics can maintain gastrointestinal homeostasis and enhance microbial diversity and richness. Furthermore, sorghum phenolics showed GI anticancer effects in both in vitro and in vivo studies against colorectal and esophageal cancers. Treatment of GI related human cancer cell lines stimulated apoptosis and suppressed proliferation. Sorghum intake and extracts treatments reduced intestinal oxidative stress and inflammatory mediators in human and in vivo studies. In addition, understanding the role and mechanisms underlying gastrointestinal health benefits of sorghum phenolics is crucial to determine treatment strategies of different GI diseases.

Hydroxycinnamic acids (HCAs) are plant compounds with anticancer potential due to their antioxidant, anti-inflammatory, apoptosis-inducing, and proliferation-inhibiting effects. This review aims to consolidate and analyze current knowledge on the anticancer effects of HCAs, exploring their mechanisms of action, bioavailability challenges, and potential therapeutic applications. A comprehensive literature search on PubMed/MedLine, Scopus, Web of Science, and Google Scholar focused on the anticancer properties, mechanisms, bioavailability, and safety profiles of HCAs. Studies have shown that HCAs, such as caffeic acid, ferulic acid, and sinapic acid, inhibit the growth of cancer cells in vitro and in vivo and sensitize cancer cells to chemotherapy and radiation therapy. These effects are mediated by mechanisms including the inhibition of cell survival pathways, modulation of gene expression, and induction of oxidative stress and DNA damage. Additionally, several studies have demonstrated that HCAs exhibit selective toxicity, with a higher propensity to induce cell death in cancerous cells compared to normal cells. However, the toxicity profile of HCAs can vary depending on the specific compound, dosage, and experimental conditions. The anticancer properties of HCAs suggest potential applications in cancer prevention and treatment. However, it is essential to distinguish between their use as dietary supplements and therapeutic agents, as the dosage and formulation suitable for dietary supplements may be insufficient for therapeutic purposes. The regulatory and practical implications of using HCAs in these different contexts require careful consideration. Further research is needed to determine appropriate dosages, formulations, long-term effects, and regulatory frameworks for HCAs as both dietary supplements and therapeutic agents.

The olive tree (Olea europaea) and olive oil hold significant cultural and historical importance in Europe. The health benefits associated with olive oil consumption have been well documented. This paper explores the mechanisms of the anti-cancer effects of olive oil and olive leaf, focusing on their key bioactive compounds, namely oleocanthal, oleacein, and oleuropein. The chemopreventive potential of oleocanthal, oleacein, and oleuropein is comprehensively examined through this systematic review. We conducted a systematic literature search to identify eligible articles from Scopus, PubMed, and Web of Science databases published up to 10 October 2023. Among 4037 identified articles, there were 88 eligible articles describing mechanisms of chemopreventive effects of oleocanthal, oleacein, and oleuropein. These compounds have the ability to inhibit cell proliferation, induce cell death (apoptosis, autophagy, and necrosis), inhibit angiogenesis, suppress tumor metastasis, and modulate cancer-associated signalling pathways. Additionally, oleocanthal and oleuropein were also reported to disrupt redox hemostasis. This review provides insights into the chemopreventive mechanisms of O. europaea-derived secoiridoids, shedding light on their role in chemoprevention. The bioactivities summarized in the paper support the epidemiological evidence demonstrating a negative correlation between olive oil consumption and cancer risk. Furthermore, the mapped and summarized secondary signalling pathways may provide information to elucidate new synergies with other chemopreventive agents to complement chemotherapies and develop novel nutrition-based anti-cancer approaches.

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.

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BACKGROUND: Twice-yearly mass distribution of azithromycin to children is a promising intervention to reduce childhood mortality in sub-Saharan Africa. The World Health Organization recommended restricting distribution to infants 1 to 11 months of age to mitigate antimicrobial resistance, although this more limited treatment had not yet been tested.
METHODS: We randomly assigned rural communities in Niger to four twice-yearly distributions of azithromycin for children 1 to 59 months of age (child azithromycin group), four twice-yearly distributions of azithromycin for infants 1 to 11 months of age and placebo for children 12 to 59 months of age (infant azithromycin group), or placebo for children 1 to 59 months of age. Census workers who were not aware of the group assignments monitored mortality twice yearly over the course of 2 years. We assessed three primary community-level mortality outcomes (deaths per 1000 person-years), each examining a different age group and pairwise group comparison.
RESULTS: A total of 1273 communities were randomly assigned to the child azithromycin group (1229 were included in the analysis), 773 to the infant azithromycin group (751 included in the analysis), and 954 to the placebo group (929 included in the analysis). Among 382,586 children, 419,440 person-years and 5503 deaths were recorded. Lower mortality among children 1 to 59 months of age was observed in the child azithromycin group (11.9 deaths per 1000 person-years; 95% confidence interval [CI], 11.3 to 12.6) than in the placebo group (13.9 deaths per 1000 person-years; 95% CI, 13.0 to 14.8) (representing 14% lower mortality with azithromycin; 95% CI, 7 to 22; P<0.001). Mortality among infants 1 to 11 months of age was not significantly lower in the infant azithromycin group (22.3 deaths per 1000 person-years; 95% CI, 20.0 to 24.7) than in the placebo group (23.9 deaths per 1000 person-years; 95% CI, 21.6 to 26.2) (representing 6% lower mortality with azithromycin; 95% CI, -8 to 19). Five serious adverse events were reported: three in the placebo group, one in the infant azithromycin group, and one in the child azithromycin group.
CONCLUSIONS: Azithromycin distributions to children 1 to 59 months of age significantly reduced mortality and was more effective than treatment of infants 1 to 11 months of age. Antimicrobial resistance must be monitored. (Funded by the Bill and Melinda Gates Foundation; AVENIR ClinicalTrials.gov number, NCT04224987.).