Effectiveness of malaria chemoprevention in the first two years of life in Cameroon and Côte d'Ivoire compared to standard of care: study protocol for a population-based prospective cohort impact evaluation study.

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. DISCUSSION: 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. TRIAL REGISTRATION: Cameroon - NCT05889052; Côte d'Ivoire - NCT05856357.

Perceived barriers and opportunities for the introduction of post-discharge malaria chemoprevention (PDMC) in five sub-Saharan countries: a qualitative survey amongst malaria key stakeholders.

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.

Upper Extremity Deep Vein Thrombosis: Incidence, Risk Factors, and Effectiveness of Chemoprophylaxis.

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.

The monthly trends of malaria cases in children under 5 years of age in Guinea: comparative analysis between a seasonal malaria chemoprevention (SMC) and a non-SMC health district.

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.

Metformin in Chemoprevention of Lung Cancer: A Retrospective Population-Based Cohort Study in Lithuania.

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.

Awareness, knowledge, attitude, and practice of adverse drug reaction reporting among health workers in primary health centres participating in seasonal malaria chemoprevention campaign in Nigeria in 2022: a cross-sectional survey.

BACKGROUND: Evaluating health workers' knowledge and practice of adverse drug reaction (ADR) reporting is an important step in identifying gaps in quality ADR reporting during public health interventions like the seasonal malaria chemoprevention (SMC) campaign. Pharmacovigilance (PV) monitoring is vital in SMC due to the number of children exposed to malaria medicines for a period of 4 or 5 months during the campaign. In Nigeria more than 10 million children are exposed to SMC medicines every year. The scale of this intervention emphasised the need for efficient and effective safety monitoring during the campaign. Thus, the objective of this study was to evaluate healthcare workers' (HCW) awareness, knowledge, attitude and practice (KAP) of ADR reporting in health facilities participating in SMC campaign to identify pharmacovigilance gaps which may suggest possible ways to ensure safety during the campaign. METHODS: World Health Organization's service availability and readiness assessment (SARA) recommendations were used to sample 2,598 out of 5,195 used as supervising health facilities (HFs) during the 2022 SMC campaign across nine states of the country. Out of the sampled HFs, 2,144 eligible and consented health facility workers (HFWs) were assessed for awareness, and KAP of ADR using the validated 45-item self-administered questionnaire. The data was analysed using descriptive statistics and correlation analysis at p < 0.05. RESULTS: The majority of the respondents are males (n = 1,333, 62.2%). The HFWs showed good awareness (n = 2,037, 95.0%) of pharmacovigilance (PV). However, only 809 (37.7%) of them had good knowledge scores. The mean ADR reporting attitude score (85.0 ± 15.3%) was good with many of the respondents (n = 1,548, 72.2%) having a good score. However, the respondents' ADR practice was suboptimal, only 1,356 (63.2%) of them had encounters with ADR, and a lot of negative perceived barriers to ADR reporting were identified in the study. For example, 493 (23%) believed that ADRs were not reported because they were not serious and life-threatening while 248 (11.6%) reported a fear of liability. Correlation analysis revealed female gender (r = 0.163, p < 0.001), older age (r = 0.207, p < 0.001) and years of practice (r = 0.050, p = 0.021) as factors significantly associated with ADR knowledge and attitude scores. CONCLUSION: The study indicated that HCWs across health facilities participating in SMC campaigns have ADR reporting knowledge and practice gaps. The study suggest training alone may not be effective in addressing gaps in ADR reporting. In addition to PV training, implementers can include continuous mentoring of health care workers or other similar interventions as part of strategy to improve ADR reporting. Also, context specific strategies to improve ADR reporting among health care worker needs to be implemented to address under-reporting of ADRs during SMC campaigns and other malaria public health interventions.

Azithromycin to Reduce Mortality - An Adaptive Cluster-Randomized Trial.

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.).

Barriers to the quality delivery of seasonal malaria chemoprevention in Chad and Burkina Faso: a qualitative exploration of caregivers and community distributors' perspectives.

BACKGROUND: Recommended since 2012 by the World Health Organization (WHO), seasonal malaria chemoprevention (SMC) is a community-based intervention to prevent malaria in children in African regions where malaria transmission follows a seasonal pattern. Following the publication of consolidated WHO guidelines for malaria, SMC is expected to reach more children in new geographies in future years. Though SMC has been shown to reduce malaria-related morbidity and mortality, there is potential for quality improvement of the intervention implementation. Assisted by ten quality standards from a framework developed by Malaria Consortium, this paper aims to better understand the quality of SMC implementation and identify potential barriers to quality delivery of SMC. METHODS: A qualitative thematic analysis on data collected after the annual SMC rounds implemented in Burkina Faso and Chad in 2019 was conducted. Sixteen focus group discussions conducted with caregivers and community distributors were analysed. Three selected quality standards for SMC delivery; planning and enumeration; community engagement; and administration of SMC medicines provided overarching quality themes under which subthemes were identified. RESULTS: Eight subthemes relating to the three quality standards were identified. Although SMC was well accepted by communities in both settings, common barriers to the quality delivery of SMC were identified including difficulty ensuring adherence to the SMC administration protocol; difficulties reaching mobile populations; concerns around adverse drug reactions; rumours, and concerns about SMC safety; and community distributors' working conditions. Context-specific barriers included: the suboptimal timeliness of the SMC round in Burkina Faso, and the lack of involvement of female caregivers in mobilization activities in Chad. CONCLUSION: In the context of increased adoption of SMC, this paper provides relevant insights and recommendations for the improved implementation of SMC programmes. These include the integration of strategies addressing communities' concerns around adverse drug reactions, gender-specific mobilization strategies, and attention to community distributors' working conditions. It also highlights the importance and utility of further, robust research on the quality of SMC delivery.

RéSUMé EN FRANçAIS: BACKGROUND: Recommandée depuis 2012 par l'Organisation mondiale de la santé (OMS), la chimioprévention du paludisme saisonnier (CPS) est une intervention communautaire visant à prévenir le paludisme chez les enfants dans les régions d'Afrique où la transmission du paludisme suit un schéma saisonnier. Suite à la publication des lignes directrices consolidées de l'OMS sur le paludisme, la CPS devrait toucher davantage d'enfants dans de nouvelles zones géographiques dans les années à venir. Bien qu'il ait été démontré que la CPS réduisait la morbidité et la mortalité liées au paludisme, il y a du potentiel pour améliorer la qualité de l'implémentation l'intervention. En s'appuyant sur un cadre de normes de qualité de la CPS développé par le Malaria Consortium, cette publication vise à mieux comprendre la qualité de la mise en œuvre de la CPS et à identifier les obstacles potentiels à la qualité de la mise en œuvre de la CPS. METHODS: Une étude qualitative basée sur l'analyse secondaire des données collectées après les tournées annuelles du SMC mises en œuvre au Burkina Faso et au Tchad en 2019 a été menée. Une analyse thématique de 16 discussions de groupe menées avec des parents/tuteurs et des distributeurs communautaires a été faite. Trois des éléments clés du cadre des normes de qualité pour le déploiement de la CPS ont fourni les thèmes de qualité principaux sous lesquels les sous-thèmes identifiés ont été placés. RéSULTATS: Huit sous-thèmes relatifs aux normes de qualité ; la planification, la sensibilisation et l'engagement des communautés ainsi que l'administration des médicaments de la CPS ont été identifiés. Bien que la CPS ait été bien acceptée par les communautés dans les deux contextes, des obstacles communs à la qualité du déploiement de la CPS ont été identifiés, notamment : la difficulté d'assurer le respect du protocole d'administration de la CPS; atteindre les populations mobiles ; les préoccupations concernant les effets indésirables des médicaments ; les rumeurs et les préoccupations concernant le SMC; et les conditions de travail des distributeurs communautaires. D'autres barrières spécifiques au contexte de déploiement ont été identifiées, telles que le choix sous-optimal de la période de déploiement au Burkina Faso ou le manque d'implication des mères/tutrices dans les activités de mobilisation au Tchad. CONCLUSION: Dans le contexte de l'adoption croissante de la CPS, cette publication fournit des informations et des recommandations pertinentes pour l'amélioration de la mise en œuvre des programmes de CMS, telles que l'intégration de stratégies répondant aux préoccupations des communautés concernant les effets indésirables des médicaments, les stratégies de mobilisation spécifiques au genre, et/ou l'attention portée aux conditions de travail des distributeurs communautaires. Cette publication souligne également l'importance et l'utilité des recherches en cours sur la qualité du déploiement de la CPS.

RESUMO EM PORTUGUêS: INTRODUçãO: Recomendada desde 2012 pela Organização Mundial de Saúde (OMS), a quimioprevenção sazonal do paludismo (SMC) é uma intervenção de base comunitária para prevenir o paludismo em crianças em zonas da África onde a transmissão do paludismo segue um padrão sazonal. Após a publicação das diretrizes consolidadas da OMS sobre o paludismo, espera-se que a SMC chegue a mais crianças em novas zonas geográficas nos próximos anos. Embora se tenha demonstrado que a SMC reduz a morbilidade e a mortalidade causadas pelo paludismo, há potencial para melhorar a qualidade da implementação da intervenção. Com ajuda dum quadro de padrões de qualidade para a SMC desenvolvido pelo Malaria Consortium, a presente publicação visa compreender melhor a qualidade da implementação da SMC e identificar potenciais barreiras à qualidade da implementação da SMC. MéTODOS: Foi realizado um estudo qualitativo baseado na análise secundária dos dados recolhidos após as rondas anuais da SMC implementadas no Burkina Faso e no Chade em 2019. Foi efectuado uma análise temática de 16 discussões de grupos focais realizadas com cuidadores e distribuidores comunitários. Tres padrões do quadro de normas de qualidade para a implementação da SMC forneceu os principais temas de qualidade sob os quais os subtemas identificados foram colocados. RESULTADOS: Foram identificados oito sub-temas relacionados com padrões de qualidade; planeamento; sensibilização e envolvimento da comunidade; e administração de drogas da SMC. Embora a SMC tenha sido bem aceita pelas comunidades em ambos os contextos, foram identificadas barreiras comuns à implementação duma SMC de qualidade, incluindo: a dificuldade de assegurar o cumprimento do protocolo de administração da SMC; atingir populações móveis; preocupações com reacções adversas aos medicamentos; rumores e preocupações com a SMC; e as condições de trabalho dos distribuidores comunitários. Foram identificados outros obstáculos específicos ao contexto de implantação, tais como a escolha subaproveitada do período de implantação no Burkina Faso ou a falta de envolvimento das cuidadoras femininas nas actividades de mobilização no Chade. CONCLUSãO: No contexto do aumento da adopção da SMC, esta publicação fornece informações e recomendações relevantes para melhorar a implementação de programas de SMC, tais como estratégias integradoras que abordam as preocupações da comunidade sobre reacções adversas aos medicamentos, estratégias de mobilização específicas de género, e/ou atenção às condições de trabalho dos distribuidores comunitários. Salienta igualmente a importância e a utilidade das investigaçãos em curso sobre a qualidade da implementação da SMC.

Can Isoflavone-Rich Legume Plants Be Useful in the Chemoprevention of Hormone-Dependent Cancers?-A Systematic Review.

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.

Coffee Bean and Its Chemical Constituent Caffeine and Chlorogenic Acid as Promising Chemoprevention Agents: Updated Biological Studies against Cancer Cells.

Cancer is a complicated and ever-evolving disease that remains a significant global cause of disease and mortality. Its complexity, which is evident at the genetic and phenotypic levels, contributes to its diversity and resistance to treatment. Numerous scientific investigations on human and animal models demonstrate the potential of phytochemicals in cancer prevention. Coffee has been shown to possess potent anti-carcinogenic properties, and studies have documented the consumption of coffee as a beverage reduces the risk of cancer occurrence. The major secondary metabolites of coffee, named caffeine and chlorogenic acid, have been linked to anti-inflammatory and antineoplastic effects through various signaling. In light of this, this review article provides a comprehensive analysis based on studies in anticancer effects of coffee, chlorogenic acid, and caffeine published between 2010 and 2023, sourced from Scopus, Pubmed, and Google Scholar databases. We summarize recent advances and scientific evidence on the association of phytochemicals found in coffee with a special emphasis on their biological activities against cancer and their molecular mechanism deemed potential to be used as a novel therapeutic target for cancer prevention and therapy.

Differential microRNAs Expression during Cancer Development, and Chemoprevention by Natural Compounds: A Comprehensive Review.

MicroRNAs are short non-coding RNAs that inhibit gene expression at the post-transcriptional level. Abnormal microRNA expression has been associated with different human diseases, including cancer. Epigenetic changes, mutation, transcriptional deregulation, DNA copy number abnormalities, and defects in the biogenesis machinery play an important role in abnormal microRNA expression. Modulation of microRNAs by natural agents has emerged to enhance the efficacy of conventional chemotherapy through combinatorial therapeutic approach. This review summarizes the current understanding of abnormal microRNA expression in cancer, the different cellular mechanisms of microRNA, and their prevention by natural compounds. Understanding microRNA expression patterns during cancer development may help to identify stage-specific molecular markers. Natural compounds that exert regulatory effects by modulating microRNAs can be used in better cancer chemopreventive strategies by directly targeting microRNAs or as a way to increase sensitivity to existing chemotherapy regimens.

Short-term versus extended chemoprophylaxis against venous thromboembolism in DIEP flap breast reconstruction: A retrospective study of 424 patients.

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.

Seasonal malaria chemoprevention and the spread of Plasmodium falciparum quintuple-mutant parasites resistant to sulfadoxine-pyrimethamine: a modelling study.

BACKGROUND: Seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine prevents millions of clinical malaria cases in children younger than 5 years in Africa's Sahel region. However, Plasmodium falciparum parasites partially resistant to sulfadoxine-pyrimethamine (with quintuple mutations) potentially threaten the protective effectiveness of SMC. We evaluated the spread of quintuple-mutant parasites and the clinical consequences. METHODS: We used an individual-based malaria transmission model with explicit parasite dynamics and drug pharmacological models to identify and quantify the influence of factors driving quintuple-mutant spread and predict the time needed for the mutant to spread from 1% to 50% of inoculations for several SMC deployment strategies. We estimated the impact of this spread on SMC effectiveness against clinical malaria. FINDINGS: Higher transmission intensity, SMC coverage, and expanded age range of chemoprevention promoted mutant spread. When SMC was implemented in a high-transmission setting (40% parasite prevalence in children aged 2-10 years) with four monthly cycles to children aged 3 months to 5 years (with 95% initial coverage declining each cycle), the quintuple mutant required 53·1 years (95% CI 50·5-56·0) to spread from 1% to 50% of inoculations. This time increased in lower-transmission settings and reduced by half when SMC was extended to children aged 3 months to 10 years, or reduced by 10-13 years when an additional monthly cycle of SMC was deployed. For the same setting, the effective reduction in clinical cases in children receiving SMC was 79·0% (95% CI 77·8-80·8) and 60·4% (58·6-62·3) during the months of SMC implementation when the quintuple mutant was absent or fixed in the population, respectively. INTERPRETATION: SMC with sulfadoxine-pyrimethamine plus amodiaquine leads to a relatively slow spread of sulfadoxine-pyrimethamine-resistant quintuple mutants and remains effective at preventing clinical malaria despite the mutant spread. SMC with sulfadoxine-pyrimethamine plus amodiaquine should be considered in seasonal settings where this mutant is already prevalent. FUNDING: Swiss National Science Foundation and Marie Curie Individual Fellowship.

Impact of seasonal malaria chemoprevention based on the number of medicines doses received on malaria burden among children aged 3-59 months in Nigeria: A propensity score-matched analysis.

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.

Synergic Role of Dietary Bioactive Compounds in Breast Cancer Chemoprevention and Combination Therapies.

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.

Aspirin as a chemopreventive agent for cutaneous melanoma: a literature review.

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.