Compliance with eight years of annual ivermectin treatment of onchocerciasis in Cameroon and Nigeria

<p>Abstract</p> <p>Background</p> <p>As the African Programme for Onchocerciasis Control (APOC) matured into its 10^thyear of ensuring community involvement in mass annual treatment of onchocerciasis with ivermectin, there was recognition of a need to study not only annual coverage of ivermectin in villages but also the compliance of individual villagers with these annual treatments. This was based on the concern that while population coverage goals may be achieved each year, there might be segments of the population who systematically are not complying with the annual regimen, thus creating a reservoir of infection and threatening program gains.</p> <p>Methods</p> <p>A multi-site study in five APOC sponsored projects in Nigeria and Cameroon was undertaken to identify the socio-demographic correlates of compliance with ivermectin treatment. A total of 8,480 villagers above 9 years of age selected through a systematic random sampling from 101 communities were surveyed to ascertain their levels of compliance, by adapting APOC's standard household ivermectin survey form. Community leaders, community directed distributors (CDDs) of ivermectin and health workers were interviewed with in-depth interview guides, while focus group discussions were held with community members to help explain how socio-demographic factors might affect compliance.</p> <p>Results</p> <p>Eight-year compliance ranged from 0 to 8 times with 42.9% taking ivermectin between 6-8 times annually (high compliance). In bivariate analysis high compliance was positively associated with being male, over 24 years of age, having been married, not being Christian, having little or no formal education and being in the ethnic majority. These variables were also confirmed through regression analysis based on total times ivermectin was taken over the period. While these factors explained only 8% of the overall variation in compliance, ethnic status and education appeared to be the strongest factors. Those with higher education may be more mobile and harder to reach while neglect of ethnic minorities has also been documented in other programs.</p> <p>Conclusion</p> <p>These findings can help managers of CDTI programmes to ensure ivermectin reaches all segments of the population equally.</p

DNA mismatch repair activity of MutLα is regulated by CK2-dependent phosphorylation of MLH1 (S477)

MutLα, a heterodimer consisting of MLH1 and PMS2, is a key player of DNA mismatch repair (MMR), yet little is known about its regulation. In this study, we used mass spectrometry to identify phosphorylated residues within MLH1 and PMS2. The most frequently detected phosphorylated amino acid was serine 477 of MLH1. Pharmacological treatment indicates‎ that Casein kinase II (CK2) could be responsible for the phosphorylation of MLH1 at serine 477 in vivo. In vitro kinase assay verified MLH1 as a substrate of CK2. Most importantly, using in vitro MMR assay we could demonstrate that p-MLH1S477 lost MMR activity. Moreover, we found that levels of p-MLH1S477 varied during the cell cycle. In summary, we identified that phosphorylation of MLH1 by CK2 at amino acid position 477 can switch off MMR activity in vitro. Since CK2 is overexpressed in many tumors and is able to inactivate MMR, the new mechanism here described could have an important impact on tumors overactive in CK2.Fil: Weßbecher, Isabel M.. Goethe Universitat Frankfurt; AlemaniaFil: Hinrichsen, Inga. Goethe Universitat Frankfurt; AlemaniaFil: Funke, Sebastian. Klinikum Der Johannes-gutenberg-universität Und Fachbereich Medizin; AlemaniaFil: Oellerich, Thomas. Goethe Universitat Frankfurt; AlemaniaFil: Plotz, Guido. Goethe Universitat Frankfurt; AlemaniaFil: Zeuzem, Stefan. Goethe Universitat Frankfurt; AlemaniaFil: Grus, Franz H.. Klinikum Der Johannes-gutenberg-universität Und Fachbereich Medizin; AlemaniaFil: Biondi, Ricardo Miguel. Goethe Universitat Frankfurt; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Brieger, Angela. Goethe Universitat Frankfurt; Alemani

Assessment of a treatment guideline to improve home management of malaria in children in rural south-west Nigeria

<p>Abstract</p> <p>Background</p> <p>Many Nigerian children with malaria are treated at home. Treatments are mostly incorrect, due to caregivers' poor knowledge of appropriate and correct dose of drugs. A comparative study was carried out in two rural health districts in southwest Nigeria to determine the effectiveness of a guideline targeted at caregivers, in the treatment of febrile children using chloroquine.</p> <p>Methods</p> <p>Baseline and post intervention knowledge, attitude and practice household surveys were conducted. The intervention strategy consisted of training a core group of mothers ("mother trainers") in selected communities on the correct treatment of malaria and distributing a newly developed treatment guideline to each household. "Mother trainers" disseminated the educational messages about malaria and the use of the guideline to their communities.</p> <p>Results</p> <p>Knowledge of cause, prevention and treatment of malaria increased with the one-year intervention. Many, (70.4%) of the respondents stated that they used the guideline each time a child was treated for malaria. There was a significant increase in the correct use of chloroquine from 2.6% at baseline to 52.3% after intervention among those who treated children at home in the intervention arm compared with 4.2% to 12.7% in the control arm. The correctness of use was significantly associated with use of the guideline. The timeliness of commencing treatment was significantly earlier in those who treated febrile children at home using chloroquine than those who took their children to the chemist or health facility (p < 0.005). Mothers considered the guideline to be explicit and useful. Mother trainers were also considered to be effective and acceptable.</p> <p>Conclusion</p> <p>The use of the guideline with adequate training significantly improved correctness of malaria treatment with chloroquine at home. Adoption of this mode of intervention is recommended to improve compliance with drug use at home. The applicability for deploying artemisinin-based combination therapy at the community level needs to be investigated.</p

Dynamic catalytic highly enantioselective 1,3‐dipolar cycloadditions

In dynamic covalent chemistry, reactions follow a thermodynamically controlled pathway through equilibria. Reversible covalent-bond formation and breaking in a dynamic process enables the interconversion of products formed under kinetic control to thermodynamically more stable isomers. Notably, enantioselective catalysis of dynamic transformations has not been reported and applied in complex molecule synthesis. We describe the discovery of dynamic covalent enantioselective metal-complex-catalyzed 1,3-dipolar cycloaddition reactions. We have developed a stereodivergent tandem synthesis of structurally and stereochemically complex molecules that generates eight stereocenters with high diastereo- and enantioselectivity through asymmetric reversible bond formation in a dynamic process in two consecutive Ag-catalyzed 1,3-dipolar cycloadditions of azomethine ylides with electron-poor olefins. Time-dependent reversible dynamic covalent-bond formation gives enantiodivergent and diastereodivergent access to structurally complex double cycloadducts with high selectivity from a common set of reagents

Intervention in acute coronary syndromes:do patients undergo intervention on the basis of their risk characteristics? The Global Registry of Acute Coronary Events (GRACE)

OBJECTIVE: To determine whether revascularisation is more likely to be performed in higher-risk patients and whether the findings are influenced by hospitals adopting more or less aggressive revascularisation strategies. METHODS: GRACE (Global Registry of Acute Coronary Events) is a multinational, observational cohort study. This study involved 24,189 patients enrolled at 73 hospitals with on-site angiographic facilities. RESULTS: Overall, 32.5% of patients with a non-ST elevation acute coronary syndrome (ACS) underwent percutaneous coronary intervention (PCI; 53.7% in ST segment elevation myocardial infarction (STEMI)) and 7.2% underwent coronary artery bypass grafting (CABG; 4.0% in STEMI). The cumulative rate of in-hospital death rose correspondingly with the GRACE risk score (variables: age, Killip class, systolic blood pressure, ST segment deviation, cardiac arrest at admission, serum creatinine, raised cardiac markers, heart rate), from 1.2% in low-risk to 3.3% in medium-risk and 13.0% in high-risk patients (c statistic = 0.83). PCI procedures were more likely to be performed in low- (40% non-STEMI, 60% STEMI) than medium- (35%, 54%) or high-risk patients (25%, 41%). No such gradient was apparent for patients undergoing CABG. These findings were seen in STEMI and non-ST elevation ACS, in all geographical regions and irrespective of whether hospitals adopted low (4.2-33.7%, n = 7210 observations), medium (35.7-51.4%, n = 7913 observations) or high rates (52.6-77.0%, n = 8942 observations) of intervention. CONCLUSIONS: A risk-averse strategy to angiography appears to be widely adopted. Proceeding to PCI relates to referral practice and angiographic findings rather than the patient\u27s risk status. Systematic and accurate risk stratification may allow higher-risk patients to be selected for revascularisation procedures, in contrast to current international practice

A founder MLH1 mutation in families from the districts of Modena and Reggio-Emilia in northern Italy with hereditary non-polyposis colorectal cancer associated with protein elongation and instability.

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Cerium Oxide Nanoparticles: Advances in Biodistribution, Toxicity, and Preclinical Exploration

Antioxidant nanoparticles have recently gained tremendous attention for their enormous potential in biomedicine. However, discrepant reports of either medical benefits or toxicity, and lack of reproducibility of many studies, generate uncertainties delaying their effective implementation. Herein, the case of cerium oxide is considered, a well‐known catalyst in the petrochemistry industry and one of the first antioxidant nanoparticles proposed for medicine. Like other nanoparticles, it is now described as a promising therapeutic alternative, now as threatening to health. Sources of these discrepancies and how this analysis helps to overcome contradictions found for other nanoparticles are summarized and discussed. For the context of this analysis, what has been reported in the liver is reviewed, where many diseases are related to oxidative stress. Since well‐dispersed nanoparticles passively accumulate in liver, it represents a major testing field for the study of new nanomedicines and their clinical translation. Even more, many contradictory works have reported in liver either cerium‐oxide‐associated toxicity or protection against oxidative stress and inflammation. Based on this, finally, the intention is to propose solutions to design improved nanoparticles that will work more precisely in medicine and safely in society

Health systems strengthening through policy-level integration of community health worker programs integration into national health systems for improved health outcomes - scorecard metrics validation: A bifactor structural equation model approach

BackgroundSubsequent to the demonstrated potential of community health workers (CHWs) in strengthening health systems to improve health outcomes, recent literature has defined context and guidelines for integrating CHW programs into mainstream health systems. However, quantitative measures for assessing the extent of CHW program integration into national health systems need to be developed. The purpose of this study was to validate a newly developed scale, Community Health Worker Program Integration Scorecard Metrics (CHWP-ISM), for assessing the degree of integration of CHW programs into national health systems in Sub-Saharan Africa (SSA).MethodsData obtained through a pilot study involving a purposively selected sample of 41 participants selected from populations involved in CHW programs work in selected countries of SSA formed the basis of a 31-item bifactor model. Data were collected between June and December 2019. By applying a latent variable approach implemented with structural equation modeling, data analysis was mainly done using the R statistical environment, applying factor analysis procedures.ResultsDimensionality, construct validity, and the CHWP-ISM scale's internal consistency were assessed. Confirmatory factor analysis of the CHW-ISM bifactor model supported a co-occurring CHW integration general factor and six unique domain-specific factors. Both the comparative fit index (CFI) and Tucker–Lewis Index (TLI) fit indices were above 0.9, while the root mean square of the residuals (RMSR) was 0.02. Cronbach's alpha (α), Guttman 6 (Lambda 6), and Omega total (ωt) were above 0.8, indicating good scale reliability.ConclusionStatistical significance of the bifactor model suggests that CHW integration has to be examined using factors that reflect a single common underlying integration construct, as well as factors that reflect unique variances for the identified six subject-specific domains. The validated CHWP-ISM could be useful to inform policy advisers, health systems, donors, non-governmental organizations, and other CHW program stakeholders with guidance on how to quantitatively assess the integration status of different components of CHW programs into respective critical functions of the health system. Improved integration could increase CHW program functionality, which could in turn strengthen the healthcare systems to improve health outcomes in the region

Rural-Urban Differences in Maternal Responses to Childhood Fever in South East Nigeria

Childhood fevers due to malaria remain a major cause of morbidity and mortality among under-five children in Nigeria. The degree of vulnerability perceived by mothers will affect their perception of the severity and threat of their child's fever and the patterns of health care use. This study was undertaken to compare maternal responses to childhood fever in urban and rural areas of Enugu, south east Nigeria.Data was collected with pre-tested interviewer-administered questionnaires from 276 and 124 urban and rural households respectively. In each household, only one woman aged 15-49 years who had lived in each of the urban and rural communities for at least one year and had at least one child less than 5 years old was interviewed. Malaria was mentioned as the commonest cause of childhood fevers. Rural mothers were more likely to recognize danger signs and symptoms than urban mothers. Rural mothers use more of informal than formal health services, and there is more home management of the fever with urban than rural mothers. Chloroquine, ACT, SP and Paracetamol are the main drugs given at home for childhood fevers, but the rural mothers were more likely to use leftover drugs from previous treatment to treat the fevers than urban mothers. The urban respondents were also more likely to use a preventive measure. Urban mothers sought actions faster than rural mothers and the total cost of treatment was also higher in urban areas.Both urban and rural mothers are aware that malaria is the major cause of childhood fevers. Although rural mothers recognize childhood fever and danger signs better than urban mothers, the urban mothers' responses to fever seem to be better than that for rural mothers. These responses and differences may be important for geographical targeting by policy makers for malaria interventions

Determinants of insecticide-treated net ownership and utilization among pregnant women in Nigeria

<p>Abstract</p> <p>Background</p> <p>Malaria during pregnancy is a major public health problem in Nigeria leading to increase in the risk of maternal mortality, low birth weight and infant mortality. This paper is aimed at highlighting key predictors of the ownership of insecticide treated nets (ITNs) and its use among pregnant women in Nigeria.</p> <p>Methods</p> <p>A total of 2348 pregnant women were selected by a multi-stage probability sampling technique. Structured interview schedule was used to elicit information on socio-demographic characteristics, ITN ownership, use, knowledge, behaviour and practices. Logistic regression was used to detect predictors of two indicators: ITN ownership, and ITN use in pregnancy among those who owned ITNs.</p> <p>Results</p> <p>ITN ownership was low; only 28.8% owned ITNs. Key predictors of ITN ownership included women who knew that ITNs prevent malaria (OR = 3.85; <it>p </it>< 0001); and registration at antenatal clinics (OR = 1.34; <it>p </it>= 0.003). The use of ITNs was equally low with only 7.5% of all pregnant women, and 25.7% of all pregnant women who owned ITNs sleeping under a net. The predictors of ITN use in pregnancy among women who owned ITNs (N = 677) identified by logistic regression were: urban residence (OR = 1.87; <it>p </it>= 0.001); knowledge that ITNs prevent malaria (OR = 2.93; <it>p </it>< 0001) and not holding misconceptions about malaria prevention (OR = 1.56; <it>p </it>= 0.036). Educational level was not significantly related to any of the two outcome variables. Although registration at ANC is significantly associated with ownership of a bednet (perhaps through free ITN distribution) this does not translate to significant use of ITNs.</p> <p>Conclusions</p> <p>ITN use lagged well behind ITN ownership. This seems to suggest that the current mass distribution of ITNs at antenatal facilities and community levels may not necessarily lead to use unless it is accompanied by behaviour change interventions that address the community level perceptions, misconceptions and positively position ITN as an effective prevention device to prevent malaria</p