Antimalarial artesunate-mefloquine versus praziquantel in African children with schistosomiasis: an open-label, randomized controlled trial.

Schistosomiasis treatment entirely relies on a single drug, praziquantel, prompting research into alternative therapeutics. Here we evaluated the efficacy and safety of the antimalarial combination artesunate-mefloquine for the treatment of schistosomiasis in a proof-of-concept, pragmatic, open-label, randomized controlled trial in primary schools of six villages endemic for schistosomiasis in northern Senegal. Children (6-14 years) were eligible if Schistosoma eggs were detected by microscopy in urine and/or stool. In total, 726 children were randomized 1:1 to praziquantel (standard care: 40 mg kg-1 single dose; n = 364) or to artesunate-mefloquine (antimalarial dosage: artesunate 4 mg kg-1 and mefloquine 8 mg kg-1 daily for three consecutive days; n = 362). Eight children not meeting the inclusion criteria were excluded from efficacy analysis. Median age of the remaining 718 participants was 9 years; 399 (55.6%) were male, and 319 (44.4%) female; 99.3% were infected with Schistosoma haematobium and 15.2% with S. mansoni. Primary outcomes were cure rate, assessed by microscopy, and frequency of drug-related adverse effects of artesunate-mefloquine versus praziquantel at 4 weeks after treatment. Cure rate was 59.6% (208/349) in the artesunate-mefloquine arm versus 62.1% (211/340) in the praziquantel arm. The difference of -2.5% (95% confidence interval (CI) -9.8 to 4.8) met the predefined criteria of noninferiority (margin set at 10%). All drug-related adverse events were mild or moderate, and reported in 28/361 children receiving artesunate-mefloquine (7.8%; 95% CI 5.4 to 11.0) versus 8/363 (2.2%; 95% CI 1.1 to 4.3) receiving praziquantel (P < 0.001). Artesunate-mefloquine at antimalarial dosage was moderately safe and noninferior to standard-care praziquantel for the treatment of schistosomiasis, predominantly due to S. haematobium. Multicentric trials in different populations and epidemiological settings are needed to confirm these findings. ClinicalTrials.gov identifier: NCT03893097 .

Perchlorate and chlorate assessment in drinking water in northern Chilean cities.

Perchlorate and chlorate are endocrine disruptors considered emerging contaminants (ECs). Both oxyanions are commonly associated with anthropogenic contamination from fertilizers, pesticides, explosives, and disinfection byproducts. However, the soils of the Atacama Desert are the most extensive natural reservoirs of perchlorate in the world, compromising drinking water sources in northern Chile. Field campaigns were carried (2014-2018) to assess the presence of these ECs in the water supply networks of twelve Chilean cities. Additionally, the occurrence of perchlorate, chlorate and other anions typically observed in drinking water matrices of the Atacama Desert (i.e., nitrate, chloride, sulfate) was evaluated using a Spearman correlation analysis to determine predictors for perchlorate and chlorate. High concentrations of perchlorate (up to 114.48 µg L-1) and chlorate (up to 9650 µg L-1) were found in three northern cities. Spatial heterogeneities were observed in the physicochemical properties and anion concentrations of the water supply network. Spearman correlation analysis indicated that nitrate, chloride, and sulfate were not useful predictors for the presence of perchlorate and chlorate in drinking water in Chile. Hence, this study highlights the need to establish systematic monitoring, regulation, and treatment for these EC of drinking water sources in northern Chilean cities for public health protection.

Evaluation of Artesunate-mefloquine as a Novel Alternative Treatment for Schistosomiasis in African Children (SchistoSAM): protocol of a proof-of-concept, open-label, two-arm, individually-randomised controlled trial.

INTRODUCTION: Alternative drugs and diagnostics are needed for the treatment and control of schistosomiasis. The exclusive use of praziquantel (PZQ) in mass drug administration programmes may result in the emergence of drug resistance. PZQ has little activity against Schistosoma larvae, thus reinfection remains a problem in high-risk communities. Furthermore, the insufficient sensitivity of conventional microscopy hinders therapeutic response assessment. Evaluation of artesunate-mefloquine (AM) as a Novel Alternative Treatment for Schistosomiasis in African Children (SchistoSAM) aims to evaluate the safety and efficacy of the antimalarial combination artesunate-mefloquine, re-purposed for the treatment of schistosomiasis, and to assess the performance of highly sensitive novel antigen-based and DNA-based assays as tools for monitoring treatment response. METHODS AND ANALYSIS: The SchistoSAM study is an open-label, two-arm, individually randomised controlled non-inferiority trial, with a follow-up of 48 weeks. Primary school-aged children from the Richard Toll district in northern Senegal, an area endemic for Schistosoma mansoni and Schistosoma haematobium, are allocated to the AM intervention arm (3-day courses at 6-week intervals) or the PZQ control arm (single dose of 40 mg/kg). The trial's primary endpoints are the efficacy (cure rate (CR), assessed by microscopy) and safety (frequency and pattern of drug-related adverse events) of one AM course versus PZQ at 4 weeks after treatment. Secondary endpoints include (1) cumulative CR, egg reduction rate and safety after each additional course of AM, and at weeks 24 and 48, (2) prevalence and severity of schistosomiasis-related morbidity and (3) malaria prevalence, incidence and morbidity, both after 24 and 48 weeks. CRs and intensity reduction rates are also assessed by antigen-based and DNA-based diagnostic assays, for which performance for treatment monitoring is evaluated. ETHICS AND DISSEMINATION: Ethics approval was obtained both in Belgium and Senegal. Oral assent from the children and signed informed consent from their legal representatives was obtained, prior to enrolment. The results will be disseminated in peer-reviewed journals and at international conferences. TRIAL REGISTRATION NUMBER: NCT03893097; pre-results.

Artemisinin-based combination therapy during pregnancy: outcome of pregnancy and infant mortality: a cohort study.

BACKGROUND: The World Health Organization (WHO) recommendation of treating uncomplicated malaria during the second and third trimester of pregnancy with an artemisinin-based combination therapy (ACT) has already been implemented by all sub-Saharan African countries. However, there is limited knowledge on the effect of ACT on pregnancy outcomes, and on newborn and infant's health. METHODS: Pregnant women with malaria in four countries (Burkina Faso, Ghana, Malawi and Zambia) were treated with either artemether-lumefantrine (AL), amodiaquine-artesunate (ASAQ), mefloquine-artesunate (MQAS), or dihydroartemisinin-piperaquine (DHA-PQ); 3127 live new-borns (822 in the AL, 775 in the ASAQ, 765 in the MQAS and 765 in the DHAPQ arms) were followed-up until their first birthday. RESULTS: Prevalence of placental malaria and low birth weight were 28.0% (738/2646) and 16.0% (480/2999), respectively, with no significant differences between treatment arms. No differences in congenital malformations (p = 0.35), perinatal mortality (p = 0.77), neonatal mortality (p = 0.21), and infant mortality (p = 0.96) were found. CONCLUSIONS: Outcome of pregnancy and infant survival were similar between treatment arms indicating that any of the four artemisinin-based combinations could be safely used during the second and third trimester of pregnancy without any adverse effect on the baby. Nevertheless, smaller safety differences between artemisinin-based combinations cannot be excluded; country-wide post-marketing surveillance would be very helpful to confirm such findings. Trial registration ClinicalTrials.gov, NCT00852423, Registered on 27 February 2009, https://clinicaltrials.gov/ct2/show/NCT00852423.

Procesamiento de estímulos novedosos como terapia de remediación cognitiva en pacientes con trastorno alimentario / Processing of novel stimuli as cognitive remediation therapy in patients with eating disorder

Resumen Estudios previos han indicado la utilidad de la terapia de remediación cognitiva (TRC) en pacientes con trastornos de conducta alimentaria (TCA). El objetivo de este estudio fue evaluar una nueva técnica de innovación cognitiva llamada "Con la cabeza en las nubes" (CCN). Participaron 22 mujeres con TCA (13 con anorexia nerviosa y 9 con bulimia nerviosa), de entre 14 y 29 años de edad (M = 19.0, DE = 3.4), quienes completaron las seis sesiones grupales de que consta dicha técnica. Bajo un diseño pre-post intervención, las participantes fueron evaluadas en cuanto a: funciones viso-constructivas (Copia de la Figura Compleja de Rey-Osterrieth [CFCR]), pensamiento creativo (Test de Pensamiento Creativo de Torrance [TPCT]), flexibilidad cognitiva (CFCR y TPCT) y control cognitivo (Test de Stroop). La intervención generó una mejora en distintos dominios cognitivos, como son: mayor coherencia global, pensamiento creativo y resistencia al cierre, así como menor fragmentación. Basada en la TRC, encaminada a estimular el procesamiento novedoso de estímulos visuales, la técnica CCN mostró mejorar algunos de los procesos cognitivos implicados en la generación de los síntomas de pacientes con TCA.

Abstract Previous studies have shown the usefulness of cognitive remediation therapy (CRT) in patients with eating disorders (ED). The objective of this study was to assess a new cognitive technique called "With the head in the clouds" (WHC). A total of 22 women with ED (13 with anorexia nervosa and nine with bulimia nervosa), between 14 and 29 years (M = 19.0, SD = 3.4), completed the six group sessions of this technique. Under a design pre-post intervention, participants were assessed in: visuo-constructive functions (Copy of the Rey-Osterrieth Complex Figure [CRCF]), creative thinking (Torrance Creative Thinking Test [TCTT]), cognitive flexibility (CRCF and TCTT), and cognitive control (Stroop Test). The intervention improved different cognitive domains, such as: greater global coherence, creative thinking and resistance to closure, as well as less fragmentation. Based on CRT, aimed at stimulating the new processing of visual stimuli, the technique WHC showed an improvement in some of the cognitive processes involved in the onset of symptoms in patients with ED.

Prevention of violence against women and girls: what does the evidence say?

In this Series paper, we review evidence for interventions to reduce the prevalence and incidence of violence against women and girls. Our reviewed studies cover a broad range of intervention models, and many forms of violence--ie, intimate partner violence, non-partner sexual assault, female genital mutilation, and child marriage. Evidence is highly skewed towards that from studies from high-income countries, with these evaluations mainly focusing on responses to violence. This evidence suggests that women-centred, advocacy, and home-visitation programmes can reduce a woman's risk of further victimisation, with less conclusive evidence for the preventive effect of programmes for perpetrators. In low-income and middle-income countries, there is a greater research focus on violence prevention, with promising evidence on the effect of group training for women and men, community mobilisation interventions, and combined livelihood and training interventions for women. Despite shortcomings in the evidence base, several studies show large effects in programmatic timeframes. Across different forms of violence, effective programmes are commonly participatory, engage multiple stakeholders, support critical discussion about gender relationships and the acceptability of violence, and support greater communication and shared decision making among family members, as well as non-violent behaviour. Further investment in intervention design and assessment is needed to address evidence gaps.

Factores asociados con el declive cognitivo en población menor de 65 años. Una revisión sistemática / Factors Associated with Cognitive Decline in a Population Less than 65 Years Old. A Systematic Review

Introducción: Se ha señalado antes del diagna que el deterioro cognitivo comienza 20 años antes del diagnóstico de la demencia. Además de la edad, diversos factores médicos, socioeconómicos y conductuales pueden estar asociados al declive cognitivo. El objetivo de esta revisión sistemática es resumir la evidencia de factores de riesgo o protectores relacionados con el declive cognitivo en población menor de 65 años. Métodos: Se realizó una revisión sistemática mediante una estrategia de búsqueda en bases de datos MEDLINE y Embase, incluyendo estudios con diseño longitudinal que analizaran el efecto de factores protectores o de riesgo en el declive cognitivo de población adulta menor de 65 años. Resultados: Se incluyeron 22 estudios en la presente revisión. Factores como diabetes mellitus, hiperinsulinemia, sobrepeso u obesidad, síndrome metabólico, nivel educativo, actividad física, estimulación cognitiva, estado civil y calidad de la dieta podrían estar relacionados con el declive cognitivo antes de los 65 años. Conclusiones: Factores de riesgo cardiovasculares y de estilos de vida pueden estar asociados al declive cognitivo en menores de 65 años. Sin embargo, la calidad de la evidencia es baja.

Introduction: Cognitive decline could begin 20 years before the diagnosis of dementia. Besides age, several factors related to medical, socioeconomic, and behavioral and genetic condition may be associated with cognitive decline. The aim of this systematic review was to summarize evidence on the risk and protective factors for cognitive decline in people under 65 years old. Methods: A systematic review was conducted using a search strategy in MEDLINE and Embase, including longitudinal studies to analyze the effect of protective or risk factors on cognitive decline in a population under 65 years old. Results: A total of 22 studies were included in this review. Factors such as diabetes, hyperinsulinemia, overweight or obesity, metabolic syndrome, education, physical activity, cognitive stimulation, marital status and diet, could be related to cognitive decline before 65 years of age. Conclusions: Cardiovascular risk factors and lifestyle conditions may be associated with cognitive decline before 65 years of age. However, the quality of the evidence was low.

[Factors Associated with Cognitive Decline in a Population Less than 65 Years Old. A Systematic Review]. / Factores asociados con el declive cognitivo en población menor de 65 años. Una revisión sistemática.

INTRODUCTION: Cognitive decline could begin 20 years before the diagnosis of dementia. Besides age, several factors related to medical, socioeconomic, and behavioral and genetic condition may be associated with cognitive decline. The aim of this systematic review was to summarize evidence on the risk and protective factors for cognitive decline in people under 65 years old. METHODS: A systematic review was conducted using a search strategy in MEDLINE and Embase, including longitudinal studies to analyze the effect of protective or risk factors on cognitive decline in a population under 65 years old. RESULTS: A total of 22 studies were included in this review. Factors such as diabetes, hyperinsulinemia, overweight or obesity, metabolic syndrome, education, physical activity, cognitive stimulation, marital status and diet, could be related to cognitive decline before 65 years of age. CONCLUSIONS: Cardiovascular risk factors and lifestyle conditions may be associated with cognitive decline before 65 years of age. However, the quality of the evidence was low.

Propiedades psicométricas y validación de la Escala de Estrategias de Coping Modificada (EEC-M) en una muestra colombiana / Psychometric properties and validation of the modified copying strategies scale (EEC-M

Se realizaron modificaciones a la Escala de Estrategias de Coping (EEC-R) en la versión de Chorot y Sandín (1993), y se identificaron las propiedades psicométricas y validez estructural. La muestra fue pensaelegida por conveniencia en estudiantes universitarios y personas laboralmente activas. Participaron 893 personas (44,7 por ciento mujeres y 55,3 por ciento hombres). La edad promedio de los participantes fue de 25 años, edad mínima de 16 y una edad máxima de 25. Se realizó el análisis factorial exploratorio de la prueba, reagrupándose los ítems en 12 factores que representaron el 58 por ciento de la varianza. El factor que mostró un mayor nivel de explicación de la varianza fue solución de problemas (12,5 por ciento), seguido por búsqueda de apoyo social, espera, religión, evitación emocional, búsqueda de apoyo profesional, reacción agresiva, evitación cognitiva, reevaluación positiva, expresión de la dificultad de afrontamiento, negación y autonomía. El alfa de Cronbach de la prueba definitiva fue de 0,847.

APOE epsilon4 and Alzheimer's disease: positive association in a Colombian clinical series and review of the Latin-American studies

OBJECTIVE: As the strength of the association between the APOE epsilon4 allele and Alzheimer's disease (AD) varies across ethnic groups, we studied if there was such an association in Colombian patients. METHOD: We performed apolipoprotein E (APOE) genotyping in a clinical sample of 83 unrelated AD patients, predominantly late-onset (>65 yrs) including familial ( n =30) and sporadic AD cases (n= 53) diagnosed according to NINCDS-ADRDA criteria and assessed by a multi-disciplinary team. Control subjects (n = 44) had no significant cognitive impairment by medical interview and neuro-psychological testing. RESULTS: We found a high association (OR= 5.1 95 percentCI 1.9 -13.6) between APOE epsilon4 and AD, in this series with predominantly late-onset cases with familial aggregation in 24 cases (28.9 percent). A significant negative association was found between epsilon2 and AD (OR= 0.2 95 percent CI 0.05-0.75). CONCLUSION: Further population-based surveys in Colombia are warranted to precise a possible dose effect of APOE epsilon4