Safety, tolerability, pharmacokinetics, and antimalarial activity of MMV533: a phase 1a first-in-human, randomised, ascending dose and food effect study, and a phase 1b Plasmodium falciparum volunteer infection study.

Background: Novel antimalarials are needed to address emerging resistance to artemisinin and partner drugs. We did two trials to evaluate safety, tolerability, pharmacokinetics, and activity against blood stage Plasmodium falciparum for the drug candidate MMV533.

Methods: A phase 1a first-in-human (FIH) trial was conducted at Nucleus Network (Melbourne, VIC, Australia).

A randomized, open-label two-period crossover pilot study to evaluate the relative bioavailability in the fed state of atovaquone-proguanil (Atoguanil™) versus atovaquone-proguanil hydrochloride (Malarone®) in healthy adult participants.

Atoguanil™ is a novel complex of atovaquone (ATV) and proguanil (PG) with enhanced ATV bioavailability compared to Malarone®. This pilot study assessed whether the relative bioavailability (F) of ATV, PG, and the primary PG metabolite cycloguanil (CG) following a single oral dose in the fed state of Atoguanil was similar to Malarone despite a 50% lower ATV dose. This open-label, single-dose, randomized 2-period, 2-treatment, balanced crossover study was conducted between 17th November 2021 and 18th March 2022.

Randomized, placebo-controlled, double-blind phase I trial of co-administered pyronaridine and piperaquine in healthy adults of sub-Saharan origin.

Drug resistance to sulfadoxine-pyrimethamine and amodiaquine threatens the efficacy of malaria chemoprevention interventions in children and pregnant women. Combining pyronaridine (PYR) and piperaquine (PQP), both components of approved antimalarial therapies, has the potential to protect vulnerable populations from severe malaria. This randomized, double-blind, placebo-controlled (double-dummy), parallel-group, single site phase I study in healthy adult males or females of Black sub-Saharan African ancestry investigated the safety, tolerability, and pharmacokinetics of PYR + PQP (n = 15), PYR + placebo (n = 8), PQP + placebo (n = 8), and double placebo (n = 6) administered orally once daily for 3 days at the registered dose for the treatment of uncomplicated malaria.

Strategies and interventions to strengthen pharmacovigilance systems in low-income and middle-income countries: a scoping review.

Objectives: The slow progress of pharmacovigilance (PV) in low-income and middle-income countries (LMIC) raises questions about core challenges on the growth of PV, and the appropriateness of strategies used so far to develop PV. Therefore, this scoping review aims to describe strategies and interventions to strengthen PV in LMIC and to propose recommendations for future investments in PV capacity building.

Inclusion Criteria: Publications included were primary studies, articles, policy and guideline papers, describing interventions to strengthen PV in LMIC.

Effectiveness of Nifurtimox Eflornithine Combination Therapy (NECT) in T. b. gambiense second stage sleeping sickness patients in the Democratic Republic of Congo: Report from a field study.

Background: Nifurtimox-eflornithine combination therapy (NECT) for the treatment of second stage gambiense human African trypanosomiasis (HAT) was added to the World Health Organization's Essential Medicines List in 2009 after demonstration of its non-inferior efficacy compared to eflornithine therapy. A study of NECT use in the field showed acceptable safety and high efficacy until hospital discharge in a wide population, including children, pregnant and breastfeeding women, and patients with a HAT treatment history. We present here the effectiveness results after the 24-month follow-up visit.

Recognition and management of clinically significant drug-drug interactions between antiretrovirals and co-medications in a cohort of people living with HIV in rural Tanzania: a prospective questionnaire-based study.

Background: The extent to which drug-drug interactions (DDIs) between antiretrovirals (ARVs) and co-medications are recognized and managed has not been thoroughly evaluated in limited-resource settings.

Objectives: This prospective questionnaire-based study aimed to determine the prevalence and risk factors for unrecognized/incorrectly managed DDIs in people living with HIV followed-up at the Chronic Diseases Clinic of Ifakara (CDCI) and enrolled in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO).

Methods: We prospectively included ARV-treated adults receiving ≥1 co-medication coming for a follow-up visit at the CDCI between March and July 2017.

Efficacy and safety of intravenous ferric carboxymaltose compared with oral iron for the treatment of iron deficiency anaemia in women after childbirth in Tanzania: a parallel-group, open-label, randomised controlled phase 3 trial.

Background: Iron deficiency anaemia is of major concern in low-income settings, especially for women of childbearing age. Oral iron substitution efficacy is limited by poor compliance and iron depletion severity. We aimed to assess the efficacy and safety of intravenous ferric carboxymaltose versus oral iron substitution following childbirth in women with iron deficiency anaemia in Tanzania.

Body adiposity measured by bioelectrical impedance is an alternative to dual-energy x-ray absorptiometry in black Africans: The Africans in America Study.

Objectives: The prevalence of cardiometabolic disease has risen in Africa and parallels the obesity epidemic. To assess cardiometabolic risk, body composition measurements by dual-energy X-ray absorptiometry (DXA) are ideal. In communities with limited resources, alternative measures may be useful but have not been compared extensively in black Africans.

Prescription of concomitant medications in patients treated with Nifurtimox Eflornithine Combination Therapy (NECT) for T.b. gambiense second stage sleeping sickness in the Democratic Republic of the Congo.

Background: Nifurtimox eflornithine combination therapy (NECT) to treat human African trypanosomiasis (HAT), commonly called sleeping sickness, was added to the World Health Organisation's (WHO) Essential Medicines List in 2009 and to the Paediatric List in 2012. NECT was further tested and documented in a phase IIIb clinical trial in the Democratic Republic of Congo (DRC) assessing the safety, effectiveness, and feasibility of implementation under field conditions (NECT-FIELD study). This trial brought a unique possibility to examine concomitant drug management.

Analysis of Hepatobiliary Disorder Reports Associated With the Use of Herbal Medicines in the Global Suspected ADR Database Vigibase.

Use of herbal medicines (HMs) is widespread across the world, with many people relying on HMs for their primary healthcare or using HMs in the context of a healthy life style. HMs originate from plant material and, as such, are often seen as "natural" and believed to be (relatively) safe by patients. Hepatobiliary disorders have been associated with numerous HMs.

Prevalence and management of drug-drug interactions with antiretroviral treatment in 2069 people living with HIV in rural Tanzania: a prospective cohort study.

Objectives: Widespread access to antiretroviral therapy (ART) has substantially increased life expectancy in sub-Saharan African countries. As a result, the rates of comorbidities and use of co-medications among people living with HIV are increasing, necessitating a sound understanding of drug-drug interactions (DDIs). We aimed to assess the prevalence and management of DDIs with ART in a rural Tanzanian setting.

Development of a pharmacovigilance system in a resource-limited country: the experience of the Democratic Republic of Congo.

Implementation of pharmacovigilance (PV) systems in resource-limited countries is a real endeavor. Despite country- and continent-specific challenges, the Democratic Republic of the Congo (DRC) has been able to develop one of the most active PV systems in the sub-Saharan Africa. The World Health Organization (WHO) regional Office identified the DRC experience to set up a PV system for antimalarial drugs safety monitoring as a 'best practice' that needed to be documented in order to help DRC improve its PV system and to be scaled up in other African countries.

Public health burden of pre-diabetes and diabetes in Luxembourg: finding from the 2013-2015 European Health Examination Survey.

Objective: The aim of this study was to determine the burden and risk factors of prediabetes and diabetes in the general adult population of Luxembourg.

Design: Cross-sectional survey between 2013 and 2015.

Setting: Data were collected as part of the European Health Examination Survey in Luxembourg (EHES-LUX).

Study design and characteristics of the Luxembourg European Health Examination Survey (EHES-LUX).

Background: The European Health Examination Survey in Luxembourg (EHES-LUX) is a population based survey performed from 2013 to 2015 with the aim to establish baseline information on the general health status of the Luxembourg population aged 25 to 64 years. The paper introduces the study design, recruitment method and representativeness of the sample, and summarizes the sociodemographic characteristics of participants and the prevalence of major health outcomes.

Methods: EHES-LUX is based on a random sample representative of the population of Luxembourg based on gender, age and district of residence.

Safety profile of fractional dosing of the 17DD Yellow Fever Vaccine among males and females: Experience of a community-based pharmacovigilance in Kinshasa, DR Congo.

Background: In early 2016, there was a Yellow Fever (YF) outbreak in Central Africa with several deaths reported from Angola and the Democratic Republic of Congo. Due to a shortage in vaccine supply, fractional dosing (0.1 ml) of 17DD Yellow Fever Vaccine (YFV) was proposed in preventive vaccination campaign in Kinshasa in August 2016.

Geographical variation of overweight, obesity and related risk factors: Findings from the European Health Examination Survey in Luxembourg, 2013-2015.

The analyses of geographic variations in the prevalence of major chronic conditions, such as overweight and obesity, are an important public health tool to identify "hot spots" and inform allocation of funding for policy and health promotion campaigns, yet rarely performed. Here we aimed at exploring, for the first time in Luxembourg, potential geographic patterns in overweight/obesity prevalence in the country, adjusted for several demographic, socioeconomic, behavioural and health status characteristics. Data came from 720 men and 764 women, 25-64 years old, who participated in the European Health Examination Survey in Luxembourg (2013-2015).

Metabolically healthy and unhealthy weight statuses, health issues and related costs: Findings from the 2013-2015 European Health Examination Survey in Luxembourg.

Aim: To investigate the relationship between metabolically healthy and unhealthy weight statuses and a wide range of related health issues, and healthcare and loss-of-productivity costs.

Methods: A total of 693 men and 729 women, aged 25-64 years, took part in the European Health Examination Survey conducted in Luxembourg between 2013 and 2015. Metabolically unhealthy normal-weight profiles were defined as having two or more cardiometabolic abnormalities (high blood pressure, high fasting glucose or triglycerides, low HDL cholesterol and/or previously diagnosed hypertension or diabetes) in people with normal weight.

Depression burden in luxembourg: Individual risk factors, geographic variations and the role of migration, 2013-2015 European Health Examination Survey.

Background: Depression is a complex mental disorder that affects an increasing proportion of the worldwide population. This study aims to estimate the prevalence of depressive symptoms in Luxembourg, associated risk factors and geographic variations. Additionally, it aims to assess whether first and second generation immigrants are at higher risk for depressive symptoms compared to non-immigrants.

Hypertension burden in Luxembourg: Individual risk factors and geographic variations, 2013 to 2015 European Health Examination Survey.

Hypertension is a modifiable risk factor for cardiovascular disease, but it remains the main cause of death in Luxembourg. We aimed to estimate the current prevalence of hypertension, associated risk factors, and its geographic variation in Luxembourg.Cross-sectional, population-based data on 1497 randomly selected Luxembourg residents aged 25 to 64 years were collected as part of the European Health Examination Survey from 2013 to 2015.

Advice on lifestyle changes (diet, red wine and physical activity) does not affect internal carotid and middle cerebral artery blood flow velocity in patients with carotid arteriosclerosis in a randomized controlled trial.

Background: A Mediterranean diet, with and without small daily amounts of red wine, and physical activity reduce the risk of cerebrovascular disease and improve cognition. An increase in cerebral blood flow may be the underlying mechanism. Under normal conditions, cerebral blood flow velocity changes in the internal carotid arteries and in large basal cerebral arteries correlate closely with cerebral blood flow changes, as the diameter of these vessels hardly changes and only the smaller vessels downstream change their diameter.

A daily glass of red wine and lifestyle changes do not affect arterial blood pressure and heart rate in patients with carotid arteriosclerosis after 4 and 20 weeks.

Background: Regular consumption of small amounts of red wine improves blood lipids. However, there is concern whether this beneficial effect might be counterbalanced by an increase in blood pressure (BP) and heart rate (HR), which are risk factors for cerebro-cardiovascular disease. In particular, we studied whether regular consumption of red wine with and without lifestyle changes (LC; healthy diet and physical activity advice) results in an increase in BP and HR.

A daily glass of red wine associated with lifestyle changes independently improves blood lipids in patients with carotid arteriosclerosis: results from a randomized controlled trial.

Background: Physical exercise and a Mediterranean diet improve serum lipid profile. The present work studied whether red wine has an effect on top of a lipid-lowering lifestyle in patients with carotid atherosclerosis.

Methods: A prospective randomised unblinded trial was performed from 2009 to 2011 in 108 patients with carotid atherosclerosis, 65% of whom were already on statin therapy with a low mean LDL of 104.

Lifestyle counseling in patients with carotid arteriosclerosis from Luxemburg should focus more on the reduction of sugar, sodium and saturated fat consumption.

Background: Healthy diet and physical activity improve risk factors for cerebrovascular disease. It is unclear whether patients with carotid artery disease from Luxemburg meet common guideline criteria and whether systematic counseling has a sustained effect.

Methods: We assessed anthropometric data, eating habits and physical activity habits in 53 patients with carotid atherosclerosis at baseline, after 4 and 20 weeks, and advised them five times for 30 min to follow a modified Mediterranean diet and to perform moderate physical exercise at least during 30 min/day.

In-hospital safety in field conditions of nifurtimox eflornithine combination therapy (NECT) for T. b. gambiense sleeping sickness.

Background: Trypanosoma brucei (T.b.) gambiense Human African trypanosomiasis (HAT; sleeping sickness) is a fatal disease.

P-glycoprotein modulation by valspodar and cyclosporin does not increase tumor uptake of doxorubicin administered via isolated lung perfusion to rats bearing sarcoma lung metastases.

Background: Isolated lung perfusion (ILP) with doxorubicin allows a regional increase in drug exposure while sparing unaffected tissues, but clinical results have so far been disappointing, presumably in part because of the limited tumor penetration of doxorubicin. The aim of this study was to assess whether tumor uptake of doxorubicin, administered locoregionally by ILP, would be increased by the administration of P-glycoprotein (P-gp) modulators.

Materials And Methods: Single-pass antegrade ILP (A-ILP) was performed with doxorubicin in rats bearing a pulmonary sarcoma nodule which were either untreated or received P-gp inhibitors cyclosporin, valspodar or the vehicle, Cremophor®, only.