Mortality, morbidity, and developmental outcomes in infants born to women who received either mefloquine or sulfadoxine-pyrimethamine as intermittent preventive treatment of malaria in pregnancy : a cohort study

Background Little is known about the effects of intermittent preventive treatment of malaria in pregnancy (IPTp) on the health of sub-Saharan African infants. We have evaluated the safety of IPTp with mefloquine (MQ) compared to sulfadoxine- pyrimethamine (SP) for important infant health and developmental outcomes. Methods and Findings In the context of a multicenter randomized controlled trial evaluating the safety and efficacy of IPTp with MQ compared to SP in pregnancy carried out in four sub-Saharan countries (Mozambique, Benin, Gabon, and Tanzania), 4,247 newborns, 2,815 born to women who received MQ and 1,432 born to women who received SP for IPTp, were followed up until 12 mo of age. Anthropometric parameters and psychomotor development were assessed at 1, 9, and 12 mo of age, and the incidence of malaria, anemia, hospital admissions, outpatient visits, and mortality were determined until 12 mo of age. No significant differences were found in the proportion of infants with stunting, underweight, wasting, and severe acute malnutrition at 1, 9, and 12 mo of age between infants born to women who were on IPTp with MQ versus SP. Except for three items evaluated at 9 mo of age, no significant differences were observed in the psychomotor development milestones assessed. Incidence of malaria, anemia, hospital admissions, outpatient visits, and mortality were similar between the two groups. Information on the outcomes at 12 mo of age was unavailable in 26% of the infants, 761 (27%) from the MQ group and 377 (26%) from the SP group. Reasons for not completing the study were death (4% of total study population), study withdrawal (6%), migration (8%), and loss to follow-up (9%). Conclusions No significant differences were found between IPTp with MQ and SP administered in pregnancy on infant mortality, morbidity, and nutritional outcomes. The poorer performance on certain psychomotor development milestones at 9 mo of age in children born to women in the MQ group compared to those in the SP group may deserve further studies

Study protocol: cross-national comparative case study of recovery-focused mental health care planning and coordination (COCAPP).

BACKGROUND: The collaborative care planning study (COCAPP) is a cross-national comparative study of care planning and coordination in community mental healthcare settings. The context and delivery of mental health care is diverging between the countries of England and Wales whilst retaining points of common interest, hence providing a rich geographical comparison for research. Across England the key vehicle for the provision of recovery-focused, personalised, collaborative mental health care is the care programme approach (CPA). The CPA is a form of case management introduced in England in 1991, then revised in 2008. In Wales the CPA was introduced in 2003 but has now been superseded by The Mental Health (Care Co-ordination and Care and Treatment Planning) (CTP) Regulations (Mental Health Measure), a new statutory framework. In both countries, the CPA/CTP requires providers to: comprehensively assess health/social care needs and risks; develop a written care plan (which may incorporate risk assessments, crisis and contingency plans, advanced directives, relapse prevention plans, etc.) in collaboration with the service user and carer(s); allocate a care coordinator; and regularly review care. The overarching aim of this study is to identify and describe the factors that ensure CPA/CTP care planning and coordination is personalised, recovery-focused and conducted collaboratively. METHODS/DESIGN: COCAPP will employ a concurrent transformative mixed methods approach with embedded case studies. Phase 1 (Macro-level) will consider the national context through a meta-narrative mapping (MNM) review of national policies and the relevant research literature. Phase 2 (Meso-level and Micro-level) will include in-depth micro-level case studies of everyday 'frontline' practice and experience with detailed qualitative data from interviews and reviews of individual care plans. This will be nested within larger meso-level survey datasets, senior-level interviews and policy reviews in order to provide potential explanations and understanding. DISCUSSION: COCAPP will help identify the key components that support and hinder the provision of personalised, recovery-focused care planning and provide an informed rationale for a future planned intervention and evaluation

Nicotinic α7 and α4β2 agonists enhance the formation and retrieval of recognition memory: potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders

YesCholinergic dysfunction has been shown to be central to the pathophysiology of Alzheimer’s disease and has also been postulated to contribute to cognitive dysfunction observed in various psychiatric disorders, including schizophrenia. Deficits are found across a number of cognitive domains and in spite of several attempts to develop new therapies, these remain an unmet clinical need. In the current study we investigated the efficacy of donepezil, risperidone and selective nicotinic α7 and α4β2 receptor agonists to reverse a delay-induced deficit in recognition memory. Adult female Hooded Lister rats received drug treatments and were tested in the novel object recognition (NOR) task following a 6 h inter-trial interval (ITI). In all treatment groups, there was no preference for the left or right identical objects in the acquisition trial. Risperidone failed to enhance recognition memory in this paradigm whereas donepezil was effective such that rats discriminated between the novel and familiar object in the retention trial following a 6 h ITI. Although a narrow dose range of PNU-282987 and RJR- 2403 was tested, only one dose of each increased recognition memory, the highest dose of PNU-282987 (10 mg/kg) and the lowest dose of RJR-2403 (0.1 mg/kg), indicative of enhanced cognitive performance. Interestingly, these compounds were also efficacious when administered either before the acquisition or the retention trial of the task, suggesting an important role for nicotinic receptor subtypes in the formation and retrieval of recognition memory.This work was conducted at the University of Bradford and was funded by b-neuro. However all our recent studies mentioned in the discussion section have been conducted at the University of Manchester (UoM), and funded by b-neuro, Autifony, Innovate UK (formerly TSB) and Uo

The effect of dose on the antimalarial efficacy of artemether-lumefantrine: a systematic review and pooled analysis of individual patient data

Background: Artemether-lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from trials done in a wide range of malaria-endemic settings. Methods: We searched PubMed for clinical trials that enrolled and treated patients with artemether-lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCR-unadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identified using Cox's regression model with frailty shared across the study sites. Findings: We included 61 studies done between January, 1998, and December, 2012, and included 14 327 patients in our analyses. The PCR-adjusted therapeutic efficacy was 97·6% (95% CI 97·4-97·9) at day 28 and 96·0% (95·6-96·5) at day 42. After controlling for age and parasitaemia, patients prescribed a higher dose of artemether had a lower risk of having parasitaemia on day 1 (adjusted odds ratio [OR] 0·92, 95% CI 0·86-0·99 for every 1 mg/kg increase in daily artemether dose; p=0·024), but not on day 2 (p=0·69) or day 3 (0·087). In Asia, children weighing 10-15 kg who received a total lumefantrine dose less than 60 mg/kg had the lowest PCR-adjusted efficacy (91·7%, 95% CI 86·5-96·9). In Africa, the risk of treatment failure was greatest in malnourished children aged 1-3 years (PCR-adjusted efficacy 94·3%, 95% CI 92·3-96·3). A higher artemether dose was associated with a lower gametocyte presence within 14 days of treatment (adjusted OR 0·92, 95% CI 0·85-0·99; p=0·037 for every 1 mg/kg increase in total artemether dose). Interpretation: The recommended dose of artemether-lumefantrine provides reliable efficacy in most patients with uncomplicated malaria. However, therapeutic efficacy was lowest in young children from Asia and young underweight children from Africa; a higher dose regimen should be assessed in these groups. Funding: Bill and Melinda Gates Foundation

Impact of helminth infection during pregnancy on cognitive and motor functions of one-year-old children

Objective To determine the effect of helminth infection during pregnancy on the cognitive and motor functions of one-year-old children. Methods Six hundred and thirty five singletons born to pregnant women enrolled before 29 weeks of gestation in a trial comparing two intermittent preventive treatments for malaria were assessed for cognitive and motor functions using the Mullen Scales of Early Learning, in the TOVI study, at twelve months of age in the district of Allada in Benin. Stool samples of pregnant women were collected at recruitment, second antenatal care (ANC) visit (at least one month after recruitment) and just before delivery, and were tested for helminths using the Kato-Katz technique. All pregnant women were administered a total of 600 mg of mebendazole (100 mg two times daily for 3 days) to be taken after the first ANC visit. The intake was not directly observed. Results Prevalence of helminth infection was 11.5%, 7.5% and 3.0% at first ANC visit, second ANC visit and at delivery, respectively. Children of mothers who were infected with hookworms at the first ANC visit had 4.9 (95% CI: 1.3–8.6) lower mean gross motor scores compared to those whose mothers were not infected with hookworms at the first ANC visit, in the adjusted model. Helminth infection at least once during pregnancy was associated with infant cognitive and gross motor functions after adjusting for maternal education, gravidity, child sex, family possessions, and quality of the home stimulation. Conclusion Helminth infection during pregnancy is associated with poor cognitive and gross motor outcomes in infants. Measures to prevent helminth infection during pregnancy should be reinforced

Genome wide linkage study, using a 250K SNP map, of Plasmodium falciparum infection and mild malaria attack in a Senegalese population

Multiple factors are involved in the variability of host's response to P. falciparum infection, like the intensity and seasonality of malaria transmission, the virulence of parasite and host characteristics like age or genetic make-up. Although admitted nowadays, the involvement of host genetic factors remains unclear. Discordant results exist, even concerning the best-known malaria resistance genes that determine the structure or function of red blood cells. Here we report on a genomewide linkage and association study for P. falciparum infection intensity and mild malaria attack among a Senegalese population of children and young adults from 2 to 18 years old. A high density single nucleotide polymorphisms (SNP) genome scan (Affimetrix GeneChip Human Mapping 250K-nsp) was performed for 626 individuals: i.e. 249 parents and 377 children out of the 504 ones included in the follow-up. The population belongs to a unique ethnic group and was closely followed-up during 3 years. Genome-wide linkage analyses were performed on four clinical and parasitological phenotypes and association analyses using the family based association tests (FBAT) method were carried out in regions previously linked to malaria phenotypes in literature and in the regions for which we identified a linkage peak. Analyses revealed three strongly suggestive evidences for linkage: between mild malaria attack and both the 6p25.1 and the 12q22 regions (empirical p-value = 5 x 10(-5) and 96 x 10(-5) respectively), and between the 20p11q11 region and the prevalence of parasite density in asymptomatic children (empirical p-value = 1.5 x 10(-4)). Family based association analysis pointed out one significant association between the intensity of plasmodial infection and a polymorphism located in ARHGAP26 gene in the 5q31-q33 region (p-value = 3.7 x 10(-5)). This study identified three candidate regions, two of them containing genes that could point out new pathways implicated in the response to malaria infection. Furthermore, we detected one gene associated with malaria infection in the 5q31-q33 region

Performance and stability of semitransparent OPVs for building integration: A benchmarking analysis

Semitransparent (ST) organic photovoltaics (OPVs) are demonstrating great potential for building integration applications, especially in windows. For that purpose, ST-OPVs should achieve adequate transparency and performance stability. In this regard, the present research deals with the experimental performance of three different building-integrated ST-OPV technologies (technology A: developed in the frame of the present study; technologies B and C: commercial modules). More specifically, spectral transmittance and electrical measurements have been conducted in order to determine the characteristics of the modules for building integration and electricity generation purposes. Results regarding the transmittance reveal that technology A outperforms technologies B and C. The stability analysis of the modules verifies that module C is the most stable one with almost no decrease (3.6%) in the power conversion efficiency (PCE). Furthermore, the PCE of technology B is slightly higher than in the case of technology C, which experiences a PCE degradation of about 10-15% over the whole time period. Finally, technology A presents a 20% reduction in PCE at around 500 h.The authors would like to acknowledge financial support from European Commission 7th Framework Programme (FP7-NMP-2013-SMALL-7) and ''Ministerio de Economía y Competitividad'' of Spain (ENE2016-81040-R)

Intermittent preventive treatment for the prevention of malaria during pregnancy in high transmission areas

Malaria in pregnancy is one of the major causes of maternal morbidity and adverse birth outcomes. In high transmission areas, its prevention has recently changed, moving from a weekly or bimonthly chemoprophylaxis to intermittent preventive treatment (IPTp). IPTp consists in the administration of a single curative dose of an efficacious anti-malarial drug at least twice during pregnancy – regardless of whether the woman is infected or not. The drug is administered under supervision during antenatal care visits. Sulphadoxine-pyrimethamine (SP) is the drug currently recommended by the WHO. While SP-IPTp seems an adequate strategy, there are many issues still to be explored to optimize it. This paper reviewed data on IPTp efficacy and discussed how to improve it. In particular, the determination of both the optimal number of doses and time of administration of the drug is essential, and this has not yet been done. As both foetal growth and deleterious effects of malaria are maximum in late pregnancy women should particularly be protected during this period. Monitoring of IPTp efficacy should be applied to all women, and not only to primi- and secondigravidae, as it has not been definitively established that multigravidae are not at risk for malaria morbidity and mortality. In HIV-positive women, there is an urgent need for specific information on drug administration patterns (need for higher doses, possible interference with sulpha-based prophylaxis of opportunistic infections). Because of the growing level of resistance of parasites to SP, alternative drugs for IPTp are urgently needed. Mefloquine is presently one of the most attractive options because of its long half life, high efficacy in sub-Saharan Africa and safety during pregnancy. Also, efforts should be made to increase IPTp coverage by improving the practices of health care workers, the motivation of women and their perception of malaria complications in pregnancy. Because IPTp is not applicable in early pregnancy, which is a period when malaria may also be deleterious for women and their offspring, there is a necessity to integrate this strategy with other preventive measures which can be applied earlier in pregnancy such as insecticide-treated nets