Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN) countries

<p>Abstract</p> <p>Background</p> <p>In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe.</p> <p>Methods</p> <p>We conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN) countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population. Here we describe the results for regulatory requirements for typical investigational medicinal products, in the ten countries.</p> <p>Results</p> <p>Our results show that the ten countries have fairly harmonised definitions of typical investigational medicinal products. Clinical trials assessing typical investigational medicinal products require authorisation from a national competent authority in each of the countries surveyed. The opinion of the competent authorities is communicated to the trial sponsor within the same timelines, i.e., no more than 60 days, in all ten countries. The authority to which the application has to be sent to in the different countries is not fully harmonised.</p> <p>Conclusion</p> <p>The Directive 2001/20/EC defined the term 'investigational medicinal product' and all regulatory requirements described therein are applicable to investigational medicinal products. Our survey showed, however, that those requirements had been adopted in ten European countries, not for investigational medicinal products overall, but rather a narrower category which we term 'typical' investigational medicinal products. The result is partial EU harmonisation of requirements and a relatively navigable landscape for the sponsor regarding typical investigational medicinal products.</p

Azithromycin-chloroquine and the intermittent preventive treatment of malaria in pregnancy

In the high malaria-transmission settings of sub-Saharan Africa, malaria in pregnancy is an important cause of maternal, perinatal and neonatal morbidity. Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) reduces the incidence of low birth-weight, pre-term delivery, intrauterine growth-retardation and maternal anaemia. However, the public health benefits of IPTp are declining due to SP resistance. The combination of azithromycin and chloroquine is a potential alternative to SP for IPTp. This review summarizes key in vitro and in vivo evidence of azithromycin and chloroquine activity against Plasmodium falciparum and Plasmodium vivax, as well as the anticipated secondary benefits that may result from their combined use in IPTp, including the cure and prevention of many sexually transmitted diseases. Drug costs and the necessity for external financing are discussed along with a range of issues related to drug resistance and surveillance. Several scientific and programmatic questions of interest to policymakers and programme managers are also presented that would need to be addressed before azithromycin-chloroquine could be adopted for use in IPTp

Reducing disease burden and health inequalities arising from chronic disease among indigenous children: an early childhood caries intervention in Aotearoa/New Zealand

BACKGROUND Maaori are the Indigenous people of New Zealand and do not enjoy the same oral health status as the non-Indigenous majority. To overcome oral health disparities, the life course approach affords a valid foundation on which to develop a process that will contribute to the protection of the oral health of young infants. The key to this process is the support that could be provided to the parents or care givers of Maaori infants during the pregnancy of the mother and the early years of the child. This study seeks to determine whether implementing a kaupapa Maaori (Maaori philosophical viewpoint) in an early childhood caries (ECC) intervention reduces dental disease burden among Maaori children. The intervention consists of four approaches to prevent early childhood caries: dental care provided during pregnancy, fluoride varnish application to the teeth of children, motivational interviewing, and anticipatory guidance. METHODS/DESIGN The participants are Maaori women who are expecting a child and who reside within the Maaori tribal area of Waikato-Tainui. This randomised-control trial will be undertaken utilising the principles of kaupapa Maaori research, which encompasses Maaori leadership, Maaori relationships, Maaori customary practices, etiquette and protocol. Participants will be monitored through clinical and self-reported information collected throughout the ECC intervention. Self-report information will be collected in a baseline questionnaire during pregnancy and when children are aged 24 and 36 months. Clinical oral health data will be collected during standardised examinations at ages 24 and 36 months by calibrated dental professionals. All participants receive the ECC intervention benefits, with the intervention delayed by 24 months for participants who are randomised to the control-delayed arm. Discussion The development and evaluation of oral health interventions may produce evidence that supports the application of the principles of kaupapa Maaori research in the research processes. This study will assess an ECC intervention which could provide a meaningful approach for Maaori for the protection and maintenance of oral health for Maaori children and their family, thus reducing oral health disparities. TRIAL REGISTRATION Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000111976.John R Broughton, Joyce Te H Maipi, Marie Person, W Murray Thomson, Kate C Morgaine, Sarah-Jane Tiakiwai, Jonathan Kilgour, Kay Berryman, Herenia P Lawrence, Lisa M Jamieso

War and wildlife: linking armed conflict to conservation

Armed conflict throughout the world's biodiversity hotspots poses a critical threat to conservation efforts. To date, research and policy have focused more on the ultimate outcomes of conflict for wildlife rather than on the ecological, social, and economic processes that create those outcomes. Yet the militarization that accompanies armed conflict, as well as consequent changes in governance, economies, and human settlement, has diverse influences on wildlife populations and habitats. To better understand these complex dynamics, we summarized 144 case studies from around the world and identified 24 distinct pathways linking armed conflict to wildlife outcomes. The most commonly cited pathways reflect changes to institutional and socioeconomic factors, rather than tactical aspects of conflict. Marked differences in the most salient pathways emerge across geographic regions and wildlife taxa. Our review demonstrates that mitigating the negative effects of conflict on biodiversity conservation requires a nuanced understanding of the ways in which conflict affects wildlife populations and communities

High-frequency stimulation of the subthalamic nucleus suppresses oscillatory beta activity in patients with Parkinson's disease in parallel with improvement in motor performance.

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is a well-established therapy for patients with severe Parkinson's disease (PD), but its mechanism of action is unclear. Exaggerated oscillatory synchronization in the beta (13-30 Hz) frequency band has been associated with bradykinesia in patients with PD. Accordingly, we tested the hypothesis that the clinical benefit exerted by STN HFS is accompanied by suppression of local beta activity. To this end, we explored the after effects of STN HFS on the oscillatory local field potential (LFP) activity recorded from the STN immediately after the cessation of HFS in 11 PD patients. Only patients that demonstrated a temporary persistence of clinical benefit after cessation of HFS were analyzed. STN HFS led to a significant reduction in STN LFP beta activity for 12 s after the end of stimulation and a decrease in motor cortical-STN coherence in the beta band over the same time period. The reduction in LFP beta activity correlated with the movement amplitude during a simple motor task, so that a smaller amount of beta activity was associated with better task performance. These features were absent when power in the 5-12 Hz frequency band was considered. Our findings suggest that HFS may act by modulating pathological patterns of synchronized oscillations, specifically by reduction of pathological beta activity in PD