Publications

19

Nov, 2020

Tools for Healthcare Workers to measure Health Research Capacity Development at an Individual Level

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Author: Bilardi D, Rapa E, Bernays S, & Lang T

Published in: European Academy of Pediatric Societies

 

Background: Despite health research capacity development (HRCD) in low and middle-income countries (LMICs) being recognised as a critical element to overcoming global health challenges, insufficient actions have been taken to tackle major barriers to HRCD. A key barrier in supporting HRCD is the lack of empirical measurement of competencies to assess skills and identify gaps in research activities. An effective tool to measure HRCD would help drive more capable teams to undertake more locally-led research.

Aims: Primary aim: Systematically search the existing literature to investigate the nature, the scope and the extensiveness of existing tools created to measure HRCD at personal level in healthcare workers (HCW) working in LMICs. Secondary aims: identify a tool using a global evidence- based competency framework suitable for a comparable, standardised and consistent analyses of long term research competency acquisition in HCW in LMICs.

Methodology: Eleven databases were searched from inception to 16 January 2020. The first 10 pages of results from Google Scholar were also considered. The search was limited to English language publications. Two authors independently screened and reviewed studies using Covidence, extracted data and performed quality assessments using the extraction log validated against the CASP qualitative checklist. The content method was used to define a meta-narrative analysis.

 

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2

Nov, 2020

Vertical transmission of Zika virus and its outcomes: a Bayesian synthesis of prospective studies

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Authors: A E Ades, Antoni Soriano-Arandes, Ana Alarcon, Francesco Bonfante, Claire Thorne, Catherine S Peckham, Carlo Giaquinto

Published in: The Lancet

Abstract
Background:  Prospective studies of Zika virus in pregnancy have reported rates of congenital Zika syndrome and other adverse outcomes by trimester. However, Zika virus can infect and damage the fetus early in utero, but clear before delivery. The true vertical transmission rate is therefore unknown. We aimed to provide the first estimates of underlying vertical transmission rates and adverse outcomes due to congenital infection with Zika virus by trimester of exposure.

Methods: This was a Bayesian latent class analysis of data from seven prospective studies of Zika virus in pregnancy. We estimated vertical transmission rates, rates of Zika-virus-related and non-Zika-virus-related adverse outcomes, and the diagnostic sensitivity of markers of congenital infection. We allowed for variation between studies in these parameters and used information from women in comparison groups with no PCR-confirmed infection, where available.

Funding: European Union Horizon 2020 programme.

 

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30

Oct, 2020

COVID and HIV: Psychological impact and awareness of COVID-19 in young people with HIV

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Authors: S. Bernardi1, E. Mozzo, M. Di Pastena, F. Leone, C. Novello, A. Oletto, N. Cotugno, P. Zangari, P. Palma, V. Santilli, P. Palma, O. Rampon, C. Giaquinto

Published in: 12th National Congress of Italian Conference on AIDS and Antiviral Research

Background: Public health emergencies may affect the health, safety, and well-being of both individuals and communities. These effects may translate into a range of emotional reactions and unhealthy behaviours. Some people may be more vulnerable than others to the psychosocial effects of pandemics. Young people living with HIV can experience solitude, depression and anxiety as a consequence of the stigma that continues to surround HIV and the daily challenge of living with a chronic infection. We investigated the psychological impact of the current COVID-19 pandemic among a group of HIV-infected young people and assessed their knowledge on HIV and COVID-19 infections.

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16

Oct, 2020

European research networks to facilitate drug research in children

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Author: Mark A. Turner, Katharine Cheng, Saskia de Wildt, Heidrun Hildebrand, Sabah Attar, Paolo Rossi, Donato Bonifazi, Adriana Ceci, Joana Claverol, Begonya Nafria, Carlo Giaquinto

Published in: British Journal of Clinical Pharmacology

Abstract: Paediatric drug development faces several barriers. These include fragmentation of stakeholders and inconsistent processes during the conduct of research. This review summarises recent efforts to overcome these barriers in Europe. Two exemplar initiatives are described. The European Paediatric Translational Research Infrastructure facilitates preclinical research and other work that underpins clinical trials. conect4children facilitates the design and implementation of clinical trials. Both these initiatives listen to the voices of children and their advocates. Coordination of research needs specific effort that supplements work on science, resources and the policy context.

 

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14

Oct, 2020

SARS-CoV-2 testing and infection control strategies in European paediatric emergency departments during the first wave of the pandemic

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Published in: European Journal of Pediatrics

 

Authors: Malte Kohns Vasconcelos & Hanna Renk & Jolanta Popielska & Maggie Nyirenda Nyang’wa & Sigita Burokiene & Despoina Gkentzi & Ewelina Gowin & Daniele Donà & Sara Villanueva-Medina & Andrew Riordan & Markus Hufnagel & Sarah Eisen & Liviana Da Dalt & Carlo Giaquinto & Julia A. Bielicki1

 

Abstract: Between February and May 2020, during the first wave of the COVID-19 pandemic, paediatric emergency departments in 12 European countries were prospectively surveyed on their implementation of SARS-CoV-2 disease (COVID-19) testing and infection control strategies. All participating departments (23) implemented standardised case definitions, testing guidelines, early triage and infection control strategies early in the outbreak. Patient testing criteria initially focused on suspect cases and later began to include screening, mainly for hospital admissions. Long turnaround times for test results likely put additional strain on healthcare resources.

Conclusion: Shortening turnaround times for SARS-CoV-2 tests should be a priority. Specific paediatric testing criteria are needed.

 

Download the full article here.KohnsVasconcelos2020_Article_SARS-CoV-2TestingAndInfectionC

17

Sep, 2020

Respiratory Syncytial Virus-Associated Hospital Admissions in Children Younger Than 5 Years in 7 European Countries Using Routinely Collected Datasets

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Authors 

Rachel M Reeves, Maarten van Wijhe, Sabine Tong, Toni Lehtonen, Luca Stona, Anne C Teirlinck, Liliana Vazquez Fernandez, You Li, Carlo Giaquinto, Thea Kølsen Fischer, Clarisse Demont, Terho Heikkinen, Irene Speltra, Michiel van Boven, Håkon Bøås, Harry Campbell, RESCEU Investigators

Background

Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infection (RTI) in young children. Registries provide opportunities to explore RSV epidemiology and burden.

Methods

We explored routinely collected hospital data on RSV in children aged < 5 years in 7 European countries. We compare RSV-associated admission rates, age, seasonality, and time trends between countries.

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7

Sep, 2020

The effect of pregnancy on the pharmacokinetics of total and unbound Dolutegravir and its main metabolite in women living with Human Immunodeficiency Virus

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Authors: Bollen P, Freriksen J, Konopnicki D, Weizsäcker K , et al; on behalf of the Pharmacokinetics of ANtiretroviral agents in HIV-infected pregNAnt women Network

Published in: Clin infect Dis2020;26.ciaa006

Background Pharmacokinetic and efficacy data on dolutegravir in pregnant women living with human immunodeficiency virus (HIV) are still limited but needed to support its use as one of the preferred antiretroviral agents.

Methods Within the multicenter Pharmacokinetics of ANtiretroviral agents in HIV-infected pregNAnt women (PANNA) study, pregnant women living with HIV and using dolutegravir once daily (50 mg, with food) underwent 24-hour pharmacokinetic profiling in their third trimester and postpartum. Dolutegravir exposure in the third trimester was considered adequate if geometric mean unbound, pharmacologically active, minimal plasma concentrations (Cmin, unbound) and ≥90% of individual Cmin, unbound levels were >0.85 µg/L, the proposed 90% inhibitory concentration for unbound dolutegravir. Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) for comparison of total and unbound pharmacokinetic parameters in the third trimester and postpartum were calculated, including the metabolic ratio for dolutegravir-glucuronide. Safety and virological data were collected.

Results Seventeen women (76% black) were enrolled (25 evaluable pharmacokinetic profiles; 15 in the third trimester, 10 in postpartum). In the third trimester, geometric mean (coefficient of variation, %) Cmin, unbound was 2.87 (87) µg/L and 93% of individual Cmin, unbound levels were >0.85 µg/L. The GMR (90% CI) in the third trimester vs postpartum was 0.86 (.68-1.10) for area under the curve (AUC0-24h), and for Cmax, 0.93 (.77-1.13). GMR (90% CI) for the trough concentrations was 0.71 (.49-1.02), based on total dolutegravir concentrations. Four serious adverse events were reported, unlikely related to dolutegravir. The HIV polymerase chain reaction test was negative in 14/17 infants (result unknown for 3 infants).

Conclusions Pharmacokinetic changes for dolutegravir in late pregnancy are not clinically relevant and support the use of dolutegravir 50 mg once daily with food in pregnancy.

7

Sep, 2020

Clinically significant lower elvitegravir exposure during third trimester of pregnant patients living with HIV: data from the PANNA study

 

Authors: Bukkems V, Necsoi C, Hidalgo Tenorio C, et al. PANNA Network

Published in: Clin infect Dis2020; 24;ciaa488.

Abstract This phase-IV study investigated the influence of pregnancy on the pharmacokinetics of elvitegravir/cobicistat in 14 HIV-1-positive women. The results support the recommendation against elvitegravir/cobicistat use during pregnancy, as the elvitegravir Ctrough was reduced by 77%, with 85% of pregnant women having a Ctrough below the EC90.

6

Aug, 2020

Simplified dolutegravir dosing for children with HIV weighing 20 kg or more: pharmacokinetic and safety substudies of the multicentre, randomised ODYSSEY trial

 

Authors: Bollen P,  Moore CL ,  Mujuru H et al; the ODYSSEY trial team

Published in: LANCET HIV. 2020;8:e533-e544

Background Paediatric dolutegravir doses approved by stringent regulatory authorities (SRAs) for children weighing 20 kg to less than 40 kg until recently required 25 mg and 10 mg film-coated tablets. These tablets are not readily available in low-resource settings where the burden of HIV is highest. We did nested pharmacokinetic substudies in patients enrolled in the ODYSSEY-trial to evaluate simplified dosing in children with HIV.

Methods We did pharmacokinetic and safety substudies within the open-label, multicentre, randomised ODYSSEY trial (NCT02259127) of children with HIV starting treatment in four research centres in Uganda and Zimbabwe. Eligible children were randomised to dolutegravir in ODYSSEY and weighed 20 kg to less than 40 kg. In children weighing 20 kg to less than 25 kg, we assessed dolutegravir’s pharmacokinetics in children given once daily 25 mg film-coated tablets (approved by the SRAs at the time of the study) in part one of the study, and 50 mg film-coated tablets (adult dose) or 30 mg dispersible tablets in part two of the study. In children weighing 25 kg to less than 40 kg, we also assessed dolutegravir pharmacokinetics within-subject on film-coated tablet doses of 25 mg or 35 mg once daily, which were approved by the SRAs for the children’s weight band; then switched to 50 mg film-coated tablets once daily. Steady-state 24 h dolutegravir plasma concentration-time pharmacokinetic profiling was done in all enrolled children at baseline and 1, 2, 3, 4, 6, and 24 h after observed dolutegravir intake. Target dolutegravir trough concentrations (Ctrough) were based on reference adult pharmacokinetic data and safety was evaluated in all children in the corresponding weight bands who consented to pharmacokinetic studies and received the studied doses.

Findings Between Sept 22, 2016, and May 31, 2018, we enrolled 62 black-African children aged from 6 years to younger than 18 years (84 pharmacokinetic-profiles). In children weighing 20 kg to less than 25 kg taking 25 mg film-coated tablets, the geometric mean (GM) Ctrough (coefficient of variation) was 0·32 mg/L (94%), which was 61% lower than the GM Ctrough of 0·83 mg/L (26%) in fasted adults on dolutegravir 50 mg once-daily; in children weighing 25 kg to less than 30 kg taking 25 mg film-coated tablets, the GM Ctrough was 0·39 mg/L (48%), which was 54% lower than the GM Ctrough in fasted adults; and in those 30 kg to less than 40 kg taking 35 mg film-coated tablets the GM Ctrough was 0·46 mg/L (63%), which was 45% lower than the GM Ctrough in fasted adults. On 50 mg film-coated tablets or 30 mg dispersible tablets, Ctrough was close to the adult reference (with similar estimates on the two formulations in children in the 20 to <25 kg weight band), with total exposure (area under the concentration-time curve from 0 h to 24 h) in between reference values in adults dosed once and twice daily, where safety data are reassuring, although maximum concentrations were higher in children weighing 20 kg to less than 25 kg than in the twice-daily adult reference. Over a 24-week follow-up period in 47 children on 30 mg dispersible tablets or 50 mg film-coated tablets, none of the three reported adverse events (cryptococcal meningitis, asymptomatic anaemia, and asymptomatic neutropenia) were considered related to dolutegravir.

Interpretation Adult dolutegravir 50 mg film-coated tablets given once daily provide appropriate pharmacokinetic profiles in children weighing 20 kg or more, with no safety signal, allowing simplified practical dosing and rapid access to dolutegravir. These results informed the WHO 2019 dolutegravir paediatric dosing guidelines and have led to US Food and Drug Administration approval of adult dosing down to 20 kg.

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29

Jul, 2020

Harmonisation preserves research resources

 

Authors: Vasconcelos MK, Epalza C, Renk H, Tagarro A, Bielicki JA

Published in: Lancet Infect Dis. 2020;24

In their Comment, the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) clinical characterisation group outline how harmonisation of clinical characterisation studies is achieved through their collaborative resource-sharing and data-sharing platform. We fully agree with both the importance of international harmonisation and the authors’ approach. Yet, in our opinion, they could have expressed more clearly how important harmonisation is to use resources in research responsibly and efficiently.

 

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