Ethical Considerations of Dissemination and Restitution of Findings in Global Health Research

Étude de cas / Case studyThis case study discusses ethical obligations regarding the extent and scope of knowledge dissemination and restitution strategies in the context of global health research.Cette étude de cas porte sur les obligations éthiques concernant l’étendue et la portée des stratégies de dissémination et de restitution des connaissances dans un contexte de recherche en santé mondiale

Report on methods of safety signal generation in paediatrics from pharmacovigilance databases

This deliverable is based on the need to develop and test methods for safety signal detection in children. Signal detection is the mainstay of detecting safety issues, but so far very few groups have specifically looked at children. We developed reference sets for positive and negative drugevent combinations and vaccine-event combinations by a systematic literature review on all combinations. We retrieved the FDA AERS database, the CDC VAERS database and EUDRAVIGILANCE database. In order to analyse the datasets we had a stepwise approach from extraction of data, cleaning (e.g. mapping MedDRA and ATC codes) and transformation into a a common data model that we defined for the spontaneous reporting databases. A statistical analysis plan was created for the testing of methods and we provided some descriptive analyses of the FAERS data. Next steps will be to complete the analyses

Foreskin cutting beliefs and practices and the acceptability of male circumcision for HIV prevention in Papua New Guinea

Background: Male circumcision (MC) reduces HIV acquisition and is a key public health intervention in settings with high HIV prevalence, heterosexual transmission and low MC rates. In Papua New Guinea (PNG), where HIV prevalence is 0.8%, there is no medical MC program for HIV prevention. There are however many different foreskin cutting practices across the country's 800 language groups. The major form exposes the glans but does not remove the foreskin. This study aimed to describe and quantify foreskin cutting styles, practices and beliefs. It also aimed to assess the acceptability of MC for HIV prevention in PNG. Methods: Cross-sectional multicentre study, at two university campuses (Madang Province and National Capital District) and at two 'rural development' sites (mining site Enga Province; palm-oil plantation in Oro Province). Structured questionnaires were completed by participants originating from all regions of PNG who were resident at each site for study or work. Results: Questionnaires were completed by 861 men and 519 women. Of men, 47% reported a longitudinal foreskin cut (cut through the dorsal surface to expose the glans but foreskin not removed); 43% reported no foreskin cut; and 10% a circumferential foreskin cut (complete removal). Frequency and type of cut varied significantly by region of origin (p<.001). Most men (72-82%) were cut between the ages of 10 - 20 years. Longitudinal cuts were most often done in a village by a friend, with circumferential cuts most often done in a clinic by a health professional. Most uncut men (71%) and longitudinal cut men (84%) stated they would remove their foreskin if it reduced the risk of HIV infection. More than 95% of uncut men and 97% of longitudinal cut men would prefer the procedure in a clinic or hospital. Most men (90%) and women (74%) stated they would remove the foreskin of their son if it reduced the risk of HIV infection. Conclusion: Although 57% of men reported some form of foreskin cut only 10% reported the complete removal of the foreskin, the procedure on which international HIV prevention strategies are based. The acceptability of MC (complete foreskin removal) is high among men (for themselves and their sons) and women (for their sons). Potential MC services need to be responsive to the diversity of beliefs and practices and consider health system constraints. A concerted research effort to investigate the potential protective effects of longitudinal cuts for HIV acquisition is essential given the scale of longitudinal cuts in PNG

Pediatric drug safety signal detection: a new drug-event reference set for performance testing of data-mining methods and systems

BACKGROUND: Better evidence regarding drug safety in the pediatric population might be generated from existing data sources such as spontaneous reporting systems and electronic healthcare records. The Global Research in Paediatrics (GRiP)-Network of Excellence aims to develop pediatric-specific methods that can be applied to these data sources. A reference set of positive and negative drug-event associations is required. OBJECTIVE: The aim of this study was to develop a pediatric-specific reference set of positive and negative drug-event associations. METHODS: Considering user patterns and expert opinion, 16 drugs that are used in individuals aged 0-18 years were selected and evaluated against 16 events, regarded as important safety outcomes. A cross-table of unique drug-event pairs was created. Each pair was classified as potential positive or negative control based on information from the drug's Summary of Product Characteristics and Micromedex. If both information sources consistently listed the event as an adverse event, the combination was reviewed as potential positive control. If both did not, the combination was evaluated as potential negative control. Further evaluation was based on published literature. RESULTS: Selected drugs include ibuprofen, flucloxacillin, domperidone, methylphenidate, montelukast, quinine, and cyproterone/ethinylestradiol. Selected events include bullous eruption, aplastic anemia, ventricular arrhythmia, sudden death, acute kidney injury, psychosis, and seizure. Altogether, 256 unique combinations were reviewed, yielding 37 positive (17 with evidence from the pediatric population and 20 with evidence from adults only) and 90 negative control pairs, with the remainder being unclassifiable. CONCLUSION: We propose a drug-event reference set that can be used to compare different signal detection methods in the pediatric population

Learning and applying research skills in order to transfer them in different clinical settings: prospective cohort studies to build research capacity

The research work here presented was conducted with the aim of developing and transferring the skills and methodologies required to promote and enhance operational research capacity in differently resourced health care settings. The program has been built on three different intertwining components: first, theoretical learning of research methods, with focus on epidemiology and biostatistics; then the application of acquired skills to develop and conduct independent original research in collaboration with international research groups and finally, transferring the research skills either in coordinating and preparing a multicenter study in a resourced-limited setting or in analyzing, reviewing and editing works of other researchers. The present thesis includes a summary of the competencies acquired at university of Padova and at the Harvard School of Public Health, reports the original research carried out by the candidate during the program and outlines the research activities in which the candidate was involved as coordinator and collaborator, The three original research works were cohort studies (prospective or retrospective) on infectious disease epidemiology or progression (HIV and gastroenteritis). The first and main original research work was a survival study realized on a multicenter cohort of HIV patients in a low-middle income country (Thailand) with an international research group. This prospective cohort’s objective was to estimate survival at 5 years for patients with HIV treated with antiretroviral treatment (ART) and to identify the risk factors for mortality occurring immediately after starting ART (early mortality, defined as 6 months). The rationale was that in resource limited settings, while early mortality is known to be high and caused by advanced disease status at the time of treatment initiation, much less is known on magnitude and predictors of long-term mortality in these settings. The candidate was involved in data collection, and was responsible for planning the study and its analysis, analyzing the data, interpreting the results and composing the corresponding paper and poster. The second work was the analysis of a multicenter prospective cohort of HIV patients in Canada. The aim of the study was to identify which variables known at baseline could predict the occurrence of end stage liver disease in patients with HIV/HCV co-infection. The candidate planned the study and its analysis, analyzed the data, interpreted the results and along with co-authors, wrote the corresponding publications . The third work was a retrospective cohort study, aimed to describe the epidemiology and management of a common infectious disease (acute gastroenteritis) at ambulatory facilities in Italy. The role of the candidate was to interpret and discuss results, as well as organize and collaboratively write the final paper. Finally, during this program, the candidate was involved in skill transferring activities: specific aspects of research (for example literature review) for teachers and formal training on epidemiology for medical students in an university in resource limited settings, site investigator and coordinator of a multicenter study on HIV prevention in resources limited settings; collaborating in results interpretation and paper writing with units in a tertiary level hospital (Padova University). In conclusion, in these years of doctoral training, the candidate acquired specific and technical competencies in research methodology, focusing on conducting and planning operational research in differently resourced settings in which medical care is provided. She further demonstrated how effectively her skills could be applied in various research environments, leading to the production of works either published, presented in international conferences or under review for publication. Finally, her skills were transferred to support the inception of new studies, leading to an enhanced research capacity in necessitous environments.Apprendimento ed applicazione di metodologia della ricerca per trasferirla in diverse realtà cliniche: pianificazione, esecuzione ed analisi di studi osservazionali prospettici per costruire capacità di ricerca Il lavoro di ricerca qui presentato è stato condotto con lo scopo d apprendere, applicare e trasferire abilità e metodologia necessarie per promuovere e potenziare la ricerca operativa in realtà sanitarie a diverso livello di risorse disponibili. Il programma è costituito dall’intreccio di tre diverse componenti : la prima è l’apprendimento teorico di nozioni di metodologia della ricerca, con particolare enfasi in epidemiologia e biostatistica; la seconda l’applicazione delle capacità acquisite nello sviluppare e condurre ricerca originale, collaborando con gruppi internazionali; la terza trasferire le capacità acquisite nel coordinare e predisporre uno studio multicentrico in un paese a risorse limitate, e nel supportare tramite analisi, revisione o edizione del lavoro di ricerca, altri ricercatori. Questa tesi presenta un sommario di quanto appreso all’inizio del dottorato nell’Università di Padova e nella Harvard University (Boston, USA); riporta gli studi originali che sono stati fatti dal candidato durante il programma di studio, ed elenca le attività di ricerca nelle quali il candidato è stato coinvolto come coordinatore o collaboratore. Gli studi principali, usati per consolidare particolari aspetti della metodologia, ritenuti uliti per esportare in ambienti diversi, sono stati studi di coorte (prospettici e retrospettivi), su epidemiologia o risposta alla terapia o progressione clinica delle malattie infettive (in particolare HIV e gastroenteriti). Il lavoro di ricerca presentato per primo, ed il principale, è uno studio multicentrico di coorte, sulla sopravvivenza di pazienti con HIV, in un paese a basso-medio livello economico (la Tailandia) realizzato in collaborazione con un gruppo internazionale di ricerca. L’obiettivo d questa coorte prospettica ere quello di stimare la sopravvivenza a 5 anni di pazienti con HIV che iniziavano la terapia antiretrovirale e di identificare i fattori di rischio per mortalità dei primi 6 mesi (mortalità “precoce”) e nei mesi successivi al 6° e fino a 5 anni (mortalità “a lungo termine”). Il razionale è che nei paesi in via di sviluppo, benché si sappia che la mortalità precoce è alta e dovuta ad uno stadio avanzato della malattia nel momento in cui si inizia la cura, sono meno note le dimensioni e rischi della mortalità a lungo termine, che avviene durante gli anni di trattamento. Il candidato è stato coinvolto in raccolta ei dati, e responsabile per pianificazione delle studio e dell’ analisi, esecuzione dell’analisi, interpretazione dei risultati e scrittura dell’articolo e poster. Il secondo lavoro è stato uno studio prospettico su una coorte multicentrica di pazienti con duplice infezione, da HIV e HCV, in Canada. Scopo dello studio per identificare le variabili conosciute all’arruolamento nella coorte e che possono predire il verificarsi di malattia epatica terminale in pazienti coinfetti da HIV e HCV. In questo caso il candidato ha pianificato lo studio e l’analisi, condotto l’analisi, interpretato i risultati e scritto la pubblicazione corrispondente, assieme con i coautori. Il terzo lavoro è stato uno studio osservazionale retrospettivo, per descrivere epidemiologia e gestione ambulatoriale della gastroenterite acuta nella popolazione pediatrica. Per questo lavoro il contributo del candidato è stato di interpretare e discutere i risultati ed organizzare, coordinare e scrivere l’articolo. Infine, durante questo dottorato, il candidato è stato coinvolto in alcune attività di ricerca che hanno permesso di iniziare a trasferire le competenze apprese. Esempi sono un worskshop su come fare ricerca sistematica della letteratura esistente per gli insegnanti della facoltà di scienze mediche e corsi di epidemiologia per studenti della stessa, in un paese a baso reddito. Oppure aver iniziato e coordinato uno studio multicentrico sulla prevenzione di HIV nella stessa università; o aver collaborato a revisione di protocolli o interpretazione di risultati e scrittura di articoli con ricercatori dell’Università di Padova. Concludendo, negli anni del programma di dottorato, il candidato ha acquisito competenze specifiche e tecniche in metodologia della ricerca, in particolare su come pianificare e condurre ricerca operativa in realtà atte a svolgere un servizio sanitario, a diversa disponibilità di risorse. Ha inoltre dimostrato come le sue capacità possano essere messe al servizio di diversi ambienti di ricerca , arrivando alla produzione di lavori pubblicati o in pubblicazione, e a presentazioni a conferenze internazionali. Non ultimo le sue capacità sono state utilizzate per promuovere una mentalità della ricerca ed iniziare nuovi studi, aumentando la capacità di conoscere e produrre ricerca in ambienti con queste necessità

Community involvement in biomedical research conducted in the global health context; what can be done to make it really matter?

Abstract Background Community involvement in research has been advocated by researchers, communities, regulatory agencies, and funders with the aim of reinforcing subjects’ protection and improving research efficiency. Community involvement also has the potential to improve dissemination, uptake, and implementation of research findings. The fields of community based participatory research conducted with indigenous populations and of participatory action research offer a large base of experience in community involvement in research. Rules on involving the population affected when conducting research have been established in these fields. But what is the role of community engagement in clinical research and observational studies conducted in biomedical research outside of these specific areas? Main body of the abstract More than 20 years ago, in the field of HIV medicine, regulatory bodies and funding agencies (such as the US National Institutes of Health) recommended the constitution of a formal organism, the Community Advisory Board (CAB), as part of the study requirements for HIV trials. More recently, CABs have been adopted and used in other fields of medical research, such as malaria. CABs are not without limitations, however, and there is little research on the effectiveness of their use in achieving community protection and participation. Nevertheless, CABs could be a model to import into clinical trials and observational research where no alternative model of community representation is currently being used. Conclusions Allocating more resources to training and shifting more power to community representatives could be part of the solution to current CAB limitations. However, for researchers to be able to apply these recommendations on community involvement, certain conditions need to be met. In particular, funding agencies need to recognize the human and financial resources required for serious community involvement, and the academic environment needs to take community involvement into account when appraising, mentoring, and training researchers

Career adaptability as a strategic competence for career development: An exploratory study of its key predictors.

Purpose: In the current labour market, the competence to adapt is becoming significantly relevant for career development and career success. The construct of career adaptability, i.e. the capability to adapt to changing career-related circumstances and predict advancement in career development, seems to provide a fruitful scientific base for successful career intervention. The purpose of the study is exploratory, with the aim of providing new findings about the key predictors of this meta-competence that are relevant for career development. Design/methodology/approach: Through a web-based survey, a convenience sample of 230 working participants completed an online questionnaire, including socio-demographic characteristics (age, gender, education), professional status (role seniority, sector of employment, professional role), professional development-related features (training, new professional assignments, financial incentives) and psychological factors (work self-efficacy, search for work self-efficacy and job satisfaction). Four-step hierarchical multiple regression analyses were conducted to understand which of these factors account for the most career adaptability variance. Findings: Results highlight that work self-efficacy, search for work self-efficacy and education play a significant role in predicting career adaptability. Surprisingly, professional development-related features and professional status do not seem to have a relevant influence. Practical implications: Training and career-development professionals can improve their understanding of which career-related skills and attitudes can increase one’s capability to cope with sudden changes and instability of the current labour market. Originality/value: This study supports previous research, addressing the importance of career adaptability in times of dramatic change. It also provides some insight into the factors that could predict it

IDENTITÀ E SVILUPPO LOCALE. IL RUOLO DEI PROCESSI SIMBOLICI NELLA PIANIFICAZIONE DEL TERRITORIO: UNA RICERCA-INTERVENTO IN UN COMUNE SARDO

Il presente contributo propone una riflessione sulle dimensioni simbolico-affettive e le culture locali entro la progettazione strutturale di spazi pubblici. Il progetto presentato nasce da una collaborazione multidisciplinare tra scienziati sociali, architetti e amministratori, al fine di fronteggiare lo spopolamento del centro di Mogoro (OR). Il progetto ha integrato il ripensamento degli spazi pubblici con l’analisi di dimensioni simbolico-affettive, evidenziando la cogenza degli aspetti rappresentazionali nel determinare la fenomenologia dello spopolamento. L’intero intervento così come la restituzione dei risultati sono stati condotti attraverso un modello partecipativo aprendo ulteriori questioni legate allo sviluppo di Mogoro, tradotte in due successivi interventi sugli spazi pubblici e la progettazione di servizi.This paper proposes a reflection on the function of the symbolic, emotional and cultural dimensions in the design and planning of public spaces. The described project was thought in a multidisciplinary way aimed at tackling the depopulation of the city center of Mogoro (OR). The project has integrated the rethinking of public spaces with the analysis of symbolic and affective dimensions, highlighting the extent to which social representations affect the depopulation phenomenology. The whole project as well as the return of its results have been arranged according to a participatory methodology opening the scene to further ideas for the development of Mogoro which have been translated into two further projects on public spaces and service design

The impact of improved detection and treatment of isoniazid resistant tuberculosis on prevalence of multi-drug resistant tuberculosis: A modelling study.

INTRODUCTION:Isoniazid-resistant, rifampin susceptible tuberculosis (INHR-TB) is the most common form of drug resistant TB globally. Treatment of INHR-TB with standard first-line therapy is associated with high rates of multidrug resistant TB (MDR-TB). We modelled the potential impact of INHR-TB detection and appropriate treatment on MDR-TB prevalence. METHODS:A decision analysis model was developed to compare three different strategies for the detection of TB (AFB smear, Xpert MTB/RIF, and Line-Probe Assays (LPA)), combined with appropriate treatment. The population evaluated were patients with a globally representative prevalence of newly diagnosed, drug-susceptible (88.6%), isoniazid-resistant (7.3%), and multidrug resistant (4.1%) pulmonary TB. Our primary outcome was the proportion of patients with MDR-TB after initial attempt at diagnosis and treatment within a 2-year period. Secondary outcomes were the proportion of i) individuals with detected TB who acquired MDR-TB ii) individuals who died after initial attempt at diagnosis and treatment. RESULTS:After initial attempt at diagnosis and treatment, LPA combined with appropriate INHR-TB therapy resulted in a lower proportion of prevalent MDR-TB (1.61%; 95% Uncertainty Range (UR: 2.5th and 97.5th percentiles generated from 10 000 Monte Carlo simulation trials) 1.61-1.65), when compared to Xpert (1.84%; 95% UR 1.82-1.85) and AFB smear (3.21%; 95% UR 3.19-3.26). LPA also resulted in fewer cases of acquired MDR-TB in those with detected TB (0.35%; 95% UR 0.34-0.35), when compared to Xpert (0.67%; 95% UR 0.65-0.67) and AFB smear (0.68%; 95% UR 0.67-0.69). The majority of acquired MDR-TB arose from the treatment of INHR-TB in all strategies. Xpert-based strategies resulted in a lower proportion of death (2.89%; 95% UR 2.87-2.90) compared to LPA (2.93%; 95% UR 2.91-2.94) and AFB smear (3.21%; 95% UR 3.19-3.23). CONCLUSION:Accurate diagnosis and tailored treatment of INHR-TB with LPA led to an almost 50% relative decrease in acquired MDR-TB when compared with an Xpert MTB/RIF strategy. Continued reliance on diagnostic and treatment protocols that ignore INHR-TB will likely result in further generation of MDR-TB