1,721,034 research outputs found
HIV infection and Infancy: From diagnosis to treatment and their setting-related issues.
No full textThe research work here presented was conducted with the aim of assessing knowledge gaps in managing HIV-infected infants and young children as well as informing the implementation and policy development for low and middle-income countries.
The present thesis, which includes a summary of the competencies acquired at the University of Padova as well as at the Medical Research Council Clinical Trial Unit and the London School of Hygiene and Tropical Medicine, reports the original research which I carried out during the program and outlines the research activities in which I was involved as coordinator or collaborator.
This project has been developed through four different intertwining components: a systematic revision of the literature; a primary data analysis of clinical data from European cohorts of HIV infected infants; three different projects of operational research informing the implementation of international standards of care in low and middle-income countries; and finally the systematic application of standard methodologies to translate evidence into policies.
The systematic revision of the literature highlighted how while there is now conclusive evidence in favour of early initiation of ART in infants, the superiority of LPV/r-based regimens as a first-line therapy is still matter of debate. Moreover, the need of additional evidence from ongoing trials to inform alternative treatment strategies such as interruptions or reuse of NNRTIs when virological suppression is achieved with LPV/r-based regimens was reinforced.
The analysis conducted on European HIV-infected infants starting treatment by the first year of age showed early treatment being effective and durable even outside trial settings. However, did not confirm the superiority of LPV-based regimen observed in trials, but showed a better viro-immunological response in those infants starting ART with a 4 drugs NVP-based regimen.
The implementation of early therapy in HIV-infected infants was shown to increase significantly the number of children eligible for treatment in a Ugandan cohort taken as example to explore the impact of new WHO guidelines at programmatic level. It was also observed that increase in eligibility occurs particularly at enrolment and that delays in initiation are considerable highlighting the need of a prompt diagnosis and rapid pre-ART counselling.
Early infant diagnosis is increasingly being recognised as a building block for treatment and care in infants. A study protocol was therefore developed to investigate the cost implications of different testing strategies and inform the budget allocation at the country level.
HIV drug resistant strains circulation represents a further challenge for the implementation of treatment, particularly in children in low-middle income countries where treatment options are limited. A surveillance study protocol was developed to investigate at a population level the prevalence of resistant viruses transmitted from the mother to the baby and inform national guidelines development.
Finally the use of standardised method to translate evidence into policies allowed investigating the implications of recommending globally in infants and young children the use of LPV/r-based regimen as first line therapy regardless of their exposure to PMTCT interventions. Significant challenges in acceptability and feasibility make the revision of recommendations difficult until new formulations will become available.
The aim of my future work will be to apply these skills to facilitate and promote research to guide the development of international policies for life-saving public health actions in the field of infectious diseases.Il progetto di ricerca di seguito presentato si pone l’obiettivo di analizzare ed espandere le attuali conoscenze sulla gestione dei lattanti con infezione da HIV e di contribuire ad informare l’implementazione e lo sviluppo di adeguate raccomandazioni per i paesi a risorse limitate.
La presente tesi raccoglie una sintesi delle competenze e dell’esperienza maturata presso l’Universita’ di Padova ed il Dipartimento di Pediatria, presso l’unita’ di clinical trial del Medical Research Council di Londra e presso la London School of Hygiene and Tropical Medicine attraverso la partecipazione a corsi avanzati in epidemiologia e biostatistica. Questo scritto illustra le attivita’ di ricerca in cui sono stata coinvolta o come principale coordinatore o come stretto collaboratore.
Questo lavoro si basa su quattro componenti fortemente interconnesse: 1) la revisione sistematica della letteratura disponibile sull’argomento; 2) l’analisi di dati osservazionali provenienti da diverse coorti europee di bambini con infezione da HIV che hanno iniziato la terapia entro il primo anno di vita; 3) tre differenti progetti di ricerca operazionale finalizzati ad informare la fase di implementazione degli standard di cure internazionali nei paesi a risorse limitate; 4) infine una parte dove l’evidenza raccolta viene utilizzata in maniera sistematica per sviluppare raccomandazioni internazionali finalizzate all’ottimizzazione della gestione della terapia nei bambini con infezione da HIV sotto l’anno di vita.
La revisione sistematica della letteratura da un lato ha messo in luce come esista già una solida evidenza a favore dell’inizio precoce della terapia anitretrovirale nei bambini sotto l’anno di vita, ma dall’altro lato ha mostrato anche che la superiorità dei regimi di prima linea contenenti Lopinavir/ritonavir è ancora oggetto di discussione. Inoltre, si è osservato come siano necessari ulteriori dati in merito all’utilizzo di strategie nuove come quelle che prevedono l’interruzione strutturate della terapia o il riutilizzo di NNRTI una volta che la soppressione virologica è raggiunta con un regime contenente Lopinavir/ritonavir.
L’analisi condotta su dati europei provenienti da bambini che hanno iniziato la terapia antiretrovirale nel primo anno di vita, ha confermato come una risposta efficace e duratura sia possibile anche al di fuori di trial clinici. Tuttavia, non ha evidenziato alcuna superiorita’ terapeutica dei regimi contenenti Lopinavir/ritonavir rispetto a quelli contenenti Nevirapina ed ha invece suggerito che un regime a quattro farmaci contenente Nevirapina sarebbe correlato ad una migliore risposta viro-immunologica .
L’implementazione della terapia precoce per tutti i bambini HIV-infetti sotto l’anno di vita ha dimostrato di aumentare significativamente il numero dei pazienti eleggibili per l’inizio della terapia in una coorte Ugandese presa come esempio per esplorare l’impatto che le nuove linee guida WHO stanno avendo a livello programmatico. E stato inoltre osservato che l’aumento del numero dei pazienti eleggibili avviene in particolare al momento dell’arruolamento e che esistono ancora considerevoli ritardi nell’inizio della terapia, sottolineando la necessità di una diagnosi precoce e di un rapido counselling pre-terapia.
La diagnosi virologica nei bambini sotto i 18 mesi è sempre più considerata come l’elemento fondamentale per lo scaling-up della terapia e delle cure nei bambini con infezione da HIV. Un protocollo di studio è stato pertanto messo a punto allo scopo di studiare le implicazioni economiche di differenti strategie diagnostiche ed informare l’ottimale utilizzazione del budget che ciascun paese ha a disposizione.
La diffusione di sottotipi virali resistenti agli attuali farmaci antiretrovirali disponibili è un’altra delle difficoltà incontrate durante la fase di implementazione ed ottimizzazione delle cure dei bambini infetti da HIV nei paesi a risorse limitate. Uno studio di sorveglianza è stato pertanto messo a punto per studiare la frequenza con cui ceppi resistenti vengono trasmessi dalla madre al bambino allo scopo di informare lo sviluppo delle linee guida nazionali.
Infine, l’utilizzo di una metodologia standardizzata per lo sviluppo di policy basate sull’evidenza ha permesso di indagare in profondità le implicazioni legate ad una revisione delle linee guida che raccomandi a livello globale l’utilizzo di un regime di prima linea contenete Lopinavir/ritonavir. Si sono riscontrate delle barriere significative in termini di accettabilità e fattibilità tali da non raccomandare attualmente una modifica delle linee guida, almeno fino a quando non saranno disponibili formulazioni più appropriate.
Il mio futuro lavoro sarà orientato verso l’utilizzo delle capacità acquisite per condurre e promuovere attività di ricerca che possano guidare lo sviluppo di adeguate politiche sanitarie internazionali nel campo delle malattie infettive
Role of non-nucleoside reverse transcriptase inhibitors in treating HIV-infected children.
No full textRetention in care of children and adolescents in an HIV programme in Kampala, Uganda: the impact of a multifaceted approach
No full textAntiretroviral Therapy in HIV Infected Children with Tuberculosis: A Systematic Review
No full textTuberculosis is the major cause of mortality in HIV-infected children globally. Current guidelines about the management of antiretroviral therapy in children with tuberculosis are based on a limited number of non-randomized studies involving small numbers of participants. The aim of the study was to systematically retrieve and critically appraise available evidence on the efficacy and safety of different antiretroviral regimens in children with HIV infection who are receiving treatment for active tuberculosis
Paediatric medicine issues and gaps from healthcare workers point of view: survey results and a narrative review from the global accelerator for paediatric formulations project
Get PDF: The WHO Model List of Essential Medicines for Children (EMLc) has not been systematically revised in the last few years. We conducted a survey addressed to healthcare professionals prescribing, preparing, or administering medicines to children and a narrative review to identify problematic paediatric formulations or missing medicines in all therapeutic fields to inform the review of the EMLc in 2023. A total of 285 physicians (63%), 28 nurses (6%) and 142 pharmacists (31%), mostly working in the hospital setting, reported at least one problematic medicine. 290 medicines were reported as missing (completely or the child-appropriate formulation). The top three most mentioned were ciprofloxacin together with phenobarbital and omeprazole. 387 medicines were reported as problematic (34% were oral liquid formulations, 34% tablets, 18% parenteral preparations. Mostly of the products were antibacterials (27%), cardiovascular medicines (11%) and antivirals (11%). The obtained responses show the perspective of healthcare workers working around the world, particularly in the European region (25%), in the African region (24%), and in the Region of the Americas (19%), with limited representation from Northern Africa and the Middle East. Our results need to be analysed with the outputs of other ongoing works before specific products can enter the WHO-hosted Global Accelerator for Paediatric formulations network prioritisation process. Efforts to develop appropriate formulations for children should be accelerated so that the uncertainties associated with off-label drug preparation and use are minimised, and therapeutic benefits are optimised
Programmatic impact of the evolution of WHO pediatric antiretroviral treatment guidelines for resource-limited countries (Tukula Fenna Project, Uganda).
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Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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