Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis.

Medici Senza Frontiere - feed -

Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis. Dahal, P; Simpson, JA; Abdulla, S; Achan, J; Adam, I; Agarwal, A; Allan, R; Anvikar, AR; Arinaitwe, E; Ashley, EA; Awab, GR; Bassat, Q; Bjorkman, A; Bompart, F; Borrmann, S; Bousema, T; Broek, I; Bukirwa, H; Carrara, VI; Corsi, M; Cot, M; D'Alessandro, U; Davis, TME; de Wit, M; Deloron, P; Desai, M; Dimbu, PR; Djalle, D; Djimde, A; Dorsey, G; Doumbo, OK; Drakeley, CJ; Duparc, S; Edstein, MD; Espie, E; Faiz, A; Falade, C; Fanello, C; Faucher, JF; Faye, B; de Jesus Fortes, F; Gadalla, NB; Gaye, O; Gil, JP; Greenwood, B; Grivoyannis, A; Hamed, K; Hien, TT; Hughes, D; Humphreys, G; Hwang, J; Ibrahim, ML; Janssens, B; Jullien, V; Juma, E; Kamugisha, E; Karema, C; Karunajeewa, HA; Kiechel, JR; Kironde, F; Kofoed, PE; Kremsner, PG; Lameyre, V; Lee, SJ; Marsh, K; Martensson, A; Mayxay, M; Menan, H; Mens, P; Mutabingwa, TK; Ndiaye, JL; Ngasala, BE; Noedl, H; Nosten, F; Offianan, AT; Oguike, M; Ogutu, BR; Olliaro, P; Ouedraogo, JB; Piola, P; Plowe, CV; Plucinski, MM; Pratt, OJ; Premji, Z; Ramharter, M; Rogier, C; Rombo, L; Rosenthal, PJ; Sawa, P; Schramm, P; Sibley, C; Sinou, V; Sirima, S; Smithuis, F; Staedke, SG; Sutanto, I; Talisua, AO; Tarning, J; Taylor, WRJ; Temu, E; Thriemer, KL; Thuy, NN; Udhayakumar, V; Ursing, J; van Herp, M; van Vugt, M; Whitty, C; William, Y; Winnips, C; Zongo, I; Guerin, P; Price, RN; Stepniewska, K BACKGROUND: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections. METHODS: Antimalarial studies typically report the risk of recrudescence derived using the Kaplan-Meier (K-M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K-M method (1 minus K-M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K-M curves was assessed using the log-rank test, and the equality of CIFs using Gray's k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray's sub-distributional hazard model. RESULTS: Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K-M approach was 0.04% (interquartile range (IQR): 0.00-0.27%, Range: 0.00-3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson's correlation coefficient (ρ): 0.38, 95% Confidence Interval (CI) 0.30-0.46] or new infection [ρ: 0.43; 95% CI 0.35-0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K-M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold. CONCLUSIONS: The 1 minus K-M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings.

Wednesday’s Daily Brief: Libya ‘war crime’ attack, Sudan, Myanmar rights violations continue, ‘xenophobia’ in Assam, South Sudan update

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In the news this Wednesday: “Outraged” Guterres demands independent inquiry into fatal Libya migrant centre airstrike; Violence and broken promises in Sudan and South Sudan, while Rohingya violations continue in Myanmar; “xenophobia” and citizenship in India’s Assam state. 

Restrictions, unmet promises, unbridled violence in Sudan, a ‘recipe for disaster’, says Bachelet

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After nationwide protests across Sudan on Sunday, UN human rights chief Michelle Bachelet on Wednesday called on Sudanese authorities to lift restrictions on the internet and launch independent investigations into all acts of violence against demonstrators, and allegations of excessive force, including attacks on hospitals.

Malnutrition in Chakradharpur, Jharkhand: an anthropological study of perceptions and care practices from India

Medici Senza Frontiere - feed -

Malnutrition in Chakradharpur, Jharkhand: an anthropological study of perceptions and care practices from India Chaand, I; Horo, M; Nair, M; Harshana, A; Mahajan, R; Kashyap, V; Falero, F; Escruela, M; Burza, S; Dasgupta, R Background This study aims to investigate the knowledge, perception and practices related to health, nutrition, care practices, and their effect on nutrition health-seeking behaviour. Methods In order to have maximum representation, we divided Chakradharpur block in Jharkhand state into three zones (north, south and centre regions) and purposively selected 2 Ambulatory Therapeutic Feeding Centre (ATFC) clusters from each zone, along with 2 villages per ATFC (12 villages from 6 ATFCs in total). In-depth interviews and natural group discussions were conducted with mothers/caregivers, frontline health workers (FHWs), Medicins Sans Frontieres (MSF) staff, community representatives, and social leaders from selected villages. Results We found that the community demonstrates a strong dependence on traditional and cultural practices for health care and nutrition for newborns, infants and young children. Furthermore, the community relies on alternative systems of medicine for treatment of childhood illnesses such as malnutrition. The study indicated that there was limited access to and utilization of local health services by the community. Lack of adequate social safety nets, limited livelihood opportunities, inadequate child care support and care, and seasonal male migration leave mothers and caregivers vulnerable and limit proper child care and feeding practices. With respect to continuum of care, services linking care across households to facilities are fragmented. Limited knowledge of child nutrition amongst mothers and caregivers as well as fragmented service provision contribute to the limited utilization of local health services. Government FHWs and MSF field staff do not have a robust understanding of screening methods, referral pathways, and counselling. Additionally, collaboration between MSF and FHWs regarding cases treated at the ATFC is lacking, disrupting the follow up process with discharged cases in the community. Conclusions For caregivers, there is a need to focus on capacity building in the area of child nutrition and health care provision post-discharge. It is also recommended that children identified as having moderate acute malnutrition be supported to prevent them from slipping into severe acute malnutrition, even if they do not qualify for admission at ATFCs. Community education and engagement are critical components of a successful CMAM program.

New UN-Syrian Action Plan signals an 'important day' for child protection, says UN envoy

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The top UN official charged with representing the interests of children caught up in armed conflict, has signed a landmark new agreement on child protection with the Force Commander of a main Syrian opposition military alliance, it was announced on Monday, aimed at ending and preventing the recruitment and use of children under the age of 18.

Al galoppo verso il precipizio

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Nell'anno 2019 della crisi climatica globale e della sesta estinzione di massa, il giorno 30 di un giugno a temperature infernali...tutto intorno a noi pare darci il segno che manca una vera presa di coscienza. Che siamo intrappolati in una frenesia distruttiva che ci rende, in realtà, ciechi.

Greta Thunberg: più consumi, più hai il dovere di cambiare

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Greta Thunberg, la giovanissima attivista svedese che ha innescato il movimento mondiale per contrastare i cambiamenti climatici, ha partecipato all'evento annuale della Brilliant Minds Foundation che si è tenuto a Stoccolma. Con un discorso che ancora una volta rappresenta un "manifesto" su cui riflettere per passare all'azione.

Thursday’s Daily Brief: dire living conditions in Idlib, migrants at US southern border, end in sight for trachoma, Human Rights Council

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This Thursday, we cover: the dire humanitarian situation in Syria’s Idlib; living conditions at the US-Mexico border denounced by the UN Children’s Fund (UNICEF); trachoma-related blindness on the verge of being eliminated; and updates from the Human Rights Council in Geneva.


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