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Background Health-related research funders, regulators and journals expect that de-identified individual-level health data be shared widely, with as few restrictions as possible; yet, in reality, the volume of shared data remains low. Main body Health researchers and other data producers are reluctant to share their data unless they are confident that their datasets are of high quality and reliable, and that they are used in accordance with the values and aims of their institutions. We argue that having an institutional, departmental or group data management and sharing policy is the first step towards encouraging researchers and healthcare professionals to share their data more widely. Our paper outlines the elements of a data management and sharing policy, which should include aims consistent with those of the institution as well as with data management procedures, models of data sharing, request procedures, consent models and cost recovery mechanisms. A policy would help an institution, department or group maximise the use of its data and protect the interests of the institution and its members. We base our recommendations on our experience collecting and curating data for large clinical trials conducted in low- and middle-income countries, facilitating the sharing of datasets with secondary users, whilst teaching data management and conducting empirical research on data sharing. Although the fundamentals of a policy are general, the paper is focused on the low- and middle-income country context. Conclusion We argue that having an institutional, departmental or group data management and sharing policy is the first step in promoting data sharing.

Visceral leishmaniasis (VL) in human immunodeficiency virus (HIV) co-infected patients requires special case management. AmBisome monotherapy at 40 mg/kg is recommended by the World Health Organization. The objective of the study was to assess if a combination of a lower dose of AmBisome with miltefosine would show acceptable efficacy at the end of treatment. An open-label, non-comparative randomized trial of AmBisome (30 mg/kg) with miltefosine (100 mg/day for 28 days), and AmBisome monotherapy (40 mg/kg) was conducted in Ethiopian VL patients co-infected with HIV (NCT02011958). A sequential design was used with a triangular continuation region. The primary outcome was parasite clearance at day 29, after the first round of treatment. Patients with clinical improvement but without parasite clearance at day 29 received a second round of the allocated treatment. Efficacy was evaluated again at day 58, after completion of treatment. Recruitment was stopped after inclusion of 19 and 39 patients in monotherapy and combination arms respectively, as per pre-specified stopping rules. At D29, intention-to-treat efficacy in the AmBisome arm was 70% (95% CI 45-87%) in the unadjusted analysis, and 50% (95% CI 27-73%) in the adjusted analysis, while in the combination arm, it was 81% (95% CI 67-90%) and 67% (95% CI 48-82%) respectively. At D58, the adjusted efficacy was 55% (95% CI 32-78%) in the monotherapy arm, and 88% (95% CI 79-98%) in the combination arm. No major safety concerns related to the study medication were identified. Ten SAEs were observed within the treatment period, and 4 deaths unrelated to the study medication. The extended treatment strategy with the combination regimen showed the highest documented efficacy in HIV-VL patients; these results support a recommendation of this regimen as first-line treatment strategy for HIV-VL patients in eastern Africa. www.clinicaltrials.gov NCT02011958.

Background The healthcare sector is rapidly evolving with the rise of digital technology and data-driven decision-making. However, traditional medical education has yet to fully integrate training on managing health-related information, resulting in a significant skills gap among medical and research professionals. This gap is pronounced in low- and middle-income countries (LMICs), where data privacy concerns and inadequate infrastructure hinder efforts to utilise and share health data. Aims To address this gap, we developed an online, modular course aimed at providing foundational skills on capturing, storing and sharing health data. Methods The course was developed using the ADDIE(Analyze, Design, Develop, Implement, Evaluate) instructional design model. A needs assessment workshop involving 25 global health proffesionals identified key training gaps which informed the curriculum’s development. A multidisciplinary team from six institutions developed the modules. The course was piloted in a face-to-face setting with 37 participants and later adapted for online delivery via the Global Health Network platform. We evaluated the course using Level 1 of Kirkpatrick’s model for training evaluation. Results Six foundational modules were developed: Introduction to Data Management, Data Quality, Data Repositories, Ethics of Data Sharing, Data Governance, and Costing for Data Management. Between December 2020 and April 2024, 6,384 individuals from 90 countries completed the course. Of these, 32% were from Africa, 15% from Asia, 16% from South/Central America and the Caribbean, and 24% from Europe. Summative evaluations, based on voluntary post-module surveys, demonstrated high relevance to participants’ learning needs (96.6%) and strong intentions to apply the skills gained (88.3%). Key motivators for enrollment included the course’s free access, relevance to professional or academic needs, and trust in the organizations and authors behind the content. Conclusions The high enrolment and broad geographical reach demonstrates the potential of online training as a cost-effective tool to equip health practitioners and researchers with data literacy skills. Future evaluations will assess its impact on participants’ knowledge, behavior, and data-sharing and reuse practices.

The long-term treatment outcome of visceral leishmaniasis (VL) patients with HIV co-infection is complicated by a high rate of relapse, especially when the CD4 count is low. Although use of secondary prophylaxis is recommended, it is not routinely practiced and data on its effectiveness and safety are limited. A prospective cohort study was conducted in Northwest Ethiopia from August 2014 to August 2017 (NCT02011958). HIV-VL patients were followed for up to 12 months. Patients with CD4 cell counts below 200/μL at the end of VL treatment received pentamidine prophylaxis starting one month after parasitological cure, while those with CD4 count ≥200 cells/μL were followed without secondary prophylaxis. Compliance, safety and relapse-free survival, using Kaplan-Meier analysis methods to account for variable time at risk, were summarised. Risk factors for relapse or death were analysed. Fifty-four HIV patients were followed. The probability of relapse-free survival at one year was 50% (95% confidence interval [CI]: 35-63%): 53% (30-71%) in 22 patients with CD4 ≥200 cells/μL without pentamidine prophylaxis and 46% (26-63%) in 29 with CD4 <200 cells/μL who started pentamidine. Three patients with CD4 <200 cells/μL did not start pentamidine. Amongst those with CD4 ≥200 cells/μL, VL relapse was an independent risk factor for subsequent relapse or death (adjusted rate ratio: 5.42, 95% CI: 1.1-25.8). Except for one case of renal failure which was considered possibly related to pentamidine, there were no drug-related safety concerns. The relapse-free survival rate for VL patients with HIV was low. Relapse-free survival of patients with CD4 count <200cells/μL given pentamidine secondary prophylaxis appeared to be comparable to patients with a CD4 count ≥200 cells/μL not given prophylaxis. Patients with relapsed VL are at higher risk for subsequent relapse and should be considered a priority for secondary prophylaxis, irrespective of their CD4 count.

  [...]actual entry of data into the system in a remote setting is faster because the delays associated with poor connectivity are eliminated and the time taken for the data to reach the DC is shortened due to the fact that paper case report forms (CRFs) do not require physical transportation, site capacity has been strengthened, and the site staff feel engaged with the project beyond patient management through participation in CDM. In the future, it should be possible to replace STATA in the QMSPlus program, which requires purchase of a license, with an alternative open-source package in order for QMSPlus to be made available as an open-access tool. Since resources are needed for training, open-source software is not necessarily cost-free, but this expense is justifiable when compared to the cost of proprietary tools for noncommercial research [8].

To determine time and cost differences between one- and two-step injectable artesunate formulations for treatment of severe malaria and compare their safety and treatment outcomes. We conducted an open-label randomized clinical trial at hospitals in Kinshasa, Democratic Republic of the Congo and Korogwe, United Republic of Tanzania in patients aged 3 months to 16 years with severe malaria. We randomly allocated patients to a new one-step injectable artesunate formulation or the conventional two-step formulation. After discharge, patients were followed for 4 weeks. The main outcomes evaluated were time and cost of administering treatment, and clinical and pharmacodynamic effects. Between 7 June 2022 and 11 August 2023, 200 patients were randomized (1:1) to either the one-step or two-step arm. Mean time to administer artesunate was 2 min 22 s (standard deviation, SD: 50 s) in the one-step arm and 3 min 41 s (SD: 95 s) in the two-step ( -value: < 0.0001). Mean cost of syringes and needles used per patient was 0.53 (SD: 0.13) United States dollars (US$) in the one-step arm versus US$ 0.84 (SD:  0.22) in the two-step ( -value: 0.0001). Parasite clearance half-lives were 2.1 h (SD: 0.9) in the one-step arm and 2.0 h (SD: 0.8) in the two-step (  -value: 0.173). Severe adverse events occurred in one patient in each arm (  -value: 1.000), while 242 and 229 ungraded adverse events occurred in the one- and two-step arms, respectively (  -value: 0.549). In children with severe malaria, one-step injectable artesunate was quicker and cheaper to administer and had equivalent safety and efficacy compared with the conventional formulation.

Triple antimalarial combination therapies combine potent and rapidly cleared artemisinins or related synthetic ozonides, such as arterolane, with two, more slowly eliminated partner drugs to reduce the risk of resistance. We aimed to assess the safety, tolerability, and efficacy of arterolane–piperaquine–mefloquine versus arterolane–piperaquine and artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in Kenyan children. In this single-centre, open-label, randomised, non-inferiority trial done in Kilifi County Hospital, Kilifi, coastal Kenya, children with uncomplicated Plasmodium falciparum malaria were recruited. Eligible patients were aged 2–12 years and had an asexual parasitaemia of 5000–250 000 parasites per μL. The exclusion criteria included the presence of an acute illness other than malaria, the inability to tolerate oral medications, treatment with an artemisinin derivative in the previous 7 days, a known hypersensitivity or contraindication to any of the study drugs, and a QT interval corrected for heart rate (QTc interval) longer than 450 ms. Patients were randomly assigned (1:1:1), by use of blocks of six, nine, and 12, and opaque, sealed, and sequentially numbered envelopes, to receive either arterolane–piperaquine, arterolane–piperaquine–mefloquine, or artemether–lumefantrine. Laboratory staff, but not the patients, the patients' parents or caregivers, clinical or medical officers, nurses, or trial statistician, were masked to the intervention groups. For 3 days, oral artemether–lumefantrine was administered twice daily (target dose 5–24 mg/kg of bodyweight of artemether and 29–144 mg/kg of bodyweight of lumefantrine), and oral arterolane–piperaquine (arterolane dose 4 mg/kg of bodyweight; piperaquine dose 20 mg/kg of bodyweight) and oral arterolane–piperaquine–mefloquine (mefloquine dose 8 mg/kg of bodyweight) were administered once daily. All patients received 0·25 mg/kg of bodyweight of oral primaquine at hour 24. All patients were admitted to Kilifi County Hospital for at least 3 consecutive days and followed up at day 7 and, thereafter, weekly for up to 42 days. The primary endpoint was 42-day PCR-corrected efficacy, defined as the absence of treatment failure in the first 42 days post-treatment, of arterolane–piperaquine–mefloquine versus artemether–lumefantrine, and, along with safety, was analysed in the intention-to-treat population, which comprised all patients who received at least one dose of a study drug. The 42-day PCR-corrected efficacy of arterolane–piperaquine–mefloquine versus arterolane–piperaquine was an important secondary endpoint and was also analysed in the intention-to-treat population. The non-inferiority margin for the risk difference between treatments was −7%. The study is registered in ClinicalTrials.gov, NCT03452475, and is completed. Between March 7, 2018, and May 2, 2019, 533 children with P falciparum were screened, of whom 217 were randomly assigned to receive either arterolane–piperaquine (n=73), arterolane–piperaquine–mefloquine (n=72), or artemether–lumefantrine (n=72) and comprised the intention-to-treat population. The 42-day PCR-corrected efficacy after treatment with arterolane–piperaquine–mefloquine (100%, 95% CI 95–100; 72/72) was non-inferior to that after treatment with artemether–lumefantrine (96%, 95% CI 88–99; 69/72; risk difference 4%, 95% CI 0–9; p=0·25). The 42-day PCR-corrected efficacy of arterolane–piperaquine–mefloquine was non-inferior to that of arterolane–piperaquine (100%, 95% CI 95–100; 73/73; risk difference 0%). Vomiting rates in the first hour post-drug administration were significantly higher in patients treated with arterolane–piperaquine (5%, 95% CI 2–9; ten of 203 drug administrations; p=0·0013) or arterolane–piperaquine–mefloquine (5%, 3–9; 11 of 209 drug administrations; p=0·0006) than in patients treated with artemether–lumefantrine (1%, 0–2; three of 415 drug administrations). Upper respiratory tract complaints (n=26 for artemether–lumefantrine; n=19 for arterolane–piperaquine–mefloquine; n=23 for arterolane–piperaquine), headache (n=13; n=4; n=5), and abdominal pain (n=7; n=5; n=5) were the most frequently reported adverse events. There were no deaths. This study shows that arterolane–piperaquine–mefloquine is an efficacious and safe treatment for uncomplicated falciparum malaria in children and could potentially be used to prevent or delay the emergence of antimalarial resistance. UK Department for International Development, The Wellcome Trust, The Bill & Melinda Gates Foundation, Sun Pharmaceutical Industries

[...]actual entry of data into the system in a remote setting is faster because the delays associated with poor connectivity are eliminated and the time taken for the data to reach the DC is shortened due to the fact that paper case report forms (CRFs) do not require physical transportation, site capacity has been strengthened, and the site staff feel engaged with the project beyond patient management through participation in CDM. In the future, it should be possible to replace STATA in the QMSPlus program, which requires purchase of a license, with an alternative open-source package in order for QMSPlus to be made available as an open-access tool. Since resources are needed for training, open-source software is not necessarily cost-free, but this expense is justifiable when compared to the cost of proprietary tools for noncommercial research [8].

Background: To restrict trial endpoints to infections acquired after vaccination in Phase IIb trials of candidate malaria vaccines, participants are treated with anti-malarial drugs to clear existing infections. Anti-malarial drugs with a long half-life may inhibit the acquisition of new infections. This study evaluated the effects of three anti-malarial drug regimens on the clearance of existing infections and acquisition of new infections. Methods: An open-label randomised controlled trial (MalPaC) was conducted between November 2013 and February 2014. Ninety adults were randomised 1:1:1 to receive one of three treatments: atovaquone/proguanil and artesunate (AP+AS); artesunate (AS); or sulphadoxine-pyrimethamine, artesunate, and primaquine (SP+AS+PQ). Parasite monitoring was determined over 84-day follow-up by assessing Plasmodium falciparum positivity by 18s qPCR, live and sexual stage parasites by RT-PCR, and recrudescence of infections by msp2 genotyping. Results : At enrolment, parasite prevalence by qPCR was 44% (40/90, day 0), which fell to 10% (9/90, day 16), then rose to almost the initial rates by day 84 (39%, 35/90). Individuals treated with AS and SP+AS+PQ were more likely to have higher qPCR positive rates compared to participants treated with AP+AS in the immediate post-treatment phase (days 16-28) (OR=7.7 [95%CI 4.6-12.8] p<0.0005 and OR=4.2 [95%CI 2.6-6.8] p<0.0005, respectively). In the immediate post-treatment phase, qPCR positivity was less likely associated with evidence of live parasites and gametocytaemia. Prevalence of “old”, “new” or “undetectable” infections did not differ significantly over time or drug regimen. However, participants on the AP+AS drug regimen were less likely to have parasite infection recrudescence compared to participants treated with AS and SP+AS+PQ. Conclusion: Falciparum DNA remained detectable by PCR post-treatment with incomplete parasite clearance regardless of drug regimen. Though AP+AS drug regimen may also have partially suppressed the acquisition of new infections during post-treatment follow-up. Trial registration: Pan African Clinical Trials Registry, 22nd of August 2013, PACTR201309000625311 .