Comparative study of the efficacy and tolerability of dihydroartemisinin - piperaquine - trimethoprim versus artemether - lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Cameroon, Ivory Coast and Senegal

<p>Abstract</p> <p>Background</p> <p>The ACT recommended by WHO is very effective and well-tolerated. However, these combinations need to be administered for three days, which may limit adherence to treatment.</p> <p>The combination of dihydroartemisinin - piperaquine phosphate - trimethoprim (Artecom^®, Odypharm Ltd), which involves treatment over two days, appears to be a good alternative, particularly in malaria-endemic areas. This study intends to compare the efficacy and tolerability of the combination dihydroartemisinin - piperaquine phosphate - trimethoprim (DPT) versus artemether - lumefantrine (AL) in the treatment of uncomplicated <it>Plasmodium falciparum </it>malaria in Cameroon, Ivory Coast and Senegal.</p> <p>Methods</p> <p>This was a randomized, controlled, open-label clinical trial with a 28-day follow-up period comparing DPT to AL as the reference drug. The study involved patients of at least two years of age, suffering from acute, uncomplicated <it>Plasmodium falciparum </it>malaria with fever. The WHO 2003 protocol was used.</p> <p>Results</p> <p>A total of 418 patients were included in the study and divided into two treatment groups: 212 in the DPT group and 206 in the AL group. The data analysis involved the 403 subjects who correctly followed the protocol (<it>per protocol </it>analysis), i.e. 206 (51.1%) in the DPT group and 197 (48.9%) in the AL group. The recovery rate at D14 was 100% in both treatment groups. The recovery rate at D28 was 99% in the DPT and AL groups before and after PCR results with one-sided 97.5% Confidence Interval of the rates difference > -1.90%. More than 96% of patients who received DPT were apyrexial 48 hours after treatment compared to 83.5% in the AL group (p < 0.001). More than 95% of the people in the DPT group had a parasite clearance time of 48 hours or less compared to approximately 90% in the AL group (p = 0.023). Both drugs were well tolerated. No serious adverse events were reported during the follow-up period. All of the adverse events observed were minor and did not result in the treatment being stopped in either treatment group. The main minor adverse events reported were vomiting, abdominal pain and pruritus.</p> <p>Conclusion</p> <p>The overall efficacy and tolerability of DPT are similar to those of AL. The ease of taking DPT and its short treatment course (two days) may help to improve adherence to treatment. Taken together, these findings make this medicinal product a treatment of choice for the effective management of malaria in Africa.</p

A systematic review of the effects of residency training on patient outcomes

<p>Abstract</p> <p>Background</p> <p>Residents are vital to the clinical workforce of today and tomorrow. Although in training to become specialists, they also provide much of the daily patient care. Residency training aims to prepare residents to provide a high quality of care. It is essential to assess the patient outcome aspects of residency training, to evaluate the effect or impact of global investments made in training programs. Therefore, we conducted a systematic review to evaluate the effects of relevant aspects of residency training on patient outcomes.</p> <p>Methods</p> <p>The literature was searched from December 2004 to February 2011 using MEDLINE, Cochrane, Embase and the Education Resources Information Center databases with terms related to residency training and (post) graduate medical education and patient outcomes, including mortality, morbidity, complications, length of stay and patient satisfaction. Included studies evaluated the impact of residency training on patient outcomes.</p> <p>Results</p> <p>Ninety-seven articles were included from 182 full-text articles of the initial 2,001 hits. All studies were of average or good quality and the majority had an observational study design.Ninety-six studies provided insight into the effect of 'the level of experience of residents' on patient outcomes during residency training. Within these studies, the start of the academic year was not without risk (five out of 19 studies), but individual progression of residents (seven studies) as well as progression through residency training (nine out of 10 studies) had a positive effect on patient outcomes. Compared with faculty, residents' care resulted mostly in similar patient outcomes when dedicated supervision and additional operation time were arranged for (34 out of 43 studies). After new, modified or improved training programs, patient outcomes remained unchanged or improved (16 out of 17 studies). Only one study focused on physicians' prior training site when assessing the quality of patient care. In this study, training programs were ranked by complication rates of their graduates, thus linking patient outcomes back to where physicians were trained.</p> <p>Conclusions</p> <p>The majority of studies included in this systematic review drew attention to the fact that patient care appears safe and of equal quality when delivered by residents. A minority of results pointed to some negative patient outcomes from the involvement of residents. Adequate supervision, room for extra operation time, and evaluation of and attention to the individual competence of residents throughout residency training could positively serve patient outcomes. Limited evidence is available on the effect of residency training on later practice. Both qualitative and quantitative research designs are needed to clarify which aspects of residency training best prepare doctors to deliver high quality care.</p

Environmental Geotechnics: Challenges and Opportunities in the Post COVID-19 World

The outbreak of the COVID-19 pandemic not only created a health crisis across the world but is expected to negatively impact the global economy and societies at a scale that maybe larger than the 2008 financial crisis. Simultaneously, it has inevitably exerted many negative consequences on the geoenvironment upon which human beings depend. The current article articulates the role of environmental geotechnics to elucidate and mitigate the effects of the current pandemic. It is the belief of all authors that the COVID-19 pandemic presents significant challenges, but also opportunities for the development of our field. Our discipline should make full use of our professional skills and expertise to look for development opportunities from this crisis, to highlight our discipline’s irreplaceable position in the global fight against pandemics, and to contribute to the health and prosperity of our communities, so as to better serve humankind. In order to reach this goal, while taking into account the specificity of the SARS-CoV-2 and the uncertainty of its environmental effects, it is believed that more emphasis should be placed on the following research directions: pathogen-soil interactions, isolation and remediation technologies for pathogen-contaminated sites, new materials for pathogen-contaminated soil, recycling and safe disposal of medical wastes, quantification of uncertainty in geoenvironmental and epidemiological problems, emerging technologies and adaptation strategies in civil, geotechnical, and geoenvironmental infrastructure, pandemic-induced environmental risk management, and model pathogen transport and fate in geoenvironment, among others. Moreover, COVID-19 has made it clear to the environmental geotechnics community the importance of urgent international cooperation and of multidisciplinary research actions that must extend to a broad range of scientific fields, including medical and public health disciplines, in order to meet the complexities posed by the COVID-19 pandemic

Tumor Targeting by a Multivalent Single-Chain Fv (scFv) Anti-Lewis Y Antibody Construct

The use of single-chain variable fragment (scFv) constructs has been investigated in cancer radioimmunotherapy (RIT) and radioimmunodetection, as these molecules permit rapid tumor penetration and clearance from the serum relative to whole IgG. Multimerization of scFv constructs has demonstrated improvements in functional affinity (i.e., avidity) and maximal tumor uptake. In this paper, we report the first biodistribution and pharmacokinetics studies of a noncovalent, direct-linked scFv (VL-0-VH) trimeric/tetrameric “multimer” of the anti-Lewis Y monoclonal antibody, hu3S193. The in vitro binding and in vivo biodistribution of the hu3S193 multimer was characterized alongside the hu3S193 F(ab′)2 following radiolabeling with the Indium-111 (111In) radioisotope. Immunoreactivities of the radiolabeled multimer and F(ab′)2 were 73% and 53.2%, and binding affinities (Ka) were 1.58 × 107 M−1 and 4.31 × 106 M−1 for the multimer and F(ab′)2, respectively. Maximal tumor uptake in Ley-positive MCF-7 breast cancer xenografted BALB/c nude mice was 12.6 ± 2.5 percent injected dose/per gram (%ID/g) at 6 hours postinjection for the multimer and 15.7 ± 2.1 %ID/g at 24 hours postinjection for the F(ab′)2. However, limited in vitro stability and high renal localization of radiolabeled constructs were observed, which, despite the observed tumor targeting of the hu3S193 multimer, most likely preclude its use in RIT and imaging modalities