Open-label trial with artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria three years after its broad introduction in Jimma Zone, Ethiopia

Background: In Jimma Zone, Ethiopia, the first-line treatment of uncomplicated falciparum malaria has been changed from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (AL) in 2006. The objective of this study was to assess the effectiveness of AL in Jimma Zone two to three years after its broad introduction. Methods: An open-label, single-arm, 42-day study of AL against falciparum malaria was conducted in four areas with moderate transmission in Jimma Zone between November 2008 and January 2009 and between August and December 2009. Patients (one-81 years) with uncomplicated Plasmodium falciparum mono-infection were consecutively enrolled. Follow-up visits were at day 2, 3, 7, 28 and 42 or any other day if symptoms reoccurred. Primary and secondary endpoints were PCR-corrected and uncorrected cure rates (molecular differentiation between recrudescence and re-infection) on days 28 and 42. Other secondary endpoints were gametocytaemia at day 7 and day 28, parasitaemia at day 2 and 3, and re-infection rates at day 28 and day 42. Results: Of 348 enrolled patients, 313 and 301 completed follow-up at day 28 and at day 42, respectively. No early treatment failure occurred. For per protocol analysis, PCR-uncorrected cure rates at day 28 and 42 were 99.1% (95% CI 98.0-100.0) and 91.1% (95% CI 87.9-94.3), respectively. PCR-corrected cure rates at day 28 and 42 were 99.4% (95% CI 98.5-100.0) and 94.7% (95% CI 92.2-97.2), respectively. PCR-corrected cure rate at day 42 for children <= 5 years was 90.6% (95% CI 82.4-98.7) only. Adverse events were in general mild to moderate. Incidence of new infections was 3.4% during 42 days, no new infections with Plasmodium vivax were observed. Microscopically detected gametocytaemia was reduced by 80% between day 0 and day 7. Conclusion: In general, AL was effective and well tolerated in Jimma Zone, Ethiopia. However, the PCR-corrected recrudescence rate per-protocol at day 42 for children <= 5 years was 9.4%. Therefore, further development should be monitored on a regular basis as recommended by WHO

Effect of training on the use of long-lasting insecticide-treated bed nets on the burden of malaria among vulnerable groups, south-west Ethiopia: baseline results of a cluster randomized trial

<p>Abstract</p> <p>Background</p> <p>In Ethiopia, the utilization of long-lasting insecticide-treated bed nets (LLITN) is hampered by behavioural factors such as low awareness and negative attitude of the community. The aim of this study was to present the design and baseline results of a cluster randomized trial on the effect of training of household heads on the use of LLITN.</p> <p>Methods</p> <p>This baseline survey was undertaken from February to March, 2009 as part of a randomized cluster trial. A total of 11 intervention and 11 control <it>Gots </it>(villages) were included in the Gilgel Gibe Field Research Centre, south-west Ethiopia. House to house visit was done in 4135 households to collect information about the use of LLITN and socio-demographic variables. For the diagnosis of malaria and anaemia, blood samples were collected from 2410 under-five children and 242 pregnant women.</p> <p>Results</p> <p>One fourth of the households in the intervention and control <it>Gots </it>had functional LLITN. Only 30% of the observed LLITN in the intervention and 28% in the control <it>Gots </it>were hanged properly. Adults were more likely to utilize LLITN than under-five children in the control and intervention <it>Gots</it>. The prevalence of malaria in under-five children in the intervention and control <it>Gots </it>was 10.5% and 8.3% respectively. The intervention and control <it>Gots </it>had no significant difference concerning the prevalence of malaria in under-five children, [OR = 1.28, (95%CI: 0.97, 1.69)]. Eight (6.1%) pregnant women in the intervention and eight (7.2%) in the control <it>Gots </it>were positive for malaria (P = 0.9). Children in the intervention <it>Gots </it>were less likely to have anaemia than children in the control <it>Gots</it>, [OR = 0.75, (95%CI: 0.62, 0.85)].</p> <p>Conclusion</p> <p>The availability and utilization of LLITN was low in the study area. The prevalence of malaria and anaemia was high. Intervention strategies of malaria should focus on high risk population and vulnerable groups.</p

Malaria and Under-Nutrition: A Community Based Study Among Under-Five Children at Risk of Malaria, South-West Ethiopia

BACKGROUND: The interaction between malaria and under-nutrition is not well elucidated in Ethiopia. The objective of this study was to assess the magnitude of under-nutrition and its correlation with malaria among under-five children in south-west Ethiopia. METHODS: This cross-sectional study was undertaken during March-February, 2009 as part of the baseline assessment of a cluster randomized trial around Gilgel Gibe Hydroelectric dam, south-west Ethiopia. A total of 2410 under-five children were included for anthropometric measurement and blood investigation for the diagnosis of malaria and anemia. The nutritional status of children was determined using the International Reference Population defined by the U.S National Center for Health Statistics (NCHS). Blood film was used to identify malaria parasite and haemoglobin concentration was determined by Hemo Cue analyzer (HemoCue Hb 301, Sweden). RESULTS: Significant proportion (40.4%) of under-five children were stunted (height-for-age<-2SD). The prevalence of under-weight was 34.2%. One third and one tenth of the children had anemia and malaria parasite respectively. Older children were more likely to have under-nutrition. There was no association between malaria and under-nutrition. Children who had malaria parasite were 1.5 times more likely to become anaemic compare to children who had no malaria parasite, [OR = 1.5, (95% CI: 1.1-2.0)]. CONCLUSION: In this study, there is no association between malaria and under-nutrition. Children who have malaria are more likely to be anaemic. Malaria prevention and control program should consider nutrition interventions particularly anemia

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Open-label trial with artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria three years after its broad introduction in Jimma Zone, Ethiopia

Background: In Jimma Zone, Ethiopia, the first-line treatment of uncomplicated falciparum malaria has been changed from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (AL) in 2006. The objective of this study was to assess the effectiveness of AL in Jimma Zone two to three years after its broad introduction. Methods: An open-label, single-arm, 42-day study of AL against falciparum malaria was conducted in four areas with moderate transmission in Jimma Zone between November 2008 and January 2009 and between August and December 2009. Patients (one-81 years) with uncomplicated Plasmodium falciparum mono-infection were consecutively enrolled. Follow-up visits were at day 2, 3, 7, 28 and 42 or any other day if symptoms reoccurred. Primary and secondary endpoints were PCR-corrected and uncorrected cure rates (molecular differentiation between recrudescence and re-infection) on days 28 and 42. Other secondary endpoints were gametocytaemia at day 7 and day 28, parasitaemia at day 2 and 3, and re-infection rates at day 28 and day 42. Results: Of 348 enrolled patients, 313 and 301 completed follow-up at day 28 and at day 42, respectively. No early treatment failure occurred. For per protocol analysis, PCR-uncorrected cure rates at day 28 and 42 were 99.1% (95% CI 98.0-100.0) and 91.1% (95% CI 87.9-94.3), respectively. PCR-corrected cure rates at day 28 and 42 were 99.4% (95% CI 98.5-100.0) and 94.7% (95% CI 92.2-97.2), respectively. PCR-corrected cure rate at day 42 for children &lt;= 5 years was 90.6% (95% CI 82.4-98.7) only. Adverse events were in general mild to moderate. Incidence of new infections was 3.4% during 42 days, no new infections with Plasmodium vivax were observed. Microscopically detected gametocytaemia was reduced by 80% between day 0 and day 7. Conclusion: In general, AL was effective and well tolerated in Jimma Zone, Ethiopia. However, the PCR-corrected recrudescence rate per-protocol at day 42 for children &lt;= 5 years was 9.4%. Therefore, further development should be monitored on a regular basis as recommended by WHO

Computational Aerodynamic Optimization of Wind-Sensitive Irregular Tall Buildings

Wind-induced loads and motions play a critical role in designing tall buildings and their lateral structural systems. Building configuration represented by its outer shape is a key parameter in determining these loads and structural responses. However, contemporary architecture trends towards creating taller buildings with more complex geometrical shapes to offer unique designs that become a signature on the map of the world. As a result, evaluating wind-induced motions on such structures becomes more challenging to be evaluated and predicted. This paper presents a computational performance-based aerodynamic optimization with minor imposed modifications that have little to no impact on architectural and structural design intent. The developed tool aims to assist both architects and engineers to seek a sustainable optimal design decision at the early stage of design by employing different computational technological tools in an automated manner. A computational optimization methodology consisting of a computational fluid dynamic coupled with finite element analysis and embedded within a radial basis function surrogate model is proposed to mitigate wind-induced loads on tall buildings. In addition, a numerical example implementing the proposed methodology on selected case study is presented and discussed. The proposed approach was able to achieve a minimization of 13.83% and 23.12% for along-wind and across-wind loads, respectively, which is translated to a reduction in structural response by 12.95% and 14.31% in maximum deflection for along-wind and across-wind directions, respectively