A mixed methods protocol to evaluate the effect and cost-effectiveness of an Integrated electronic Diagnosis Approach (IeDA) for the management of childhood illnesses at primary health facilities in Burkina Faso.

BACKGROUND: Burkina Faso introduced the Integrated Management of Childhood Illnesses (IMCI) strategy in 2003. However, an evaluation conducted in 2013 found that only 28 % of children were assessed for three danger signs as recommended by IMCI, and only 15 % of children were correctly classified. About 30 % of children were correctly prescribed with an antibiotic for suspected pneumonia or oral rehydration salts (ORS) for diarrhoea, and 40 % were correctly referred. Recent advances in information and communication technologies (ICT) and use of electronic clinical protocols hold the potential to transform healthcare delivery in low-income countries. However, no evidence is available on the effect of ICT on adherence to IMCI. This paper describes the research protocol of a mixed methods study that aims to measure the effect of the Integrated electronic Diagnosis Approach innovation (an electronic IMCI protocol provided to nurses) in two regions of Burkina Faso. METHODS/DESIGN: The study combines a stepped-wedge trial, a realistic evaluation and an economic study in order to capture the effect of the innovation after its introduction on the level of adherence, cost and acceptability. DISCUSSION: The main challenge is to interconnect the three substudies. In integrating outcome, process and cost data, we focus on three key questions: (i) How does the effectiveness and the cost of the intervention vary by type of health worker and type of health centre? (ii) What is the impact of changes in the content, coverage and quality of the IeDA intervention on adherence and cost-effectiveness? (iii) What mechanisms of change (including costs) might explain the relationship between the IeDA intervention and adherence? TRIAL REGISTRATION: Clinicaltrials.gov, NCT02341469

An Integrated eDiagnosis Approach (IeDA) versus standard IMCI for assessing and managing childhood illness in Burkina Faso: a stepped-wedge cluster randomised trial.

BACKGROUND: The Integrated eDiagnosis Approach (IeDA), centred on an electronic Clinical Decision Support System (eCDSS) developed in line with national Integrated Management of Childhood Illness (IMCI) guidelines, was implemented in primary health facilities of two regions of Burkina Faso. An evaluation was performed using a stepped-wedge cluster randomised design with the aim of determining whether the IeDA intervention increased Health Care Workers' (HCW) adherence to the IMCI guidelines. METHODS: Ten randomly selected facilities per district were visited at each step by two trained nurses: One observed under-five consultations and the second conducted a repeat consultation. The primary outcomes were: overall adherence to clinical assessment tasks; overall correct classification ignoring the severity of the classifications; and overall correct prescription according to HCWs' classifications. Statistical comparisons between trial arms were performed on cluster/step-level summaries. RESULTS: On average, 54 and 79% of clinical assessment tasks were observed to be completed by HCWs in the control and intervention districts respectively (cluster-level mean difference = 29.9%; P-value = 0.002). The proportion of children for whom the validation nurses and the HCWs recorded the same classifications (ignoring the severity) was 73 and 79% in the control and intervention districts respectively (cluster-level mean difference = 10.1%; P-value = 0.004). The proportion of children who received correct prescriptions in accordance with HCWs' classifications were similar across arms, 78% in the control arm and 77% in the intervention arm (cluster-level mean difference = - 1.1%; P-value = 0.788). CONCLUSION: The IeDA intervention improved substantially HCWs' adherence to IMCI's clinical assessment tasks, leading to some overall increase in correct classifications but to no overall improvement in correct prescriptions. The largest improvements tended to be observed for less common conditions. For more common conditions, HCWs in the control districts performed relatively well, thus limiting the scope to detect an overall impact. TRIAL REGISTRATION: ClinicalTrials.gov NCT02341469 ; First submitted August 272,014, posted January 19, 2015

Fat and Carbohydrate Interact to Potentiate Food Reward in Healthy Weight but Not in Overweight or Obesity

Prior work suggests that actual, but not estimated, energy density drives the reinforcing value of food and that energy from fat and carbohydrate can interact to potentiate reward. Here we sought to replicate these findings in an American sample and to determine if the effects are influenced by body mass index (BMI). Thirty participants with healthy weight (HW; BMI 21.92 ± 1.77; M ± SD) and 30 participants with overweight/obesity (OW/OB; BMI 29.42 ± 4.44) rated pictures of common American snacks in 120-kcal portions for liking, familiarity, frequency of consumption, expected satiety, healthiness, energy content, energy density, and price. Participants then completed an auction task where they bid for the opportunity to consume each food. Snacks contained either primarily carbohydrate, primarily fat, or roughly equal portions of fat and carbohydrate (combo). Replicating prior work, we found that participants with HW bid the most for combo foods in linear mixed model analyses. This effect was not observed among individuals with OW/OB. Additionally, in contrast with previous reports, our linear regression analyses revealed a negative relationship between the actual energy density of the snacks and bid amount that was mediated by food price. Our findings support altered macronutrient reinforcement in obesity and highlight potential influences of the food environment on the regulation of food reward

Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect

PurposeAutosomal dominant optic atrophy (ADOA, OMIM 165500), an inherited optic neuropathy that leads to retinal ganglion cell degeneration and reduced visual acuity during the early decades of life, is mainly associated with mutations in the OPA1 gene. Here we report a novel ADOA phenotype associated with a new pathogenic OPA1 gene mutation. Methods The patient, a 62-year-old woman, was referred for acute, painless, and severe visual loss in her right eye. Acute visual loss in her left eye occurred a year after initial presentation. MRI confirmed the diagnosis of isolated atrophic bilateral optic neuropathy. We performed DNA sequencing of the entire coding sequence and the exon/intron junctions of the OPA1 gene, and we searched for the mitochondrial DNA mutations responsible for Leber hereditary optic atrophy by sequencing entirely mitochondrial DNA. Mitochondrial respiratory chain complex activity and mitochondrial morphology were investigated in skin fibroblasts from the patient and controls. Results We identified a novel heterozygous missense mutation (c.2794C>T) in exon 27 of the OPA1 gene, resulting in an amino acid change (p.R932C) in the protein. This mutation, which affects a highly conserved amino acids, has not been previously reported, and was absent in 400 control chromosomes. Mitochondrial DNA sequence analysis did not reveal any mutation associated with Leber hereditary optic neuropathy or any pathogenic mutations. The investigation of skin fibroblasts from the patient revealed a coupling defect of oxidative phosphorylation and a larger proportion of short mitochondria than in controls. Conclusions The presence of an OPA1 mutation indicates that this sporadic, late-onset acute case of optic neuropathy is related to ADOA and to a mitochondrial energetic defect. This suggests that the mutational screening of the OPA1 gene would be justified in atypical cases of optic nerve atrophy with no evident cause

BMJ Med

OBJECTIVE: To evaluate the efficacy of covid-19 convalescent plasma to treat patients admitted to hospital for moderate covid-19 disease with or without underlying immunodeficiency (CORIPLASM trial). DESIGN: Open label, randomised clinical trial. SETTING: CORIMUNO-19 cohort (publicly supported platform of open label, randomised controlled trials of immune modulatory drugs in patients admitted to hospital with moderate or severe covid-19 disease) based on 19 university and general hospitals across France, from 16 April 2020 to 21 April 2021. PARTICIPANTS: 120 adults (n=60 in the covid-19 convalescent plasma group, n=60 in the usual care group) admitted to hospital with a positive SARS-CoV2 test result, duration of symptoms 40. MAIN OUTCOME MEASURES: Primary outcomes were proportion of patients with a WHO Clinical Progression Scale score of ≥6 on the 10 point scale on day 4 (higher values indicate a worse outcome), and survival without assisted ventilation or additional immunomodulatory treatment by day 14. Secondary outcomes were changes in WHO Clinical Progression Scale scores, overall survival, time to discharge, and time to end of dependence on oxygen supply. Predefined subgroups analyses included immunosuppression status, duration of symptoms before randomisation, and use of steroids. RESULTS: 120 patients were recruited and assigned to covid-19 convalescent plasma (n=60) or usual care (n=60), including 22 (covid-19 convalescent plasma) and 27 (usual care) patients who were immunocompromised. 13 (22%) patients who received convalescent plasma had a WHO Clinical Progression Scale score of ≥6 at day 4 versus eight (13%) patients who received usual care (adjusted odds ratio 1.88, 95% credible interval 0.71 to 5.24). By day 14, 19 (31.6%) patients in the convalescent plasma group and 20 (33.3%) patients in the usual care group needed ventilation, additional immunomodulatory treatment, or had died. For cumulative incidence of death, three (5%) patients in the convalescent plasma group and eight (13%) in the usual care group died by day 14 (adjusted hazard ratio 0.40, 95% confidence interval 0.10 to 1.53), and seven (12%) patients in the convalescent plasma group and 12 (20%) in the usual care group by day 28 (adjusted hazard ratio 0.51, 0.20 to 1.32). In a subgroup analysis performed in patients who were immunocompromised, transfusion of covid-19 convalescent plasma was associated with mortality (hazard ratio 0.39, 95% confidence interval 0.14 to 1.10). CONCLUSIONS: In this study, covid-19 convalescent plasma did not improve early outcomes in patients with moderate covid-19 disease. The efficacy of convalescent plasma in patients who are immunocompromised should be investigated further. TRIAL REGISTRATION: ClinicalTrials.gov NCT04345991

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe