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The main source of error in body composition assessment of bedridden patients by bioelectrical impedance analysis (BIA) is the electrode inadequacy and placement. As electrocardiogram (ECG) electrodes are often used for BIA measurements, this study aimed to compare three of them with a reference BIA electrode.BIA was performed sequentially on 24 healthy subjects in the supine position, using 3 different ECG electrodes (3M® Red Dot® 2330; Ambu® BlueSensor 2300; Ambu® BlueSensor SU-00-C) and the reference electrode (Bianostic AT®) for the BIA device (Nutriguard-M®, Data Input, Germany). Resistance (R), reactance (Xc), phase angle (PhA), appendicular skeletal muscle index (ASMI), fat-free mass index (FFMI) and fat mass percentage (FM%) obtained with the different electrodes were compared using Bland-Altman plots, repeated measures one-way ANOVA and paired t-test. Patient characteristics potentially involved in BIA measurement differences were assessed using linear regression analysis.The study population consisted of 9 men and 15 women, 33% and 47% of whom were overweight, respectively. The measured R was within the physiological range for all men (428-561 Ω) and women (472-678 Ω), regardless of the type of electrodes used. Compared to the reference electrode, the 3M® Red Dot® 2330 and Ambu® BlueSensor SU-00-C electrodes gave significantly different Xc and PhA values, but only the Ambu® BlueSensor SU-00-C gave significantly different ASMI, FFMI and FM% at 50 kHz, with biases of -0.2 kg/mThe use of electrodes with small gel area affects BIA measurement in the supine position, especially when PhA is used as an indicator of the nutritional status. Therefore, it is essential to specify the type of electrodes and carry out comparative tests before changing consumables for body composition assessment, to ensure BIA measurement reliability in clinical and research settings.

BACKGROUND & AIMS Bioelectrical impedance analysis (BIA) could be facilitated in subjects who are able to stand by using scales without (BIAstd4) or with a retractable handle (BIAstd8), provided that they are as precise as BIA devices commonly used in the supine position in the hospital setting (BIAsup). This observational prospective cross-sectional study aimed to compare the precision and accuracy of BIAstd4, BIAstd8 and BIAsup in a Caucasian population. METHODS Fat mass percentage (FM%) was measured in 160 healthy Caucasian subjects (80 men/80 women) aged 20-60 years, with a body mass index (BMI) ≥18.5 and

BACKGROUND: Saliva reverse transcriptase-Polymerase chain reaction (RT-PCR) is an attractive alternative for the detection of severe acute respiratory syndrome coronavirus 2 in adults with less known in children. METHODS: Children with coronavirus disease 2019 symptoms were prospectively enrolled in a 1-month comparative clinical trial of saliva and nasopharyngeal (NP) RT-PCR. Detection rates and sensitivities of saliva and NP RT-PCR were compared as well as discordant NP and saliva RT-PCR findings including viral loads (VLs). RESULTS: Of 405 patients enrolled, 397 patients had 2 tests performed. Mean age was 12.7 years (range, 1.2-17.9). Sensitivity of saliva was 85.2% (95% confidence interval: 78.2%-92.1%) when using NP as the standard; sensitivity of NP was 94.5% (89.8%-99.2%) when saliva was considered as the standard. For a NP RT-PCR VL threshold of ≥103 and ≥104 copies/mL, sensitivity of saliva increases to 88.7% and 95.2%, respectively. Sensitivity of saliva and NP swabs was, respectively, 89.5% and 95.3% in patient with symptoms less than 4 days (P = 0.249) and 70.0% and 95.0% in those with symptoms ≥4-7 days (P = 0.096). The 15 patients who had an isolated positive NP RT-PCR were younger (P = 0.034), had lower NP VL (median 5.6 × 103 vs. 3.9 × 107, P < 0.001), and could not drool saliva at the end of the sampling (P = 0.002). VLs were lower with saliva than with NP RT-PCR (median 8.7 cp/mL × 104; interquartile range 1.2 × 104-5.2 × 105; vs. median 4.0 × 107 cp/mL; interquartile range, 8.6 × 105-1 × 108; P < 0.001). CONCLUSIONS: While RT-PCR testing on saliva performed more poorly in younger children and likely after longer duration of symptoms, saliva remains an attractive alternative to NP swabs in children.

Objective To assess the feasibility of balloon catheter occlusion of the internal carotid artery (ICA), external carotid artery (ECA), and maxillary artery (MA) in standing horses. Study design Experimental and clinical cases series. Animals Eight healthy horses (phase 1) and 11 clinical cases (phase 2). Methods Occlusions were performed on standing horses under sedation and local anesthesia. In phase 1, four horses underwent bilateral ICA balloon catheter occlusion, and four horses underwent balloon catheter occlusion of the ECA and MA. In phase 2, horses were treated by occlusion of ICA (n = 7), ECA (n = 2), or ECA and ICA (n = 2). Results Internal carotid artery occlusion was successful in seven of eight and seven of nine arteries in phases 1 and 2, respectively. The procedures lasted 53 and 50 minutes, respectively, and catheters were inserted over 13 ± 0.7 cm (mean ± SD). External carotid artery occlusion was successful in seven of seven and four of four arteries in phases 1 and 2, respectively, with mean durations of 31 and 26 minutes, respectively, and a mean distance of catheter insertion of 11.9 cm. Maxillary artery occlusion was successful in five of seven arteries (phase 1), with a mean surgical duration of 47 minutes and a mean distance of catheter insertion of 42.8 cm. Conclusion Balloon catheter occlusion of the ICA, ECA, and MA was achieved in most standing horses. Clinical significance Balloon catheter occlusion in standing horses provides an alternative to prevent or treat hemorrhage related to guttural pouch mycosis, particularly in horses in which general anesthesia might pose a risk.

Background: Malaria in pregnancy affects both the mother and the fetus. However, evidence supporting treatment guidelines for uncomplicated (including asymptomatic) falciparum malaria in pregnant women is scarce and assessed in varied ways. We did a systematic literature review and individual patient data (IPD) meta-analysis to compare the efficacy and tolerability of different artemisinin-based or quinine-based treatments for malaria in pregnant women. Methods: We did a systematic review of interventional or observational cohort studies assessing the efficacy of artemisinin-based or quinine-based treatments in pregnancy. Seven databases (MEDLINE, Embase, Global Health, Cochrane Library, Scopus, Web of Science, and Literatura Latino Americana em Ciencias da Saude) and two clinical trial registries (International Clinical Trials Registry Platform and ClinicalTrials.gov) were searched. The final search was done on April 26, 2019. Studies that assessed PCR-corrected treatment efficacy in pregnancy with follow-up of 28 days or more were included. Investigators of identified studies were invited to share data from individual patients. The outcomes assessed included PCR-corrected efficacy, PCR-uncorrected efficacy, parasite clearance, fever clearance, gametocyte development, and acute adverse events. One-stage IPD meta-analysis using Cox and logistic regression with random-effects was done to estimate the risk factors associated with PCR-corrected treatment failure, using artemether-lumefantrine as the reference. This study is registered with PROSPERO, CRD42018104013. Findings: Of the 30 studies assessed, 19 were included, representing 92% of patients in the literature (4968 of 5360 episodes). Risk of PCR-corrected treatment failure was higher for the quinine monotherapy (n=244, adjusted hazard ratio [aHR] 6·11, 95% CI 2·57–14·54, p Interpretation: Efficacy and tolerability of artemisinin-based combination therapies (ACTs) in pregnant women are better than quinine. The lower efficacy of artemether-lumefantrine compared with other ACTs might require dose optimisation.

This paper summarizes the main knowledge on mRNA vaccines in September 2021. The only contraindication for a 1st dose of vaccine is an allergy to one of the components of the vaccine, but a specialized consultation is possible for an eventual split vaccination under medical supervision. Serious side effects are rare and consist mainly of myocarditis, shingles and appendicitis, but the risk/benefit ratio is always favorable for vaccination. Efficacy against severe COVID-19 is > 90 % after 6 months, and this against all variants. It is recommended to vaccinate pregnant women. A 3rd dose is not recommended at this time, except for immunosuppressed individuals without detectable antibodies after 2 doses. Vaccine mixing is possible, including with a viral vector vaccine.

This paper summarizes the main knowledge on mRNA vaccines in September 2021. The only contraindication for a 1st dose of vaccine is an allergy to one of the components of the vaccine, but a specialized consultation is possible for an eventual split vaccination under medical supervision. Serious side effects are rare and consist mainly of myocarditis, shingles and appendicitis, but the risk/benefit ratio is always favorable for vaccination. Efficacy against severe COVID-19 is90 % after 6 months, and this against all variants. It is recommended to vaccinate pregnant women. A 3rd dose is not recommended at this time, except for immunosuppressed individuals without detectable antibodies after 2 doses. Vaccine mixing is possible, including with a viral vector vaccine.Cet article résume les connaissances principales sur les vaccins à ARN messager en septembre 2021. La seule contre-indication pour une 1

Energy metabolism is tightly linked with circadian rhythms, exposure to ambient light, sleep/wake, fasting/eating, and rest/activity cycles. External factors, such as shift work, lead to a disruption of these rhythms, often called circadian misalignment. Circadian misalignment has an impact on some physiological markers. However, these proxy measurements do not immediately translate into major clinical health outcomes, as shown by later detrimental health effects of shift work and cardio-metabolic disorders. This review focuses on the effects of shift work on circadian rhythms and its implications in cardio-metabolic disorders and eating patterns. Shift work appears to be a risk factor of overweight, obesity, type 2 diabetes, elevated blood pressure, and the metabolic syndrome. However, past studies showed discordant findings regarding the changes of lipid profile and eating patterns. Most studies were either small and short lab studies, or bigger and longer cohort studies, which could not measure health outcomes in a detailed manner. These two designs explain the heterogeneity of shift schedules, occupations, sample size, and methods across studies. Given the burden of non-communicable diseases and the growing concerns about shift workers’ health, novel approaches to study shift work in real contexts are needed and would allow a better understanding of the interlocked risk factors and potential mechanisms involved in the onset of metabolic disorders.

Children with malnutrition compared with those without are at higher risk of infection, with more severe outcomes. How clinicians assess nutritional risk factors in febrile children in primary care varies. We conducted a post hoc subgroup analysis of febrile children with severe malnutrition enrolled in a randomized, controlled trial in primary care centers in Tanzania. The clinical outcome of children with severe malnutrition defined by anthropometric measures and clinical signs was compared between two electronic clinical diagnostic algorithms: ePOCT, which uses weight-for-age and mid-upper arm circumference to identify and manage severe malnutrition, and ALMANACH, which uses the clinical signs of edema of both feet and visible severe wasting. Those identified as having severe malnutrition by the algorithms in each arm were prescribed antibiotics and referred to the hospital. From December 2014 to February 2016, 106 febrile children were enrolled and randomized in the parent study, and met the criteria to be included in the present analysis. ePOCT identified 56/57 children with severe malnutrition using anthropometric measures, whereas ALMANACH identified 2/49 children with severe malnutrition using clinical signs. The proportion of clinical failure, defined as the development of severe symptoms by day 7 or persisting symptoms at day 7 (per-protocol), was 1.8% (1/56) in the ePOCT arm versus 16.7% (8/48) in the Algorithm for the MANagement of Childhood illnesses arm (risk difference −14.9%, 95% CI −26.0%, −3.8%; risk ratio 0.11, 95% CI 0.01, 0.83). Using anthropometric measures to identify and manage febrile children with severe malnutrition may have resulted in better clinical outcomes than by using clinical signs alone.

Purpose Perampanel (PER) was added to the anticonvulsant regimen of 71 patients with Lennox-Gastaut Syndrome (LGS) to evaluate its efficacy against seizures and its tolerability. Method We evaluated at 3-month intervals 62 with pure LGS and 9 with LGS-like epileptic encephalopathy (28 females, 43 males, mean age 40.1 ± 11.5 yrs, median 38, range 20–71) in whom PER was introduced by 2 mg steps at 2- to 4-week intervals up to 6 mg/day, with possible dose reduction or increases after that. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were followed. Results Mean PER exposure was 538.9 days ± 425 (median 429), with 44 patients (62 %) on PER at last follow-up. About 2/3 of patients were responders, including 35.2 % that had a ≥75 % decrease in their seizures. Among these 16.9 % had a ≥90 % decrease. No improvement was seen in 14 patients; 5 had a less than 50 % response, and 6 had seizure aggravation. Therefore, 25 (35.2 %) were considered non-responders. Half of the patients developed at least one side-effect. Significant negative changes in behavior were noted in 1/3 of the cases, including irritability (8.5 %) and aggressivity (7 %). Contrastingly, 4 patients reported positive behavioral and psychological well-being side-effects. Conclusions This retrospective, open-label study provides evidence that PER may significantly help in LGS. PER should be tried in LGS patients who are not satisfactorily controlled. Its use may be limited in some patients due to behavioral side-effects occurring, particularly at doses ≥ 6 mg/d.

Background: Home artificial nutrition (HAN) is an established treatment for malnourished patients. Since July 2012, the costs for oral nutrition supplements (ONS) are covered by the compulsory health insurance providers in Switzerland if the patient has a medical indication based on the Swiss Society for Clinical Nutrition guidelines. Therefore, the purpose of our study was to analyse the development of HAN, including ONS, before and after July 2012. Methods: We obtained the retrospective and anonymized data from the Swiss association for joint tasks of health insurers (SVK), who registered patients on HAN. Since not all health insurers are working with SVK, this retrospective study recorded nearly 65% of all new patients on HAN in Switzerland from January 1, 2010, to December 31, 2015. Results: A total of 33,410 patients (49.1% men and 50.9% women) with a mean BMI of 21.3 ± 4.5 kg/m2 and mean age of 68.9 ± 17.8 years were recorded. The number of patient cases on ONS increased from 808 cases in 2010 to 18,538 cases in 2015, while patient cases on home enteral nutrition (HEN) and home parenteral nutrition (HPN) remained approximately the same. The relative distribution of type of HAN changed from 26.2% cases on ONS, 68.7% cases on HEN and 5.1% cases on HPN in 2010 to 86.1% cases on ONS, 12.8% cases on HEN, and 1.1% cases on HPN in 2015. Treatment duration decreased for ONS from 698 ± 637 days to 171 ± 274 days, for HEN from 416 ± 553 days to 262 ± 459 days, and for HPN from 96 ± 206 days to 72 ± 123 days. Mean costs per patient decreased for ONS from 1,330 CHF in 2010 to 606 CHF in 2015. Total costs for HAN increased from 16,895,373 CHF in 2010 to 32,868,361 CHF in 2015. Conclusion: Our epidemiological follow-up study showed an immense increase in number of patients on HAN in Switzerland after July 2012. Due to shorter therapy duration and reduced mean costs per patient, total costs were only doubled while the number of patients increased 7-fold.

OBJECTIVE: To report the feasibility of standing MRI (sMRI) and document the value of sMRI in surgical planning for surgical repair of limb fractures in the horse. STUDY DESIGN: Retrospective case series. ANIMALS: Thirty‐one horses with preoperative sMRI. METHODS: Medical records were reviewed for fracture type, application of a polyester cast, sMRI sequences performed, technical variables, and image quality. Fracture geometry and concomitant lesions were compared between sMRI and radiography. The relative value of sMRI with regard to surgical planning was classified as minor (sMRI did not provide additional findings), intermediate (additional lesions found or slight modification to surgical plan), or major (sMRI led to significant alternations in surgical plan). RESULTS: Standing MRI provided good studies in all horses. Standing MRI was classified as having major relevance in 12 of 31 horses, intermediate relevance in 14 of 31 horses, and minor relevance in 5 of 31 horses. CONCLUSION: Preoperative sMRI produced good studies in all horses and influenced the surgical planning in the majority of fractures in this study. Application of a polyester cast seemed to improve comfort without appreciable loss of image quality. CLINICAL SIGNIFICANCE: Standing MRI can be considered as an adjunct to plan the repair of equine fractures, and a polyester cast does not impair image quality.

BACKGROUND & AIMS Patients with amyotrophic lateral sclerosis (ALS) develop swallowing difficulties with the progression of the disease. The present study aimed at comparing oral function and body composition between ALS patients and healthy controls, and at evaluating which parameters are the most discriminant between both groups. METHODS We included ALS patients at the start of their multidisciplinary follow-up at the Geneva University Hospitals and healthy age-, gender-, and dental status-matched adults. We assessed the severity of the disease through the ALS Functional Rating Scale and the swallowing difficulties through the EAT-10 score. We performed an intraoral examination of the dental status, and measured chewing performance, bite, lip and tongue force, saliva weight, and body composition. Group comparisons were performed with t-tests or Mann-Whitney tests as appropriate. Linear discriminant analysis was used to determine the most discriminant parameters between groups. RESULTS Twenty-six ALS patients (bulbar onset: n = 7, median (IQR) ALS Functional Rating Scale: 37 (11)) were included. The ALS patients had a significantly lower chewing performance (p

Background The management of childhood infections remains inadequate in resource-limited countries, resulting in high mortality and irrational use of antimicrobials. Current disease management tools, such as the Integrated Management of Childhood Illness (IMCI) algorithm, rely solely on clinical signs and have not made use of available point-of-care tests (POCTs) that can help to identify children with severe infections and children in need of antibiotic treatment. e-POCT is a novel electronic algorithm based on current evidence; it guides clinicians through the entire consultation and recommends treatment based on a few clinical signs and POCT results, some performed in all patients (malaria rapid diagnostic test, hemoglobin, oximeter) and others in selected subgroups only (C-reactive protein, procalcitonin, glucometer). The objective of this trial was to determine whether the clinical outcome of febrile children managed by the e-POCT tool was non-inferior to that of febrile children managed by a validated electronic algorithm derived from IMCI (ALMANACH), while reducing the proportion with antibiotic prescription. Methods and findings We performed a randomized (at patient level, blocks of 4), controlled non-inferiority study among children aged 2–59 months presenting with acute febrile illness to 9 outpatient clinics in Dar es Salaam, Tanzania. In parallel, routine care was documented in 2 health centers. The primary outcome was the proportion of clinical failures (development of severe symptoms, clinical pneumonia on/after day 3, or persistent symptoms at day 7) by day 7 of follow-up. Non-inferiority would be declared if the proportion of clinical failures with e-POCT was no worse than the proportion of clinical failures with ALMANACH, within statistical variability, by a margin of 3%. The secondary outcomes included the proportion with antibiotics prescribed on day 0, primary referrals, and severe adverse events by day 30 (secondary hospitalizations and deaths). We enrolled 3,192 patients between December 2014 and February 2016 into the randomized study; 3,169 patients (e-POCT: 1,586; control [ALMANACH]: 1,583) completed the intervention and day 7 follow-up. Using e-POCT, in the per-protocol population, the absolute proportion of clinical failures was 2.3% (37/1,586), as compared with 4.1% (65/1,583) in the ALMANACH arm (risk difference of clinical failure −1.7, 95% CI −3.0, −0.5), meeting the prespecified criterion for non-inferiority. In a non-prespecified superiority analysis, we observed a 43% reduction in the relative risk of clinical failure when using e-POCT compared to ALMANACH (risk ratio [RR] 0.57, 95% CI 0.38, 0.85, p = 0.005). The proportion of severe adverse events was 0.6% in the e-POCT arm compared with 1.5% in the ALMANACH arm (RR 0.42, 95% CI 0.20, 0.87, p = 0.02). The proportion of antibiotic prescriptions was substantially lower, 11.5% compared to 29.7% (RR 0.39, 95% CI 0.33, 0.45, p < 0.001). Using e-POCT, the most common indication for antibiotic prescription was severe disease (57%, 103/182 prescriptions), while it was non-severe respiratory infections using the control algorithm (ALMANACH) (70%, 330/470 prescriptions). The proportion of clinical failures among the 544 children in the routine care cohort was 4.6% (25/544); 94.9% (516/544) of patients received antibiotics on day 0, and 1.1% (6/544) experienced severe adverse events. e-POCT achieved a 49% reduction in the relative risk of clinical failure compared to routine care (RR 0.51, 95% CI 0.31, 0.84, p = 0.007) and lowered antibiotic prescriptions to 11.5% from 94.9% (p < 0.001). Though this safety study was an important first step to evaluate e-POCT, its true utility should be evaluated through future implementation studies since adherence to the algorithm will be an important factor in making use of e-POCT’s advantages in terms of clinical outcome and antibiotic prescription. Conclusions e-POCT, an innovative electronic algorithm using host biomarker POCTs, including C-reactive protein and procalcitonin, has the potential to improve the clinical outcome of children with febrile illnesses while reducing antibiotic use through improved identification of children with severe infections, and better targeting of children in need of antibiotic prescription. Trial registration ClinicalTrials.gov NCT02225769, In a randomized controlled non-inferiority trial, Kristina Keitel and colleagues compare the use of an electronic algorithm using host biomarker point-of-care-tests to routine care for the management of febrile illnesses in Tanzanian children., Author summary Why was this study done? Case management of children with infections remains inadequate, and antibiotic overprescription is a major challenge. To improve case management of children with acute infections, we developed an innovative tool: e-POCT, a smartphone-based algorithm that uses tests performed at the patient care site (point-of-care tests: oximetry, hemoglobin, C-reactive protein, and procalcitonin). Given the innovative nature of this algorithm, we assessed the safety of e-POCT in treating children with acute infections. What did the researchers do and find? In a randomized trial in Dar es Salaam, Tanzania, we compared the clinical outcomes of 1,586 children under 5 years with acute infections treated using e-POCT with that of 1,583 children treated using the current reference smartphone algorithm (ALMANACH). We observed that e-POCT improved clinical outcomes while reducing antibiotic prescription from 30% to 11%. e-POCT better targeted those children truly in need of antibiotic treatment through enhanced identification of children with severe diseases. What do these findings mean? e-POCT, an innovative smartphone algorithm using point-of-care tests, has the potential to improve clinical outcomes for children with acute infections and to increase the rational use of antibiotics. Future studies should assess e-POCT’s performance in routine care settings.

Summary Background & aims The COVID-19 pandemic has caused major organizational challenges to healthcare systems concerning staff, material and bed availability. Nutrition was not a priority in the intensive care unit (ICU) at the beginning of the pandemic with the need for simplified protocols. We aimed to assess the impact of a simplified nutritional protocol for critically ill COVID-19 patients during the pandemic first wave. Methods We included all patients with SARS-CoV-2 infections, admitted to the ICU of the Geneva University Hospitals for at least 4 days from March 9 to May 19, 2020. Data on the route and solution of nutritional therapy, prescribed and received volume, calorie and protein intake, amount of insulin, propofol and glucose administered were collected daily during the entire ICU stay. We compared nutritional outcomes between patients admitted to the ICU before and after implementing the simplified nutritional protocol using unpaired t-test. Results Out of 119 patients, 48 were hospitalized in the ICU before, 47 across and 24 after the implementation of the nutritional protocol. The mean age was 63.2 (±12.7) years and 76% were men without significant difference between before and after group. The nutritional protocol implementation led to an increase in caloric intake (1070 vs. 1357 kcal/day, p = 0.018) and in the percentage of days within 80–100% of the energy target (11 vs. 20%, p = 0.021). The protein debt decreased significantly from 48 g/day to 37 g/day (p = 0.015). No significant difference in the percentage of days within the protein target (80–100%) was observed. Conclusions Calorie and protein coverage improved after the implementation of the simplified nutritional protocol in critically ill COVID-19 patients. Further studies are needed to assess the impact of such an approach on patients’ clinical outcomes.

INTRODUCTION Although recommended, the implementation of early advance care planning is suboptimal in amyotrophic lateral sclerosis (ALS) patients. Barriers to advance care planning include healthcare professionals’ and patients’ reluctance, and uncertainty about the right time to initiate a discussion. AIM OF THE STUDY To determine how often advance care planning was initiated, and the content of the discussion in a first routine palliative care consultation integrated within a multidisciplinary management programme. METHODS Between June 2012 and September 2016, a prospective cohort study was conducted in Geneva University Hospitals. Sixty-eight patients were seen every 3 months for a 1-day clinical evaluation in a day care centre. RESULTS The patients’ mean ± standard deviation age was 68.6 ± 11.9 years, 50% were women. Four patients were excluded because of dementia. Advance care planning was initiated with 49 (77%) patients in the first palliative care consultation. Interventions most often addressed were cardiopulmonary resuscitation (49%), intubation and tracheostomy (47%) and palliative sedation (36.7%). Assisted suicide was discussed with 16 patients (36.6%). Functional disability was the only factor associated with initiation of advance care planning. Nearly half of the patients wrote advance directives (45%) or designated a healthcare surrogate (41%). Bulbar onset, functional disability and noninvasive ventilation were not associated with the completion of advance directives. CONCLUSION Early initiation of advance care planning is feasible in most ALS patients during a routine consultation, and relevant treatment issues can be discussed. All ALS patients should be offered the opportunity to write advance directives as completion was not associated with disease severity. (Registered at clinicaltrials.gov: No. NCT03536962.)

Background Protein energy wasting is associated with negative outcome in patients under chronic haemodialysis (HD). Branched‐chain amino acids (BCAAs) may increase the muscle mass. This post hoc analysis of a controlled double‐blind randomized crossover study assessed the impact of BCAAs on nutritional status, physical function, and quality of life. Methods We included 36 chronic HD patient features of protein energy wasting as plasma albumin 80% of packs) and completed the study. BCAA did not affect lean body mass index and body weight, but significantly decreased fat‐free mass index, as compared with glycine (coeff −0.27, 95% confidence interval −0.43 to −0.10, P = 0.002, respectively). BCAA and glycine intake had no effect on the other clinical parameters, blood chemistry tests, or plasma amino acids. Conclusions Branched‐chain amino acid did not improve lean body mass as compared with glycine. Unexpectedly, glycine improved fat‐free mass index in HD patients, as compared with BCAA. Whether long‐term supplementation with glycine improves the clinical outcome remains to be demonstrated.

In this multicentre cohort study, we evaluated the risks of maternal ZIKV infections and adverse pregnancy outcomes among exposed travellers compared to women living in areas with ZIKV circulation (residents). The risk of maternal infection was lower among travellers compared to residents: 25.0% (n = 36/144) versus 42.9% (n = 309/721), aRR 0.6, 95%CI 0.5–0.8. Risk factors associated with maternal infection among travellers were travelling during the epidemic period (i.e., June 2015 to December 2016) (aOR 29.4, 95%CI 3.7-228.1), travelling to the Caribbean Islands (aOR 3.2, 95%CI 1.2-8.7) and stay duration &gt, 2 weeks (aOR 8.7, 95%CI 1.1–71.5). Adverse pregnancy outcomes were observed in 8.3% (n = 3/36) of infected travellers and 12.7% (n = 39/309) of infected residents. Overall, the risk of maternal infections is lower among travellers compared to residents and related to the presence of ongoing outbreaks and stay duration, with stays &lt, 2 weeks associated with minimal risk in the absence of ongoing outbreaks.

Purpose To describe the typical and atypical clinical and electroencephalographic (EEG) features of 40 patients with Jeavons syndrome (JS). Method Retrospective analysis from two French tertiary centers. Results Forty patients were enrolled (31 females and 9 males; sex ratio F/M = 3.44; mean age at epilepsy onset: 6.2 ± 3.4 years [range: 1–15 years]). A positive family history of generalized genetic epilepsy was reported by 13 patients (32.5 %). Eyelid myoclonias with or without absence were the seizure onset in 29 patients (72.5 %), and generalized tonic-clonic seizures in 11 (27.5 %). Over the course of the disease, all had absences. Intellectual disability and psychiatric disorders were reported in 14 (35 %) and 18 patients (45 %), respectively. Focal EEG abnormalities were observed in 65 % of patients, with a posterior (57.7 %) or anterior (30 %) distribution. Generalized EEG discharges were identified in 37 patients (92.5 %). Epileptiform abnormalities were activated during NREM sleep and increased upon awakening. Response to intermittent light stimulation (ILS) was observed in 34 patients (85 %), with an unusual pattern of epileptiform abnormalities at the same frequency of the flashes in 20 patients. Patients with all seizure types were more likely to have this response (p = 0.017). Conclusion JS is a lifelong genetic epileptic syndrome with onset in childhood, female preponderance, and a positive family history of epilepsy in one-third of the cases. Focal EEG abnormalities are frequent. Response to ILS appears different from other photosensitive syndromes, with an unusual pattern of photo-induced abnormal synchronization. Intellectual disability and psychiatric disorders are not rare.

Background & aims: COVID-19 pandemic had resulted in a massive increase in the number of patients admitted to intensive care units (ICUs). This created significant organizational challenges including numerous non-specialist ICU caregivers who came to work in the ICU. In this context, pragmatic protocols were essential to simplify nutritional care. We aimed at providing a simple and easy-to-prescribe nutritional protocol and evaluated its usefulness with questionnaires sent to physicians involved in the care of ICU COVID-19 patients.Methods: A simplified nutrition protocol was distributed to all physicians (n = 122) of the ICU medical team during COVID-19 pandemic. Clinical dieticians estimated energy targets for acute and post-acute phases at patient's admission and suggested adaptations of nutrition therapy. More complex situations were discussed with clinical nutrition doctors and, if required, a clinical evaluation was performed. To further facilitate the procedure, a chart with prescription aids was also distributed to the whole medical ICU team. At the end of the current pandemic wave, a 13-item questionnaire was emailed to the ICU medical team to obtain their opinion on the suggested nutritional therapy.Results: Answers were received from 81/122 medical doctors (MDs) (66% response rate), from intensive care physicians (41%), anaesthesiologists (53%) and MDs from other specialties (6%). Thirty-two percent of MDs felt that their knowledge of nutrition management was insufficient and 45% of the physicians surveyed did not face nutrition management in their daily practice prior to the pandemic. The initially proposed nutritional protocol, the chart with prescription aids and the suggested nutritional proposals were considered as useful to very useful by the majority of physicians surveyed (89.9, 90.7 and 92.1% respectively). The protocol was followed by 92% of MDs, and almost all participants (95%) were convinced that adaptations of nutritional therapy had beneficial effects on patients' outcomes.Conclusions: Nutritional therapy in critically ill COVID-19 patients is a challenge and the implementation of this specific pandemic simplified nutritional protocol was assessed as useful by a great majority of physicians. Pragmatic and simplified protocols are useful for ensuring the quality of nutritional therapy and could be used in future studies to assess its actual impact on the clinical outcomes of COVID-19 patients.

Background Safety of live vaccines in patients treated with immunosuppressive therapies is not well known, resulting in contradictory vaccination recommendations. We describe here the first case of vaccine-associated measles in a patient on natalizumab treatment. Case presentation A young female patient with relapsing-remitting multiple sclerosis on natalizumab treatment received the live attenuated measles, mumps, and rubella vaccine in preparation for a change in her treatment in favour of fingolimod, with established immunosuppressive qualities. Seven days after receiving the vaccine, our patient experienced diffuse muscle pain, fatigue, and thereafter developed a fever and then an erythematous maculopapular rash, compatible with vaccine associated measles. This was later confirmed by a positive measles RT-PCR throat swab. The patient’s symptoms resolved without any sequelae. Conclusion In this case report we review the immunosuppressive qualities of natalizumab and the evidence in favour and against live vaccines in patients on this treatment. Our findings reveal the insufficient understanding of the immunosuppressive effects of new immunomodulators, and thus of the safety of live vaccines in patients on such medications. While this case triggers precaution, there is insufficient evidence to conclude that natalizumab treatment could favor the onset of vaccine-associated measles.

Background Malaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development. Individual patient data (IPD) meta-analysis was conducted to compare the association between antimalarial treatments and adverse pregnancy outcomes, including placental malaria, accompanied with the gestational age at diagnosis of uncomplicated falciparum malaria infection. Methods A systematic review and one-stage IPD meta-analysis of studies assessing the efficacy of artemisinin-based and quinine-based treatments for patent microscopic uncomplicated falciparum malaria infection (hereinafter uncomplicated falciparum malaria) in pregnancy was conducted. The risks of stillbirth (pregnancy loss at ≥ 28.0 weeks of gestation), moderate to late preterm birth (PTB, live birth between 32.0 and Results Of the 22 eligible studies (n = 5015), IPD from16 studies were shared, representing 95.0% (n = 4765) of the women enrolled in literature. Malaria treatment in this pooled analysis mostly occurred in the second (68.4%, 3064/4501) or third trimester (31.6%, 1421/4501), with gestational age confirmed by ultrasound in 91.5% (4120/4503). Quinine (n = 184) and five commonly used artemisinin-based combination therapies (ACTs) were included: artemether-lumefantrine (n = 1087), artesunate-amodiaquine (n = 775), artesunate-mefloquine (n = 965), and dihydroartemisinin-piperaquine (n = 837). The overall pooled proportion of stillbirth was 1.1% (84/4361), PTB 10.0% (619/4131), SGA 32.3% (1007/3707), and placental malaria 80.1% (2543/3035), and there were no significant differences of considered outcomes by ACT. Higher parasitaemia before treatment was associated with a higher risk of SGA (adjusted odds ratio [aOR] 1.14 per 10-fold increase, 95% confidence interval [CI] 1.03 to 1.26, p = 0.009) and deposition of malaria pigment in the placenta (aOR 1.67 per 10-fold increase, 95% CI 1.42 to 1.96, p Conclusions The risks of stillbirth, PTB, SGA, and placental malaria were not different between the commonly used ACTs. The risk of SGA was high among pregnant women infected with falciparum malaria despite treatment with highly effective drugs. Reduction of malaria-associated adverse birth outcomes requires effective prevention in pregnant women.

Juvenile myoclonic epilepsy (JME) is both a frequent and a very characteristic epileptic syndrome with female preponderance. Treatment of JME in women of childbearing potential must consider multiple factors such as desire for pregnancy, use of contraception, seizure control and previously used antiepileptic drugs (AEDs). Approximately 85% of cases are well controlled with valproate, which remains the reference AED in JME but is nowadays considered unsafe for the expecting mother and her fetus. The prescription of valproate is now severely restricted in women of childbearing potential but may still be considered, at the lowest possible dose and when pregnancies can be reliably planned, with temporary alternatives to valproate prescribed before fertilization. Alternatives have emerged, especially lamotrigine and levetiracetam, but also topiramate, zonisamide, and recently perampanel, but none of these AEDs can be considered fully safe in the context of pregnancy. In special settings, benzodiazepines and barbiturates may be useful. In some cases, combination therapy, especially lamotrigine and levetiracetam, may be useful or even required. However, lamotrigine may have the potential to aggravate JME, with promyoclonic effects. Carbamazepine, oxcarbazepine and phenytoin must be avoided. Valproate, levetiracetam, zonisamide, topiramate if the daily dose is ≤ 200 mg and perampanel if the daily dose is ≤ 10 mg do not affect combined hormonal contraception. Lamotrigine ≥ 300 mg/day has been shown to decrease levonorgestrel levels by 20% but does not compromise combined hormonal contraception. Patients with JME taking oral contraceptive should be counselled on the fact that the estrogenic component can reduce concentrations of lamotrigine by over 50%, putting patients at risk of increased seizures. Pregnancy is a therapeutic challenge, and the risk/benefit ratio for the mother and fetus must be considered when choosing the appropriate drug. Lamotrigine (

Objectives: sarcopenia is common especially in hospitalised older populations. The aim of this study was to assess the prevalence of sarcopenia, defined as low skeletal mass and muscle strength, and its impact on 1-year mortality in older patients with cancer. Methods: skeletal muscle mass was estimated using bioelectric impedance analysis and related to height2 (SMI; Janssen et al. 2002). Grip strength was measured with the JAMAR dynamometer and the cut-offs suggested by the European Sarcopenia and 1-year mortality in cancer 413 Downloaded from https://academic.oup.com/ageing/article-abstract/48/3/413/5272750 by Université de Genève user on 26 November 2019 Working Group on Sarcopenia in Older People (EWGSOP) were applied. One-year mortality was assessed by telephone follow-up and the local cancer death registry. Results: of the 439 consecutively recruited cancer patients (60–95 years; 43.5% women), 119 (27.1%) had sarcopenia. Of the patients with sarcopenia, 62 (52.5%) died within 1 year after study entry compared to 108 (35.1%) patients who did not have sarcopenia (P = 0.001). In a stepwise, forward Cox proportional hazards analysis, sarcopenia (HR = 1.53; 95% CI: 1.034–2.250; P < 0.05), advanced disease (HR = 1.87; 95% CI: 1.228–2.847; P < 0.05), number of drugs/day (HR = 1.11; 95% CI: 1.057–1.170; P < 0.001), tumour diagnosis (overall P < 0.05) and Karnofsky index (HR = 0.98, 95% CI: 0.963–0.995; P < 0.05) associated with 1-year mortality risk. The factors sex, age, co-morbidities and involuntary 6-month weight loss ≥5% were insignificant. Conclusions: sarcopenia was present in 27.1% of older patients with cancer and was independently associated with 1-year mortality. The fact that sarcopenia was nearly as predictive for 1-year mortality as an advanced disease stage underlines the importance of preservation of muscle mass and function as a potential target of intervention in older patients with cancer.

Background Although the incidence of dengue across Africa is high, severe dengue is reported infrequently. We describe the clinical features and the outcome of dengue according to raceduring an outbreak in Dar es Salaam, Tanzania that occurred in both native and expatriate populations. Methods Adults with confirmed dengue (NS1 and/or IgM on rapid diagnostic test and/or PCR positive) were included between December 2013 and July 2014 in outpatient clinics. Seven-day outcome was assessed by a visit or a call. Association between black race and clinical presentation, including warning signs, was assessed by logistic regression adjusted for age, malaria coinfection, secondary dengue and duration of symptoms at inclusion. The independent association between demographic and comorbidities characteristics of the patients and severe dengue was evaluated by multivariate logistic regression that included potential confounders. Results After exclusion of 3 patients of mixed race, 431 patients with dengue (serotype 2, genotype Cosmopolitan) were included: 241 of black and 190 of non-black race. Black patients were younger (median age 30 versus 41 years; p

PURPOSE A high phase angle measured by the Nutriguard(®) bioelectrical impedance analysis device is associated with a reduced mortality risk in older people. This retrospective study aims to analyze whether this association persists with the other devices that have been used in our hospital. METHODS This study encompasses all people 65 yrs and older who underwent a phase angle measurement between 1990 and 2011 at the Geneva University Hospitals, with the RJL-101(®) (RJL Systems), Xitron 4000B(®) (Xitron Technologies), Eugedia(®) (Eugedia-Spengler) and Bio-Z(®) (Spengler). Diseases at the time of phase angle measurement were reported in the form of the Cumulative Illness Rating Scale. Date of death was retrieved until December 2012. Phase angle values were categorized into sex- and device-specific quartiles, where quartile 1 represents the lowest quartile and reference value. Cox regressions were performed to evaluate the association between phase angle quartiles and mortality. RESULTS We considered 1878 people (969 women), of whom 1151 had died. In univariate sex-specific Cox regressions, the death risk decreased progressively as the phase angle quartile measured by the Bio-Z(®) or RJL-101(®) increased. The HR (95% CI) in quartile 4 was 0.36 (0.26, 0.50) and 0.38 (0.29, 052) in women and men measured with the Bio-Z(®) (both p

Objective To determine predictors of in-hospital mortality related to COVID-19 in older patients. Design Retrospective cohort study. Setting and Participants Patients aged 65 years and older hospitalized for a diagnosis of COVID-19. Methods Data from hospital admission was collected from the electronic medical records. Logistic regression and Cox proportional-hazard models were used to predict mortality, our primary outcome. Variables at hospital admission were categorized according to the following domains: demographics, clinical history, comorbidities, previous treatment, clinical status, vital signs, clinical scales and scores, routine laboratory analysis and imaging results. Results Of a total of 235 Caucasian patients, 43% were male, with a mean age of 86 ± 6.5 years. Seventy-six patients (32%) died. Non-survivors had a shorter number of days from initial symptoms to hospitalization (p=0.007) and the length of stay in acute wards than survivors (p, Brief Summary: This study showed that male sex, functional decline, an increased fraction of inspired oxygen and the presence of crackles were the best predictors of mortality in the oldest old with COVID-19 and differences in age were not a significant prognostic factor within this very old group.

OBJECTIVE To describe the innervation of the thyrohyoideus (TH) muscle and to confirm our findings with stimulation of first cervical (C1) nerve branches. STUDY DESIGN Ex vivo phase 1 and clinical phase 2. ANIMALS Fourteen head and neck specimens and 17 client-owned horses. METHODS In phase 1, the cranial nerve (CN) XII and the C1 nerve were dissected with their branches in 20 dissections were performed on 14 specimens (6 left and right side and 8 only left or right) Anatomy was noted. Samples of nerve bifurcations were collected for histological confirmation of anatomical findings. First cervical nerve branches were stimulated in horses undergoing cervical nerve graft to treat laryngeal hemiplegia. RESULTS The nerve innervating the TH muscle arose directly from the C1 nerve in 17 of 20 dissections, from an anastomotic branch between CN XII and the C1 nerve in two of 20 dissections, and from the C1 nerve and the anastomotic branch in one of 20 dissections. No direct connection between the TH muscle and CN XII was found. Histological examination revealed that the anastomosis was composed of C1 nerve fibers passing over to CN XII. First cervical stimulation resulted in TH muscle contraction in 16 of 17 horses. CONCLUSIONS The innervation of the TH muscle originated from the C1 nerve according to dissection, histological, and conduction studies, with variation in the branching pattern. CLINICAL SIGNIFICANCE Care should be taken to preserve the C1 nerve during prosthetic laryngoplasty. The surgical technique for C1 nerve grafts should be reconsidered in light of these findings, along with new options to treat dorsal displacement of the soft palate..

Background Health-workers in developing countries rely on clinical algorithms, such as the Integrated Management of Childhood Illnesses (IMCI), for the management of patients, including diagnosis of serious bacterial infections (SBI). The diagnostic accuracy of IMCI in detecting children with SBI is unknown. Prediction rules and guidelines for SBI from well-resourced countries at outpatient level may help to improve current guidelines; however, their diagnostic performance has not been evaluated in resource-limited countries, where clinical conditions, access to care, and diagnostic capacity differ. The aim of this study was to estimate the diagnostic accuracy of existing prediction rules and clinical guidelines in identifying children with SBI in a cohort of febrile children attending outpatient health facilities in Tanzania. Methods Structured literature review to identify available prediction rules and guidelines aimed at detecting SBI and retrospective, external validation on a dataset containing 1005 febrile Tanzanian children with acute infections. The reference standard, SBI, was established based on rigorous clinical and microbiological criteria. Results Four prediction rules and five guidelines, including IMCI, could be validated. All examined rules and guidelines had insufficient diagnostic accuracy for ruling-in or ruling-out SBI with positive and negative likelihood ratios ranging from 1.04–1.87 to 0.47–0.92, respectively. IMCI had a sensitivity of 36.7% (95% CI 29.4–44.6%) at a specificity of 70.3% (67.1–73.4%). Rules that use a combination of clinical and laboratory testing had better performance compared to rules and guidelines using only clinical and or laboratory elements. Conclusions Currently applied guidelines for managing children with febrile illness have insufficient diagnostic accuracy in detecting children with SBI. Revised clinical algorithms including simple point-of-care tests with improved accuracy for detecting SBI targeting in tropical resource-poor settings are needed. They should undergo careful external validation against clinical outcome before implementation, given the inherent limitations of gold standards for SBI. Electronic supplementary material The online version of this article (10.1186/s12879-019-4371-y) contains supplementary material, which is available to authorized users.

Rationale for reviewYoung adults of childbearing age and pregnant women are travelling more frequently to tropical areas, exposing them to specific arboviral infections such as dengue, zika and chikungunya viruses, which may impact ongoing and future pregnancies. In this narrative review, we analyse their potential consequences on pregnancy outcomes and discuss current travel recommendations.Main findingsDengue virus may be associated with severe maternal complications, particularly post-partum haemorrhage. Its association with adverse fetal outcomes remains unclear, but prematurity, growth retardation and stillbirths may occur, particularly in cases of severe maternal infection. Zika virus is a teratogenic infectious agent associated with severe brain lesions, with similar risks to other well-known TORCH pathogens. Implications of chikungunya virus in pregnancy are mostly related to intrapartum transmission that may be associated with severe neonatal infections and long-term morbidity.Travel recommendationsFew agencies provide specific travel recommendations for travelling pregnant patients or couples trying to conceive and discrepancies exist, particularly regarding Zika virus prevention. The risks significantly depend on epidemiological factors that may be difficult to predict. Prevention relies principally on mosquito control measures. Couples trying to conceive and pregnant women should receive adequate information about the potential risks. It seems reasonable to advise pregnant women to avoid unnecessary travel to Aedes spp. endemic regions. The current rationale to avoid travel and delay conception is debatable in the absence of any epidemic. Post-travel laboratory testing should be reserved for symptomatic patients.

A low fat mass is associated with a good running performance. This study explores whether modifications in body composition predicted changes in running speed. We included people who underwent several measurements of body composition by bioelectrical impedance analysis between 1999 and 2016, at the &ldquo, Course de l&rsquo, Escalade&rdquo, taking place yearly in Geneva. Body composition was reported as a fat-free mass index (FFMI) and fat mass index (FMI). Running distances (men: 7.2 km, women: 4.8 km) and running times were used to calculate speed in km/h. We performed multivariate linear mixed regression models to determine whether modifications of body mass index, FFMI, FMI or the combination of FFMI and FMI predicted changes in running speed. The study population included 377 women (1419 observations) and 509 men (2161 observations). Changes in running speed were best predicted by the combination of FFMI and FMI. Running speed improved with a reduction of FMI in both sexes (women: &szlig, &minus, 0.31, 95% CI &minus, 0.35 to &minus, 0.27, p &lt, 0.001. men: &szlig, 0.43, 0.48 to &minus, 0.39, p &lt, 0.001) and a reduction of FFMI in men (&szlig, 0.20, 0.26 to &minus, 0.15, p &lt, 0.001). Adjusted for body composition, the decline in running performance occurred from 50 years onward, but appeared earlier with a body mass, FFMI or FMI above the median value at baseline. Changes of running speed are determined mostly by changes in FMI. The decline in running performance occurs from 50 years onward but appears earlier in people with a high body mass index, FFMI or FMI at baseline.

SummaryObjective Perampanel (PER) was used in 12 patients with Unverricht-Lundborg disease (ULD) to evaluate its efficacy against myoclonus and seizures. Methods We treated 11 patients with EPM1 mutations (6 F, 5 M, aged 13–62 years) and a 43-year-old man with de novo KCNC1 mutation. PER was introduced by 2 mg steps at 2–4 week intervals until 6 mg/day, with a possible dose reduction or dose increase. Results Ten patients had a clear clinical response of myoclonus, and five were able to reduce concomitant therapy. Improvement was noted sometimes as soon as with 2 mg/day. Epileptic seizures stopped on PER in the six patients who still had experienced generalized tonic–clonic or myoclonic seizures (100%). Some abatement of efficacy on myoclonus was seen in two patients who still retained some benefit. Weight gain was reported in six patients (50%). Psychological and behavioral side-effects were observed in six patients (50%) and led to withdrawal of PER in three cases and dose reduction in three, with abatement of the problems. Significance This study provides evidence that for ULD patients, PER may show marked efficacy even in severe cases, particularly against myoclonus, but also against seizures. PER should thus be tried in ULD patients whose seizures are not satisfactorily controlled. Its use is limited because of psychological and behavioral side effects, with higher doses of approximately 6 mg/day or greater likely risk factors.

Summary Purpose This study evaluates the relationship between body mass index (BMI), fat mass index (FMI) and fat-free mass index (FFMI) changes and mortality in persons ≥65 years. Methods Adults ≥65 years with at least two body composition measurements (BCM) between 1990 and 2011 were included. We excluded persons who died within one month of the second BCM and who had two single BCM in a one-month timeframe. Mortality data was retrieved until December 2012. For each person, we calculated the regression slopes for BMI, FMI and FFMI changes. Significant positive slopes were categorized as “gain”, negative slopes as “loss” and the others as “maintenance”. The impact of body composition changes was evaluated by Cox regression models while adjusting for sex, age, co-morbidities and body composition at the last measurement. Results We included 791 persons with 3049 BCM. After adjustment for sex, and age and co-morbidities, a loss of FFMI, but not of FMI or BMI, increased the risk of mortality (HR 2.02, 95%CI 1.28–3.19). The prediction of mortality with FFMI loss remained significant when further adjusting for FMI loss and the last available body composition (HR 1.68, 95%CI 1.04–2.70). Conclusions FFMI loss is related to increased mortality in older persons.

Objectives Exploring fever aetiologies improves patient management. Most febrile adults are outpatients, but all previous studies were conducted in inpatients. This study describes the spectrum of diseases in adults attending outpatient clinics in urban Tanzania. Methods We recruited consecutive adults with temperature ≥38°C in a prospective cohort study. We collected medical history and performed a clinical examination. We performed 27 364 microbiological diagnostic tests (rapid tests, serologies, cultures and molecular analyses) for a large range of pathogens on blood and nasopharyngeal samples. We based our diagnosis on predefined clinical and microbiological criteria. Results Of 519 individuals, 469 (89%) had a clinically or microbiologically documented infection and 128 (25%) were human immunodeficiency virus (HIV) -infected. We identified 643 diagnoses: 264 (41%) acute respiratory infections (36 (5.6%) pneumonia, 39 (6.1%) tuberculosis), 71 (11%) infections with another focus (31 (4.8%) gastrointestinal, 26 (4.0%) urogenital, 8 (1.2%) central nervous system) and 252 (39%) infections without focus (134 (21%) dengue, 30 (4.7%) malaria, 28 (4.4%) typhoid). Of the 519 individuals, 318 (61%), 179 (34%), 30 (6%) and 15 (3%), respectively, had a viral, bacterial, parasitic and fungal acute infection. HIV-infected individuals had more bacterial infections than HIV-negative (80/122 (66%) versus 100/391 (26%); p 200 cells/mm3, p 0.02). Conclusions Viral diseases caused most febrile episodes in adults attending outpatient clinics except in HIV-infected patients. HIV status and a low CD4 level strongly determined the need for antibiotics. Systematic HIV screening is essential to appropriately manage febrile patients.

BackgroundThe intermittent preventive treatment in infants (IPTi) trial that took place in Papua New Guinea showed an overall reduction of 29% of the risk of malaria when delivering single-dose sulfadoxine-pyrimethamine (SP) associated to 3 days of amodiaquine (AQ) every three months to children during the first year of life. The aim of the present study was to assess if the last two doses of AQ were truly administered as prescribed by the parents at home based on drug level measurement and PK modelling, which is a good proxy of medication adherence. It provides also important information to discuss the efficacy of the intervention and on feasibility of self-administered preventive malaria treatment.Methods and findingsDuring the three-arm randomized double-blinded IPTi trial, each child was prescribed one dose of SP (day 0) and 3 doses of either AQ or artesunate (AS) at day 0, 1 & 2 adjusted to weight or placebo. Treatments were given at 3, 6, 9 and 12 months of age. The first day of treatment was delivered by nursing staff (initiation under directly observed treatment (DOT)) and the two last doses of AQ or AS by parents at home without supervision. For this cross-sectional study, 206 consecutive children already involved in the IPTi trial were enrolled over a 2-month period. At the time of the survey, allocation of the children to one of the three arms was not known. Blood samples for drug level measurement were collected from finger pricks one day after the planned last third dose intake. Only children allocated to the SP-AQ arm were included in the present analysis. Indeed, the half-life of AS is too short to assess if drugs were given on not. Because of the short half-life of AQ, desethyl-AQ (metabolite of AQ (DAQ)) measurements were used to investigate AQ medication adherence. Two PK (PK) models from previously published studies in paediatric populations were applied to the dataset using non-linear mixed effect modelling (NONMEM) to estimate the number of doses really given by the parents. The study nurse reported the administration time for the first AQ dose while it was estimated by the parents for the remaining two doses. Out of 206 children, 64 were in the SP-AQ arm. The adjusted dosing history for each individual was identified as the one with the lowest difference between observed and individual predicted concentrations estimated by the two PK models for all the possible adherence schemes. The median (range) blood concentration AQ in AQ arm was 9.3 ng/mL (0-1427.8 ng/mL), (Quartiles 1-3: 2.4 ng/mL -22.2 ng/mL). The median (range) for DAQ was 162.0 ng/mL (0-712 ng/mL), (Quartiles 1-3: 80.4 ng/mL-267.7 ng/mL). Under the assumption of full adherence for all participants, a marked underprediction of concentrations was observed using both PK models. Our results suggest that only 39-50% of children received the three scheduled doses of AQ as prescribed, 33-37% two doses and 17-24% received only the first dose administered by the study nurse. Both models were highly congruent to classify adherence patterns.ConclusionsConsidering the IPTi intervention, our results seem to indicate that medication adherence is low in the ideal trial research setting and is likely to be even lower if given in day-to-day practice, questioning the real impact that this intervention might have. More generally, the estimation of the number of doses truly administered, a proxy measure of adherence and an assessment of the feasibility of the mode of administration, should be more thoroughly studied when discussing the efficacy of the interventions in trials investigating self-administered malaria preventive treatments.

ObjectiveThis secondary analysis of data of a randomized controlled trial (RCT) retrospectively investigated the performance of pulse oximetry in identifying children with severe illnesses, with and without respiratory signs/symptoms, in a cohort of children followed for morbid episodes in an intervention trial assessing the efficacy of Intermittent Preventive Treatment for malaria in infants (IPTi) in Papua New Guinea (PNG) from June 2006 to May 2010.SettingThe IPTi study was conducted in a paediatric population visiting two health centres on the north coast of PNG in the Mugil area of the Sumkar District.ParticipantsA total of 669 children visited the clinic and a total of 1921 illness episodes were recorded. Inclusion criteria were: age between 3 and 27 months, full clinical record (signs/symptoms) and pulse oximetry used systematically to assess sick children at all visits. Children were excluded if they visited the clinic in the previous 14 days.OutcomesThe outcome measures were severe illness, severe pneumonia, pneumonia, defined by the Integrated Management of Childhood Illness (IMCI) definitions, and hospitalization.ResultsOut of 1921 illness episodes, 1663 fulfilled the inclusion criteria. A total of 139 severe illnesses were identified, of which 93 were severe pneumonia. The ROC curves of pulse oximetry (continuous variable) showed an AUC of 0.63, 0.68 and 0.65 for prediction of severe illness, severe pneumonia and hospitalization, respectively. Pulse oximetry allowed better discrimination between severe and non-severe illness, severe and non-severe pneumonia, admitted and non-admitted patients, in children ≤12-months of age relative to older patients. For the threshold of peripheral arterial oxygen saturation ≤ 94% measured by pulse oximetry (SpO2), unadjusted odds ratios for severe illness, severe pneumonia and hospitalization were 6.1 (95% Confidence Interval (CI) 3.9-9.8), 8.5 (4.9-14.6) and 5.9 (3.4-10.3), respectively.ConclusionPulse oximetry was helpful in identifying children with severe illness in outpatient facilities in PNG. A SpO2 of 94% seems the most discriminative threshold. Considering its affordability and ease of use, pulse oximetry could be a valuable additional tool assisting the decision to admit for treatment.

Objective The importance of body composition for running performance is unclear in the general population. The aim of this study was to evaluate whether body composition influences running speed and whether it is a better predictor of running speed than body mass index (BMI). Methods The study included 1353 women (38.2 ± 12.1 y of age) and 1771 men (39.6 ± 12.1 y of age) who underwent, for the first time, a measurement of body composition by bioelectrical impedance analysis between 1999 and 2016, before a timed run occurring annually in Geneva. The running distances and times were converted to average speed (km/h). Body composition was expressed as sex-specific quartiles, where quartile 1 (lowest values) was the reference quartile. The relationships between speed and BMI or body composition were analyzed by multivariate linear regressions. Results Multivariate regressions showed that the higher the fat mass index (FMI) quartile, the lower the running speed in women and men (all P 20 kg/m2) was associated with a poor running performance (r = –0.50, P Conclusions Running speed is negatively associated with BMI and FMI in both sexes. Body composition is a better predictor of running performance than BMI.

Background: Motor neuron disease (MND) invariably impacts on inspiratory muscle strength leading to respiratory failure. Regular assessment of sniff nasal inspiratory pressure (SNIP) and/or maximal mouth inspiratory pressure (MIP) contributes to early detection of a requirement for ventilatory support. Objectives: The aim of this study was to compare the feasibility, agreement, and performance of both tests in MND. Methods: Patients with MND followed by a multidisciplinary consultation were prospectively included. Pulmonary follow-up included forced expiratory volumes, vital capacity (VC) seated and supine, MIP, SNIP, pulse oximetry, and daytime arterial blood gases. Results: A total of 61 patients were included. SNIP and MIP could not be performed in 14 (21%) subjects; 74% of the subjects showed a decrease in MIP or SNIP at inclusion versus 31% for VC. Correlation between MIP and SNIP (Pearson’s rho: 0.68, p < 0.001) was moderate, with a non-significant bias in favor of SNIP (3.6 cm H2O) and wide limits of agreement (–34 to 41 cm H2O). Results were similar in “bulbar” versus “non-bulbar” patients. At different proposed cut-off values for identifying patients at risk of respiratory failure, the agreement between MIP and SNIP (64–79%) and kappa values (0.29–0.53) was moderate. Conclusions: MIP and SNIP were equally feasible. There was no significant bias in favor of either test, but a considerable disparity in results between tests, suggesting that use of both tests is warranted to screen for early detection of patients at risk of respiratory failure and avoid over diagnoses. SNIP, MIP, and VC all follow a relatively linear downhill course with a steeper slope for “bulbar” versus “non-bulbar” patients.

The WHO recommends screening of Latin American migrants for Chagas disease to reduce morbidity and mortality and increase the likelihood of eradicating the disease. The objective was to assess the feasibility and acceptability of a screening strategy in one Swiss canton. From February 2011 to September 2012, people attending six healthcare centres of different types were offered a rapid diagnostic test if they or their mother were of Latin American origin (or, at the blood donation centre, if they had travelled for ≥1 year in Latin America). In addition, testing was offered during events where Latin Americans gathered. In total, 1,010 people were tested, mainly originating from Brazil (24%), Ecuador (13%) and Chile (10%). 54% were born in Latin America, 15% had a Latin American mother, and 29% were travellers. The prevalence of Chagas disease was 2.3% among migrants (15.5% in the community testing) and 0% among travellers. The prevalence was 18.0%, 0.8%, 0.5% and 0% among Bolivians, Ecuadorians, Brazilians and other countries respectively. Predictors for Chagas disease were: born in Latin America (OR = infinite, p 35 years OR = 3.4, 95% CI: 1.1–10.5, p = 0.03). The prevalence of Chagas disease was much higher in people attending social events than healthcare centres, suggesting that observations based only on health facility data underestimate the real prevalence of Chagas disease. Screening in the community was well accepted and should be promoted to reach the population at highest risk.

International audience; Social dispersal is an important feature of population dynamics. When female mammals occur in polygynous groups, their dispersal decisions are conditioned by various female‐, male‐, and group‐related factors. Among them, the influence of disease often remains difficult to assess. To address this challenge, we used long‐term monitoring data from two gorilla populations (Gorilla gorilla gorilla) affected by infectious skin disease lesions. After controlling for other potentially influential factors, we investigated to which extent disease avoidance drives the dispersal decisions of gorilla females. We showed that the infection of a silverback of a breeding group by the skin disease increased the probability of adult females to emigrate. Moreover, adult females avoided breeding groups with a high prevalence of skin disease by emigrating from them and immigrating into healthier ones. Age of the breeding group was also an important factor. Adult females left older groups, near the end of a male tenure, to join younger ones led by younger fully grown silverbacks that could be of high reproductive and protective value. Our study highlights that, although females select for high‐quality males, disease avoidance is a critical driver of their dispersion decision.

BackgroundThe safety and efficacy of using C-reactive protein (CRP) to decide on antibiotic prescription among febrile children at risk of pneumonia has not been tested.MethodsThis was a randomized (1:1) controlled noninferiority trial in 9 primary care centers in Tanzania (substudy of the ePOCT trial evaluating a novel electronic decision algorithm). Children aged 2–59 months with fever and cough and without life-threatening conditions received an antibiotic based on a CRP-informed strategy (combination of CRP ≥80 mg/L plus age/temperature-corrected tachypnea and/or chest indrawing) or current World Health Organization standard (respiratory rate ≥50 breaths/minute). The primary outcome was clinical failure by day (D) 7; the secondary outcomes were antibiotic prescription at D0, secondary hospitalization, or death by D30.ResultsA total of 1726 children were included (intervention: 868, control: 858; 0.7% lost to follow-up). The proportion of clinical failure by D7 was 2.9% (25/865) in the intervention arm vs 4.8% (41/854) in the control arm (risk difference, –1.9% [95% confidence interval {CI}, –3.7% to –.1%]; risk ratio [RR], 0.60 [95% CI, .37–.98]). Twenty of 865 (2.3%) children in the intervention arm vs 345 of 854 (40.4%) in the control arm received antibiotics at D0 (RR, 0.06 [95% CI, .04–.09]). There were fewer secondary hospitalizations and deaths in the CRP arm: 0.5% (4/865) vs 1.5% (13/854) (RR, 0.30 [95% CI, .10–.93]).ConclusionsCRP testing using a cutoff of ≥80 mg/L, integrated into an electronic decision algorithm, was able to improve clinical outcome in children with respiratory infections while substantially reducing antibiotic prescription.Clinical Trials RegistrationNCT02225769.

BACKGROUND:Understanding pattern of antimalarials use at large scale helps ensuring appropriate use of treatments and preventing the spread of resistant parasites. We estimated the proportion of individuals in community surveys with residual antimalarials in their blood and identified the factors associated with the presence of the most commonly detected drugs, lumefantrine and/or desbutyl-lumefantrine (LF/DLF) or sulfadoxine-pyrimethamine (SP). METHODS:A cross-sectional survey was conducted in 2015 in three regions of Tanzania with different levels of malaria endemicity. Interviews were conducted and blood samples collected through household surveys for further antimalarial measurements using liquid chromatography coupled to tandem mass spectrometry. In addition, diagnosis and treatment availability was investigated through outlet surveys. Multilevel mixed effects logistic regression models were used to estimate odds ratios for having LF/DLF or SP in the blood. RESULTS:Amongst 6391 participants, 12.4% (792/6391) had LF/DLF and 8.0% (510/6391) SP in the blood. Factors associated with higher odds of detecting LF/DLF in the blood included fever in the previous two weeks (OR = 2.6, p

Objective: To evaluate whether classification of patients as having low, moderate, or high stress based on clinical parameters is associated with plasma levels of stress hormone Design and setting: Prospective, blinded, observational study in an 18-bed medical ICU. Patients: Eighty-eight consecutive patients Interventions: Patients were classified as low (n=28), moderate (n=33) or high stress (n=27) on days 0 and 3 of ICU stay, based on 1 point for each abnormal parameter: body temperature, heart rate, systemic arterial pressure, respiratory rate, physical agitation, presence of infection and catecholamine administration. The stress categories were: high: 4 points or more, moderate 2-3 points, low 1 point. Plasma growth hormone (GH), insulin-like growth factor 1 (IGF-1), insulin, glucagon, cortisol were measured on days 0 and 3. Measurements and results: Plasma cortisol and glucagon were significantly higher and IGF-1 lower in high vs. low stress patients on days 0 and 3. High stress patients were more likely to have high cortisol levels (odds ratio 5.8, confidence interval 1.8-18.9), high glucagon (8.7, 2.1-36.1), and low IGF-1 levels (5.9, 1.8-19.0) than low stress patients on day 0. Moderate stress patients were also more likely to have high cortisol and glucagon levels than low stress patients. Insulin and GH did not differ significantly. Results were similar for day 3. Conclusions: Moderate and severe stress was significantly associated with high catabolic (cortisol, glucagon) and low anabolic (IGF-1) hormone levels. The hormonal stress level in ICU patients can be estimated from simple clinical parameters during routine clinical evaluation

OBJECTIVES To assess the prognostic significance of high vs. low grade coronary artery ectasia (CAE) and the impact of antithrombotic or anticoagulant therapy on adverse cardiac outcomes. BACKGROUND There is paucity of knowledge on the impact of angiographic characteristics in CAE or that of antithrombotic or anticoagulant therapy on outcomes. METHODS AND RESULTS In this retrospective study, we reviewed angiograms and medical records of all cases of confirmed CAE (2001-2011). Extent of CAE was categorized using the Markis classification. Types 1 and 2 were categorized as high-grade and types 3 and 4 as low-grade CAE. Angiographic flow was recorded as normal or sluggish (

Background Monitoring the impact of case management strategies at large scale is essential to evaluate the public health benefit they confer. The use of methodologies relying on objective and standardized endpoints, such as drug levels in the blood, should be encouraged. Population drug use, diagnosis and treatment appropriateness in case of fever according to patient history and anti-malarials blood concentration was evaluated. Methods A cross-sectional survey took place between May and August 2015 in three regions of Tanzania with different levels of malaria endemicity. Interviews were conducted and blood samples were collected by dried blood spots through household surveys for further anti-malarial measurements. Appropriate testing when individuals attended care was defined as a patient with history of fever being tested for malaria and appropriate treatment as (i) having anti-malarial in the blood if the test result was positive (ii) having anti-malarial in the blood if the person was not tested, and (iii) no anti-malarial in the blood when the test result was negative. Results Amongst 6391 participants included in the anti-malarial analysis, 20.8% (1330/6391) had anti-malarial drug detected in the blood. Only 28.0% (372/1330) of the individuals with anti-malarials in their blood reported the use of anti-malarials within the previous month. Amongst all participants, 16.0% (1021/6391) reported having had a fever in the previous 2 weeks and 37.5% of them (383/1021) had detectable levels of anti-malarials in the blood. Of the individuals who sought care in health facilities, 69.4% (172/248) were tested and 52.0% (129/248) appropriately treated. When other providers were sought, 6% (23/382) of the persons were appropriately tested and 44.2% (169/382) appropriately treated. Overall, the proportion of individuals treated was larger than that being tested [47.3% (298/630) treated, 31.0% (195/630) tested]. Conclusion This study showed high prevalence of circulating anti-malarial drug in the sampled population. Efforts should be made to increase rapid diagnostic tests use at all levels of health care and improve compliance to test result in order to target febrile patients that are sick with malaria and reduce drug pressure. Objective drug measurements collected at community level represent a reliable tool to evaluate overall impact of case management strategies on population drug pressure.

In 2011, a patient was admitted to our hospital with acute schistosomiasis after having returned from Madagascar and having bathed at the Lily waterfalls. On the basis of this patient's indication, infection was suspected in 41 other subjects. This study investigated (1) the knowledge of the travelers about the risks of schistosomiasis and their related behavior to evaluate the appropriateness of prevention messages and (2) the diagnostic workup of symptomatic travelers by general practitioners to evaluate medical care of travelers with a history of freshwater exposure in tropical areas.; A questionnaire was sent to the 42 travelers with potential exposure to schistosomiasis. It focused on pre-travel knowledge of the disease, bathing conditions, clinical presentation, first suspected diagnosis, and treatment.; Of the 42 questionnaires, 40 (95%) were returned, among which 37 travelers (92%) reported an exposure to freshwater, and 18 (45%) were aware of the risk of schistosomiasis. Among these latter subjects, 16 (89%) still reported an exposure to freshwater. Serology was positive in 28 (78%) of 36 exposed subjects at least 3 months after exposure. Of the 28 infected travelers, 23 (82%) exhibited symptoms and 16 (70%) consulted their general practitioner before the information about the outbreak had spread, but none of these patients had a serology for schistosomiasis done during the first consultation.; The usual prevention message of avoiding freshwater contact when traveling in tropical regions had no impact on the behavior of these travelers, who still went swimming at the Lily waterfalls. This prevention message should, therefore, be either modified or abandoned. The clinical presentation of acute schistosomiasis is often misleading. General practitioners should at least request an eosinophil count, when confronted with a returning traveler with fever. If eosinophilia is detected, it should prompt the search for a parasitic disease.

BACKGROUND A low or high body mass index (BMI) has been associated with increased mortality risk in older subjects without taking fat mass index (FMI) and fat-free mass index (FFMI) into account. This information is essential because FMI is modulated through different healthcare strategies than is FFMI. OBJECTIVE We aimed to determine the relation between body composition and mortality in older subjects. DESIGN We included all adults ≥65 y old who were living in Switzerland and had a body-composition measurement by bioelectrical impedance analysis at the Geneva University Hospitals between 1990 and 2011. FMI and FFMI were divided into sex-specific quartiles. Quartile 1 (i.e., the reference category) corresponded to the lowest FMI or FFMI quartile. Mortality data were retrieved from the hospital database, the Geneva death register, and the Swiss National Cohort until December 2012. Comorbidities were assessed by using the Cumulative Illness Rating Scale. RESULTS Of 3181 subjects included, 766 women and 1007 men died at a mean age of 82.8 and 78.5 y, respectively. Sex-specific Cox regression models, which were used to adjust for age, BMI, smoking, ambulatory or hospitalized state, and calendar time, showed that body composition did not predict mortality in women irrespective of whether comorbidities were taken into account. In men, risk of mortality was lower with FFMI in quartiles 3 and 4 [HR: 0.78 (95% CI: 0.62, 0.98) and 0.64 (95% CI: 0.49, 0.85), respectively] but was not affected by FMI. When comorbidities were adjusted for, FFMI in quartile 4 (>19.5 kg/m(2)) still predicted a lower risk of mortality (HR: 0.72; 95% CI: 0.54, 0.96). CONCLUSIONS Low FFMI is a stronger predictor of mortality than is BMI in older men but not older women. FMI had no impact on mortality. These results suggest potential benefits of preventive interventions with the aim of maintaining muscle mass in older men. This trial was registered at clinicaltrials.gov as NCT01472679.

International audience

Background P27A is an unstructured 104mer synthetic peptide from Plasmodium falciparum trophozoite exported protein 1 (TEX1), the target of human antibodies inhibiting parasite growth. The present project aimed at evaluating the safety and immunogenicity of P27A peptide vaccine in malaria-nonexposed European and malaria-exposed African adults. Methods This study was designed as a staggered, fast-track, randomized, antigen and adjuvant dose-finding, multicenter phase 1a/1b trial, conducted in Switzerland and Tanzania. P27A antigen (10 or 50 μg), adjuvanted with Alhydrogel or glucopyranosil lipid adjuvant stable emulsion (GLA-SE; 2.5 or 5 μg), or control rabies vaccine (Verorab) were administered intramuscularly to 16 malaria-nonexposed and 40 malaria-exposed subjects on days 0, 28, and 56. Local and systemic adverse events (AEs) as well as humoral and cellular immune responses were assessed after each injection and during the 34-week follow-up. Results Most AEs were mild to moderate and resolved completely within 48 hours. Systemic AEs were more frequent in the formulation with alum as compared to GLA-SE, whereas local AEs were more frequent after GLA-SE. No serious AEs occurred. Supported by a mixed Th1/Th2 cell-mediated immunity, P27A induced a marked specific antibody response able to recognize TEX1 in infected erythrocytes and to inhibit parasite growth through an antibody-dependent cellular inhibition mechanism. Incidence of AEs and antibody responses were significantly lower in malaria-exposed Tanzanian subjects than in nonexposed European subjects. Conclusions The candidate vaccine P27A was safe and induced a particularly robust immunogenic response in combination with GLA-SE. This formulation should be considered for future efficacy trials. Clinical Trials Registration NCT01949909, PACTR201310000683408.