LOw-dose CT Or Lung UltraSonography versus standard of care based-strategies for the diagnosis of pneumonia in the elderly: protocol for a multicentre randomised controlled trial (OCTOPLUS).

INTRODUCTION Pneumonia is a leading cause of mortality and a common indication for antibiotic in elderly patients. However, its diagnosis is often inaccurate. We aim to compare the diagnostic accuracy, the clinical and cost outcomes and the use of antibiotics associated with three imaging strategies in patients >65 years old with suspected pneumonia in the emergency room (ER): chest X-ray (CXR, standard of care), low-dose CT scan (LDCT) or lung ultrasonography (LUS). METHODS AND ANALYSIS This is a multicentre randomised superiority clinical trial with three parallel arms. Patients will be allocated in the ER to a diagnostic strategy based on either CXR, LDCT or LUS. All three imaging modalities will be performed but the results of two of them will be masked during 5 days to the patients, the physicians in charge of the patients and the investigators according to random allocation. The primary objective is to compare the accuracy of LDCT versus CXR-based strategies. As secondary objectives, antibiotics prescription, clinical and cost outcomes will be compared, and the same analyses repeated to compare the LUS and CXR strategies. The reference diagnosis will be established a posteriori by a panel of experts. Based on a previous study, we expect an improvement of 16% of the accuracy of pneumonia diagnosis using LDCT instead of CXR. Under this assumption, and accounting for 10% of drop-out, the enrolment of 495 patients is needed to prove the superiority of LDCT over CRX (alpha error=0.05, beta error=0.10). ETHICS AND DISSEMINATION Ethical approval: CER Geneva 2019-01288. TRIAL REGISTRATION NUMBER NCT04978116

A Population-Based Trachoma Prevalence Survey Covering Seven Districts of Sangha and Likouala Departments, Republic of the Congo.

PURPOSE: We set out to estimate the prevalence of trachoma and access to water and sanitation in seven suspected-trachoma-endemic districts of northern Congo, surveyed as a single evaluation unit. METHODS: From a complete list of rural villages in the seven districts, we systematically selected 22 with probability proportional to village size. In selected villages, we included all households where there were fewer than 25 in total, or used compact segment sampling to select a group of approximately 20 households by random draw. In each selected household, all consenting residents aged ≥1 year were examined by Global Trachoma Mapping Project-certified trachoma graders, and data collected on household-level access to water and sanitation. RESULTS: In November and December 2015, 466 households were visited in 22 villages, and 2081 (88%) of 2377 residents of those households were examined. No examined individual had trichiasis. The age-adjusted prevalence of the active trachoma sign trachomatous inflammation-follicular (TF) in 1-9-year-olds was 2.5% (95%CI 0.9-4.5%). Only 39% (95%CI 35-44%) of households had access to an improved source of drinking water. Only 10% (95%CI 7-13%) of households had access to an improved sanitation facility. CONCLUSION: Trachoma is not a public health problem in this part of Congo. Access to water and sanitation is inadequate

Prevalence of trachoma in the Republic of Chad: results of 41 population-based surveys.

PURPOSE: To estimate the prevalence of trachoma in suspected-endemic areas of Chad, and thereby determine whether trachoma is a public health problem requiring intervention. METHODS: We divided the suspected-endemic population living in secure districts into 46 evaluation units (EUs), and used the standardized methodologies of the Global Trachoma Mapping Project. A two-stage cluster-sampling procedure was adopted. In each EU, the goal was to examine at least 1019 children aged 1-9 years by recruiting 649 households; all consenting residents aged ≥ 1 year living in those households were examined. Each participant was examined for trachomatous inflammation-follicular (TF), trachomatous inflammation-intense (TI), and trichiasis. RESULTS: Two EUs had data that could not be validated, and were excluded from the analysis. GPS data for three other pairs of EUs suggested that EU divisions were inaccurate; data for each pair were combined within the pair. In the 41 resulting EUs, 29,924 households in 967 clusters were visited, and 104,584 people were examined. The age-adjusted EU-level prevalence of TF in 1-9-year-olds ranged from 0.0% to 23.3%, and the age- and gender-adjusted EU-level prevalence of trichiasis in ≥ 15-year-olds ranged from 0.02% to 1.3%. TF was above the WHO elimination threshold in 16 EUs (39%) and trichiasis was above the WHO elimination threshold in 29 EUs (71%). Women had a higher prevalence of trichiasis than did men in 31 EUs (76%). A higher ratio of trichiasis prevalence in women to trichiasis prevalence in men was associated (p = 0.03) with a higher prevalence of trichiasis at EU level. CONCLUSION: Public health-level interventions against trachoma are needed in Chad. Over 10,000 people need management of their trichiasis; women account for about two-thirds of this total. The association between a higher ratio of trichiasis prevalence in women to that in men with higher overall trichiasis prevalence needs further investigation

A cluster of multidrug-resistant Mycobacterium tuberculosis among patients arriving in Europe from the Horn of Africa: a molecular epidemiological study

SummaryBackground The risk of tuberculosis outbreaks among people fleeing hardship for refuge in Europe is heightened. We describe the cross-border European response to an outbreak of multidrug-resistant tuberculosis among patients from the Horn of Africa and Sudan. Methods On April 29 and May 30, 2016, the Swiss and German National Mycobacterial Reference Laboratories independently triggered an outbreak investigation after four patients were diagnosed with multidrug-resistant tuberculosis. In this molecular epidemiological study, we prospectively defined outbreak cases with 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) profiles; phenotypic resistance to isoniazid, rifampicin, ethambutol, pyrazinamide, and capreomycin; and corresponding drug resistance mutations. We whole-genome sequenced all Mycobacterium tuberculosis isolates and clustered them using a threshold of five single nucleotide polymorphisms (SNPs). We collated epidemiological data from host countries from the European Centre for Disease Prevention and Control. Findings Between Feb 12, 2016, and April 19, 2017, 29 patients were diagnosed with multidrug-resistant tuberculosis in seven European countries. All originated from the Horn of Africa or Sudan, with all isolates two SNPs or fewer apart. 22 (76%) patients reported their travel routes, with clear spatiotemporal overlap between routes. We identified a further 29 MIRU-VNTR-linked cases from the Horn of Africa that predated the outbreak, but all were more than five SNPs from the outbreak. However all 58 isolates shared a capreomycin resistance-associated tlyA mutation. Interpretation Our data suggest that source cases are linked to an M tuberculosis clone circulating in northern Somalia or Djibouti and that transmission probably occurred en route before arrival in Europe. We hypothesise that the shared mutation of tlyA is a drug resistance mutation and phylogenetic marker, the first of its kind in M tuberculosis sensu stricto. Funding The Swiss Federal Office of Public Health, the University of Zurich, the Wellcome Trust, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), the Medical Research Council, BELTA-TBnet, the European Union, the German Center for Infection Research, and Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG)

A Population-Based Trachoma Prevalence Survey Covering Seven Districts of Sangha and Likouala Departments, Republic of the Congo.

PurposeWe set out to estimate the prevalence of trachoma and access to water and sanitation in seven suspected-trachoma-endemic districts of northern Congo, surveyed as a single evaluation unit.MethodsFrom a complete list of rural villages in the seven districts, we systematically selected 22 with probability proportional to village size. In selected villages, we included all households where there were fewer than 25 in total, or used compact segment sampling to select a group of approximately 20 households by random draw. In each selected household, all consenting residents aged ≥1 year were examined by Global Trachoma Mapping Project-certified trachoma graders, and data collected on household-level access to water and sanitation.ResultsIn November and December 2015, 466 households were visited in 22 villages, and 2081 (88%) of 2377 residents of those households were examined. No examined individual had trichiasis. The age-adjusted prevalence of the active trachoma sign trachomatous inflammation-follicular (TF) in 1-9-year-olds was 2.5% (95%CI 0.9-4.5%). Only 39% (95%CI 35-44%) of households had access to an improved source of drinking water. Only 10% (95%CI 7-13%) of households had access to an improved sanitation facility.ConclusionTrachoma is not a public health problem in this part of Congo. Access to water and sanitation is inadequate

Prevalence of trachoma in the Republic of Chad: results of 41 population-based surveys.

PurposeTo estimate the prevalence of trachoma in suspected-endemic areas of Chad, and thereby determine whether trachoma is a public health problem requiring intervention.MethodsWe divided the suspected-endemic population living in secure districts into 46 evaluation units (EUs), and used the standardized methodologies of the Global Trachoma Mapping Project. A two-stage cluster-sampling procedure was adopted. In each EU, the goal was to examine at least 1019 children aged 1-9 years by recruiting 649 households; all consenting residents aged ≥ 1 year living in those households were examined. Each participant was examined for trachomatous inflammation-follicular (TF), trachomatous inflammation-intense (TI), and trichiasis.ResultsTwo EUs had data that could not be validated, and were excluded from the analysis. GPS data for three other pairs of EUs suggested that EU divisions were inaccurate; data for each pair were combined within the pair. In the 41 resulting EUs, 29,924 households in 967 clusters were visited, and 104,584 people were examined. The age-adjusted EU-level prevalence of TF in 1-9-year-olds ranged from 0.0% to 23.3%, and the age- and gender-adjusted EU-level prevalence of trichiasis in ≥ 15-year-olds ranged from 0.02% to 1.3%. TF was above the WHO elimination threshold in 16 EUs (39%) and trichiasis was above the WHO elimination threshold in 29 EUs (71%). Women had a higher prevalence of trichiasis than did men in 31 EUs (76%). A higher ratio of trichiasis prevalence in women to trichiasis prevalence in men was associated (p = 0.03) with a higher prevalence of trichiasis at EU level.ConclusionPublic health-level interventions against trachoma are needed in Chad. Over 10,000 people need management of their trichiasis; women account for about two-thirds of this total. The association between a higher ratio of trichiasis prevalence in women to that in men with higher overall trichiasis prevalence needs further investigation

Impact of interactive computerised decision support for hospital antibiotic use (COMPASS): an open-label, cluster-randomised trial in three Swiss hospitals

Background: Computerised decision-support systems (CDSSs) for antibiotic stewardship could help to assist physicians in the appropriate prescribing of antibiotics. However, high-quality evidence for their effect on the quantity and quality of antibiotic use remains scarce. The aim of our study was to assess whether a computerised decision support for antimicrobial stewardship combined with feedback on prescribing indicators can reduce antimicrobial prescriptions for adults admitted to hospital. Methods: The Computerised Antibiotic Stewardship Study (COMPASS) was a multicentre, cluster-randomised, parallel-group, open-label superiority trial that aimed to assess whether a multimodal computerised antibiotic-stewardship intervention is effective in reducing antibiotic use for adults admitted to hospital. After pairwise matching, 24 wards in three Swiss tertiary-care and secondary-care hospitals were randomised (1:1) to the CDSS intervention or to standard antibiotic stewardship measures using an online random sequence generator. The multimodal intervention consisted of a CDSS providing support for choice, duration, and re-evaluation of antimicrobial therapy, and feedback on antimicrobial prescribing quality. The primary outcome was overall systemic antibiotic use measured in days of therapy per admission, using adjusted-hurdle negative-binomial mixed-effects models. The analysis was done by intention to treat and per protocol. The study was registered with ClinicalTrials.gov (identifier NCT03120975). Findings: 24 clusters (16 at Geneva University Hospitals and eight at Ticino Regional Hospitals) were eligible and randomly assigned to control or intervention between Oct 1, 2018, and Dec 31, 2019. Overall, 4578 (40·2%) of 11 384 admissions received antibiotic therapy in the intervention group and 4142 (42·8%) of 9673 in the control group. The unadjusted overall mean days of therapy per admission was slightly lower in the intervention group than in the control group (3·2 days of therapy per admission, SD 6·2, vs 3·5 days of therapy per admission, SD 6·8; p&amp;lt;0·0001), and was similar among patients receiving antibiotics (7·9 days of therapy per admission, SD 7·6, vs 8·1 days of therapy per admission, SD 8·4; p=0·50). After adjusting for confounders, there was no statistically significant difference between groups for the odds of an admission receiving antibiotics (odds ratio [OR] for intervention vs control 1·12, 95% CI 0·94-1·33). For admissions with antibiotic exposure, days of therapy per admission were also similar (incidence rate ratio 0·98, 95% CI 0·90-1·07). Overall, the CDSS was used at least once in 3466 (75·7%) of 4578 admissions with any antibiotic prescription, but from the first day of antibiotic treatment for only 1602 (58·9%) of 2721 admissions in Geneva. For those for whom the CDSS was not used from the first day, mean time to use of CDSS was 8·9 days. Based on the manual review of 1195 randomly selected charts, transition from intravenous to oral therapy was significantly more frequent in the intervention group after adjusting for confounders (154 [76·6%] of 201 vs 187 [87%] of 215, +10·4%; OR 1·9, 95% CI 1·1-3·3). Consultations by infectious disease specialists were less frequent in the intervention group (388 [13·4%] of 2889) versus the control group (405 [16·9%] of 2390; OR 0·84, 95% CI 0·59-1·25). [...]</p

Risk of congenital malformation following first trimester mRNA COVID-19 vaccine exposure in pregnancy: the COVI-PREG prospective cohort.

OBJECTIVES This study aimed to evaluate the risk of congenital malformation among pregnant women exposed to the mRNA COVID-19 vaccines during the first trimester of pregnancy, which is a developmental period where the fetus is at risk of teratogenicity. METHODS Pregnant women were prospectively enrolled from March 2021 to March 2022, at the time of COVID-19 vaccination. Pregnant women exposed to at least one dose of mRNA COVID-19 vaccine from conception to 11 weeks of gestations and 6 days were compared to pregnant women exposed to the vaccine from 12 weeks to the end of pregnancy. The primary outcome was a confirmed congenital malformation at birth. RESULTS A total of 1450 pregnant women were enrolled including 124 in the first trimester and 1326 in the second and third trimester. The overall proportion of congenital malformation was 0.81% (n=1/124; 95%CI 0.02-4.41) and 0.83% (n=11/1326; 95% CI 0.41-1.48) among pregnant exposed to the COVID-19 vaccine during the first and second/third trimester, respectively. First trimester exposure was not associated with a higher risk of congenital malformation with a relative risk (RR) of 0.89 (95%CI 0.12-6.80) with no significant changes after adjustment through exploratory analysis. CONCLUSION Pregnant women exposed to mRNA COVID-19 vaccine before 12 weeks of gestation did not have an increased risk of congenital malformation compared to women exposed outside the teratogenic window. As vaccination is safe and effective, emphasis must be placed on promoting vaccination during pregnancy

Risk of congenital malformation following first trimester mRNA COVID-19 vaccine exposure in pregnancy: the COVI-PREG prospective cohort.

This study aimed to evaluate the risk of congenital malformation among pregnant women exposed to the mRNA COVID-19 vaccines during the first trimester of pregnancy, which is a developmental period where the fetus is at risk of teratogenicity. Pregnant women were prospectively enrolled from March 2021 to March 2022, at the time of COVID-19 vaccination. Pregnant women exposed to at least one dose of mRNA COVID-19 vaccine from conception to 11 weeks of gestations and 6 days were compared to pregnant women exposed to the vaccine from 12 weeks to the end of pregnancy. The primary outcome was a confirmed congenital malformation at birth. A total of 1450 pregnant women were enrolled including 124 in the first trimester and 1326 in the second and third trimester. The overall proportion of congenital malformation was 0.81% (n=1/124; 95%CI 0.02-4.41) and 0.83% (n=11/1326; 95% CI 0.41-1.48) among pregnant exposed to the COVID-19 vaccine during the first and second/third trimester, respectively. First trimester exposure was not associated with a higher risk of congenital malformation with a relative risk (RR) of 0.89 (95%CI 0.12-6.80) with no significant changes after adjustment through exploratory analysis. Pregnant women exposed to mRNA COVID-19 vaccine before 12 weeks of gestation did not have an increased risk of congenital malformation compared to women exposed outside the teratogenic window. As vaccination is safe and effective, emphasis must be placed on promoting vaccination during pregnancy

Systems prediction of chronic lung allograft dysfunction: Results and perspectives from the Cohort of Lung Transplantation and Systems prediction of Chronic Lung Allograft Dysfunction cohorts

International audienceBackground : Chronic lung allograft dysfunction (CLAD) is the leading cause of poor long-term survival after lung transplantation (LT). Systems prediction of Chronic Lung Allograft Dysfunction (SysCLAD) aimed to predict CLAD. Methods : To predict CLAD, we investigated the clinicome of patients with LT; the exposome through assessment of airway microbiota in bronchoalveolar lavage cells and air pollution studies; the immunome with works on activation of dendritic cells, the role of T cells to promote the secretion of matrix metalloproteinase-9, and subpopulations of T and B cells; genome polymorphisms; blood transcriptome; plasma proteome studies and assessment of MSK1 expression. Results : Clinicome: the best multivariate logistic regression analysis model for early-onset CLAD in 422 LT eligible patients generated a ROC curve with an area under the curve of 0.77. Exposome: chronic exposure to air pollutants appears deleterious on lung function levels in LT recipients (LTRs), might be modified by macrolides, and increases mortality. Our findings established a link between the lung microbial ecosystem, human lung function, and clinical stability post-transplant. Immunome: a decreased expression of CLEC1A in human lung transplants is predictive of the development of chronic rejection and associated with a higher level of interleukin 17A; Immune cells support airway remodeling through the production of plasma MMP-9 levels, a potential predictive biomarker of CLAD. Blood CD9-expressing B cells appear to favor the maintenance of long-term stable graft function and are a potential new predictive biomarker of BOS-free survival. An early increase of blood CD4 + CD57 + ILT2+ T cells after LT may be associated with CLAD onset. Genome: Donor Club cell secretory protein G38A polymorphism is associated with a decreased risk of severe primary graft dysfunction after LT. Transcriptome: blood POU class 2 associating factor 1, T-cell leukemia/lymphoma domain, and B cell lymphocytes, were validated as predictive biomarkers of CLAD phenotypes more than 6 months before diagnosis. Proteome: blood A2MG is an independent predictor of CLAD, and MSK1 kinase overexpression is either a marker or a potential therapeutic target in CLAD. Conclusion : Systems prediction of Chronic Lung Allograft Dysfunction generated multiple fingerprints that enabled the development of predictors of CLAD. These results open the way to the integration of these fingerprints into a predictive handprint