Publications by authors named "Jérémie F Cohen"

69 Publications

Morocco as a possible source for acquisition of Rhinocladiella mackenziei.

PLoS Negl Trop Dis 2021 Aug 19;15(8):e0009563. Epub 2021 Aug 19.

Université de Paris, Necker-Pasteur Center for Infectious Diseases and Tropical Medicine, Necker-Enfants Malades Hospital, APHP, Imagine Institute, Paris, France.

Rhinocladiella mackenziei cerebral phaeohyphomycosis is a rare severe disease that has been typically described in the Middle East. Here, we report 2 cases of R. mackenziei cerebral phaeohyphomycosis in patients from Morocco, diagnosed and treated in France, and raise a concern about the ever-going extension of the area at risk for this devastating invasive fungal infection.
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http://dx.doi.org/10.1371/journal.pntd.0009563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376069PMC
August 2021

Evaluating tests for diagnosing COVID-19 in the absence of a reliable reference standard: pitfalls and potential solutions.

J Clin Epidemiol 2021 Aug 3. Epub 2021 Aug 3.

Department of General Pediatrics and Pediatric Infectious Diseases, Necker-Enfants malades University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Université de Paris, Paris, France; Centre of Research in Epidemiology and Statistics (CRESS), INSERM, EPOPé team, Université de Paris, Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.jclinepi.2021.07.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330140PMC
August 2021

Monitoring outpatient antibiotic utilization using reimbursement and retail sales data: a population-based comparison in France, 2012-17.

J Antimicrob Chemother 2021 Aug;76(9):2446-2452

Université de Paris, Epidemiology and Statistics Research Center-CRESS, INSERM, Obstetrical, Perinatal and Pediatric Epidemiology research team, F-75004, Paris, France.

Objectives: To assess whether a retail sales database could be used to monitor antibiotic utilization in the outpatient setting at the national level.

Methods: We extracted 2012-17 outpatient antibiotic extrapolated retail sales (IQVIA's Xponent) and reimbursement data from the National Health Insurance (SNDS) in metropolitan France. We compared estimates of antibiotic use and consumption [number of antibiotic drug deliveries (DrID) and defined daily doses (DID) per 1000 inhabitants per day]. We relied on relative differences, Pearson's r statistics and time series using autoregressive integrated moving average (ARIMA) modelling to study: (i) differences in point estimates, (ii) correlation, and (iii) consistency in time trends between Xponent and SNDS. The analysis was conducted overall and in subgroups (age groups, therapeutic classes, major antimicrobial agents and regions).

Results: We analysed approximately 377 million antibiotic drug deliveries, comprising nearly 3.4 billion DDDs. Overall, Xponent slightly overestimated SNDS point estimates with yearly relative differences of +3.5% for DrID and +3.3% for DID. Peaks in relative differences were observed for July and August months. Relative differences were <5% in most subgroups, except for fosfomycin and three French regions. Overall and across most subgroups, the correlation between Xponent and SNDS monthly aggregated estimates was almost perfect (r ≥ 0.992 for all subgroups, except for one region). ARIMA modelling showed high consistency between Xponent's and SDNS's DrID time series, but detected timepoints where the series significantly diverged.

Conclusions: IQVIA's Xponent and SNDS data were highly consistent. Xponent database seems suitable for monitoring outpatient antibiotic utilization in France.
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http://dx.doi.org/10.1093/jac/dkab185DOI Listing
August 2021

Diagnostic accuracy of rapid nucleic acid tests for group A streptococcal pharyngitis: systematic review and meta-analysis.

Clin Microbiol Infect 2021 May 6. Epub 2021 May 6.

Université de Paris, Centre of Research in Epidemiology and Statistics (CRESS), INSERM, Paris, France; Necker-Enfants malades Hospital, APHP, Université de Paris, Department of General Paediatrics and Paediatric Infectious Diseases, Paris, France. Electronic address:

Background: Acute pharyngitis is one of the most common conditions in outpatient settings and an important source of inappropriate antibiotic prescribing. Rapid antigen detection tests (RADTs) offer diagnosis of group A streptococcus at the point of care but have limited sensitivity. Rapid nucleic acid tests (RNATs) are now available; a systematic review of their accuracy is lacking.

Objectives: To evaluate the accuracy of RNATs in patients with pharyngitis; to explore test-level and study-level factors that could explain variability in accuracy; and to compare the accuracy of RNATs with that of RADTs.

Data Sources: MEDLINE, Embase, Web of Science (1990-2020).

Study Eligibility Criteria: Cross-sectional studies and randomized trials.

Participants: Patients with pharyngitis.

Index Test/s And Reference Standards: RNAT commercial kits compared with throat culture.

Methods: We assessed risk of bias and applicability using QUADAS-2. We performed meta-analysis of sensitivity and specificity using the bivariate random-effects model. Variability was explored by subgroup analyses and meta-regression.

Results: We included 38 studies (46 test evaluations; 17 411 test results). RNATs were most often performed in a laboratory. The overall methodological quality of primary studies was uncertain because of incomplete reporting. RNATs had a summary sensitivity of 97.5% (95% CI 96.2%-98.3%) and a summary specificity of 95.1% (95% CI 93.6%-96.3%). There was low variability in estimates across studies. Variability in sensitivity and specificity was partially explained by test type (p < 0.05 for both). Sensitivity analyses limited to studies with low risk of bias showed robust accuracy estimates. RNATs were more sensitive than RADTs (13 studies; 96.8% versus 82.3%, p 0.004); there was no difference in specificity (p 0.92).

Conclusions: The high diagnostic accuracy of RNATs may allow their use as stand-alone tests to diagnose group A streptococcus pharyngitis. Based on direct comparisons, RNATs have greater sensitivity than RADTs and equal specificity. Further studies should evaluate RNATs in point-of-care settings.
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http://dx.doi.org/10.1016/j.cmi.2021.04.021DOI Listing
May 2021

A 3-Year-Old Child With Fever, Severe Cheilitis, and Blisters of the Palms and Soles.

Clin Infect Dis 2021 05;72(9):1667-1668

Department of General Pediatrics and Pediatric Infectious Diseases, Necker Hospital for Sick Children, AP-HP, Université de Paris, Paris, France.

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http://dx.doi.org/10.1093/cid/ciaa1699DOI Listing
May 2021

Clinical Prediction of Iron Deficiency at Age 2 Years: A National Cross-sectional Study in France.

J Pediatr 2021 Aug 6;235:212-219. Epub 2021 Apr 6.

Center of Research in Epidemiology and Statistics, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, INSERM UMR 1153, Université de Paris, Paris, France; Department of General Pediatrics and Pediatric Infectious Diseases, Necker Sick Children Hospital, Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France.

Objective: To assess the diagnostic accuracy of existing clinical criteria and to develop prediction tools for iron deficiency in 2-year-old children.

Study Design: In a national cross-sectional study conducted in primary care pediatricians' practices throughout France, 2-year-old children were consecutively included (2016-2017). Multivariable logistic regression modeling and bootstrapping were used to develop several clinical models to predict iron deficiency (serum ferritin <12 μg/L). These models used the best criteria and combinations among the American Academy of Pediatrics' (AAP) criteria adapted to the European context (n = 10), then all potential predictors (n = 19). One model was then simplified into a simple prediction tool.

Results: Among 568 included infants, 38 had iron deficiency (6.7%). In univariable analyses, no significant association with iron deficiency was observed for 8 of the 10 adapted AAP criteria. Three criteria (both parents born outside the European Union, low weight at 1 year old, and weaning to cow's milk without supplemental iron) were retained in the AAP model, which area under the receiver operating characteristic curve, sensitivity, and specificity were 0.62 (95% CI, 0.58-0.67), 30% (95% CI, 22%-39%), and 95% (95% CI, 92%-97%), respectively. Four criteria were retained in a newly derived simple prediction tool (≥1 criterion among the 3 previous plus duration of iron-rich formula consumption <12 months), which area under the receiver operating characteristic curve, sensitivity, and specificity were 0.72 (95% CI, 0.65-0.79), 63% (95% CI, 47%-80%), and 81% (95% CI, 70%-91%), respectively.

Conclusions: All prediction tools achieved acceptable diagnostic accuracy. The newly derived simple prediction tool offered potential ease of use.

Trial Registration: ClinicalTrials.gov NCT02484274.
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http://dx.doi.org/10.1016/j.jpeds.2021.03.072DOI Listing
August 2021

PRISMA-DTA for Abstracts: a new addition to the toolbox for test accuracy research.

Diagn Progn Res 2021 Apr 2;5(1). Epub 2021 Apr 2.

Department of General Pediatrics and Pediatric Infectious Diseases, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

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http://dx.doi.org/10.1186/s41512-021-00097-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017829PMC
April 2021

Thoracic imaging tests for the diagnosis of COVID-19.

Cochrane Database Syst Rev 2021 03 16;3:CD013639. Epub 2021 Mar 16.

NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK.

Background: The respiratory illness caused by SARS-CoV-2 infection continues to present diagnostic challenges. Our 2020 edition of this review showed thoracic (chest) imaging to be sensitive and moderately specific in the diagnosis of coronavirus disease 2019 (COVID-19). In this update, we include new relevant studies, and have removed studies with case-control designs, and those not intended to be diagnostic test accuracy studies.

Objectives: To evaluate the diagnostic accuracy of thoracic imaging (computed tomography (CT), X-ray and ultrasound) in people with suspected COVID-19.

Search Methods: We searched the COVID-19 Living Evidence Database from the University of Bern, the Cochrane COVID-19 Study Register, The Stephen B. Thacker CDC Library, and repositories of COVID-19 publications through to 30 September 2020. We did not apply any language restrictions.

Selection Criteria: We included studies of all designs, except for case-control, that recruited participants of any age group suspected to have COVID-19 and that reported estimates of test accuracy or provided data from which we could compute estimates.

Data Collection And Analysis: The review authors independently and in duplicate screened articles, extracted data and assessed risk of bias and applicability concerns using the QUADAS-2 domain-list. We presented the results of estimated sensitivity and specificity using paired forest plots, and we summarised pooled estimates in tables. We used a bivariate meta-analysis model where appropriate. We presented the uncertainty of accuracy estimates using 95% confidence intervals (CIs).

Main Results: We included 51 studies with 19,775 participants suspected of having COVID-19, of whom 10,155 (51%) had a final diagnosis of COVID-19. Forty-seven studies evaluated one imaging modality each, and four studies evaluated two imaging modalities each. All studies used RT-PCR as the reference standard for the diagnosis of COVID-19, with 47 studies using only RT-PCR and four studies using a combination of RT-PCR and other criteria (such as clinical signs, imaging tests, positive contacts, and follow-up phone calls) as the reference standard. Studies were conducted in Europe (33), Asia (13), North America (3) and South America (2); including only adults (26), all ages (21), children only (1), adults over 70 years (1), and unclear (2); in inpatients (2), outpatients (32), and setting unclear (17). Risk of bias was high or unclear in thirty-two (63%) studies with respect to participant selection, 40 (78%) studies with respect to reference standard, 30 (59%) studies with respect to index test, and 24 (47%) studies with respect to participant flow. For chest CT (41 studies, 16,133 participants, 8110 (50%) cases), the sensitivity ranged from 56.3% to 100%, and specificity ranged from 25.4% to 97.4%. The pooled sensitivity of chest CT was 87.9% (95% CI 84.6 to 90.6) and the pooled specificity was 80.0% (95% CI 74.9 to 84.3). There was no statistical evidence indicating that reference standard conduct and definition for index test positivity were sources of heterogeneity for CT studies. Nine chest CT studies (2807 participants, 1139 (41%) cases) used the COVID-19 Reporting and Data System (CO-RADS) scoring system, which has five thresholds to define index test positivity. At a CO-RADS threshold of 5 (7 studies), the sensitivity ranged from 41.5% to 77.9% and the pooled sensitivity was 67.0% (95% CI 56.4 to 76.2); the specificity ranged from 83.5% to 96.2%; and the pooled specificity was 91.3% (95% CI 87.6 to 94.0). At a CO-RADS threshold of 4 (7 studies), the sensitivity ranged from 56.3% to 92.9% and the pooled sensitivity was 83.5% (95% CI 74.4 to 89.7); the specificity ranged from 77.2% to 90.4% and the pooled specificity was 83.6% (95% CI 80.5 to 86.4). For chest X-ray (9 studies, 3694 participants, 2111 (57%) cases) the sensitivity ranged from 51.9% to 94.4% and specificity ranged from 40.4% to 88.9%. The pooled sensitivity of chest X-ray was 80.6% (95% CI 69.1 to 88.6) and the pooled specificity was 71.5% (95% CI 59.8 to 80.8). For ultrasound of the lungs (5 studies, 446 participants, 211 (47%) cases) the sensitivity ranged from 68.2% to 96.8% and specificity ranged from 21.3% to 78.9%. The pooled sensitivity of ultrasound was 86.4% (95% CI 72.7 to 93.9) and the pooled specificity was 54.6% (95% CI 35.3 to 72.6). Based on an indirect comparison using all included studies, chest CT had a higher specificity than ultrasound. For indirect comparisons of chest CT and chest X-ray, or chest X-ray and ultrasound, the data did not show differences in specificity or sensitivity.

Authors' Conclusions: Our findings indicate that chest CT is sensitive and moderately specific for the diagnosis of COVID-19. Chest X-ray is moderately sensitive and moderately specific for the diagnosis of COVID-19. Ultrasound is sensitive but not specific for the diagnosis of COVID-19. Thus, chest CT and ultrasound may have more utility for excluding COVID-19 than for differentiating SARS-CoV-2 infection from other causes of respiratory illness. Future diagnostic accuracy studies should pre-define positive imaging findings, include direct comparisons of the various modalities of interest in the same participant population, and implement improved reporting practices.
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http://dx.doi.org/10.1002/14651858.CD013639.pub4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078565PMC
March 2021

COVID-19-Related Fatalities and Intensive-Care-Unit Admissions by Age Groups in Europe: A Meta-Analysis.

Front Med (Lausanne) 2020 14;7:560685. Epub 2021 Jan 14.

Department of General Pediatrics and Pediatric Infectious Diseases, AP-HP, Necker Hospital for Sick Children, Université de Paris, Paris, France.

Precise international estimates of the age breakdown of COVID-19-related deaths and intensive-care-unit (ICU) admissions are lacking. We evaluated the distribution of COVID-19-related fatalities and ICU admissions by age groups in Europe. On April 6, 2020, we systematically reviewed official COVID-19-related data from 32 European countries. We included countries that provided data regarding more than 10 COVID-19-related deaths stratified by age according to pre-specified age groups (i.e., <40, 40-69, ≥70 years). We used random-effects meta-analysis to summarize the data. Thirteen European countries were included in the review, for a total of 31,864 COVID-19-related deaths (range: 27-14,381 per country). In the main meta-analysis (including data from Germany, Hungary, Italy, The Netherlands, Portugal, Spain, Switzerland; 21,522 COVID-19-related fatalities), the summary proportions of individuals <40, 40-69, and ≥70 years old among all COVID-19-related deaths were 0.1% (0.0-0.2; 28.6%), 13.0% (10.8-15.4; 91.5%), and 86.6% (84.2-88.9; 91.5%), respectively. ICU data were available for four countries (France, Greece, Spain, Sweden). The summary proportions of individuals around <40-50, around 40-69, and around ≥60-70 years old among all COVID-19-related ICU admissions were 5.4% (3.4-7.8; 89.0%), 52.6% (41.8-63.3; 98.1%), and 41.8% (32.0-51.9; 99%), respectively. People under 40 years old represent a small fraction of most severe COVID-19 cases in Europe. These results may help health authorities respond to public concerns and guide future physical distancing and mitigation strategies. Specific measures to protect older people should be considered.
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http://dx.doi.org/10.3389/fmed.2020.560685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840596PMC
January 2021

Gastrointestinal Symptoms Followed by Shock in a Febrile 7-Year-Old Child during the COVID-19 Pandemic.

Clin Chem 2021 01;67(1):54-58

Department of General Pediatrics and Pediatric Infectious Diseases, Necker-Enfants-Malades University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Université de Paris, Paris, France.

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http://dx.doi.org/10.1093/clinchem/hvaa279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929030PMC
January 2021

Distinctive Features of Kawasaki Disease Following SARS-CoV-2 Infection: a Controlled Study in Paris, France.

J Clin Immunol 2021 04 4;41(3):526-535. Epub 2021 Jan 4.

Department of General Pediatrics and Pediatric Infectious Diseases, Necker-Enfants Malades University Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Necker Hospital for Sick Children, Université de Paris, 75015, Paris, France.

Background: An outbreak of multisystem inflammatory syndrome in children, including Kawasaki disease (KD), emerged during COVID-19 pandemic. We explored whether Kawasaki-like disease (KD), when associated with confirmed SARS-CoV-2 infection, has specific characteristics.

Methods: We included children and adolescents with KD criteria admitted in the department of general pediatrics of a university hospital in Paris, France, between January 1, 2018, and May 26, 2020. The incidence of KD was compared between the outbreak and a pre-outbreak control period (January 1, 2018, to April 25). Characteristics of patients with positive SARS-CoV-2 testing (KD-SARS-CoV-2) were compared to those of the pre-outbreak period (classic KD).

Results: A total of 30 and 59 children with KD were admitted during the outbreak and pre-outbreak periods, respectively (incidence ratio 13.2 [8.3-21.0]). During the outbreak, 23/30 (77%) children were diagnosed as KD-SARS-CoV-2. When compared with patients with classic KD, those with KD-SARS-CoV-2 were more frequently of sub-Saharan African ancestry (OR 4.4 [1.6-12.6]) and older (median 8.2 vs. 4.0 years, p < 0.001), had more often initial gastrointestinal (OR 84 [4.9-1456]) and neurological (OR 7.3 [1.9-27.7] manifestations, and shock syndrome (OR 13.7 [4.2-45.1]). They had significantly higher CRP and ferritin levels. Noticeably, they had more frequently myocarditis (OR 387 [38-3933]).

Conclusions: Children and adolescents with KD-SARS-CoV-2 have specific features when compared with those with classic KD. These findings should raise awareness and facilitate the study of their pathogenesis.
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http://dx.doi.org/10.1007/s10875-020-00941-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780601PMC
April 2021

Stewardship program on carbapenem prescriptions in a tertiary hospital for adults and children in France: a cohort study.

Eur J Clin Microbiol Infect Dis 2021 May 3;40(5):1039-1048. Epub 2021 Jan 3.

Department of General Paediatrics and Paediatric Infectious Diseases, Hôpital Necker-Enfants Malades, APHP, Université de Paris, 149 rue de Sèvres, 75015, Paris, France.

Antimicrobial stewardship programs aim at reducing the overuse of broad-spectrum antibiotics such as carbapenems, but their impact remains unclear. We compared the use of carbapenems between paediatric and adult subjects admitted to a French tertiary hospital and described the intervention of an antibiotic stewardship team (AST). As part of AST routine activity, all adult and paediatric patients receiving carbapenems are identified in real time using a computer-generated alert system and reviewed by the AST. Data associated with carbapenem prescriptions were extracted for 2 years (2014-2015) and were compared between paediatric and adult wards. Prescription appropriateness (i.e. no clinically suitable narrower spectrum alternative to carbapenem for de-escalation) and AST intervention were analysed. In total, 775 carbapenem prescriptions for 291 children and 262 adults were included. Most patients (95%) had a comordity and 52% had known recent carriage of extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBLE). Most carbapenem prescriptions came from intensive care units (n = 269, 35%) and were initiated for urinary tract (n = 200, 27%), sepsis (n = 181, 25%), and lung (n = 153, 21%) infections. Carbapenems were initiated empirically in 537 (70%) cases, and an organism was isolated in 523 (67%) cases. Among the isolated organisms, 47% (n = 246) were ESBLE and 90% (n = 468) were susceptible to carbapenems, but an alternative existed in 61% (n = 320) of cases according to antibiotic susceptibility testing. Among prescriptions reviewed by the AST, 39% (n = 255) were considered non-appropriate and led to either antibiotic discontinuation (n = 47, 7%) or de-escalation (n = 208, 32%). Non-appropriate prescriptions were more frequent in paediatric wards (p = 0.01) and in microbiologically documented infections (p = 0.013), and less observed in immunocompromised patients (p = 0.009) or with a known ESBLE carriage (p < 0.001). Tailored stewardship programs are essential to better control carbapenem use and subsequent antimicrobial resistance.
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http://dx.doi.org/10.1007/s10096-020-04103-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778866PMC
May 2021

Stewardship program on carbapenem prescriptions in a tertiary hospital for adults and children in France: a cohort study.

Eur J Clin Microbiol Infect Dis 2021 May 3;40(5):1039-1048. Epub 2021 Jan 3.

Department of General Paediatrics and Paediatric Infectious Diseases, Hôpital Necker-Enfants Malades, APHP, Université de Paris, 149 rue de Sèvres, 75015, Paris, France.

Antimicrobial stewardship programs aim at reducing the overuse of broad-spectrum antibiotics such as carbapenems, but their impact remains unclear. We compared the use of carbapenems between paediatric and adult subjects admitted to a French tertiary hospital and described the intervention of an antibiotic stewardship team (AST). As part of AST routine activity, all adult and paediatric patients receiving carbapenems are identified in real time using a computer-generated alert system and reviewed by the AST. Data associated with carbapenem prescriptions were extracted for 2 years (2014-2015) and were compared between paediatric and adult wards. Prescription appropriateness (i.e. no clinically suitable narrower spectrum alternative to carbapenem for de-escalation) and AST intervention were analysed. In total, 775 carbapenem prescriptions for 291 children and 262 adults were included. Most patients (95%) had a comordity and 52% had known recent carriage of extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBLE). Most carbapenem prescriptions came from intensive care units (n = 269, 35%) and were initiated for urinary tract (n = 200, 27%), sepsis (n = 181, 25%), and lung (n = 153, 21%) infections. Carbapenems were initiated empirically in 537 (70%) cases, and an organism was isolated in 523 (67%) cases. Among the isolated organisms, 47% (n = 246) were ESBLE and 90% (n = 468) were susceptible to carbapenems, but an alternative existed in 61% (n = 320) of cases according to antibiotic susceptibility testing. Among prescriptions reviewed by the AST, 39% (n = 255) were considered non-appropriate and led to either antibiotic discontinuation (n = 47, 7%) or de-escalation (n = 208, 32%). Non-appropriate prescriptions were more frequent in paediatric wards (p = 0.01) and in microbiologically documented infections (p = 0.013), and less observed in immunocompromised patients (p = 0.009) or with a known ESBLE carriage (p < 0.001). Tailored stewardship programs are essential to better control carbapenem use and subsequent antimicrobial resistance.
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http://dx.doi.org/10.1007/s10096-020-04103-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778866PMC
May 2021

Association between SARS-CoV-2 infection and Kawasaki-like multisystem inflammatory syndrome: a retrospective matched case-control study, Paris, France, April to May 2020.

Euro Surveill 2020 12;25(48)

Université de Paris, Centre of Research in Epidemiology and Statistics - CRESS, INSERM, F-75004 Paris, France.

We assessed the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and Kawasaki disease (KD)-like multisystem inflammatory syndrome in a retrospective case-control study in France. RT-PCR and serological tests revealed SARS-CoV-2 infection in 17/23 cases vs 11/102 controls (matched odds ratio: 26.4; 95% confidence interval: 6.0-116.9), indicating strong association between SARS-CoV-2 infection and KD-like illness. Clinicians should keep a high level of suspicion for KD-like illness during the COVID-19 pandemic.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.48.2001813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716402PMC
December 2020

YEARS Algorithm Versus Wells' Score: Incomplete Reporting Undermines Study Quality Assessment-Part 2.

Crit Care Med 2020 12;48(12):e1377-e1378

Department of Respiratory Medicine, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, the Netherlands.

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http://dx.doi.org/10.1097/CCM.0000000000004608DOI Listing
December 2020

Thoracic imaging tests for the diagnosis of COVID-19.

Cochrane Database Syst Rev 2020 11 26;11:CD013639. Epub 2020 Nov 26.

NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK.

Background: The respiratory illness caused by SARS-CoV-2 infection continues to present diagnostic challenges. Early research showed thoracic (chest) imaging to be sensitive but not specific in the diagnosis of coronavirus disease 2019 (COVID-19). However, this is a rapidly developing field and these findings need to be re-evaluated in the light of new research. This is the first update of this 'living systematic review'. This update focuses on people suspected of having COVID-19 and excludes studies with only confirmed COVID-19 participants.

Objectives: To evaluate the diagnostic accuracy of thoracic imaging (computed tomography (CT), X-ray and ultrasound) in people with suspected COVID-19.

Search Methods: We searched the COVID-19 Living Evidence Database from the University of Bern, the Cochrane COVID-19 Study Register, The Stephen B. Thacker CDC Library, and repositories of COVID-19 publications through to 22 June 2020. We did not apply any language restrictions.

Selection Criteria: We included studies of all designs that recruited participants of any age group suspected to have COVID-19, and which reported estimates of test accuracy, or provided data from which estimates could be computed. When studies used a variety of reference standards, we retained the classification of participants as COVID-19 positive or negative as used in the study.

Data Collection And Analysis: We screened studies, extracted data, and assessed the risk of bias and applicability concerns using the QUADAS-2 domain-list independently, in duplicate. We categorised included studies into three groups based on classification of index test results: studies that reported specific criteria for index test positivity (group 1); studies that did not report specific criteria, but had the test reader(s) explicitly classify the imaging test result as either COVID-19 positive or negative (group 2); and studies that reported an overview of index test findings, without explicitly classifying the imaging test as either COVID-19 positive or negative (group 3). We presented the results of estimated sensitivity and specificity using paired forest plots, and summarised in tables. We used a bivariate meta-analysis model where appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs).

Main Results: We included 34 studies: 30 were cross-sectional studies with 8491 participants suspected of COVID-19, of which 4575 (54%) had a final diagnosis of COVID-19; four were case-control studies with 848 cases and controls in total, of which 464 (55%) had a final diagnosis of COVID-19. Chest CT was evaluated in 31 studies (8014 participants, 4224 (53%) cases), chest X-ray in three studies (1243 participants, 784 (63%) cases), and ultrasound of the lungs in one study (100 participants, 31 (31%) cases). Twenty-six per cent (9/34) of all studies were available only as preprints. Nineteen studies were conducted in Asia, 10 in Europe, four in North America and one in Australia. Sixteen studies included only adults, 15 studies included both adults and children and one included only children. Two studies did not report the ages of participants. Twenty-four studies included inpatients, four studies included outpatients, while the remaining six studies were conducted in unclear settings. The majority of included studies had a high or unclear risk of bias with respect to participant selection, index test, reference standard, and participant flow. For chest CT in suspected COVID-19 participants (31 studies, 8014 participants, 4224 (53%) cases) the sensitivity ranged from 57.4% to 100%, and specificity ranged from 0% to 96.0%. The pooled sensitivity of chest CT in suspected COVID-19 participants was 89.9% (95% CI 85.7 to 92.9) and the pooled specificity was 61.1% (95% CI 42.3 to 77.1). Sensitivity analyses showed that when the studies from China were excluded, the studies from other countries demonstrated higher specificity compared to the overall included studies. When studies that did not classify index tests as positive or negative for COVID-19 (group 3) were excluded, the remaining studies (groups 1 and 2) demonstrated higher specificity compared to the overall included studies. Sensitivity analyses limited to cross-sectional studies, or studies where at least two reverse transcriptase polymerase chain reaction (RT-PCR) tests were conducted if the first was negative, did not substantively alter the accuracy estimates. We did not identify publication status as a source of heterogeneity. For chest X-ray in suspected COVID-19 participants (3 studies, 1243 participants, 784 (63%) cases) the sensitivity ranged from 56.9% to 89.0% and specificity from 11.1% to 88.9%. The sensitivity and specificity of ultrasound of the lungs in suspected COVID-19 participants (1 study, 100 participants, 31 (31%) cases) were 96.8% and 62.3%, respectively. We could not perform a meta-analysis for chest X-ray or ultrasound due to the limited number of included studies.

Authors' Conclusions: Our findings indicate that chest CT is sensitive and moderately specific for the diagnosis of COVID-19 in suspected patients, meaning that CT may have limited capability in differentiating SARS-CoV-2 infection from other causes of respiratory illness. However, we are limited in our confidence in these results due to the poor study quality and the heterogeneity of included studies. Because of limited data, accuracy estimates of chest X-ray and ultrasound of the lungs for the diagnosis of suspected COVID-19 cases should be carefully interpreted. Future diagnostic accuracy studies should pre-define positive imaging findings, include direct comparisons of the various modalities of interest on the same participant population, and implement improved reporting practices. Planned updates of this review will aim to: increase precision around the accuracy estimates for chest CT (ideally with low risk of bias studies); obtain further data to inform accuracy of chest X-rays and ultrasound; and obtain data to further fulfil secondary objectives (e.g. 'threshold' effects, comparing accuracy estimates across different imaging modalities) to inform the utility of imaging along different diagnostic pathways.
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November 2020

Bone Scintigraphy After a Negative Radiological Skeletal Survey Improves the Detection Rate of Inflicted Skeletal Injury in Children.

Front Pediatr 2020 25;8:498. Epub 2020 Sep 25.

Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Epidemiology and Statistics Research Center, Université de Paris, INSERM, Paris, France.

Timely diagnosis of child physical abuse is of paramount importance. The added value of bone scintigraphy (BS) after a negative radiological skeletal survey (RSS) in children with suspected physical abuse has never been evaluated. The objective of this study was to assess the extent to which BS could improve the detection rate of skeletal injury in children with suspected physical abuse with an initial negative RSS. We used discharge codes to retrospectively identify children evaluated for suspected physical abuse in a university hospital (Nantes, France). We included all consecutive children younger than 3 years old who underwent both RSS and BS, with an interval of ≤96 h between tests, from 2013 to 2019. BS and RSS results were interpreted independently during the study period. We specifically analyzed BS results for children with a negative RSS to assess the value of BS as an add-on test. Among the 268 children ≤3 years old with suspected physical abuse who underwent RSS, 140 (52%) also underwent BS within 96 h and were included in the analysis. The median age was 6 months old (interquartile range: 3-8). The detection rate of ≥1 skeletal injury with RSS alone was 49% ( = 69/140, 95% CI: 41-58%) vs. 58% ( = 81/140, 50-66%) with RSS followed by add-on BS, for an absolute increase in the detection rate of 9% points (95% CI: 4-14%). The number of children with a negative RSS who would need to undergo BS to detect one additional child with ≥1 skeletal injury was 6 (95% CI: 4-11). In young children with suspected physical abuse with a negative RSS, add-on BS would allow for a clinically significant improvement in the detection rate of skeletal injuries for a limited number of BS procedures required. Prospective multicenter studies are needed to confirm these findings.
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http://dx.doi.org/10.3389/fped.2020.00498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545028PMC
September 2020

Add-on bone scintigraphy after negative radiological skeletal survey for the diagnosis of skeletal injury in children suspected of physical abuse: a systematic review and meta-analysis.

Arch Dis Child 2021 04 30;106(4):361-366. Epub 2020 Sep 30.

Obstetrical, Perinatal and Pediatric Epidemiology Research team, Epidemiology and Statistics Research Center, Université de Paris, INSERM, F-75004 Paris, France.

Objectives: To systematically assess the extent to which bone scintigraphy (BS) could improve the detection rate of skeletal injury in children suspected of physical abuse with an initial negative radiological skeletal survey (RSS).

Study Design: We searched MEDLINE and Web of Science for series of ≥20 children suspected of physical abuse who underwent RSS and add-on BS. We assessed the risk of bias and the heterogeneity and performed random-effects meta-analyses.

Results: After screening 1140 unique search results, we reviewed 51 full-text articles, and included 7 studies (783 children, mostly ≤3 years old). All studies were of either high or unclear risk of bias. Substantial heterogeneity was observed in meta-analyses. The summary detection rate of skeletal injury with RSS alone was 52% (95% CI 37 to 68). The summary absolute increase in detection rate with add-on BS was 10 percentage points (95% CI 6 to 15); the summary relative detection rate was 1.19 (95% CI 1.13 to 1.25); the summary number of children with a negative RSS who needed to undergo a BS to detect one additional child with skeletal injury (number needed to test) was 3 (95% CI 2 to 7).

Conclusions: From the available evidence, add-on BS in young children suspected of physical abuse with a negative RSS might allow for a clinically significant improvement of the detection rate of children with skeletal injury, for a limited number of BS procedures required. The quality of the reviewed evidence was low, pointing to the need for high-quality studies in this field.
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April 2021

Thoracic imaging tests for the diagnosis of COVID-19.

Cochrane Database Syst Rev 2020 09 30;9:CD013639. Epub 2020 Sep 30.

Department of Radiology, University of Ottawa, Ottawa, Canada.

Background: The diagnosis of infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents major challenges. Reverse transcriptase polymerase chain reaction (RT-PCR) testing is used to diagnose a current infection, but its utility as a reference standard is constrained by sampling errors, limited sensitivity (71% to 98%), and dependence on the timing of specimen collection. Chest imaging tests are being used in the diagnosis of COVID-19 disease, or when RT-PCR testing is unavailable.

Objectives: To determine the diagnostic accuracy of chest imaging (computed tomography (CT), X-ray and ultrasound) in people with suspected or confirmed COVID-19.

Search Methods: We searched the COVID-19 Living Evidence Database from the University of Bern, the Cochrane COVID-19 Study Register, and The Stephen B. Thacker CDC Library. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. We conducted searches for this review iteration up to 5 May 2020.

Selection Criteria: We included studies of all designs that produce estimates of test accuracy or provide data from which estimates can be computed. We included two types of cross-sectional designs: a) where all patients suspected of the target condition enter the study through the same route and b) where it is not clear up front who has and who does not have the target condition, or where the patients with the target condition are recruited in a different way or from a different population from the patients without the target condition. When studies used a variety of reference standards, we included all of them.

Data Collection And Analysis: We screened studies and extracted data independently, in duplicate. We also assessed the risk of bias and applicability concerns independently, in duplicate, using the QUADAS-2 checklist and presented the results of estimated sensitivity and specificity, using paired forest plots, and summarised in tables. We used a hierarchical meta-analysis model where appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs).

Main Results: We included 84 studies, falling into two categories: studies with participants with confirmed diagnoses of COVID-19 at the time of recruitment (71 studies with 6331 participants) and studies with participants suspected of COVID-19 (13 studies with 1948 participants, including three case-control studies with 549 cases and controls). Chest CT was evaluated in 78 studies (8105 participants), chest X-ray in nine studies (682 COVID-19 cases), and chest ultrasound in two studies (32 COVID-19 cases). All evaluations of chest X-ray and ultrasound were conducted in studies with confirmed diagnoses only. Twenty-five per cent (21/84) of all studies were available only as preprints, 15/71 studies in the confirmed cases group and 6/13 of the studies in the suspected group. Among 71 studies that included confirmed cases, 41 studies had included symptomatic cases only, 25 studies had included cases regardless of their symptoms, five studies had included asymptomatic cases only, three of which included a combination of confirmed and suspected cases. Seventy studies were conducted in Asia, 2 in Europe, 2 in North America and one in South America. Fifty-one studies included inpatients while the remaining 24 studies were conducted in mixed or unclear settings. Risk of bias was high in most studies, mainly due to concerns about selection of participants and applicability. Among the 13 studies that included suspected cases, nine studies were conducted in Asia, and one in Europe. Seven studies included inpatients while the remaining three studies were conducted in mixed or unclear settings. In studies that included confirmed cases the pooled sensitivity of chest CT was 93.1% (95%CI: 90.2 - 95.0 (65 studies, 5759 cases); and for X-ray 82.1% (95%CI: 62.5 to 92.7 (9 studies, 682 cases). Heterogeneity judged by visual assessment of the ROC plots was considerable. Two studies evaluated the diagnostic accuracy of point-of-care ultrasound and both reported zero false negatives (with 10 and 22 participants having undergone ultrasound, respectively). These studies only reported True Positive and False Negative data, therefore it was not possible to pool and derive estimates of specificity. In studies that included suspected cases, the pooled sensitivity of CT was 86.2% (95%CI: 71.9 to 93.8 (13 studies, 2346 participants) and specificity was 18.1% (95%CI: 3.71 to 55.8). Heterogeneity judged by visual assessment of the forest plots was high. Chest CT may give approximately the same proportion of positive results for patients with and without a SARS-CoV-2 infection: the chances of getting a positive CT result are 86% (95% CI: 72 to 94) in patient with a SARS-CoV-2 infection and 82% (95% CI: 44 to 96) in patients without.

Authors' Conclusions: The uncertainty resulting from the poor study quality and the heterogeneity of included studies limit our ability to confidently draw conclusions based on our results. Our findings indicate that chest CT is sensitive but not specific for the diagnosis of COVID-19 in suspected patients, meaning that CT may not be capable of differentiating SARS-CoV-2 infection from other causes of respiratory illness. This low specificity could also be the result of the poor sensitivity of the reference standard (RT-PCR), as CT could potentially be more sensitive than RT-PCR in some cases. Because of limited data, accuracy estimates of chest X-ray and ultrasound of the lungs for the diagnosis of COVID-19 should be carefully interpreted. Future diagnostic accuracy studies should avoid cases-only studies and pre-define positive imaging findings. Planned updates of this review will aim to: increase precision around the accuracy estimates for CT (ideally with low risk of bias studies); obtain further data to inform accuracy of chest X rays and ultrasound; and continue to search for studies that fulfil secondary objectives to inform the utility of imaging along different diagnostic pathways.
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http://dx.doi.org/10.1002/14651858.CD013639.pub2DOI Listing
September 2020

Cryptococcal Antigen in Serum and Cerebrospinal Fluid for Detecting Cryptococcal Meningitis in Adults Living With Human Immunodeficiency Virus: Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies.

Clin Infect Dis 2021 04;72(7):1268-1278

Institut Pasteur, Centre National de la Recherche Scientifique, Molecular Mycology Unit Unite Mixte de Recherche 2000, Paris, France.

Cryptococcal antigen (CrAg) detection could direct the timely initiation of antifungal therapy. We searched MEDLINE and Embase for studies where CrAg detection in serum/cerebrospinal fluid (CSF) and CSF fungal culture were done on adults living with human immunodeficiency virus (HIV) who had suspected cryptococcal meningitis (CM). With Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), we evaluated the risk of bias in 11 included studies with 3600 participants, and used a random-effects meta-analysis to obtain summary sensitivity and specificity of serum and CSF CrAg, as well as agreement between CSF CrAg and CSF culture. Summary sensitivity and specificity of serum CrAg were 99.7% (97.4-100) and 94.1% (88.3-98.1), respectively, and summary sensitivity and specificity of CSF CrAg were 98.8% (96.2-99.6) and 99.3% (96.7-99.9), respectively. Agreement between CSF CrAg and CSF culture was 98% (97-99). In adults living with HIV who have CM symptoms, serum CrAg negativity may rule out CM, while positivity should prompt induction antifungal therapy if lumbar puncture is not feasible. In a first episode of CM, CSF CrAg positivity is diagnostic.
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http://dx.doi.org/10.1093/cid/ciaa1243DOI Listing
April 2021

YEARS Algorithm Versus Wells' Score: Incomplete Reporting Undermines Study Quality Assessment.

Crit Care Med 2020 08;48(8):e730

Department of Respiratory Medicine, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands, and Department of Respiratory Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.

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http://dx.doi.org/10.1097/CCM.0000000000004369DOI Listing
August 2020

Voriconazole topical cream formulation: evidence for stability and antifungal activity.

Int J Antimicrob Agents 2020 Sep 10;56(3):106083. Epub 2020 Jul 10.

Department of Pharmacy, Necker - Enfants Malades Hospital, AP-HP, Paris, France. Electronic address:

Systemic use of voriconazole (VCZ) might be restricted by adverse events, such as hepatotoxicity and neurotoxicity, or drug-drug interactions. Topical VCZ application to skin may help to treat local infection more effectively and limit unwanted whole-body exposure. Topical VCZ cream was stable for 90 days when refrigerated. A patient with cutaneous Fusarium solani infection on his right forearm was successfully treated with topical 1% VCZ cream after failure of oral VCZ treatment.
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http://dx.doi.org/10.1016/j.ijantimicag.2020.106083DOI Listing
September 2020

Efficacy and safety of rapid tests to guide antibiotic prescriptions for sore throat.

Cochrane Database Syst Rev 2020 06 4;6:CD012431. Epub 2020 Jun 4.

Department of General Pediatrics and Pediatric Infectious Diseases, AP-HP, Hôpital Necker, Paris, France.

Background: Sore throat is a common condition caused by viruses or bacteria, and is a leading cause of antibiotic prescription in primary care. The most common bacterial species is group A streptococcus ('strep throat'). Between 50% to 70% of pharyngitis cases are treated with antibiotics, despite the majority of cases being viral in origin. One strategy to reduce antibiotics is to use rapid tests for group A streptococcus to guide antibiotic prescriptions. Rapid tests can be used alone or in combination with a clinical scoring system.

Objectives: To assess the efficacy and safety of strategies based on rapid tests to guide antibiotic prescriptions for sore throat in primary care settings.

Search Methods: We searched CENTRAL, MEDLINE, Embase, CINAHL, Web of Science, and LILACS, as well as the trial registries ClinicalTrials.gov and the WHO ICTRP on 5 June 2019.

Selection Criteria: We included randomised controlled trials (RCTs) comparing rapid tests with management based on clinical grounds to guide the prescription of antibiotics for people with a sore throat in ambulatory care settings. We included trials that randomised individuals, as well as cluster-RCTs in which individual practitioners (or practices) or emergency departments were randomised.

Data Collection And Analysis: Two review authors independently extracted data on the primary outcomes (number of participants provided with an antibiotic prescription; number of participants with an antibiotic dispensed) and secondary outcomes (duration of sore throat symptoms; duration of other symptoms; quality of life measures; number of participants with a complication attributed to the index infection; number of participants in need of re-consultation by the end of follow-up; number of participants in need of hospital admission by the end of follow-up; number of satisfied participants; number of participants with an adverse event attributed to the rapid test). We assessed the risk of bias of all included trials and used GRADE to assess the certainty of the evidence. We performed meta-analyses and sensitivity analyses when feasible.

Main Results: We included five trials (2891 children and adult participants in total; 2545 participants after adjusting for clustering). Management in the intervention group was as follows: in three trials rapid tests were used in combination with a clinical scoring system; in one trial, some physicians were asked to use rapid tests alone, while others were asked to use rapid tests in combination with a clinical scoring system; in one trial, rapid tests were used alone. Based on data from five trials (2545 participants), a large reduction in prescribed antibiotics was found in the rapid test group (481/1197) versus management based on clinical grounds (865/1348), for a summary risk difference (RD) of -25%, 95% confidence interval (CI) -31% to -18%; I = 62%; moderate-certainty evidence. Estimates of effect on antibiotic prescription rates were stable in various sensitivity analyses. Based on data from two trials (900 people) originating from the same overarching study, the evidence suggests that rapid tests may not reduce dispensed antibiotic treatments: rapid test group (156/445) versus management based on clinical grounds (197/455); summary RD -7%, 95% CI -17% to 2%; I = 53%; low-certainty evidence. Four trials (2075 participants) reported data on the number of participants with a complication attributed to the index infection; the summary odds ratio (OR) was 0.85, 95% CI 0.03 to 26.65; P = 0.93; I = 62%; very low-certainty evidence, which means that people in the rapid testing group were less likely to develop complications of the index infection, but the evidence is very uncertain. Two trials (1161 participants) reported on the number of participants in need of re-consultation by the end of follow-up; the summary OR was 1.12, 95% CI 0.57 to 2.21; P = 0.74; I = 59%; low-certainty evidence, which means that participants in the rapid testing group were more likely to be in need of re-consultation by the end of the study follow-up, but the evidence is uncertain. Lack of data impeded assessment of other secondary outcomes (including safety outcomes) and of sources of heterogeneity.  AUTHORS' CONCLUSIONS: Rapid testing to guide antibiotic treatment for sore throat in primary care probably reduces antibiotic prescription rates by 25% (absolute risk difference), but may have little or no impact on antibiotic dispensing. More studies are needed to assess the efficacy and safety of rapid test-guided antibiotic prescribing, notably to evaluate patient-centred outcomes and variability across subgroups (e.g. adults versus children).
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http://dx.doi.org/10.1002/14651858.CD012431.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271976PMC
June 2020

Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study.

BMJ 2020 06 3;369:m2094. Epub 2020 Jun 3.

Department of General Paediatrics and Paediatric Infectious Diseases, Necker-Enfants Malades University Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Université de Paris, 149 rue de Sèvres, 75015 Paris, France.

Objectives: To describe the characteristics of children and adolescents affected by an outbreak of Kawasaki-like multisystem inflammatory syndrome and to evaluate a potential temporal association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Design: Prospective observational study.

Setting: General paediatric department of a university hospital in Paris, France.

Participants: 21 children and adolescents (aged ≤18 years) with features of Kawasaki disease who were admitted to hospital between 27 April and 11 May 2020 and followed up until discharge by 15 May 2020.

Main Outcome Measures: The primary outcomes were clinical and biological data, imaging and echocardiographic findings, treatment, and outcomes. Nasopharyngeal swabs were prospectively tested for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) and blood samples were tested for IgG antibodies to the virus.

Results: 21 children and adolescents (median age 7.9 (range 3.7-16.6) years) were admitted with features of Kawasaki disease over a 15 day period, with 12 (57%) of African ancestry. 12 (57%) presented with Kawasaki disease shock syndrome and 16 (76%) with myocarditis. 17 (81%) required intensive care support. All 21 patients had noticeable gastrointestinal symptoms during the early stage of illness and high levels of inflammatory markers. 19 (90%) had evidence of recent SARS-CoV-2 infection (positive RT-PCR result in 8/21, positive IgG antibody detection in 19/21). All 21 patients received intravenous immunoglobulin and 10 (48%) also received corticosteroids. The clinical outcome was favourable in all patients. Moderate coronary artery dilations were detected in 5 (24%) of the patients during hospital stay. By 15 May 2020, after 8 (5-17) days of hospital stay, all patients were discharged home.

Conclusions: The ongoing outbreak of Kawasaki-like multisystem inflammatory syndrome among children and adolescents in the Paris area might be related to SARS-CoV-2. In this study an unusually high proportion of the affected children and adolescents had gastrointestinal symptoms, Kawasaki disease shock syndrome, and were of African ancestry.
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http://dx.doi.org/10.1136/bmj.m2094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500538PMC
June 2020

Community antibiotic prescribing for children in France from 2015 to 2017: a cross-sectional national study.

J Antimicrob Chemother 2020 08;75(8):2344-2352

Université de Paris, Epidemiology and Statistics Research Center - CRESS, INSERM, Obstetrical, Perinatal and Pediatric Epidemiology research team, F-75004 Paris, France.

Objectives: To assess recent community antibiotic prescribing for French children and identify areas of potential improvement.

Methods: We analysed 221 768 paediatric (<15 years) visits in a national sample of 680 French GPs and 70 community paediatricians (IQVIA's EPPM database), from March 2015 to February 2017, excluding well-child visits. We calculated antibiotic prescription rates per 100 visits, separately for GPs and paediatricians. For respiratory tract infections (RTIs), we described broad-spectrum antibiotic use and duration of treatment. We used Poisson regression to identify factors associated with antibiotic prescribing.

Results: GPs prescribed more antibiotics than paediatricians [prescription rate 26.1 (95% CI 25.9-26.3) versus 21.6 (95% CI 21.0-22.2) per 100 visits, respectively; P < 0.0001]. RTIs accounted for more than 80% of antibiotic prescriptions, with presumed viral RTIs being responsible for 40.8% and 23.6% of all antibiotic prescriptions by GPs and paediatricians, respectively. For RTIs, antibiotic prescription rates per 100 visits were: otitis, 68.1 and 79.8; pharyngitis, 67.3 and 53.3; sinusitis, 67.9 and 77.3; pneumonia, 80.0 and 99.2; bronchitis, 65.2 and 47.3; common cold, 21.7 and 11.6; bronchiolitis 31.6 and 20.1; and other presumed viral RTIs, 24.1 and 11.0, for GPs and paediatricians, respectively. For RTIs, GPs prescribed more broad-spectrum antibiotics [49.8% (95% CI 49.3-50.3) versus 35.6% (95% CI 34.1-37.1), P < 0.0001] and antibiotic courses of similar duration (P = 0.21). After adjustment for diagnosis, antibiotic prescription rates were not associated with season and patient age, but were significantly higher among GPs aged ≥50 years.

Conclusions: Future antibiotic stewardship campaigns should target presumed viral RTIs, broad-spectrum antibiotic use and GPs aged ≥50 years.
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http://dx.doi.org/10.1093/jac/dkaa162DOI Listing
August 2020

Reporting guidelines for journal and conference abstracts.

J Clin Epidemiol 2020 08 18;124:186-192. Epub 2020 Apr 18.

Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

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http://dx.doi.org/10.1016/j.jclinepi.2020.04.012DOI Listing
August 2020

Serum (1 → 3)-β-D-glucan could be useful to rule out invasive candidiasis in neonates with an adapted cut-off.

Acta Paediatr 2021 01 22;110(1):79-84. Epub 2020 May 22.

Clinical Investigation Center (CIC004), University Hospital of Nantes, Nantes, France.

Aim: We assessed the diagnostic accuracy of serum (1 → 3)-β-D-glucan (BDG) for neonatal invasive candidiasis (NIC) using the recommended cut-off usually used in adults for detecting invasive candidiasis and searched for an optimal cut-off for ruling out NIC.

Methods: We conducted a prospective cross-sectional study at Nantes University medical centre from January 2017 to July 2018. All consecutive newborn infants of less than 28 days of corrected age, with clinically suspected NIC, who underwent BDG assay, were included. Sensitivity and specificity were calculated by using the recommended cut-off of 80 pg/mL. Receiver operating characteristic curve analysis was used to identify an optimal cut-off value.

Results: We included 55 newborn infants with 61 episodes of suspected NIC. Their median gestational and chronological ages were 28.0 weeks (interquartile range [IQR] 26.4-34.1) and 10.0 days (IQR 6.0-22.0), respectively. Of 61 episodes, seven revealed NIC. Sensitivity and specificity were 85.7% (95% confidence interval [CI] 42.1%-99.6%) and 51.9% (37.8%-65.7%) with the recommended cut-off, respectively. An optimal cut-off of 174 pg/mL offered the same sensitivity but higher specificity 77.8% (64.4%-88.0%).

Conclusion: The recommended cut-off of 80 pg/mL was probably too low for ruling out NIC. A higher cut-off might have been more appropriate.
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http://dx.doi.org/10.1111/apa.15321DOI Listing
January 2021

Searching practices and inclusion of unpublished studies in systematic reviews of diagnostic accuracy.

Res Synth Methods 2020 May 5;11(3):343-353. Epub 2020 Feb 5.

Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, the Netherlands.

Introduction: Many diagnostic accuracy studies are never reported in full in a peer-reviewed journal. Searching for unpublished studies may avoid bias due to selective publication, enrich the power of systematic reviews, and thereby help to reduce research waste. We assessed searching practices among recent systematic reviews of diagnostic accuracy.

Methods: We extracted data from 100 non-Cochrane systematic reviews of diagnostic accuracy indexed in MEDLINE and published between October 2017 and January 2018 and from all 100 Cochrane systematic reviews of diagnostic accuracy published by December 2018, irrespective of whether meta-analysis had been performed.

Results: Non-Cochrane and Cochrane reviews searched a median of 4 (IQR 3-5) and 6 (IQR 5-9) databases, respectively; most often MEDLINE/PubMed (n = 100 and n = 100) and EMBASE (n = 81 and n = 100). Additional efforts to identify studies beyond searching bibliographic databases were performed in 76 and 98 reviews, most often through screening reference lists (n = 71 and n = 96), review/guideline articles (n = 18 and n = 52), or citing articles (n = 3 and n = 42). Specific sources of unpublished studies were searched in 22 and 68 reviews, for example, conference proceedings (n = 4 and n = 18), databases only containing conference abstracts (n = 2 and n = 33), or trial registries (n = 12 and n = 39). At least one unpublished study was included in 17 and 23 reviews. Overall, 39 of 2082 studies (1.9%) included in non-Cochrane reviews were unpublished, and 64 of 2780 studies (2.3%) in Cochrane reviews, most often conference abstracts (97/103).

Conclusion: Searching practices vary considerably across systematic reviews of diagnostic accuracy. Unpublished studies are a minimal fraction of the evidence included in recent reviews.
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http://dx.doi.org/10.1002/jrsm.1389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317757PMC
May 2020
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