On Dec 31, 2019, China reported a cluster of cases of pneumonia in people at Wuhan, Hubei Province. The responsible pathogen is a novel coronavirus, named severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2). We report the relevant features of the first cases in Europe of confirmed infection, named coronavirus disease 2019 (COVID-19), with the first patient diagnosed with the disease on Jan 24, 2020.
In this case series, we followed five patients admitted to Bichat-Claude Bernard University Hospital (Paris, France) and Pellegrin University Hospital (Bordeaux, France) and diagnosed with COVID-19 by semi-quantitative RT-PCR on nasopharyngeal swabs. We assessed patterns of clinical disease and viral load from different samples (nasopharyngeal and blood, urine, and stool samples), which were obtained once daily for 3 days from hospital admission, and once every 2 or 3 days until patient discharge. All samples were refrigerated and shipped to laboratories in the National Reference Center for Respiratory Viruses (The Institut Pasteur, Paris, and Hospices Civils de Lyon, Lyon, France), where RNA extraction, real-time RT-PCR, and virus isolation and titration procedures were done.
The patients were three men (aged 31 years, 48 years, and 80 years) and two women (aged 30 years and 46 years), all of Chinese origin, who had travelled to France from China around mid-January, 2020. Three different clinical evolutions are described: (1) two paucisymptomatic women diagnosed within a day of exhibiting symptoms, with high nasopharyngeal titres of SARS-CoV-2 within the first 24 h of the illness onset (5·2 and 7·4 log10 copies per 1000 cells, respectively) and viral RNA detection in stools; (2) a two-step disease progression in two young men, with a secondary worsening around 10 days after disease onset despite a decreasing viral load in nasopharyngeal samples; and (3) an 80-year-old man with a rapid evolution towards multiple organ failure and a persistent high viral load in lower and upper respiratory tract with systemic virus dissemination and virus detection in plasma. The 80-year-old patient died on day 14 of illness (Feb 14, 2020); all other patients had recovered and been discharged by Feb 19, 2020.
We illustrated three different clinical and biological types of evolution in five patients infected with SARS-CoV-2 with detailed and comprehensive viral sampling strategy. We believe that these findings will contribute to a better understanding of the natural history of the disease and will contribute to advances in the implementation of more efficient infection control strategies.
REACTing (Research & Action Emerging Infectious Diseases).
Health-care workers are crucial to any health-care system. During the ongoing COVID-19 pandemic, health-care workers are at a substantially increased risk of becoming infected with severe acute ...respiratory syndrome coronavirus 2 (SARS-CoV-2) and could come to considerable harm as a result. Depending on the phase of the pandemic, patients with COVID-19 might not be the main source of SARS-CoV-2 infection and health-care workers could be exposed to atypical patients, infected family members, contacts, and colleagues, or live in communities of active transmission. Clear strategies to support and appropriately manage exposed and infected health-care workers are essential to ensure effective staff management and to engender trust in the workplace. These management strategies should focus on risk stratification, suitable clinical monitoring, low-threshold access to diagnostics, and decision making about removal from and return to work. Policy makers need to support health-care facilities in interpreting guidance during a pandemic that will probably be characterised by fluctuating local incidence of SARS-CoV-2 to mitigate the impact of this pandemic on their workforce.
In a phase 1 clinical study, coadministration of the adsorbent-based DAV132 product together with the fluoroquinolone antibiotic moxifloxacin, while not affecting the plasma concentrations of the ...antibiotic, reduced by >99% exposure of the intestinal microbiota to the moxifloxacin.
Abstract
Background
Antibiotics are life-saving drugs but severely affect the gut microbiome with short-term consequences including diarrhea and selection of antibiotic-resistant bacteria. Long-term links to allergy and obesity are also suggested. We devised a product, DAV132, and previously showed its ability to deliver a powerful adsorbent, activated charcoal, in the late ileum of human volunteers.
Methods
We performed a randomized controlled trial in 28 human volunteers treated with a 5-day clinical regimen of the fluoroquinolone antibiotic moxifloxacin in 2 parallel groups, with or without DAV132 coadministration. Two control goups of 8 volunteers each receiving DAV132 alone, or a nonactive substitute, were added.
Results
The coadministration of DAV132 decreased free moxifloxacin fecal concentrations by 99%, while plasmatic levels were unaffected. Shotgun quantitative metagenomics showed that the richness and composition of the intestinal microbiota were largely preserved in subjects co-treated with DAV132 in addition to moxifloxacin. No adverse effect was observed. In addition, DAV132 efficiently adsorbed a wide range of clinically relevant antibiotics ex vivo.
Conclusions
DAV132 was highly effective to protect the gut microbiome of moxifloxacin-treated healthy volunteers and may constitute a clinical breakthrough by preventing adverse health consequences of a wide range of antibiotic treatments.
Clinical Trials Registration
NCT02176005.
To evaluate the efficacy and safety of cetuximab, a monoclonal antibody that inhibits the epidermal growth factor receptor (EGFR), as a first-line monotherapy in patients with unresectable squamous ...cell carcinoma of the skin (SCCS).
Thirty-six patients received cetuximab (initial dose of 400 mg/m(2) followed by subsequent weekly doses of 250 mg/m(2)) for at least 6 weeks with a 48-week follow-up. The primary end point was the disease control rate (DCR) at 6 weeks (according to Response Evaluation Criteria in Solid Tumors RECIST criteria). Secondary end points included best response rate, overall survival, progression-free survival (PFS), and toxicity assessment. Association of treatment efficacy with RAS mutations or FcγR genotypes was investigated.
Median age of the study population was 79 years. DCR at 6 weeks was obtained in 25 of 36 patients (69%; 95% CI, 52% to 84%) of the intention-to-treat population. The best responses were eight partial responses and two complete responses. There were no cetuximab-related deaths. There were three related serious adverse events: two grade 4 infusion reactions and one grade 3 interstitial pneumopathy. Grade 1 to 2 acne-like rash occurred in 78% of patients and was associated with prolonged PFS. One HRAS mutation was identified. Combined FcγRIIa-131H/H and/or FcγRIIIa-158V/V polymorphisms were not associated with the clinical outcomes.
As a first-line treatment in patients with unresectable SCCS, cetuximab achieved 69% DCR. A randomized phase III trial is warranted to confirm that cetuximab may be considered as a therapeutic option especially in elderly patients. The low frequency of RAS mutations in SCCS makes SCCS tumors attractive for EGFR inhibition.
Abstract
Background
Although bacterial infections are frequent during pregnancy, the prescription of antibiotics to pregnant women represents a challenge for physicians, driven by the benefit–risk ...balance.
Objectives
To assess the extent of prenatal antibiotic exposure and its associated factors.
Methods
This study included pregnancies in the National Mother-Child EPI-MERES Register 2010–19 (built from the French Healthcare Data System) regardless of outcome. Antibiotic exposure was defined as having at least one antibiotic prescription filled during pregnancy. The prevalence of pregnancies exposed to antibiotics was estimated. Univariable Poisson regression with generalized estimating equations was used to compare the number of antibiotic prescriptions filled during pregnancy and the period after pregnancy with the period 1 year before pregnancy. Multivariable Poisson regression was used to investigate factors associated with antibiotic exposure during pregnancy.
Results
Among 9 769 764 pregnancies, 3 501 294 (35.8%) were exposed to antibiotics and amoxicillin was the most common. Compared with a similar period 1 year before pregnancy, the number of filled antibiotic prescriptions was lower during pregnancy incidence rate ratio (IRR) 0.903 (95% CI 0.902–0.905) and during the period 1 year after pregnancy IRR 0.880 (95% CI 0.879–0.881). Region of residence, deprivation index, smoking-related conditions and chronic diseases (especially chronic respiratory diseases) were associated with antibiotic exposure during pregnancy.
Conclusions
Antibiotic prescriptions are filled less frequently during pregnancy than during the preceding year. This may be due to a more relevant benefit–risk assessment. Pregnant women living with social deprivation, those with smoking-related conditions and those with chronic diseases are more likely to fill antibiotic prescriptions.
Background. Observational studies showed that the profile of infective endocarditis (IE) significantly changed over the past decades. However, most studies involved referral centers. We conducted a ...population-based study to control for this referral bias. The objective was to update the description of characteristics of IE in France and to compare the profile of community-acquired versus healthcare-associated IE. Methods. A prospective population-based observational study conducted in all medical facilities from 7 French regions (32% of French individuals aged ≥18 years) identified 497 adults with Duke-Li—definite IE who were first admitted to the hospital in 2008. Main measures included age-standardized and sex-standardized incidence of IE and multivariate Cox regression analysis for risk factors of in-hospital death. Results. The age-standardized and sex-standardized annual incidence of IE was 33.8 (95% confidence interval CI, 30.8-36.9) cases per million inhabitants. The incidence was highest in men aged 75-79 years. A majority of patients had no previously known heart disease. Staphylococci were the most common causal agents, accounting for 36.2% of cases (Staphylococcus aureus, 26.6%; coagulase-negative staphylococci, 9.7%). Healthcare-associated IE represented 26.7% of all cases and exhibited a clinical pattern significantly different from that of community-acquired IE. S. aureus as the causal agent of IE was the most important factor associated with in-hospital death in community-acquired IE (hazard ratio HR, 2.82 95% CI, 1.72-4.61) and the single factor in healthcare-associated IE (HR, 2.54 95% CI, 1.33-4.85). Conclusions. S. aureus became both the leading cause and the most important prognostic factor of IE, and healthcare-associated IE appeared as a major subgroup of the disease.
Clinical decision making relative to community-acquired pneumonia (CAP) diagnosis is difficult. Chest radiograph is key in establishing parenchymal lung involvement. However, radiologic performance ...may lead to misdiagnosis, rendering questionable the use of chest computed tomography (CT) scan in patients with clinically suspected CAP.
To assess whether early multidetector chest CT scan affects diagnosis and management of patients visiting the emergency department with suspected CAP.
A total of 319 prospectively enrolled patients with clinically suspected CAP underwent multidetector chest CT scan within 4 hours. CAP diagnosis probability (definite, probable, possible, or excluded) and therapeutic plans (antibiotic initiation/discontinuation, hospitalization/discharge) were established by emergency physicians before and after CT scan results. The adjudication committee established the final CAP classification on Day 28.
Chest radiograph revealed a parenchymal infiltrate in 188 patients. CAP was initially classified as definite in 143 patients (44.8%), probable or possible in 172 (53.8%), and excluded in 4 (1.2%). CT scan revealed a parenchymal infiltrate in 40 (33%) of the patients without infiltrate on chest radiograph and excluded CAP in 56 (29.8%) of the 188 with parenchymal infiltrate on radiograph. CT scan modified classification in 187 (58.6%; 95% confidence interval, 53.2-64.0), leading to 50.8% definite CAP and 28.8% excluded CAP, and 80% of modifications were in accordance with adjudication committee classification. Because of CT scan, antibiotics were initiated in 51 (16%) and discontinued in 29 (9%), and hospitalization was decided in 22 and discharge in 23.
In CAP-suspected patients visiting the emergency unit, early CT scan findings complementary to chest radiograph markedly affect both diagnosis and clinical management. Clinical trial registered with www.clinicaltrials.gov (NCT 01574066).
Objective
Infective endocarditis (IE) mimics primary systemic vasculitis, and there are sporadic reports of positivity for antineutrophil cytoplasmic antibodies (ANCAs) among patients with IE. ...Because the frequency of ANCAs in IE is unknown, this study was undertaken to assess the seroprevalence of ANCAs in a large number of patients with IE.
Methods
The study was conducted in the framework of a single‐center prospective cohort study of incident IE cases. Demographic, clinical, laboratory, and microbiologic data were collected, and magnetic resonance imaging of the brain was performed at diagnosis. For those patients whose serum had been stored at diagnosis, ANCAs were assessed by indirect immunofluorescence assay in ethanol‐, formalin‐, and methanol‐fixed neutrophils. In addition, ANCA specificity for proteinase 3 (PR3) and myeloperoxidase (MPO) was assessed by enzyme‐linked immunosorbent assay. Rheumatoid factor (RF), antinuclear antibodies (ANAs), anticardiolipin antibodies (aCL), and serum Ig levels were also measured. Comparisons between groups were made using Wilcoxon's rank sum and chi‐square or Fisher's exact tests.
Results
Among 109 patients with IE, 18% had cytoplasmic ANCAs (cANCA) and/or perinuclear ANCAs (pANCA) and 8% had PR3‐ANCAs or MPO‐ANCAs, some with very high titers. Positivity for both cANCA or pANCA and PR3‐ANCAs or MPO‐ANCAs was found in 6% of patients, and RF, ANAs, and aCL were detected in 35%, 16%, and 23% of samples, respectively. No consistent clinical pattern of IE was observed in the anti‐PR3/anti‐MPO–positive IE patients, whereas positivity for cANCA/pANCA was associated with younger age (P = 0.022), more frequent occurrence of echocardiographic vegetations (P = 0.043), and above‐normal serum IgG levels (P = 0.017).
Conclusion
ANCAs, including PR3‐ and MPO‐ANCAs, occur in a substantial proportion of patients with IE. The link between cANCA/pANCA and specific features of IE requires further study.
Community Acute Bacterial Meningitis (CABM) is a rare infectious disease leading to important impairments. Our aim was to describe CABM survivors' quality of life (QOL) 12 months post-CABM and to ...assess its associations with CABM sequelae.
Patients included in the CABM COMBAT cohort were evaluated one year after the CABM episode. Data were collected by questionnaire, via phone calls with the patients. The WHOQOL-BREF was used to measure CABM survivors' QOL. Hierarchical multivariate linear regressions were performed.
Study population was composed of 284 patients. At 12 months, 53.9% (153/284) reported at least incident headache/worsening headache intensity at 12 months post-CABM, and/or incident hearing impairment, and/or unfavourable disability outcome (GOS). Unfavourable disability outcome was associated with lower physical health QOL (B = -30.35, p<0.001), lower mental health QOL (B = -15.31, p<0.001), lower environmental QOL (B = -11.08, p<0.001) and lower social relationships QOL (B = -9.62, p<0.001). Incident headache/worsening headache since meningitis onset was associated with lower psychological health (B = -5.62, p = 0.010). Incident hearing impairment was associated with lower physical QOL (B = -5.34, p = 0.030). Hierarchical regressions showed that CABM impairments significantly increase explanatory power of multivariate models (for physical health R2 change = 0.42, p<0.001, for psychological health R2 change = 0.23, p<0.001, for social relationships R2 change = 0.06, p<0.001 and for environment domain R2 change was 0.15, p<0.001).
12 month-CABM burden is heavy. Early detection and management of CABM impairments should be performed in clinical practice as early as possible to optimize patients' psychological and psychosocial functioning.
NCT01730690.
Rapid identification of patients with high suspicion of COVID-19 will become a challenge with the co-circulation of multiple respiratory viruses (RVs). We have identified clinical or biological ...characteristics to help distinguish SARS-CoV-2 from other RVs.
We used a prospective cohort including all consecutive patients admitted through the emergency department's (ED) and presenting respiratory symptoms from November 2019 to April 2020. Patients were tested for RV using multiplex polymerase chain reaction (mPCR) and SARS-CoV-2 RT-PCR.
203/508 patients were positive for an RV during the non-SARS-CoV-2 epidemic period (November to February), and 268/596 patients were SARS-CoV-2 positive during the SARS-CoV-2 epidemic (March to April). Younger age, male gender, fever, absence of expectoration and absence of chronic lung disease were statistically associated with SARS-CoV-2 detection. Combining these variables allowed for the distinguishing of SARS-CoV-2 infections with 83, 65, 75 and 76% sensitivity, specificity, PPV and NPV, respectively.
Patients' characteristics associated with a positive PCR are common between SARS-CoV-2 and other RVs, but a simple discrimination of strong SARS-CoV-2 suspicion with a limited set of clinical features seems possible. Such scoring could be useful but has to be prospectively evaluated and will not eliminate the need for rapid PCR assays.
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