The European Centre for Disease Prevention and Control (ECDC) pilot point prevalence survey of healthcare-associated infections and antimicrobial use

A standardised methodology for a combined point prevalence survey (PPS) on healthcare-associated infections (HAIs) and antimicrobial use in European acute care hospitals developed by the European Centre for Disease Prevention and Control was piloted across Europe. Variables were collected at national, hospital and patient level in 66 hospitals from 23 countries. A patient-based and a unit-based protocol were available. Feasibility was assessed via national and hospital questionnaires. Of 19,888 surveyed patients, 7.1% had an HAI and 34.6% were receiving at least one antimicrobial agent. Prevalence results were highest in intensive care units, with 28.1% patients with HAI, and 61.4% patients with antimicrobial use. Pneumonia and other lower respiratory tract infections (2.0% of patients; 95% confidence interval (CI): 1.8-2.2%) represented the most common type (25.7%) of HAI. Surgical prophylaxis was the indication for 17.3% of used antimicrobials and exceeded one day in 60.7% of cases. Risk factors in the patient-based protocol were provided for 98% or more of the included patients and all were independently associated with both presence of HAI and receiving an antimicrobial agent. The patient-based protocol required more work than the unit-based protocol, but allowed collecting detailed data and analysis of risk factors for HAI and antimicrobial use.peer-reviewe

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Outpatient Antibiotic Prescriptions in France: Patients and Providers Characteristics and Impact of the COVID-19 Pandemic

International audienceIn France, despite several successive plans to control antimicrobial resistance, antibiotic use remains high in the outpatient setting. This study aims to better understand outpatient antibiotic use and prescription in order to identify tailored targets for future public health actions. Using data from the French National Health Data System, we described and compared the individual characteristics of patients with and without an antibiotic prescription. The prescribed antibiotics (ATC-J01) were detailed and compared between 2019 and 2020. Antibiotic prescribing indicators that take prescriber activity into account were estimated and compared. Patients who were female, advanced age, and the presence of comorbidities were associated with antibiotic prescriptions. The overall prescription rate was estimated at 134 per 1000 consultations and 326 per 1000 patients seen in 2019. General practitioners (GPs), dentists and paediatricians were associated with 78.0%, 12.2% and 2.2% of antibiotic prescriptions, respectively, with high prescription rates (391, 447, and 313 p. 1000 patients seen, respectively). In comparison with 2019, this rate decreased in 2020 for paediatricians (−30.4%) and GPs (−17.9%) whereas it increased among dentists (+17.9%). The reduction was twice as high among the male prescribers than among their female counterparts (−26.6 and −12.0, respectively). The reduction in prescriptions observed in 2020 (−18.2%) was more marked in children (−35.8%) but less so among individuals ≥65 years (−13.1%) and those with comorbidities (−12.5%). The decrease in penicillin prescriptions represents 67.3% of the overall reduction observed in 2020. The heterogeneous decrease in prescriptions by age and antibiotic class could be explained by the impact of COVID-19 control measures on the spread of respiratory viruses; thus, a substantial proportion of the prescriptions avoided in 2020 is likely inappropriate, particularly among children. In order to keep the rate of prescriptions comparable to that observed in 2020, male prescribers, paediatricians and GPs should be encouraged to maintain that level, while a campaign to raise awareness of the appropriate use of antibiotics should be aimed at dentists in particular

The expanding spectrum of COL2A1 gene variants IN 136 patients with a skeletal dysplasia phenotype

International audienceHeterozygous COL2A1 variants cause a wide spectrum of skeletal dysplasia termed type II collagenopathies. We assessed the impact of this gene in our French series. A decision tree was applied to select 136 probands (71 Stickler cases, 21 Spondyloepiphyseal dysplasia congenita cases, 11 Kniest dysplasia cases, and 34 other dysplasia cases) before molecular diagnosis by Sanger sequencing. We identified 66 different variants among the 71 positive patients. Among those patients, 18 belonged to multiplex families and 53 were sporadic. Most variants (38/44, 86%) were located in the triple helical domain of the collagen chain and glycine substitutions were mainly observed in severe phenotypes, whereas arginine to cysteine changes were more often encountered in moderate phenotypes. This series of skeletal dysplasia is one of the largest reported so far, adding 44 novel variants (15%) to published data. We have confirmed that about half of our Stickler patients (46%) carried a COL2A1 variant, and that the molecular spectrum was different across the phenotypes. To further address the question of genotype-phenotype correlation, we plan to screen our patients for other candidate genes using a targeted next-generation sequencing approach.European Journal of Human Genetics advance online publication, 2 December 2015; doi:10.1038/ejhg.2015.25

Outcome after failure of allogeneic hematopoietic stem cell transplantation in children with acute leukemia: a study by the société Francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

International audienc