Variation in antibiotic use among and within different settings: a systematic review

Objectives: Variation in antibiotic use may reflect inappropriate use. We aimed to systematically describe the variation in measures for antibiotic use among settings or providers. This study was conducted as part of the innovative medicines initiative (IMI)-funded international project DRIVE-AB. Methods: We searched for studies published in MEDLINE from January 2004 to January 2015 reporting variation in measures for systemic antibiotic use (e.g. DDDs) in inpatient and outpatient settings. The ratio between a study's reported maximumand minimumvalues of a given measure [maximum: minimumratio (MMR)] was calculated as a measure of variation. Similar measures were grouped into categories and when possible the overall median ratio and IQR were calculated. Results: One hundred and forty-three studies were included, of which 85 (59.4%) were conducted in Europe and 12 (8.4%) in low-to middle-income countries. Most studies described the variation in the quantity of antibiotic use in the inpatient setting (81/143, 56.6%), especially among hospitals (41/81, 50.6%). Themost frequentmeasure was DDDs with different denominators, reported in 23/81 (28.4%) inpatient studies and in 28/62 (45.2%) outpatient studies. For this measure, we found a median MMR of 3.7 (IQR 2.6-5.0) in 4 studies reporting antibiotic use in ICUs in DDDs/1000 patient-days and a median MMR of 2.3 (IQR 1.5-3.2) in 18 studies reporting outpatient antibiotic use in DDDs/1000 inhabitant-days. Substantial variationwas also identified in othermeasures. Conclusions: Our review confirms the large variation in antibiotic use even across similar settings and providers. Data from low-and middle-income countries are under-represented. Further studies should try to better elucidate reasons for the observed variation to facilitate interventions that reduce unwarranted practice variation. In addition, the heterogeneity of reported measures clearly shows that there is need for standardization

Innate Sensing of HIV-Infected Cells

Cell-free HIV-1 virions are poor stimulators of type I interferon (IFN) production. We examined here how HIV-infected cells are recognized by plasmacytoid dendritic cells (pDCs) and by other cells. We show that infected lymphocytes are more potent inducers of IFN than virions. There are target cell-type differences in the recognition of infected lymphocytes. In primary pDCs and pDC-like cells, recognition occurs in large part through TLR7, as demonstrated by the use of inhibitors and by TLR7 silencing. Donor cells expressing replication-defective viruses, carrying mutated reverse transcriptase, integrase or nucleocapsid proteins induced IFN production by target cells as potently as wild-type virus. In contrast, Env-deleted or fusion defective HIV-1 mutants were less efficient, suggesting that in addition to TLR7, cytoplasmic cellular sensors may also mediate sensing of infected cells. Furthermore, in a model of TLR7-negative cells, we demonstrate that the IRF3 pathway, through a process requiring access of incoming viral material to the cytoplasm, allows sensing of HIV-infected lymphocytes. Therefore, detection of HIV-infected lymphocytes occurs through both endosomal and cytoplasmic pathways. Characterization of the mechanisms of innate recognition of HIV-infected cells allows a better understanding of the pathogenic and exacerbated immunologic events associated with HIV infection

Antibiotic research and development: business as usual?

This article contends that poor economic incentives are an important reason for the lack of new drugs and explains how the DRIVE-AB intends to change the landscape by harnessing the expertise, motivation and diversity of its partner

Metrics to assess the quantity of antibiotic use in the outpatient setting: a systematic review followed by an international multidisciplinary consensus procedure

Background The international Innovative Medicines Initiative (IMI) project DRIVE-AB (Driving Reinvestment in Research and Development and Responsible Antibiotic Use) aims to develop a global definition of ‘responsible’ antibiotic use. Objectives To identify consensually validated quantity metrics for antibiotic use in the outpatient setting. Methods First, outpatient quantity metrics (OQMs) were identified by a systematic search of literature and web sites published until 12 December 2014. Identified OQMs were evaluated by a multidisciplinary, international stakeholder panel using a RAND-modified Delphi procedure. Two online questionnaires and a face-to-face meeting between them were conducted to assess OQM relevance for measuring the quantity of antibiotic use on a nine-point Likert scale, to add comments or to propose new metrics. Results A total of 597 articles were screened, 177 studies met criteria for full-text screening and 138 were finally included. Twenty different OQMs were identified and appraised by 23 stakeholders. During the first survey, 14 OQMs were excluded and 6 qualified for discussion. During the face-to-face meeting, 10 stakeholders retained five OQMs and suggestions were made considering context and combination of metrics. The final set of metrics included defined daily doses, treatments/courses and prescriptions per defined population, treatments/courses and prescriptions per defined number of physician contacts and seasonal variation of total antibiotic use. Conclusions A small set of consensually validated metrics to assess the quantity of antibiotic use in the outpatient setting was obtained, enabling (inter)national comparisons. The OQMs will help build a global conceptual framework for responsible antibiotic use

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Quality indicators for responsible antibiotic use in the inpatient setting: a systematic review followed by an international multidisciplinary consensus procedure

Background This study was conducted as part of the Driving Reinvestment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) project and aimed to develop generic quality indicators (QIs) for responsible antibiotic use in the inpatient setting. Methods A RAND-modified Delphi method was applied. First, QIs were identified by a systematic review. A complementary search was performed on web sites of relevant organizations. Duplicates were removed and disease and patient-specific QIs were combined into generic indicators. The relevance of these QIs was appraised by a multidisciplinary international stakeholder panel through two questionnaires and an in-between consensus meeting. Results The systematic review retrieved 70 potential generic QIs. The QIs were appraised by 25 international stakeholders with diverse backgrounds (medical community, public health, patients, antibiotic research and development, regulators, governments). Ultimately, 51 QIs were selected in consensus. QIs with the highest relevance score included: (i) an antibiotic plan should be documented in the medical record at the start of the antibiotic treatment; (ii) the results of bacteriological susceptibility testing should be documented in the medical record; (iii) the local guidelines should correspond to the national guidelines but should be adapted based on local resistance patterns; (iv) an antibiotic stewardship programme should be in place at the healthcare facility; and (v) allergy status should be taken into account when antibiotics are prescribed. Conclusions This systematic and stepwise method combining evidence from literature and stakeholder opinion led to multidisciplinary international consensus on generic inpatient QIs that can be used globally to assess the quality of antibiotic use

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Achery (Aisne). Rue Charles-de-Gaulle

Achery se positionne sur le rebord de la première terrasse qui domine la plaine alluviale de l’Oise. L’intervention rue Charles-de-Gaulle est liée à la construction de deux futurs pavillons et d’une voie de passage sur un total de 2 500 m2. En 2012, un habitat du haut Moyen Âge avait été mis au jour en limite septentrionale. Les structures, creusées dans un sédiment limoneux de couleur orangée, apparaissent en moyenne à 0,50 m. Il faut noter que la route départementale a sans doute protégé la..