Impact estimates of nosocomial bloodstream infection: looking from a different angle

Mortality associated with nosocomial bloodstream infection is multifactorial. Source of infection, etiology, age, underlying disease, acute illness, and appropriateness of antimicrobial therapy all contribute to the final outcome. As such, estimates of mortality attributable to bloodstream infection may differ largely according to the presence or absence of risk factors in distinct patient populations. The adverse effect of nosocomial bloodstream infection for the individual patient is substantial, with about a doubling of the risk of death. Yet, in settings with a high standard of care in terms of infection prevention and control, the occurrence rate of bloodstream infection is relatively low and therefore its impact on overall ICU mortality rather limited. As a consequence, untargeted interventional studies focused on infection prevention should use occurrence rate of infection rather than mortality as outcome variable

Les trajectoires d'adhésion à l'hormonothérapie adjuvante au cours des cinq ans suivant l'initiation chez les femmes ayant eu un cancer du sein non-métastatique

Malgré les bénéfices de l’hormonothérapie adjuvante (HA) pour réduire les risques de récidive et de mortalité suite à un cancer du sein hormono dépendant, l’adhésion à l’HA est sous-optimale pour une grande proportion de femmes. Toutefois, les connaissances sur les patrons longitudinaux d’adhésion à l’HA demeurent limitées. Cette étude visait à : 1)identifier les trajectoires d’adhésion à l’HA pour les cinq ans suivant l’initiation; 2) décrire les trajectoires en utilisant des mesures traditionnelles d’adhésion (p.ex. la proportion de jours couverts (PJC)); 3) explorer les facteurs associés aux trajectoires. Une étude de cohorte a été réalisée à partir d’une enquête nationale française incluant des données administratives de dispensation d’HA. Les femmes ayant un diagnostic de cancer du sein non-métastatiqueet ≥1 dispensation d’HA au cours des 12 mois suivant le diagnostic ont été incluses. Le Group-based trajectory modeling a permis d’identifier les trajectoires d’adhésion en regroupant des patrons similaires de dispensations mensuelles d’HA. Des régressions logistiques polytomiques ont permis d’identifier les facteurs associés aux trajectoires. Parmi les 674 femmes incluses, cinq trajectoires d’adhésion à l’HA ont été identifiées : 1) déclin rapide et arrêt (5,2%), 2) déclin modéré et arrêt (6,4%), 3) déclin lent (17,2%), 4) adhésion élevée (30,0%), 5) maintien d’une adhésion très élevée (41,2%). La PJC moyenne pour les cinq ans était de 80%, mais variait de 10% à 97% selon les trajectoires. Les femmes n’ayant pas reçu de chimiothérapie ou de programme personnalisé de soins étaient plus susceptibles d’appartenir à des trajectoires présentant un déclin de l’adhésion suivi de l’arrêt de l’HA. Nos résultats fournissent des informations sur les patrons longitudinaux de l’adhésion à l’HA, les facteurs associés à ceux-ci et les moments critiques pour l’adhésion qui pourront être utilisés par les professionnels de la santé impliqués auprès de ces femmes.Despite the benefits of adjuvant endocrine therapy (AET) for reducing recurrence andmortality risks after hormone-sensitive breast cancer, AET adherence is sub-optimal for ahigh proportion of women. However, little is known about long-term patterns of AETadherence over the minimally recommended 5 years. Our objectives were to: 1) identify fiveyear AET adherence trajectory groups; 2) describe trajectory groups according to adherencemeasures traditionally used (i.e. the proportion of days covered (PDC)); 3) explore factorsassociated with trajectories. We conducted a five-year cohort study using data from a Frenchnational study that included AET dispensing administrative data. Women diagnosed withfirst non-metastatic breast cancer and having ≥1 AET dispensing in the 12 months afterdiagnosis were included. Group-based trajectory modeling was used to identify adherencetrajectory groups by clustering similar patterns of monthly AET dispensing. Multinomiallogistic regressions were used to identify factors associated with trajectories. Among 674women, five AET adherence trajectory groups were identified: 1) quick decline and stop(5.2% of women); 2) moderate decline and stop (6.4%); 3) slow decline (17.2%); 4) highadherence (30.0%); 5) maintenance of very high adherence (41.2%). Mean 5-year PDCvaried from 10% to 97% according to trajectories. Women who did not receive chemotherapyor a personalized care plan were more likely assigned to trajectories where AET adherencedeclined and stopped. Our results provide information on the diversity of longitudinal AETadherence patterns, the timing of decline and discontinuation and associated factors thatcould inform healthcare professionals

The Belgian policy of funding antimicrobial stewardship in hospitals and trends of selected quality indicators for antimicrobial use, 1999-2010: a longitudinal study

Objectives: In order to improve antimicrobial (AM) use, a policy of providing technical and financial support to AM management teams (AMTs) was rolled out in all Belgian hospitals between 2002 and 2008. We aimed to analyse the association of this policy with AM use for the two indications accounting for the largest number of patients receiving AM: prophylaxis for major lower limb orthopaedic surgery and pneumonia. Design, setting, participants: We used patient-level data routinely collected in all Belgian acute care hospitals between 1999 and 2010. We modelled trends for selected quality indicators (QIs) using the year of AMT implementation in each hospital as the main 'change point', with fine-tuned case-mix adjustment. Of all admissions for lower limb orthopaedic surgery, and pneumonia between 1999 and 2010, 90% (325 094) and 95% (327 635), respectively, were found eligible for analyses. Outcomes: The surgery QI was defined as: cefazolin, dose in the expected range, and no use of other AM. For pneumonia, QIs were: ratio of oral/parenteral defined daily doses (DDD, O/P QI), and mean number of DDD minus penicillin, per 100 days of hospitalisation (DDD QI). Results: Between 1999 and 2010, the surgery QI improved from 59% to 71%, the O/P QI from 0.72 to 0.97, and the DDD QI from 96 to 64. Heterogeneity between hospitals was high. Overall, no association was found with the year of implementation of the AMT. Conclusions: Improvements have been observed but could not be related at the national level to the policy under study. However, these results cannot be extrapolated to other QIs for AM use in hospitals. Our findings do not question the need for AMT, nor the need for continuation of AMT funding. Several recommendations can be made in order to make the best of Belgium's unique political and financial commitments in that field

Prevention of ventilator-associated pneumonia in intensive care units: an international online survey

Background: On average 7% of patients admitted to intensive-care units (ICUs) suffer from a potentially preventable ventilator-associated pneumonia (VAP). Our objective was to survey attitudes and practices of ICUs doctors in the field of VAP prevention. Methods: A questionnaire was made available online in 6 languages from April, 1st to September 1st, 2012 and disseminated through international and national ICU societies. We investigated reported practices as regards (1) established clinical guidelines for VAP prevention, and (2) measurement of process and outcomes, under the assumption "if you cannot measure it, you cannot improve it"; as well as attitudes towards the implementation of a measurement system. Weighted estimations for Europe were computed based on countries for which at least 10 completed replies were available, using total country population as a weight. Data from other countries were pooled together. Detailed country-specific results are presented in an online additional file. Results: A total of 1730 replies were received from 77 countries; 1281 from 16 countries were used to compute weighted European estimates, as follows: care for intubated patients, combined with a measure of compliance to this guideline at least once a year, was reported by 57% of the respondents (95% CI: 54-60) for hand hygiene, 28% (95% CI: 24-33) for systematic daily interruption of sedation and weaning protocol, and 27% (95%: 23-30) for oral care with chlorhexidine. Only 20% (95% CI: 17-22) were able to provide an estimation of outcome data (VAP rate) in their ICU, still 93% (95% CI: 91-94) agreed that "Monitoring of VAP-related measures stimulates quality improvement". Results for 449 respondents from 61 countries not included in the European estimates are broadly comparable. Conclusions: This study shows a low compliance with VAP prevention practices, as reported by ICU doctors in Europe and elsewhere, and identifies priorities for improvement

Molecular Aspects of HTLV-1 Entry: Functional Domains of the HTLV-1 Surface Subunit (SU) and Their Relationships to the Entry Receptors

The initial step in retroviral infection involves specific interactions between viral envelope proteins (Env) and specific receptors on the surface of target cells. For many years, little was known about the entry receptors for HTLV-1. During this time, however, functional domains of the HTLV-1 Env were identified by analyzing the effects of neutralizing antibodies and specific mutations in Env on HTLV-1 infectivity. More recent studies have revealed that HTLV-1 infectivity involves interactions with three different molecules: heparan sulfate proteoglycans (HSPG), the VEGF-165 receptor Neuropilin 1 (NRP-1) and glucose transporter type 1 (GLUT1). Here, we revisit previously published data on the functional domains of Env in regard to the recent knowledge acquired about this multi-receptor complex. We also discuss the similarities and differences between HTLV-1 and other deltaretroviruses in regards to receptor usage

Predicting probing depth reduction after periodontal non-surgical treatment in smokers according to the nicotine dependence and the number of cigarette consumed.

peer reviewed[en] Introduction: Smoking is considered as a risk factor for the poor outcomes after periodontitis non-surgical treatment (PNST). The aim of this short communication is to predict probing depth reduction after periodontal non-surgical treatment in smokers according to the nicotine dependence (FTND) and the number of cigarette consumed (NCC). Methods: This work is a post-hoc study of a prospective controlled study on the effect of oral hygiene instructions and PNST on periodontal outcomes. This short communication focused only on the current conventional smokers (N = 34), based on specific smoking indicators, and on probing depth (PD) parameter that were recorded at baseline (time 0), after oral hygiene instruction (time 1) and 3 months after PNST (time 2). Results: The 34 smokers had a mean age 46.5 ± 11.5 years. The NCC- and FTND-based predictions allowed to show in a specific nomogram the PD values 3 months after PNST for each NCC and FTND category. Conclusion: Two nomograms are proposed for prognostic purposes and allow patients to understand the impact of smoking on periodontitis according to the number of cigarette consumed and the level of nicotine dependence. These nomograms might be also used for supporting smoking cessation. Clinical significance: In smoker patients with periodontitis, there is a need to predict, for both patient and clinicians, the impact of the number of cigarettes consumed and the level of nicotine dependence on probing depth after oral hygiene instructions and debridement. Two nomograms are proposed for prognostic purposes

Real-life effectiveness of omalizumab in difficult-to-treat versus severe asthma: A national cohort study in Belgium

Background: Guidelines recommend omalizumab in patients with uncontrolled severe allergic asthma. We investigated real-life use of omalizumab, the proportion of patients fulfilling eligibility criteria, its costs and its effectiveness. Method: In a cohort of asthma patients initiating treatment with omalizumab in Belgium between 2010 and 2016, we investigated fulfilment of eligibility criteria (chronic use of high-dose inhaled corticosteroids (ICSs) plus long-acting β2-agonists (LABAs) and ⩾2 severe asthma exacerbations in previous year), and compared hospitalisations and systemic corticosteroid consumption in the year before and after omalizumab initiation. We computed healthcare costs in the respective time periods and compared the cost per prevented hospitalisation in patients fulfilling eligibility criteria versus those who did not. Results: Between 2010 and 2016, omalizumab treatment was initiated in 2068 patients with asthma; only 24% fulfilled the eligibility criteria, mainly due to nonadherence to high-dose ICSs + LABAs. The proportion of patients hospitalised f

Endoplasmic reticulum stress does not contribute to steatohepatitis in obese and insulin resistant high-fat diet fed foz/foz mice

Non-alcoholic fatty liver (steatosis) and steatohepatitis [non-alcoholic steatohepatitis (NASH)] are hepatic complications of the metabolic syndrome. Endoplasmic reticulum (ER) stress is proposed as a crucial disease mechanism in obese and insulin-resistant animals (such as ob/ob mice) with simple steatosis, but its role in NASH remains controversial. We therefore evaluated the role of ER stress as a disease mechanism in foz/foz mice, which develop both the metabolic and histological features that mimic human NASH. We explored ER stress markers in the liver of foz/foz mice in response to a high-fat diet (HFD) at several time points. We then evaluated the effect of treatment with an ER stress inducer tunicamycin, or conversely with the ER protectant tauroursodeoxycholic acid (TUDCA), on the metabolic and hepatic features. foz/foz mice are obese, glucose intolerant and develop NASH characterized by steatosis, inflammation, ballooned hepatocytes and apoptosis from 6 weeks of HFD feeding. This was not associated with activation of the upstream unfolded protein response [phospho-eukaryotic initiation factor 2α (eIF2α), inositol-requiring enzyme 1α (IRE1α) activity and spliced X-box-binding protein 1 (Xbp1)]. Activation of c-Jun N-terminal kinase (JNK) and up-regulation of activating transcription factor-4 (Atf4) and CCAAT/enhancer-binding protein-homologous protein (Chop) transcripts were however compatible with a ‘pathological’ response to ER stress. We tested this by using intervention experiments. Induction of chronic ER stress failed to worsen obesity, glucose intolerance and NASH pathology in HFD-fed foz/foz mice. In addition, the ER protectant TUDCA, although reducing steatosis, failed to improve glucose intolerance, hepatic inflammation and apoptosis in HFD-fed foz/foz mice. These results show that signals driving hepatic inflammation, apoptosis and insulin resistance are independent of ER stress in obese diabetic mice with steatohepatitis

Canadian Healthcare Professionals’ Views and Attitudes toward Risk-Stratified Breast Cancer Screening

Given the controversy over the effectiveness of age-based breast cancer (BC) screening, offering risk-stratified screening to women may be a way to improve patient outcomes with detection of earlier-stage disease. While this approach seems promising, its integration requires the buy-in of many stakeholders. In this cross-sectional study, we surveyed Canadian healthcare professionals about their views and attitudes toward a risk-stratified BC screening approach. An anonymous online questionnaire was disseminated through Canadian healthcare professional associations between November 2020 and May 2021. Information collected included attitudes toward BC screening recommendations based on individual risk, comfort and perceived readiness related to the possible implementation of this approach. Close to 90% of the 593 respondents agreed with increased frequency and earlier initiation of BC screening for women at high risk. However, only 9% agreed with the idea of not offering BC screening to women at very low risk. Respondents indicated that primary care physicians and nurse practitioners should play a leading role in the risk-stratified BC screening approach. This survey identifies health services and policy enhancements that would be needed to support future implementation of a risk-stratified BC screening approach in healthcare systems in Canada and other countries

Does Plasminogen Activator Inhibitor-1 Drive Lymphangiogenesis?

The purpose of this study is to explore the function of plasminogen activator inhibitor-1 (PAI-1) during pathological lymphangiogenesis. PAI-1, the main physiological inhibitor of plasminogen activators is involved in pathological angiogenesis at least by controlling extracellular proteolysis and by regulating endothelial cell survival and migration. Protease system's role in lymphangiogenesis is unknown yet. Thus, based on its important pro-angiogenic effect, we hypothesized that PAI-1 may regulate lymphangiogenesis associated at least with metastatic dissemination of cancer cells. To address this issue, we studied the impact of PAI-1 deficiency in various murine models of tumoral lymphangiogenesis. Wild-type PAI-1 proficient mice were used as controls. We provide for the first time evidence that PAI-1 is dispensable for tumoral lymphangiogenesis associated with breast cancers either induced by mammary carcinoma cell injection or spontaneously appearing in transgenic mice expressing the polyomavirus middle T antigen (PymT) under the control of a mouse mammary tumor virus long-terminal repeat promoter (MMTV-LTR). We also investigated inflammation-related lymphatic vessel recruitment by using two inflammatory models. PAI-1 deficiency did neither affect the development of lymphangioma nor burn-induced corneal lymphangiogenesis. These novel data suggest that vascular remodelling associated with lymphangiogenesis and angiogenesis involve different molecular determinants. PAI-1 does not appear as a potential therapeutic target to counteract pathological lymphangiogenesis