French Hospitals Research Articles

Predictors of daytime blood pressure, nighttime blood pressure, and nocturnal dipping in patients with chronic kidney disease.

Increasing attention has recently been paid to discrepancies between office and ambulatory blood pressure (BP) control in patients with chronic kidney disease (CKD), but information on mechanisms underlying circadian BP variations in CKD remains scarce. We described circadian BP patterns and their predictors in patients with CKD stages 1 to 5 referred for kidney function testing in a French tertiary hospital: 1122 ambulatory BP measurements from 635 participants. Factors associated with daytime and nighttime systolic BP (SBP) as well as with nocturnal SBP dipping (ratio of average nighttime to daytime SBP) were analyzed with linear mixed regression models. Participants (mean age 55 ± 16 years; 36% female, mean GFR 51 ± 22 mL/min/1.73m2) had a mean daytime and nighttime SBP of 130 ± 17 and 118 ± 18 mm Hg, respectively. The prevalence of impaired dipping (nighttime over daytime SBP ratio ≥ 0.9) increased from 32% in CKD stage 1 to 68% in CKD stages 4-5. After multivariable adjustment, measured GFR, diabetes, and sub-Saharan African origin were more strongly associated with nighttime than with daytime SBP, which led to significant associations with altered nocturnal BP dipping. For a 1 SD decrease in measured GFR, nighttime BP was 2.87 mmHg (95%CI, 1.44-4.30) higher and nocturnal SBP dipping ratio was 1.55% higher (95%CI, 0.85-2.26%). In conclusion, the prevalence of impaired nocturnal BP dipping increases substantially across the spectrum of CKD. Along with sub-Saharan African origin and diabetes, lower measured GFR was a robust and specific predictor of higher nighttime BP and blunted nocturnal BP decline.

Intensive therapeutic education strategy for patients with acute heart failure (EduStra-HF): Design of a randomized controlled trial

BackgroundHeart failure is associated with reduced quality of life, hospitalizations, death and high healthcare costs. Despite care improvements, the rehospitalization rate after an acute heart failure episode, especially for acute heart failure, remains high. MethodsThe Education Strategy for patients with acute Heart Failure (EduStra-HF; ClinicalTrials.gov Identifier NCT03035123) study will randomize patients admitted for acute heart failure in six French hospitals to usual care (control) or therapeutic education (intervention). All patients will be evaluated at baseline and will meet with a therapeutic education nurse before discharge. Those in the usual care arm will have standard appointments with their cardiologist and general practitioner. Those in the intervention arm will have an intensive follow-up schedule of phone calls, home visits and text messages from the therapeutic education nurses, plus cardiologist visits. Patients will be stratified by discharge location (home or cardiac rehabilitation centre) before randomization, and will be followed up for 1 year. The primary outcome will be the readmission rates for acute heart failure during 1 year in the two groups. Secondary outcomes will include: quality of life; time from inclusion to first readmission for acute heart failure; non-heart failure cardiovascular rehospitalization rates; length of stay for heart failure; cardiovascular and all-cause death; rates of patients receiving optimal medical therapies; evolution of knowledge about heart failure; and cost-effectiveness. ConclusionsThis study will assess the efficacy and feasibility of a standardized management strategy for the care and follow-up of patients discharged after hospitalization for acute heart failure. The EduStra-HF strategy will combine various nurse care methods to help prevent rehospitalization.

From reliability to pragmatism: Hospital management in the context of radical uncertainty

AbstractThe COVID‐19 pandemic presented a scenario of radical uncertainty that hospitals had to manage. Two strands of research can illuminate this management. The first puts forward the high‐reliability organization (HRO) principles that the hospital sector has applied for two decades. The second is based on pragmatism and underscores experimental, trial‐and‐error strategies appropriate for radical uncertainty. This strategy, utilized primarily in the political governance of crises, can be applied in hospital management as well. The results of our qualitative research into French hospitals (109 online interviews over 2020–2021) highlight the importance of pragmatic rationality in crisis management based on organizing collective inquiries. This concept of pragmatic rationality questions the notion of reliability, sticking to pre‐existing performance standards not applicable in such contexts. It invites to propose the concept of high pragmatic organization based on five principles that partially integrate those of an HRO.

Characteristics of pruritus in lichen planopilaris and frontal fibrosing alopecia: A cohort study in a French hospital

Characteristics of pruritus in lichen planopilaris and frontal fibrosing alopecia: A cohort study in a French hospital

Real-life data on biliary tract cancers in France: The nested Amber study from the French ACABi GERCOR PRONOBIL retro-prospective, observational cohort

Background and aimsTo gather real-life data on biliary tract cancer (BTC) in France, an ambispective ACABi GERCOR Pronobil cohort was initiated. This nested study, Amber, utilized data from this cohort to document clinical practices in this setting. MethodsInclusion criteria encompassed patients with locally advanced/metastatic BTC managed between 2019 and 2021 in nine French referral hospitals. Objectives included describing demographic and clinical data, treatments outcomes (safety and efficacy), and overall survival. ResultsOf the 138 patients (median age 65 years, a balanced sex ratio) included, most displayed ECOG 0–1 (83 %), at least one comorbidity (79 %), and had intrahepatic (56 %) and metastatic (82 %) BTC. Among surgically-resected patients, 60 % received adjuvant chemotherapy, mainly capecitabine (67 %). CisGem, the primary first-line palliative chemotherapy (69 %), showed a 23 % objective response rate, a median progression-free survival of 5.3 months, and a median overall survival of 13.4 months. Second-, third-, and fourth-line were given to 75 % (FOLFOX: 35 %, targeted therapy: 14 %), 32 %, and 13 % of patients. In total, 67 % of patients had a molecular profile (IDH1 mutations and FGFR2 fusions: accounting for 21 % each in intrahepatic cholangiocarcinoma). ConclusionBTC patients were predominantly treated according to international recommendations. The obtained demographic, tumor, and molecular data were consistent with existing literature.

MASLD-related HCC: Multicenter study comparing patients with and without cirrhosis

Background and AimsDespite its growing incidence, hepatocellular carcinoma (HCC) related to metabolic dysfunction-associated steatotic liver disease (MASLD) in non-cirrhotic liver remains poorly characterized. We compared the characteristics, management, survival, and trends of MASLD-related HCC in patients with or without underlying cirrhosis in a large multicenter cohort. Methods354 patients with MASLD-related HCC presented at the liver tumor meetings of four French university hospitals between 2007 and 2018, were included in the study. Data were extracted from the meetings’ databases and from the French Birth and Death Registry. Results35% of HCC cases occurred in the absence of cirrhosis. HCC was diagnosed through screening in 60% of patients with cirrhosis, and incidentally in 72% of patients without it. Non-cirrhotic patients were older, had a greater tumor burden, but also better liver function than cirrhotic patients. Non-cirrhotic patients showed better overall survival than those with cirrhosis (p=0.043). However, cirrhosis was not independently associated with overall survival, the independent predictors were age, liver function, tumor burden and BCLC classification. Non-cirrhotic patients underwent surgery more frequently than cirrhotic patients did (41% versus 11%, p<0.001), even in cases where the largest tumors were ≥5 cm (42% versus 14%, p=0.002) or there were four or more lesions (19% versus 2%, p=0.024). Among the cirrhotic and non-cirrhotic patients who underwent surgery, survival was not significantly different. The cirrhosis / no cirrhosis ratio remained stable over the study period. ConclusionsIn MASLD-related HCC, non-cirrhotic patients account for 35% of cases and have poor prognostic factors (higher age and larger tumors) but also better liver function, resulting in more aggressive management of advanced tumors and better survival compared to cirrhotic patients. Impact and implicationsThe incidence of hepatocellular carcinoma related to MASLD is projected to increase by 47% to 130% by year 2030 with one third occurring in non cirrhotic livers, making them inaccessible to screening with tumors more advanced at diagnosis. Our study shows that survival in MASLD patients with hepatocellular carcinoma relies on age, tumor burden and underlying liver function and the preserved liver function of these non-cirrhotic patients allows them to be managed surgically. A better understanding of the pathophysiological processes driving HCC occurrence in non-cirrhotic MASLD patients to screen and early management of these patients.

Nurses’ moral judgements during emergency department triage – A prospective mixed multicenter study

IntroductionIn EDs, triage ensures that patients whose condition requires immediate care are prioritized while reducing overcrowding. Previous studies have described the manifestation of caregivers’ moral judgements of patients in EDs. The equal treatment of patients in clinical practice presents a major issue. Studying the impact of prejudice on clinical practice in the ED setting provides an opportunity to rethink clinical tools, organizations and future training needs. Our study sought to describe the moral judgements expressed by triage nurses during admission interviews in emergency departments and to assess their impact on patient management. MethodsAn exploratory sequential mixed-method study was performed. The study was conducted between January 1, 2018, and February 18, 2018, in the EDs of three French hospitals. Five hundred and three patients and 79 triage nurses participated in the study. Audio recordings, observations and written handover reports made by nurses during admission triage interviews were analyzed with a view to discerning whether moral judgements were expressed in them. We studied the impact of moral judgements on patient management in the emergency department. ResultsAbstract Moral judgements were made in 70% of the triage situations studied (n=351/503). They could be classified in seven categories. Patients were more likely to be subjected to moral judgements if they were over 75 years old, visibly disabled or if they had visible signs of alcohol intoxication. Being subjected to moral judgement was associated with differential treatment, including assignment of a triage score that differed from the theoretical triage score. ConclusionMore than two thirds of patients admitted to EDs were triaged using moral criteria. Patients who were morally judged at the admission interview were more likely to be treated differently.

Nurse middle managers’ proactive work behavior: antecedents and consequences on innovative work behavior and job performance

PurposeHealthcare organizations require more proactive behaviors from nursing professionals. However, nurse managers’ proactivity has rarely been analyzed in the literature and little is known about the antecedents and consequences of their proactive behavior at work. This study examines the relationships between job characteristics (i.e. job autonomy and job variety), psychological empowerment, proactive work behavior and job effectiveness indicators (i.e. innovative work behavior, job performance). We tested a model in which psychological empowerment and proactive work behavior sequentially mediate the relationship between job characteristics and job effectiveness.Design/methodology/approachA cross-sectional study was conducted among nurse middle managers from a French hospital (N = 321). A hypothetical model was developed based on existing theory. Structural equation modeling was used to test the hypotheses.FindingsResults show that psychological empowerment and proactive work behavior fully mediate the relationship between job characteristics and innovative work behavior, and partially mediate the relationship between job characteristics and job performance.Originality/valueThis study provides insights for understanding how job characteristics can contribute to fostering the proactivity of nurse middle managers and how their proactive work behavior can be positively related to innovative work behavior and job performance. Findings raise several implications for hospital administrators and upper management seeking new ways to enhance nurse middle managers' proactive work behavior and push further their effectiveness at work.

MDB-58. REDUCED CRANIOSPINAL DOSE FOR NEWLY DIAGNOSED HIGH-RISK MEDULLOBLASTOMA IN CHILDREN YOUNGER THAN 5 YEARS OLD: RETROSPECTIVE EXPERIENCE FROM SFCE

Abstract BACKGROUND High Risk medulloblastoma (MB) treatment strategy is based on an intensive multimodal treatment including surgery, chemotherapy and radiotherapy. French adapted PNET HR +5 is based on high-dose chemotherapy and age-stratified (18 Gy &amp;lt; 3 yo, 23 for 3-5 yo, 36 Gy for &amp;gt; 5 yo) craniospinal dose irradiation to reduce long-term side-effects of radiotherapy. METHODS To estimate progression-free (PFS) in a national multi-institutional retrospective study, we enrolled children younger than 5 yo with newly diagnosed high-risk MB treated according to adapted PNET HR +5 trial. RESULTS Thirty-seven children from 15 French hospitals (median age, 3.4 yo; range, 0.7-4.8) with confirmed high-risk MB were included. 15 patients (39%) were less than 3 years old. 29 patients (81%) had metastatic disease. Group 3 was the most represented molecular subgroup. 5-year PFS and OS was 59 % and 77 %, respectively. According to dose of craniospinal irradiation, PFS for 18 Gy, 23.4 Gy and 36 Gy patient groups were 100 %, 75 % and 45%, respectively. Treatment was well tolerated. One toxic death was declared. Analysis of longitudinal neurocognitive performance is ongoing. CONCLUSIONS the French strategy comprising high-dose chemotherapy and age-adapted craniospinal irradiation is promising with a high rate of survival in young children and must be confirmed by a prospective trial.

Deaths and major cardiovascular events in patients with lymphoma: Analysis from a French nationwide hospitalization database

BackgroundThere are few data assessing the risk of death and cardiovascular events in patients with lymphoma. AimUsing a nationwide hospitalization database, we aimed to address cardiovascular outcomes in patients with lymphoma. MethodsFrom 01 January to 31 December 2013, 3,381,472 adults were hospitalized in French hospitals; 22,544 of these patients had a lymphoma. The outcome analysis (all-cause or cardiovascular death, myocardial infarction, ischaemic stroke, bleedings, new-onset heart failure and new-onset atrial fibrillation) was performed over a 5-year follow-up period. Each patient with lymphoma was matched with a patient without a lymphoma or other cancer (1:1). A competing risk analysis was also performed. ResultsAfter adjustment on all risk factors, cardiovascular and non-cardiovascular co-morbidities, the subdistribution hazard ratios for all-cause death, major bleeding, intracranial bleeding, new-onset heart failure and new-onset atrial fibrillation were higher in patients with lymphoma; conversely, the subdistribution hazard ratios for cardiovascular death, myocardial infarction and ischaemic stroke were lower in patients with lymphoma. In the matched analysis, the risk of all-cause death (subdistribution hazard ratio 1.936, 95% confidence interval 1.881–1.992) and major bleeding (subdistribution hazard ratio 1.117, 95% confidence interval 1.049–1.188) remained higher in patients with lymphoma. ConclusionIn this large nationwide cohort study, patients with lymphoma had a higher incidence of all-cause death and major bleeding.

Salvage strategy for long-term central venous catheter-associated Staphylococcus aureus infections in children: a multi-centre retrospective study in France

Catheter removal is recommended in adults with Staphylococcus aureus central-line-associated bloodstream infection (CLABSI) but is controversial in children with long-term central venous catheters (LTCVC). We evaluated the occurrence of catheter salvage strategy (CSS) in children with S.aureus LTCVC-associated CLABSI and assessed determinants of CSS failure. We retrospectively included children (<18 years) with an LTCVC and hospitalized with S.aureus CLABSI in eight French tertiary-care hospitals (2010-2018). CSS was defined as an LTCVC left in place ≥72h after initiating empiric antibiotic treatment for suspected bacteraemia. Characteristics of patients were reviewed, and multi-variable logistic regression was performed to identify factors associated with CSS failure (i.e., persistence, recurrence or complications of bacteraemia). We included 273 episodes of S.aureus LTCVC-associated CLABSI. CSS was chosen in 194 out of 273 (71%) cases and failed in 74 of them (38%). The main type of CSS failure was the persistence of bacteraemia (39 of 74 cases, 53%). Factors independently associated with CSS failure were: history of catheter infection (adjusted odds ratio (aOR) 3.18, 95% confidence interval (CI) 1.38-7.36), CLABSI occurring on an implantable venous access device (aOR 7.61, 95% CI 1.98-29.20) when compared with tunnelled-cuffed CVC, polymicrobial CLABSI (aOR 3.45, 95% CI 1.25-9.50), and severe sepsis at the initial stage of infection (aOR 4.46, 95% CI 1.18-16.82). CSS was frequently chosen in children with S.aureus LTCVC-associated CLABSI, and failure occurred in one-third of cases. The identified risk factors may help clinicians identify children at risk for CSS failure.

Disentangling Multiple Sclerosis heterogeneity in the French territory among genetic and environmental factors via Bayesian heritability analysis

BackgroundThis study aimed to investigate the factors contributing to the variability of Multiple Sclerosis (MS) among individuals born and residing in France. Geographical variation in MS prevalence was observed in France, but the role of genetic and environmental factors in explaining this heterogeneity has not been yet elucidated. MethodsWe employed a heritability analysis on a cohort of 403 trios with an MS-affected proband in the French population. This sample was retrieved from REFGENSEP register of MS cases collected in 23 French hospital centers from 1992 to 2017. Our objective was to quantify the proportion of MS liability variability explained by genetic variability, sex, shared environment effects, region of birth and year of birth. We further considered gene x environment (GxE) interaction effects between genetic variability and region of birth. We have implemented a Bayesian liability threshold model to obtain posterior distributions for the parameters of interest adjusting for ascertainment bias. ResultsOur analysis revealed that GxE interaction effects between genetic variability and region of birth represent the primary significant explanatory factor for MS liability variability in French individuals (29 % [95 %CI: 5 %; 53 %]), suggesting that additive genetic effects are modified by environmental factors associated to the region of birth. The individual contributions of genetic variability and region of birth explained, respectively, ≈15 % and ≈16 % of MS variability, highlighting a significantly higher MS liability in individuals born in the Northern regions compared to the Southern region. Overall, the joint contribution of genetic variability, region of birth, and their interaction was then estimated to explain 65 % [95 %CI: 35 %; 92 %] of MS liability variability. The remaining proportion of MS variability is attributed to environmental exposures associated with the year of birth, shared within the same household, and specific to individuals. ConclusionOverall, our analysis highlighted the interaction between genetic variability and environmental exposures linked to the region of birth as the main factor explaining MS variability within individuals born and residing in France. Among the environmental exposures prevalent in the Northern regions, and potentially interacting with genetic variability, lower vitamin D levels due to reduced sun exposure, higher obesity prevalence and higher pollution levels represent the main risk factors in influencing MS risk. These findings emphasize the importance of accounting for environmental factors linked to geographical location in the investigation of MS risk factors, as well as to further explore the influence of GxE interactions in modifying genetic risk.

Correlation between Muscle Mass and Physical Activity Level in Older Adults at Risk of Falling: The FITNESS Study

BackgroundThe study investigates the correlation between muscle mass and physical activity level measured objectively and subjectively in older adults who fall or are at high risk of falling.MethodsFITNESS (Fall Interest to Target Newly Sarcopenic Society) is a multi-center (French university hospitals of Angers, Lille, Limoges and Orléans), cross-sectional, observational study of routine care within a French multidisciplinary hospital consultation. Inclusion criteria were ≥ 75 years old, living at home and consulting for fall or gait disorder. A standardized geriatric assessment, muscle mass evaluation by impedancemetry, physical activity by continuous actimetry (5 days) and Incidental and Planned Exercise Questionnaire (IPEQ) were performed at patient inclusion.Results170 people aged 75 and over were included in the FITNESS study (mean age 82.9 ± 4.7 years, women 72.9%). Muscle mass (whole body and lower limbs) correlated with active energy expenditure (AEE, ρ whole body = 0.32, p-value < 0.001; ρ lower limbs = 0.25, p-value = 0.003), but not with number of daily steps, nor with IPEQ score. Multivariate analysis of whole-body muscle mass showed a positive and significant association with AEE and albumin levels and for lower limb muscle mass, a positive association with AEE and Charlson.ConclusionThis study suggests that in the particular population of older adults who fall and/or are at high risk of falling, loss of muscle mass correlates with reduced physical activity. So subjects who fall or at high risk of falling constitute a special group for whom the fight against sedentary lifestyles and the maintenance of physical activity should be a dual priority.

SAT-430 Vaccir study: evaluation of vaccination coverage against diphtheria-tetanus-poliomyelitis, pneumococcus, hepatitis A and B, influenza and SARS-COV2 in cirrhotic patients in 17 french general hospitals

SAT-430 Vaccir study: evaluation of vaccination coverage against diphtheria-tetanus-poliomyelitis, pneumococcus, hepatitis A and B, influenza and SARS-COV2 in cirrhotic patients in 17 french general hospitals

Knowledge, behaviours, practices, and expectations regarding climate change and environmental sustainability among health workers in France: a multicentre, cross-sectional study

Faced with climate change, hospitals are confronted with a dual challenge. On one hand, they need to embark on a far-reaching ecological transformation to reduce their contribution to greenhouse gas emissions and other environmental impacts; on the other hand, they need to limit the effects of climate change on their activities. We aimed to evaluate the knowledge, behaviours, practices, and expectations of health workers in French hospitals regarding climate change and environmental sustainability. This multicentre, cross-sectional study was carried out in six French hospitals from June 1, 2021 to Dec 31, 2022. All health workers at the hospitals were eligible to participate and were recruited through internal publicity. We designed a structured questionnaire consisting of five parts: participant characteristics, knowledge and perceptions of climate change, pro-environmental behaviours, practices concerning environmental sustainability actions, and expectations. A multilevel logistic regression model was used to evaluate associations between the knowledge, behaviours, and practices of health workers and the characteristics of the health workers and hospitals. Of 57 034 health workers across the six hospitals, 4552 (8·0%) participated in the study. Of those for whom gender data were available, 3518 (78·2%) participants were women and 979 (21·8%) were men. Participants considered energy consumption (71·0%) and waste and discharges related to medical activities (55·6%) and non-medical activities (50·2%) to be the three activities with the greatest environmental impact. On a scale of 1 (not a priority) to 10 (high priority), the median rating attributed by the participants to the commitment of their hospitals to ecological transformation was 5·0 (IQR 3·0-6·0). 1079 (23·7%) of 4552 participants had already initiated at least one environmental sustainability action in their hospital. Barriers reported by participants to the implementation of environmental sustainability-related projects were the lack of dedicated time (40·4%), hierarchical support (32·5%), methodological support (28·9%), and access to training (23·7%). The presence of a sustainable development steering committee, especially one with more than 5 years of activity, was positively associated with health workers feeling better informed about the ecological transformation of their hospital (adjusted odds ratio 1·78 [95% CI 1·29-2·45]), having better knowledge of the environmental impacts of their hospital (1·83 [1·32-2·53]), and initiating a larger number of environmental sustainability actions (1·74 [1·33-2·29]). We showed that health workers in French hospitals seem to be committed to the ecological transformation of their workplaces, and identified some drivers and barriers to further support these essential transformations. There is an urgent need to bolster training for all health workers, enhance structural frameworks within hospitals, and encourage future interdisciplinary research on the vulnerability of health-care facilities to climate change. The University Hospital of Poitiers.

Prognostic role of unmeasured anions determined by the Stewart approach in septic shock: A prospective cohort study

Background: Unlike standard methods for the analysis of acid-base disturbances, the Stewart approach allows for a precise quantification of unmeasured anions (strong ion gap, SIG). The prognostic value of these unmeasured anions has been reported in various clinical situations in the intensive care unit (ICU), but not specifically in septic shock. The aim of the present study was to assess whether or not the SIG could be a prognostic marker for 28-day mortality in critically ill patients admitted to the ICU for septic shock. Methods: This prospective cohort study was conducted from June 2016 to December 2017 in three ICUs of a French teaching hospital. All patients admitted to the ICU for septic shock and equipped with an arterial blood line were eligible. Oral consent was collected after delivering oral and written information to the patient or his/her family. The SIG was calculated from a complete blood sampling (blood electrolytes and arterial blood gas) collected immediately upon ICU admission. Receiver operating characteristics (ROC) curves were determined to assess the ability of SIG to predict 28-day mortality. Results: A total of 116 patients were analyzed. The 28-day mortality rate was 41.4%. Median (interquartile range [IQR]) SIG at admission was 7.1 (4.6-9.6) mEq/L for the 28-day survivors and 8.0 (6.1-10.3) mEq/L for non-survivors (P = 0.051). The area under ROC of SIG at admission for 28-day mortality prediction was 0.607 (95% confidence interval [CI] 0.504-0.710; P = 0.051). Conclusion: SIG is not a relevant prognostic marker for mortality in septic shock.

Predictive Modeling of COVID-19 Intensive Care Unit Patient Flows and Nursing Complexity: A Monte Carlo Simulation Study.

This study aimed to develop a Monte Carlo simulation model to forecast the number of ICU beds needed for COVID-19 patients and the subsequent nursing complexity in a French teaching hospital during the first and second pandemic outbreaks. The model used patient data from March 2020 to September 2021, including age, sex, ICU length of stay, and number of patients on mechanical ventilation or extracorporeal membrane oxygenation. Nursing complexity was assessed using a simple scale with three levels based on patient status. The simulation was performed 1000 times to generate a scenario, and the mean outcome was compared with the observed outcome. The model also allowed for a 7-day forecast of ICU occupancy. The simulation output had a good fit with the actual data, with an R2 of 0.998 and a root mean square error of 0.22. The study demonstrated the usefulness of the Monte Carlo simulation model for predicting the demand for ICU beds and could help optimize resource allocation during a pandemic. The model's extrinsic validity was confirmed using open data from the French Public Health Authority. This study provides a valuable tool for healthcare systems to anticipate and manage surges in ICU demand during pandemics.

Effectiveness and safety of cefazolin versus cloxacillin in endocarditis due to methicillin-susceptible Staphylococcus spp.: a multicenter propensity weighted cohort study.

To compare the effectiveness and safety of cefazolin versus cloxacillin for the treatment of infective endocarditis (IE) due to methicillin-sensitive Staphylococci (MSS). Data were retrospectively collected on patients treated for a definite MSS endocarditis who received cefazolin or cloxacillin for at least 10 consecutive days in six French hospitals between January-1 2014 and December-31 2020. The primary endpoint was treatment failure defined as a composite of death within 90 days of starting antibiotherapy, or embolic event during antibiotherapy, or relapse of IE within 90 days of stopping antibiotherapy. We used Cox regression adjusted for the inverse probability of treatment weighting of receiving cefazolin. 192 patients were included (median age 67.8 years). IE was caused by S.aureus in 175 (91.1%) and by coagulase-negative staphylococci in 17 (8.9%). Ninety-four patients (48.9%) received cefazolin, and 98 (51%) received cloxacillin. 34 patients (34.7%) with cefazolin and 26 (27.7%) with cloxacillin met the composite primary endpoint, with no significant differences between groups (adjusted HR = 1.13, 95% CI 0.63 to 2.03). There were no significant differences in secondary efficacy endpoints or biological safety events. The effectiveness of cefazolin did not significantly differ from cloxacillin for the treatment of MSS endocarditis.

Determinants of pharmacists' confidence to participate in antimicrobial stewardship: A confirmatory factor analysis.

Pharmacists are essential members of hospital antimicrobial stewardship (AMS) teams. A lack of self-perceived confidence can limit pharmacists' involvement and contributions. Pharmacists working in AMS have reported a lack of confidence. There is currently a lack of validated measures to assess pharmacists' self-perceived confidence when working in AMS and contributors to this confidence. This study aimed to identify variables contributing to pharmacist self-perceived confidence and validate an AMS hospital pharmacist survey tool using confirmatory factor analysis (CFA). Responses from a survey of Australian and French hospital pharmacists were used to undertake CFA and path analysis on factors related to pharmacists' self-perceived confidence. It was hypothesized that pharmacists' self-perceived confidence would be impacted by time working in AMS, perceived importance of AMS programmes, perceived barriers to participating in AMS and current participation. CFA demonstrated a good model fit between the factors. Items included in the model loaded well to their respective factors with acceptable reliability. Path analysis demonstrated that time working in AMS had a significant impact on pharmacists' self-perceived confidence, while perceived barriers had a negatively significant relationship. Pharmacy participation in AMS and perceived importance of AMS programmes had a non-significant impact. Findings demonstrated that the survey tool showed good validity and identified factors that can impact pharmacists' self-perceived confidence when working in hospital AMS programmes. Having a validated survey tool can identify factors that can reduce pharmacists' self-perceived confidence. Strategies can then be developed to address these factors and subsequently improve pharmacists' self-perceived confidence.

#992 Protocol based on PLA2R1 epitope recognition is superior to standard protocol in achieving remission in PLA2R1-associated membranous nephropathy

Abstract Background and Aims Membranous nephropathy (MN) is a rare, but severe autoimmune disease affecting kidney glomeruli. Clinical evolution is variable, ranging from spontaneous remission to persistent nephrotic syndrome and kidney failure. The major autoantigen in MN is PLA2R1 protein associated with 50-70% of all cases. Patients may present antibodies against a single immunodominant CysR domain or may develop additional antibodies against CTLD1 and/or CTLD7 and/or CTLD8 domains of PLA2R1 defining a cascade immunization or epitope spreading. The mechanism of epitope spreading has been described in a variety of contexts: it can reinforce immune response to eliminate a pathogen, but can also be associated with the aggravation of autoantibody-mediated autoimmune pathologies. The value of this marker in the management of MN patients remains debated. Our initial study (confirmed on an independent cohort) has shown that the single domain recognition (non-spreader patients) is associated with a higher chance of spontaneous remission (45% vs 0.05% in GEMRITUX cohort) and a better response to treatment (100% of remission regardless of the dose of rituximab used). The patients with multi domain recognition (spreader patients) of CTLD1 and/or CTLD7 domains, on the other hand, have poor prognosis and are less likely to achieve remission requiring high doses of rituximab. Based on these studies we have proposed a personalized treatment protocol with either low or high dose Rituximab based on patients’ PLA2R1 epitope spreading status. The aim of this study was to evaluate the efficacy of this personalized treatment in comparison to the established GEMRITUX protocol. Method A multicenter, randomized, controlled, prospective clinical trial was conducted in 12 French hospitals. Sixty-four consecutive patients with PLA2R1-related MN were randomly assigned to either the control group following the GEMRITUX protocol (symptomatic treatment for 6 months, two 375 mg/m2 rituximab infusions at month-6 in case of persistent nephrotic syndrome (NS)) or the personalized treatment (PMMN) group (patients with no epitope spreading at month-0 were treated as per GEMRITUX protocol, while patients with epitope spreading at month-0 or month-6 with persistent NS were treated immediately with two 1 g rituximab infusions). The primary study outcome was the rate of clinical remission at month-12. The secondary outcomes were complete and partial remission, immunological remission, proteinuria, albuminuria, serum creatinine, and PLA2R1 antibody titer. Results From 64 patients included, three were excluded from final analyses due to loss to follow-up. There was no difference in age, gender, albumin, UPCR, anti-PLA2R1 titer and the rate of PLA2R1 epitope spreading at baseline between the two groups. At M12, 34% of patients from the GEMRITUX group and 69% of patients from PMMN group achieved partial clinical remission (P = .0105) defined as UPCR &amp;lt; 3.5 g/g with a decrease greater than 50% from baseline; improvement or normalization of serum albumin; and increase of serum creatinine lower than 20%. While there was no difference in remission rate between the GEMRITUX group and PMMN group for patients with single domain recognition (38% vs 50%, respectively, P = .7107), multi-domain recognizers (spreaders) were more likely to achieve remission with personalized protocol (36% vs. 87%, P = .0078). The rate of complete clinical remission between the two experimental groups, defined as UPCR &amp;lt;0.3 g/g and normal albumin, was close to statistical significance (0% vs 16%, P = .0538). Conclusion Personalized treatment protocol based on the stratification of patients with PLA2R1-related MN according to their epitope spreading status, is superior to the standard GEMRITUX protocol in achieving partial clinical remission at 12 months. Patients with multiple domain recognition should be treated immediately with high doses of rituximab to increase their chances of remission.