Acute respiratory failure (ARF) is the most frequent complication in patients with hematological malignancies and is associated with high morbidity and mortality. ARF etiologies are numerous, and despite extensive diagnostic workflow, some patients remain with undetermined ARF etiology.This is a post-hoc study of a prospective multicenter cohort performed on 1011 critically ill hematological patients. Relationship between ARF etiology and hospital mortality was assessed using a multivariable regression model adjusting for confounders.This study included 604 patients with ARF. All patients underwent noninvasive diagnostic tests, and a bronchoscopy and bronchoalveolar lavage (BAL) was performed in 155 (25.6%). Definite diagnoses were classified into four exclusive etiological categories: pneumonia (44.4%), non-infectious diagnoses (32.6%), opportunistic infection (10.1%) and undetermined (12.9%), with corresponding hospital mortality rates of 40, 35, 55 and 59%, respectively. Overall hospital mortality was 42%. By multivariable analysis, factors associated with hospital mortality were invasive pulmonary aspergillosis (OR 7.57 (95% CI 3.06-21.62); p < 0.005), use of invasive mechanical ventilation (OR 1.65 (95% CI 1.07-2.55); p = 0.02), a SOFA score >7 (OR 3.32 (95% CI 2.15-5.15); p < 0.005) and an undetermined ARF etiology (OR 2.92 (95% CI 1.71-5.07); p < 0.005).In patients with hematological malignancies and ARF, up to 13% remain with undetermined ARF etiology despite comprehensive diagnostic workup. Undetermined ARF etiology is independently associated with hospital mortality. Studies to guide second-line diagnostic strategies are warranted. ClinicalTrials.Gov NCT01172132.
Cytomegalovirus (CMV) is the leading cause of congenital infection worldwide. Reference anti-CMV treatment is valganciclovir/ganciclovir, which is contraindicated in pregnancy given questions about teratogenicity.We analysed reports from VigiBase, the world's largest safety database, and performed a disproportionality analysis of adverse pregnancy outcomes associated with (val)ganciclovir compared with any other drugs or with (val)aciclovir as comparators.Among 3 104 984 reports related to childbearing-age women or to pregnancy topics, 6186 were exposed to (val)ganciclovir or (val)aciclovir including 251 adverse pregnancy outcomes with (val)ganciclovir (n = 34) or (val)aciclovir (n = 217). We did not evidence any increased reporting of any adverse pregnancy outcome [miscarriage, stillbirth, small weight for gestational age, preterm birth (<37 weeks of gestation)] or birth defects with (val)ganciclovir compared with the use of (val)aciclovir during pregnancy. Four cases of oesophageal and anorectal atresia were identified with (val)ganciclovir, which may be related to concomitant drugs/medical conditions and require further analyses.These preliminary results require confirmation but suggest the possibility for trial evaluation of val(ganciclovir) in severe maternal or fetal CMV infections.
Several cases of herpes zoster (HZ) following mRNA COVID-19 vaccination (BNT162b2 and mRNA-1273) have been reported, and first epidemiological evidences suggest an increased risk. We used the worldwide pharmacovigilance database VigiBase to describe HZ cases following mRNA COVID-19 vaccination. We performed disproportionality analyses (case/non-case statistical approach) to assess the relative risk of HZ reporting in mRNA COVID-19 vaccine recipients compared to influenza vaccine recipients and according to patient age. Until 30th June 2021, of 716,928 reports about mRNA COVID-19 vaccines, we found 7,728 HZ cases. When compared to influenza vaccines, mRNA COVID-19 vaccines were associated with a significantly higher reporting of HZ (reporting odds-ratio 1.9, 95%CI [1.8-2.1]). Furthermore, we found a reduced risk of reporting HZ among under 40 year-old persons compared to older persons (reporting odds-ratio 0.39, 95%CI [0.36-0.41]). For the first time, we could assess at a global level the risk of HZ after mRNA COVID-19 vaccination.
Pelvic bone and/or soft tissue sarcoma removal surgeries are associated with a high rate of surgical site infection (SSI). The recommended antibiotic prophylaxis (ABP) duration is 24-48 h. We aimed to assess the impact of extended ABP (5 days) on the SSI rate and describe the microbiology of SSI in bone and/or soft tissue pelvic sarcomas.We retrospectively included all consecutive patients who underwent pelvic bone and/or soft tissue sarcoma removal surgery between January 2010 and June 2020.We analyzed 146 patients with pelvic bone (45, 31%) or soft tissue (101, 69%). Sixty patients (41%) developed SSI. SSI occurred in 13/28 (46.4%) in the extended ABP group versus 47/118 (39.8%) in the standard group (p = 0.53). In multivariable analysis, risk factors for SSI were surgery duration (OR: 1.94 [1.41-2.92] per h), stay in postoperative ICU for more than 2 days (12.0 [2.8-61.3]), and shred or autologous skin flap (39.3 [5.8-409.5]). Extended ABP was not associated with SSI. SSI were mainly polymicrobial with Enterobacterales (57.4%) and Enterococcus (45%).Pelvic bone and/or soft tissue sarcoma removal surgery is highly prone to postoperative infection. Extending the ABP to 5 days does not reduce the level of SSI.
Abstract In this case-control study on 564 healthcare workers of a university hospital in Paris (France), contacts without protection with coronavirus disease 2019 (COVID-19) patients or with colleagues were associated with infection with severe acute respiratory syndrome coronavirus 2, whereas working in a COVID-dedicated unit and having children kept in childcare facilities were not.
Abstract In this case-control study on 564 healthcare workers of a university hospital in Paris (France), contacts without protection with COVID-19 patients or with colleagues were associated with infection with SARS-CoV-2, while working in a COVID-dedicated unit, using public transportation and having children kept in childcare facilities were not.
Objective The clinical benefit of pharmaceutical cares in improving the quality-of-care outcomes is well demonstrated. Clinical pharmacy services are not systematically deployed in cancer units in the absence of economic data. The aim of this prospective, observational 1-year study was to evaluate the clinical, economic and organisational impacts of pharmaceutical care into a multidisciplinary day hospital for patients treated with oral cancer drugs. Methods All pharmacists' interventions (PI) were documented and their impact and the probability of adverse drug events were assessed using the clinical, economic and organisational tool. Results Among 360 admissions, an average of 1.81 PI per admission was accepted. Among 452 PI leading to a clinical benefit on the patient, 16.9% had a major impact, and 1.9% had an impact on survival. The large majority of PIs (87%) increased the quality-of-care organisation. The budget impact model showed a total cost savings and cost avoidance of €539,047 per year and a cost–benefit ratio of 7.07:1. The direct cost–benefit was €201,741, and the cost avoidance was €337,306. Conclusion Multidisciplinary care and pharmaceutical care are key elements to improve cancer patients' outcomes and avoid evitable healthcare costs.
Abstract Background The 2011 4th European Conference on Infections in Leukemia (ECIL4) guidelines recommend antibiotics de-escalation/discontinuation in selected febrile neutropenia (FN) patients. We aimed to assess the impact of an antimicrobial stewardship (AMS) program based on these guidelines on antibiotics use and clinical outcomes in high-risk FN patients. Methods We conducted an observational study in the hematology department of Cochin University Hospital in Paris, France. An ECIL4-based antibiotics de-escalation and discontinuation strategy was implemented jointly by the hematologists and the AMS team. The pre-intervention (January–October 2018) and post-intervention (January-October 2019) periods were compared. We retrospectively collected clinical and microbiological data. We compiled antibiotics consumptions via hospital pharmacy data and standardized them by calculating defined daily doses per 1000 patient-days. We analyzed the two-monthly antibiotic consumption using an interrupted time series method and built a composite endpoint for clinical outcomes based on transfer to the intensive care unit (ICU) and/or hospital death. Results Overall, 273 hospital stays (164 patients) in the pre-intervention and 217 (148 patients) in the post-intervention periods were analyzed. Patients were mainly hospitalized for intensive chemotherapy for acute leukemia or autologous stem-cell transplant for myeloma. Patients were slightly younger in the pre-intervention compared to the post-intervention period (median age 60.4 vs 65.2 years, p = 0.049), but otherwise comparable. After implementation of the AMS program, glycopeptide and carbapenem use decreased by 85% (p = 0.03) and 72% (p = 0.04), respectively. After adjustment on confounders, the risk of transfer to the ICU/death decreased significantly after implementation of the AMS program (post-intervention period: odds-ratio = 0.29, 95% Confidence Interval: 0.15–0.53, p < 0.001). Conclusion Implementation of a multidisciplinary AMS program for high-risk neutropenic patients was associated with lower carbapenem and glycopeptide use and improved clinical outcomes.
