Introduction
Healthcare workers are exposed to hazardous drugs such as antineoplastic drugs, which have potential carcinogenic, mutagenic and teratogenic effects. Protective measures must be taken ...after appropriate staff training to handle antineoplastic drugs in a safe way. The objective was to assess perception, knowledge, practices and training regarding the risk of exposure of healthcare workers in three French compounding units.
Methods
This descriptive study was based on a questionnaire made of 33 questions divided into five sections related to the handling of antineoplastic drugs: perception of the risks, knowledge of the risks, protection practices, specific training and general questions.
Results
Among the 39 participants, over half considered their overall risk of exposure to antineoplastic drugs not being very low. Inhalation was known to 69.2% of them as possible route of contamination. The breakroom was identified by 28.9% of them as a place of contamination. The procedure in case of accidental exposure to antineoplastic drugs was known by 69.2%, but only half could explain it. Only 38.5% said they changed their gloves every 30 min as recommended. Barely half said that they had been trained specifically for the handling of antineoplastic drugs during an initial training. Over half wished to be informed, trained and aware of the proper handling of antineoplastic drugs.
Conclusion
Although some of these results are encouraging, specifically when compared to the other settings where antineoplastic drugs are handled, there is still room for improvement. Efforts to build an adapted and impactful training program must pursue.
Clinical trial registration
Study CONTACT, ref. 19-504.
To treat colorectal liver metastases, intra-arterial chemotherapies may complete therapeutic arsenal. Drugs using intra-arterially are very heterogeneous. The aim of this study was to select the most ...efficient drug on a panel of colorectal cancer (CRC) cell lines (Caco-2, HCT 116, HT 29, SW 48, SW 480, SW 620) exposed for 30 min to 12 cytotoxic agents (doxorubicin, epirubicin, idarubicin, 5-FU, raltitrexed, gemcitabine, cisplatin, oxaliplatin, mitomycin C, irinotecan, streptozocin, paclitaxel) at different concentrations. The effect on cell viability was measured using the WST-1 cell viability assay. For each drug and cell line, the IC50 and IC90 were calculated, which respectively correspond to the drug concentration (mg/mL) required to obtain 50% and 90% of cell death. We also quantified the cytotoxic index (CyI90 = C Max/IC90) to compare drug efficacy. The main findings of this study are that idarubicin emerged as the most cytotoxic agent to most of the tested CRC cell lines (Caco-2, HT29, HCT116, SW620 and SW480). Gemcitabine seemed to be the most efficient chemotherapy for SW48. Interestingly, the most commonly used cytotoxic agents in the systemic and intra-arterial treatment of colorectal liver metastasis (CRLM) (oxaliplatin, 5-FU, irinotecan) showed very limited cytotoxicity to all the cell lines.
Background
A significant number of clinical pharmacy services have shown to improve in-hospital medication safety and patient outcome. Prescription review and pharmacist interventions are a ...fundamental part of hospital clinical pharmacy activities. In a context of restricted financial resources, proving the economic and clinical impact of this activity seems necessary.
Objective
The aim of this study was to assess the clinical impact on patient outcomes and economic benefit of prescription review by pharmacists.
Setting
1624-bed tertiary French university teaching hospital.
Method
Prospective single center study evaluating prescriptions for which a pharmacist intervention was issued over a 6-month period. The clinical impact of every pharmacist intervention was evaluated by a multidisciplinary experts committee. Economic benefit was evaluated from the public health care system spending standpoint.
Main outcome measures
Number of avoided hospitalization days and associated public health care system cost-avoidance.
Results
Prescription review and interventions by pharmacists prevented 73 intensive care unit hospitalization days, 74 continuous monitoring unit hospitalization days and 66 days of conventional hospitalization. €252,294.00 in public health expenditure were thus prevented. For every Euro invested in the prescription review activity, €5.09 of public health spending were potentially saved.
Conclusion
Our study shows that prescription review and clinical pharmacists’ interventions had an impact on clinical outcomes which translated into prevented hospitalization days. Prescription optimization through pharmacist interventions allows significant health care cost savings which makes this service highly efficient.
Antineoplastic drug exposure is a major problem in regard to caregivers' health. The aim of the present study was to assess the perception, knowledge, and handling practices of all occupation level ...categories of two oncology day hospitalization units and two compounding units regarding the risk of exposure to antineoplastic drugs.
This descriptive study, performed through face-to-face interviews, concurrently assessed the perception, knowledge, and handling practices of antineoplastic drugs in five different job categories in four different settings. This work was part of a larger comprehensive project examining surface and blood contamination. Different scores were assigned to evaluate responses to a questionnaire about the perception, knowledge, and handling practices of healthcare workers, a risk global score including a risk perception score, and education/knowledge and handling practices scores.
In the survey, continuous training was associated with the global risk score (
= 0.03), particularly with the handling practices risk score (
= 0.01). Job category was also significantly associated with the global risk score (
< 0.001), particularly with the handling practices risk score (
< 0.001) and the education/knowledge score (
< 0.001). Pharmacy technicians had the highest score regarding risk perception (71.4%), indicating a higher perception of risk, and had a lower score regarding handling practices (25.0%) as well as a lower score (15.7%) regarding risk knowledge. Nurses and physicians had a high score (50%) regarding the risk of handling practices and a score of 57.1% regarding risk perception, indicating an increased perception of safety. Auxiliary caregivers had the highest global score (43.5%) and a score of 30.0% regarding handling practices.
This study identified significant differences among healthcare workers depending on job categories in the antineoplastic drug handling practices and in the knowledge of the risks associated with occupational exposure to antineoplastic drugs. These differences were particularly important between trained and untrained participants, revealing the importance of implementing a continuous training program.
N2O is a powerful greenhouse gas contributing both to global warming and ozone depletion. While fungi have been identified as a putative source of N2O, little is known about their production of this ...greenhouse gas. Here we investigated the N2O-producing ability of a collection of 207 fungal isolates. Seventy strains producing N2O in pure culture were identified. They were mostly species from the order Hypocreales order-particularly Fusarium oxysporum and Trichoderma spp.-and to a lesser extent species from the orders Eurotiales, Sordariales, and Chaetosphaeriales. The N2O (15)N site preference (SP) values of the fungal strains ranged from 15.8‰ to 36.7‰, and we observed a significant taxa effect, with Penicillium strains displaying lower SP values than the other fungal genera. Inoculation of 15 N2O-producing strains into pre-sterilized arable, forest and grassland soils confirmed the ability of the strains to produce N2O in soil with a significant strain-by-soil effect. The copper-containing nitrite reductase gene (nirK) was amplified from 45 N2O-producing strains, and its genetic variability showed a strong congruence with the ITS phylogeny, indicating vertical inheritance of this trait. Taken together, this comprehensive set of findings should enhance our knowledge of fungi as a source of N2O in the environment.
Although capillary electrophoresis coupled to mass spectrometry (CE-MS) has potential application in the field of metabolite profiling, very few studies actually used CE-MS to identify clinically ...useful body fluid metabolites. Here we present an optimized CE-MS setup and analysis pipeline to reproducibly explore the metabolite content of urine. We show that the use of a beveled tip capillary improves the sensitivity of detection over a flat tip. We also present a novel normalization procedure based on the use of endogenous stable urinary metabolites identified in the combined metabolome of 75 different urine samples from healthy and diseased individuals. This method allows a highly reproducible comparison of the same sample analyzed nearly 130 times over a range of 4 years. To demonstrate the use of this pipeline in clinical research we compared the urinary metabolome of 34 newborns with ureteropelvic junction (UPJ) obstruction and 15 healthy newborns. We identified 32 features with differential urinary abundance. Combination of the 32 compounds in a SVM classifier predicted with 76% sensitivity and 86% specificity UPJ obstruction in a separate validation cohort of 24 individuals. Thus, this study demonstrates the feasibility to use CE-MS as a tool for the identification of clinically relevant urinary metabolites.
Metabolic syndrome can induce chronic kidney disease in humans. Genetically engineered mice on a C57BL/6 background are highly used for mechanistic studies. Although it has been shown that metabolic ...syndrome induces cardiovascular lesions in C57BL/6 mice, in depth renal phenotyping has never been performed. Therefore in this study we characterized renal function and injury in C57BL/6 mice with long-term metabolic syndrome induced by a high fat and fructose diet (HFFD). C57BL/6 mice received an 8 months HFFD diet enriched with fat (45% energy from fat) and drinking water enriched with fructose (30%). Body weight, food/water consumption, energy intake, fat/lean mass ratio, plasma glucose, HDL, LDL, triglycerides and cholesterol levels were monitored. At 3, 6 and 8 months, renal function was determined by inulin clearance and measure of albuminuria. At sacrifice, kidneys and liver were collected. Metabolic syndrome in C57BL/6 mice fed a HFFD was observed as early 4 weeks with development of type 2 diabetes at 8 weeks after initiation of diet. However, detailed analysis of kidney structure and function showed only minimal renal injury after 8 months of HFFD. HFFD induced moderate glomerular hyperfiltration (436,4 µL/min vs 289,8 µL/min; p-value=0.0418) together with a 2-fold increase in albuminuria only after 8 months of HFFD. This was accompanied by a 2-fold increase in renal inflammation (p-value=0.0217) but without renal fibrosis or mesangial matrix expansion. In addition, electron microscopy did not show alterations in glomeruli such as basal membrane thickening and foot process effacement. Finally, comparison of the urinary peptidome of these mice with the urinary peptidome from humans with diabetic nephropathy also suggested absence of diabetic nephropathy in this model. This study provides evidence that the HFFD C57BL/6 model is not the optimal model to study the effects of metabolic syndrome on the development of diabetic kidney disease.
Abstract
Background
Sentinel networks composed of general practitioners (GPs) represent a powerful tool for epidemiologic surveillance and ad-hoc studies. Globalization necesitates greater ...international cooperation among sentinel networks. The aim of this study was to inventory GP sentinel networks involved in epidemiological surveillance on a global scale.
Methods
GP sentinel surveillance networks were inventoried globally between July 2016 and December 2019. Each identified network was required to fill out an electronic descriptive survey for inclusion.
Results
A total of 148 networks were identified as potential surveillance networks in general practice and were contacted. Among them, 48 were included in the study. Geographically, 33 networks (68.8%) were located in Europe and 38 (79.2%) had national coverage. The number of GPs registered in these networks represented between 0.1 and 100% of the total number of GPs in the network’s country or region, with a median of 2.5%. All networks were involved in continuous epidemiologic surveillance and 47 (97.9%) monitored influenza-like illness. Data collection methods were paper-based forms (
n
= 26, 55.3%), electronic forms on a dedicated website (
n
= 18, 38.3%), electronic forms on a dedicated software program (
n
= 14, 29.8%), and direct extraction from electronic medical records (
n
= 14, 29.8%). Along with this study, a website has been created to share all data collected.
Conclusions
This study represents the first global geographic mapping of GP sentinel surveillance networks. By sharing this information, collaboration between networks will be easier, which can strengthen the quality of international epidemiologic surveillance. In the face of crises like that of COVID-19, this is more imperative than ever before.
Bilateral congenital abnormalities of the kidney and urinary tract (CAKUT), although are individually rare diseases, remain the main cause of chronic kidney disease in infants worldwide. Bilateral ...CAKUT display a wide spectrum of pre- and postnatal outcomes ranging from death in utero to normal postnatal renal function. Methods to predict these outcomes in utero are controversial and, in several cases, lead to unjustified termination of pregnancy. Using capillary electrophoresis coupled with mass spectrometry, we have analyzed the urinary proteome of fetuses with posterior urethral valves (PUV), the prototypic bilateral CAKUT, for the presence of biomarkers predicting postnatal renal function. Among more than 4000 fetal urinary peptide candidates, 26 peptides were identified that were specifically associated with PUV in 13 patients with early end-stage renal disease (ESRD) compared to 15 patients with absence of ESRD before the age of 2. A classifier based on these peptides correctly predicted postnatal renal function with 88% sensitivity and 95% specificity in an independent blinded validation cohort of 38 PUV patients, outperforming classical methods, including fetal urine biochemistry and fetal ultrasound. This study demonstrates that fetal urine is an important pool of peptides that can predict postnatal renal function and thus be used to make clinical decisions regarding pregnancy.
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