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Two surgical techniques used for peritoneal metastasis involve a risk of exposure to antineoplastic drugs (ADs): hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). The objective of this study was to assess the differences in perception, training, and knowledge of the risks as well as in the protection practices and occupational exposures of all worker categories.

Abstract Gut microbiota dysbiosis has been implicated in a variety of systemic disorders, notably metabolic diseases including obesity and impaired liver function, but the underlying mechanisms are uncertain. To investigate this question, we transferred caecal microbiota from either obese or lean mice to antibiotic‐free, conventional wild‐type mice. We found that transferring obese‐mouse gut microbiota to mice on normal chow (NC) acutely reduces markers of hepatic gluconeogenesis with decreased hepatic PEPCK activity, compared to non‐inoculated mice, a phenotypic trait blunted in conventional NOD2 KO mice. Furthermore, transferring of obese‐mouse microbiota changes both the gut microbiota and the microbiome of recipient mice. We also found that transferring obese gut microbiota to NC‐fed mice then fed with a high‐fat diet (HFD) acutely impacts hepatic metabolism and prevents HFD‐increased hepatic gluconeogenesis compared to non‐inoculated mice. Moreover, the recipient mice exhibit reduced hepatic PEPCK and G6Pase activity, fed glycaemia and adiposity. Conversely, transfer of lean‐mouse microbiota does not affect markers of hepatic gluconeogenesis. Our findings provide a new perspective on gut microbiota dysbiosis, potentially useful to better understand the aetiology of metabolic diseases.

Objective: To demonstrate that glycemia and insulin resistance are controlled by a mechanism involving the adaptive immune system and gut microbiota crosstalk. Methods: We triggered the immune system with microbial extracts specifically from the intestinal ileum contents of HFD-diabetic mice by the process of immunization. 35 days later, immunized mice were fed a HFD for up to two months in order to challenge the development of metabolic features. The immune responses were quantified. Eventually, adoptive transfer of immune cells from the microbiota-immunized mice to naïve mice was performed to demonstrate the causality of the microbiota-stimulated adaptive immune system on the development of metabolic disease. The gut microbiota of the immunized HFD-fed mice was characterized in order to demonstrate whether the manipulation of the microbiota to immune system interaction reverses the causal deleterious effect of gut microbiota dysbiosis on metabolic disease. Results: Subcutaneous injection (immunization procedure) of ileum microbial extracts prevented hyperglycemia and insulin resistance in a dose-dependent manner in response to a HFD. The immunization enhanced the proliferation of CD4 and CD8 T cells in lymphoid organs, also increased cytokine production and antibody secretion. As a mechanism explaining the metabolic improvement, the immunization procedure reversed gut microbiota dysbiosis. Finally, adoptive transfer of immune cells from immunized mice improved metabolic features in response to HFD. Conclusions: Glycemia and insulin sensitivity can be regulated by triggering the adaptive immunity to microbiota interaction. This reduces the gut microbiota dysbiosis induced by a fat-enriched diet. Keywords: Gut microbiota and metabolic diseases, Immunity, Insulin resistance

Social and cultural capital are critical components of success among college students. In this paper, we examine the creation, accumulation, and distribution of social and cultural capital by and among underserved college students who participated in a summer bridge program at one regional public state university. Using qualitative data from interviews with participants, the analysis highlights the importance of trust, sense of belonging and use of noncognitive strategies. We argue that in addition to traditional achievement measures such as GPA and test scores, social and cultural capital need to be considered. While quantitative measures often label these students as below benchmarks, this study highlights how social and cultural capital are assets to be nurtured and facilitated. [Note: The publication year (2021) shown on the PDF is incorrect. The correct publication year for this article is 2022.]

This article discusses the efficacy of a second round of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in patients with diffuse large B-cell lymphoma (DLBCL) who did not respond to the initial treatment. The article highlights the limited treatment options for patients who do not respond to CAR T-cell therapy and presents data from various studies on the efficacy of a second infusion of CAR T-cells. The case study presented in the article demonstrates the potential for a second round of CAR T-cell therapy to achieve a prolonged complete response and the importance of considering a second infusion when B-cells reappear. The article emphasizes the need for further research on the benefits of CAR T-cell reinfusion after initial treatment failure. [Extracted from the article]

The 17-institution Connecticut State Colleges & Universities System (CSCU) formed a systemwide open educational resources (OER) Council in 2017 that was primarily focused on the adoption of no-cost or low-cost (NOLO) course materials as a means to provide equitable access to learning materials. The CSCU consortium of library directors partnered with the OER Council to construct a website, OpenCSCU, providing curated OER, a support network and a faculty-recognition program. With the OpenCSCU site established as a clearinghouse for OER-related information, it was a natural progression to take advantage of the existing technology for a new communications effort. The OpenCSCU Blog was launched in September 2021. It is intended to provide guidance and support to readers by demonstrating the value of open content and practices to better serve student success.

Aims: We propose using glomerular filtration rate (GFR) as the physiological basis for distinguishing components of renal clearance. Methods: Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed‐effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age and serum creatinine. A dataset created from 18 sources resulted in 27,338 drug concentrations from 9,901 patients. Body size and composition, maturation and renal function were used to describe differences in drug clearance and volume of distribution. Results: This study demonstrates that GFR is a predictor of two distinct components of renal elimination clearance: (1) GFR clearance associated with normal GFR and (2) non‐GFR clearance not associated with normal GFR. All three drugs had GFR clearance estimated as a drug‐specific percentage of normal GFR (gentamicin 39%, amikacin 90% and vancomycin 57%). The total clearance (sum of GFR and non‐GFR clearance), standardized to 70 kg total body mass, 176 cm, male, renal function 1, was 5.58 L/h (95% confidence interval [CI] 5.50‐5.69) (gentamicin), 7.77 L/h (95% CI 7.26‐8.19) (amikacin) and 4.70 L/h (95% CI 4.61‐4.80) (vancomycin). Conclusions: GFR provides a physiological basis for renal drug elimination. It has been used to distinguish two elimination components. This physiological approach has been applied to describe clearance and volume of distribution from premature neonates to elderly adults with a wide dispersion of size, body composition and renal function. Dose individualization has been implemented using target concentration intervention. [ABSTRACT FROM AUTHOR]

Introduction: Compounding robots are increasingly being implemented in hospital pharmacies. In our hospital, the recent acquisition of a robot (RIVATM, ARxIUM) for intravenous cancer drug compounding obliged us to replace the previously used infusion devices. The objective of the present study was to assess and qualify the new intravenous sets prior to their use in our hospital and prior to the implementation of the compounding robot. Materials and Methods: The ChemoLockTM (ICU Medical) was compared with the devices used previously for compounding (BD PhaSealTM, Becton-Dickinson) and infusion (Connect-ZTM, Codan Medical). The connection/disconnection of infusion devices to/from 50 mL infusion bags was tested with a dynamometer (Multitest-i, Mecmesin). Leakage contamination was visualized by a methylene blue assay and was quantified in simulated pump infusions with 20 mg/mL quinine sulfate (N = 36/group); after the analytical assay had been validated, quinine was detected by UV-spectrophotometry at 280 and 330 nm. Groups were compared using chi-squared or Mann–Whitney U tests. Results: The connection/disconnection test showed that although all the devices complied with the current standard, there was a statistically significant difference in the mean ± standard deviation compression force (51.5 ± 11.6 for the Connect-ZTM vs. 60.3 ± 11.7 for the ChemoLockTM; p = 0.0005). Leaks were detected in 32 (29.1%) of the 110 tests of the ChemoLockTM. The contamination rates were also significantly different: 13.9% for the BD PhaSealTM versus 75.0% for the ChemoLockTM; p < 0.0001). Discussion/conclusion: Our results showed that the new infusion device complied with current standards. However, the presence of contamination emphasizes the need for operators to use the recommended personal protective equipment. Further studies of contamination with cancer drugs are required. [ABSTRACT FROM AUTHOR]

The new generation of students, Generation Z students, have different expectations of their education. They value inclusivity, social consciousness, and hands-on learning experiences. To meet their expectations, we argue that educators should use renewable assignments. These assignments add value beyond the course by creating Open Educational Resources (OER), openly licensed with the 5R: retain, reuse, revise, remix, and redistribute. In this article, we first present renewable assignments, OER-enabled pedagogy, the assignments that students used to develop openly licensed educational material and the products they created. Then, we offer step-by-step guidance on crafting effective renewable assignments. Finally, the two students who coauthored this paper examine how OER-enabled pedagogy follows the learning skills of Generation Z: independence, collaboration, and engagement. [ABSTRACT FROM AUTHOR]

To avoid the failures in therapy with psychotropic drugs, treatments can be personalized by applying the results of therapeutic drug monitoring and pharmacogenetic testing. The objective of the present single-center observational study was to describe the changes in psychotropic drug management prompted by therapeutic drug monitoring and pharmacogenetic testing, and to compare the effective drug concentration based on metabolic status with the dose predicted using an in silico decision tool for drug–drug interactions. The study was conducted in psychiatry wards at Lille University Hospital (Lille, France) between 2016 and 2020. Patients with data for at least one therapeutic drug monitoring session or pharmacogenetic test were included. Blood tests were performed for 490 inpatients (mainly indicated by treatment monitoring or failure) and mainly concerned clozapine (21.4%) and quetiapine (13.7%). Of the 617 initial therapeutic drug monitoring tests, 245 (40%) complied with good sampling practice. Of the patients, 51% had a drug concentration within the therapeutic range. Regardless of the drug concentration, the drug management did not change in 83% of cases. Thirty patients underwent pharmacogenetic testing (twenty-seven had also undergone therapeutic drug monitoring) for treatment failure; the plasma drug concentration was outside the reference range in 93% of cases. The patient's metabolic status explained the treatment failure in 12 cases (40%), and prompted a switch to a drug metabolized by another CYP450 pathway in 5 cases (42%). Of the six tests that could be analyzed with the in silico decision tool, all of the drug concentrations after adjustment were included in the range estimated by the tool. Knowledge of a patient's drug concentration and metabolic status (for CYD2D6 and CYP2C19) can help clinicians to optimize psychotropic drug adjustment. Drug management can be optimized with good sampling practice, support from a multidisciplinary team (a physician, a geneticist, and clinical pharmacist), and decision support tools. [ABSTRACT FROM AUTHOR]

Introduction: In a few regions of the globe, deliberate botanical intoxication may induce significant rates of toxicity and fatality. The objective of this report was to describe plant self-intoxication using the experiences of the southeastern France poison control center (PCC) between 2002 and 2021. Results: During those 20 years, 262 deliberate plants poisonings were reported involving 35 various plants. In most of the cases, poisoning was caused by Nerium oleander (n = 186, 71%), followed by the Datura genus (4.2%), Ricinus communis (3.8%), Taxus baccata (1.9%), Digitalis purpurea (1.2%), Aconitum nape (1.9%), Myristica fragans (1.5%), and Pyracantha coccine (1.2%). Through the 262 plants poisonings, 19 patients among the 186 Nerium oleander poisonings received Digifab as an antidote and 1 patient received physostigmine among the 11 Datura poisonings. Only four deaths were reported for this review, each involving Nerium oleander. Discussion: The first involved species was Nerium oleander (71% of all plants poisonings), then Datura sp and Ricinus communis. It is explained by this native local species' important repartition. Most patients must be admitted to an emergency department for adapted medical care; however, only 41 of them described severe poisonings symptoms. Even fewer needed an antidote, only 20 patients. There is no protocol for the use of a specific treatment, and it might be interesting to develop one for this purpose. Material and Methods: This retrospective review was realized with files managed by the southeastern France PCC based in Marseille from 2002 to 2021. Our department covers the complete French Mediterranean coast, Corsica, and tropical islands (Reunion Island, Mayotte). For every patient, toxicity was evaluated using the Poison Severity Score (PSS). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Button battery ingestion in children can be fatal if oesophageal perforation occurs. Such children require chest radiography in the emergency department to determine the button battery position and number. Current guidelines recommend that a button battery impacted in the oesophagus should be removed within two hours. We developed a clinical tool (the button battery impaction score) to estimate the risk of oesophageal impaction and help determine the most appropriate healthcare facility for initial assessment, either a local medical centre or a medical centre with the infrastructure for endoscopic retrieval. A multi-centre retrospective study was conducted over seven years in eight French poison centres. We included patients aged less than 12 years with radiography showing the button battery position and a symptom description before radiography. Button battery impaction scores were calculated using backward stepwise selection. A total of 1,430 patients were included, of whom 86, 461, and 375 had a button battery in their oesophagus, stomach, and post-pyloric position, respectively. No button batteries were identified by radiography in 508 patients. Sixteen of thirty-five factors independently predicted oesophageal impaction before chest radiography (P < 0.05). After the backward stepwise selection, the following seven factors contributed to the button battery impaction score: cough, drooling, dysphagia/food refusal, fever, pain (unspecified location), vomiting, and button battery ≥ 15 mm. The button battery impaction score showed an area under the curve value of 0.87, a negative predictive value of 0.98, and a sensitivity of 0.86. No cases of death, stricture, or haemorrhage were observed in patients with negative scores, including those with oesophageal impaction. A button battery impaction score used readily available data to predict the risk of oesophageal impaction after button battery ingestion and before chest radiography. When further validated, this rapid tool may be widely applicable in determining an appropriate facility for patient transfer to either a local medical centre or a medical centre with the infrastructure for endoscopic retrieval. [ABSTRACT FROM AUTHOR]

Introduction: Ever since the late 1970s, occupational exposure associated with the handling of antineoplastic drugs (ADs) in the healthcare environment has been highlighted and demonstrated. Contamination was detected in both operating rooms (OR) and compounding units (CU), where healthcare workers handle and are exposed to ADs in different ways. In the OR, the risk of exposure is higher and the staff receives less training in handling ADs than in the CU. This study aimed to assess and compare knowledge and practices about the safe handling of ADs by caregivers working in these two locations, namely the CU and OR. Methods: Two questionnaires (one each for the OR and CU) were created by two investigator pharmacists and were completed during a personal interview of 20 min. The questions were related to the following topics: training, knowledge about occupational exposure and questions related to protective practices. A scoring system was implemented to assess the knowledge and practices of each participant. Results: In total, 38 caregivers working in the OR and 39 in the CU were included in our study. Significantly more CU staff had specific initial training (p < 0.001) and ongoing training (p < 0.001) in handling ADs. Concerning the knowledge score, OR caregivers had a significantly lower median score for contamination routes (p < 0.001), contamination surfaces (p < 0.001), existing procedures (p < 0.001) and total knowledge (p < 0.001) than CU caregivers. Concerning protective handling practices of ADs, the two locations had nonsignificantly different median scores (p = 0.892). Conclusion: This study suggests that there is still room for improvement in terms of knowledge and protection practices when handling ADs. An appropriate and tailored training program should be developed and provided to all caregivers who handle or come in contact with ADs. Clinical trial registration Study CONTACT, ref. 19-504. [ABSTRACT FROM AUTHOR]

Purpose: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide and are involved in several drug interactions. Recently, several studies have suggested that PPIs may interfere with the efficacy of capecitabine. This study primarily aimed to investigate the effects of PPI intake on the pathologic response rate of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy with capecitabine. Method: A retrospective study was conducted at a French Comprehensive Cancer Center. Patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were included in the study. Demographic parameters, treatment characteristics, survival data, and PPI intake data were collected. Frequencies and percentages were reported for categorical variables and medians and interquartile ranges for continuous variables. Distribution of variables was compared according to PPI treatment using the chi-square test or Fisher's exact test for categorical data and nonparametric Wilcoxon tests for continuous variables. Survival data were estimated using the Kaplan–Meier method and compared using the log-rank test. Results: In total, 215 patients were included, of whom 135 (62.8%) were men. The PPI intake frequency was 16.1%. The rate of complete pathological response was not significantly lower in patients on PPIs than in those not on PPIs (8.7% vs. 19%, p = 0.36). PPI intake was not associated with a statistically significant decrease in recurrence-free survival (hazard ratio [HR] = 1.26, 95% confidence interval [CI] 0.61–2.60, p = 0.54) or overall survival (HR = 0.95, 95% CI 0.33–2.76, p = 0.93). Conclusion: No significant association was observed between PPI co-medication and complete pathological response or survival in patients treated for locally advanced rectal cancer. However, the safety of PPIs could not be confirmed. Further ancillary studies of prospective clinical trials or studies using the Health Data Hub are necessary to explore the effects of PPIs on rectal cancer more accurately. [ABSTRACT FROM AUTHOR]

Background: Stability study of a 10 mg/mL injectable cisatracurium solution stored refrigerated in amber glass ampoules for 18 months (M18). Methods: 4000 ampoules were aseptically compounded using European Pharmacopoeia (EP)-grade cisatracurium besylate, sterile water for injection, and benzenesulfonic acid. We developed and validated a stability-indicating HPLC-UV method for cisatracurium and laudanosine. At each stability study time point, we recorded the visual aspect, cisatracurium and laudanosine levels, pH, and osmolality. Sterility, bacterial endotoxin content, and non-visible particles in solution were checked after compounding (T0) and after M12 and M18 of storage. We used HPLC-MS/MS to identify the degradation products (DPs). Results: During the study, osmolality remained stable, pH decreased slightly, and the organoleptic properties did not change. The number of non-visible particles remained below the EP's threshold. Sterility was preserved, and bacterial endotoxin level remained below the calculated threshold. Cisatracurium concentration remained within the ±10% acceptance interval for 15 months and then decreased to 88.7% of C0 after M18. The laudanosine generated accounted for less than a fifth of the cisatracurium degradation, and three DPs were generated—identified as EP impurity A, impurities E/F, and impurities N/O. Conclusion: Compounded 10 mg/mL cisatracurium injectable solution is stable for at least 15 months. [ABSTRACT FROM AUTHOR]

Although poisonings due to a toxic substance being decanted into a secondary container are often reported to poison centers, we were unable to locate prior European data about their circumstances, incidence and consequences. We sought to describe the circumstances and outcomes of this behavior. We conducted a prospective study of all poison exposures involving transfer to a secondary container reported to our poison center during a six month interval (January 1, 2021 through June 30, 2021). We called patients and clinicians for follow up the next day. We used a prepared questionnaire and added the responses to the national database for French poison centers. We identified and included 238 patients (104 male, 134 female) with a median age of 39 years [range 0–94 y]. Exposure was mainly oral (n = 221), the secondary container was mainly a water bottle (n = 173), toxic substances were essentially cleaning products (n = 63) or bleach (n = 48). Symptoms were gastrointestinal (vomiting, diarrhea, abdominal pain) (n = 143) or respiratory (cough, dyspnea, aspiration pneumonia) (n = 15). The World Health Organisation/International Programme on Chemical Safety/European Commission/European Association of Poison Centres and Clinical Toxicologists Poisoning Severity Score was none in 76 cases (31.9%), minor in 147 (61.8%), moderate in 12 (5%), and severe in three cases (1.3%). Products that led to severe poisoning contained either ammonium hydroxide or sodium hydroxide. Two of the patients required intensive care treatment. At the end of the follow-up, 235 patients fully recovered, and three patients had sequelae. The study illustrates the risk of toxic substance transfer. Water bottles were the secondary containers in most exposures to decanted substances. Most had minor or no effects, but nearly one-quarter were admitted to the hospital. The few severe exposures involved either ammonium hydroxide or sodium hydroxide. [ABSTRACT FROM AUTHOR]