Attributes for a discrete-choice experiment on preferences of patients for oncology pharmacy consultations.

PURPOSE: To ensure the safe use of oral anticancer drugs, oncology pharmacy consultations (OPCs) have been established in France. They are conditioned by the needs, expectations, and involvement of the patients in their care. Thus, it is essential to elicit their preferences. The discrete-choice experiment (DCE) is a method recommended by the ISPOR for such a task. The "selection and validation of attributes and their values" step is fundamental in this process. In this context, the aim of this study was to present our research approach to identify and validate the attributes that characterize an OPC and their values. METHODS: Due to the lack of relevant published data in the literature, the focus-group method was used in accordance with good research practices for the application of conjoint-analysis of the ISPOR. The two-round Delphi method was used to validate the attributes and their values identified by the focus-group method. RESULTS: The focus-group method enabled identification of nine attributes. Thirty-seven healthcare professionals at a national level, including 30 pharmacists and seven physicians, were selected to take part in the Delphi procedure. Seven attributes (frequency, planification, operation mode, duration, content, written support, and report) and their values were thus validated. CONCLUSION: Based on these results, the next step will be to elicit patient preferences for OPCs and to then shed light on the issues of pharmaceutical support for patients by comparing their preferences with those of informal caregivers and, in particular, those of the healthcare professionals involved in their care.

Retrospective comparison of a weight-based dose every 2 weeks with a fixed dose every month: a real-life analysis of nivolumab in the treatment of advanced melanoma.

Nivolumab was first authorized at a weight-based dose (WBD) of 3 mg/kg every two weeks (Q2W). Since 2017, a fixed dose (FD) regimen [first 240 mg Q2W and then 480 mg per month (Q4W)] was allowed. The objective of the study was to compare a WBD regimen and an FD regimen with regard to effectiveness and safety. We conducted a single-center, retrospective, real-life study of consecutive adult patients who had received a WBD of nivolumab or an FD of 480 mg Q4W. The primary endpoint was the occurrence of grade ≥3 immune-related adverse events (irAEs). The secondary endpoints were overall survival and cost of the treatment. In all, 342 patients were included: 71 in the WBD cohort and 271 in the FD cohort. Of these patients, 201 patients (59.6%) experienced an irAE, and 24 of these events were graded as ≥3. At 12 months, there was no significant difference in irAE occurrence between the two cohorts [hazard ratio (95% confidence interval): 0.54 (0.21-1.36), P  = 0.19]. The 12-month overall survival rate was significantly lower in the WBD cohort ( P  < 0.001). Switching from a fortnightly weight dose to a fixed monthly dose halves the cost of hospitalization. Our results did not show a significant difference between WBD and FD cohort in the occurrence of severe irAEs. However overall survival appeared to be significantly higher in FD group. Some clinical trials are investigating a hybrid dosing regimen in which a WBD is capped by an FD. The present results need to be confirmed in prospective studies.

Combination of a propofol emulsion with alpha-2 adrenergic receptor agonists used for multimodal analgesia or sedation in intensive care units: a physicochemical stability study.

OBJECTIVES: To assess the physicochemical stability of the combination of a propofol emulsion with an alpha-2 (α2) adrenergic receptor agonist (α2A; clonidine or dexmedetomidine) under conditions mimicking routine practice in an intensive care unit or in multimodal analgesia procedures. METHODS: We developed and validated three stability-indicating methods based on high-performance liquid chromatography with ultraviolet (HPLC-UV) detection. Eight different conditions per combination were evaluated in triplicate, with variations in the simulated, bodyweight-adjusted dose level and the drugs' flow rate. The drugs were mixed in clinically relevant concentrations and proportions and then stored unprotected from light, in clear glass vials at room temperature for 96 hours. At each sampling point, we assessed the chemical stability (the HPLC-UV drug level, pH, and osmolality) and physical compatibility (visual aspect, zeta potential (ZP), mean droplet diameter (MDD, Z-average) and polydispersity index (PDI)). We validated our stability findings in positive and negative control experiments. RESULTS: Over the 96-hour test, the concentrations of propofol, clonidine and dexmedetomidine did not fall below 90% of the initial value, and the pH and osmolality were stable. The visual aspect of the mixed propofol emulsions did not change. The MDD remained below 500 nm (range 165-195 nm). The PDI was always below 0.4; 78.7% of the measurements were below 0.1 and 21.3% were between 0.1 and 0.4. The ZP measurements (-31.3 to -42.9 mV) suggested that the emulsion was stable. The MDD and PDI increased slightly at 96 hours under some conditions, which might indicate early destabilisation of the emulsion. Given that the MDD remained below 500 nm, these emulsions are compatible with intravenous administration. CONCLUSIONS: Our results demonstrate the chemical and physical compatibility of propofol-α2 agonist mixtures at concentrations and in proportions representative of standard protocols when stored unprotected from light at room temperature for 96 hours.

A physiological approach to renal clearance: From premature neonates to adults.

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.

Evaluation of cancer drug infusion devices prior to the implementation of a compounding robot.

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.

Can inhaled cannabis users accurately evaluate impaired driving ability? A randomized controlled trial.

Aims: To study the effect of inhaled cannabis on self-assessed predicted driving ability and its relation to reaction times and driving ability on a driving simulator. Participants and methods: 30 healthy male volunteers aged 18-34: 15 chronic (1-2 joints /day) and 15 occasional (1-2 joints/week) consumers. Self-assessed driving confidence (visual analog scale), vigilance (Karolinska), reaction time (mean reciprocal reaction time mRRT, psychomotor vigilance test), driving ability (standard deviation of lane position SDLP on a York driving simulator) and blood concentrations of delta-9-tétrahydrocannabinol (THC) were measured before and repeatedly after controlled inhalation of placebo, 10 mg or 30 mg of THC mixed with tobacco in a cigarette. Results: Cannabis consumption (at 10 and 30 mg) led to a marked decrease in driving confidence over the first 2 h which remained below baseline at 8 h. Driving confidence was related to THC dose and to THC concentrations in the effective compartment with a low concentration of 0.11 ng/ml for the EC50 and a rapid onset of action (T1/2 37 min). Driving ability and reaction times were reduced by cannabis consumption. Driving confidence was shown to be related to driving ability and reaction times in both chronic and occasional consumers. Conclusions: Cannabis consumption leads to a rapid reduction in driving confidence which is related to reduced ability on a driving simulator. Clinical trial registration: ClinicalTrials.gov, identifier: NCT02061020.

Deliberate Self-Poisoning with Plants in Southeastern France, a Poison Center 20-Year Report.

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).

Cultivation-based characterization of biliary microbiota in bile samples collected during routine endoscopic retrograde cholangiography: 10 years of experience at a tertiary center.

INTRODUCTION: Bile has long been considered sterile. Recent studies show that bacteria can frequently be detected in bile and certain bacterial species are associated with bile duct-associated liver disease. OBJECTIVES: To detect bacterial species and antibiotic resistance in bile in bile duct-associated liver disease. METHODOLOGY: To evaluate microbiological findings of bile samples obtained during ERCP at a tertiary center from 2009 to 2019. RESULTS: There were 1885 bile samples from 992 patients examined by cultural microbiological analysis. Germs were detected in 91% of the samples. Most bile samples (n) were obtained from patients who had undergone liver transplantation (LTX; n = 556), followed by patients with primary sclerosing cholangitis (PSC; n = 287). Enterococci were detected in 67% of samples, followed by E. coli (32.2%) and Klebsiella (28.2%). Of 1151 enterococci detected, 13.1% were vancomycin (VRE)s and of 216 staphylococci detected, 10% were ORSA. The proportion of VRE increased with the number of tests performed during ERCPs ( P  < 0.01; chi-square) and increased 2.5-fold over 10 years, whereas the detection of ORSA remained stable. Patients with cholecystolithiasis were significantly more likely to have evidence of VRE in bile compared to LTX and PSC patients ( P  = 0.02, P  < 0.01; chi-square). The most abundant bacterial genera showed highly statistically significant differences in their levels of liver enzymes and c-reactive protein ( P  < 0.001). CONCLUSION: Knowledge of the bacterial composition of bile in various bile duct-associated liver diseases may allow more targeted antibiotic use in the future.

Use of Machine Learning for Dosage Individualization of Vancomycin in Neonates.

BACKGROUND AND OBJECTIVE: High variability in vancomycin exposure in neonates requires advanced individualized dosing regimens. Achieving steady-state trough concentration (C0) and steady-state area-under-curve (AUC0-24) targets is important to optimize treatment. The objective was to evaluate whether machine learning (ML) can be used to predict these treatment targets to calculate optimal individual dosing regimens under intermittent administration conditions. METHODS: C0 were retrieved from a large neonatal vancomycin dataset. Individual estimates of AUC0-24 were obtained from Bayesian post hoc estimation. Various ML algorithms were used for model building to C0 and AUC0-24. An external dataset was used for predictive performance evaluation. RESULTS: Before starting treatment, C0 can be predicted a priori using the Catboost-based C0-ML model combined with dosing regimen and nine covariates. External validation results showed a 42.5% improvement in prediction accuracy by using the ML model compared with the population pharmacokinetic model. The virtual trial showed that using the ML optimized dose; 80.3% of the virtual neonates achieved the pharmacodynamic target (C0 in the range of 10-20 mg/L), much higher than the international standard dose (37.7-61.5%). Once therapeutic drug monitoring (TDM) measurements (C0) in patients have been obtained, AUC0-24 can be further predicted using the Catboost-based AUC-ML model combined with C0 and nine covariates. External validation results showed that the AUC-ML model can achieve an prediction accuracy of 80.3%. CONCLUSION: C0-based and AUC0-24-based ML models were developed accurately and precisely. These can be used for individual dose recommendations of vancomycin in neonates before treatment and dose revision after the first TDM result is obtained, respectively.

Signaling-specific inhibition of the CB1 receptor for cannabis use disorder: phase 1 and phase 2a randomized trials.

Cannabis use disorder (CUD) is widespread, and there is no pharmacotherapy to facilitate its treatment. AEF0117, the first of a new pharmacological class, is a signaling-specific inhibitor of the cannabinoid receptor 1 (CB1-SSi). AEF0117 selectively inhibits a subset of intracellular effects resulting from Δ9-tetrahydrocannabinol (THC) binding without modifying behavior per se. In mice and non-human primates, AEF0117 decreased cannabinoid self-administration and THC-related behavioral impairment without producing significant adverse effects. In single-ascending-dose (0.2 mg, 0.6 mg, 2 mg and 6 mg; n = 40) and multiple-ascending-dose (0.6 mg, 2 mg and 6 mg; n = 24) phase 1 trials, healthy volunteers were randomized to ascending-dose cohorts (n = 8 per cohort; 6:2 AEF0117 to placebo randomization). In both studies, AEF0117 was safe and well tolerated (primary outcome measurements). In a double-blind, placebo-controlled, crossover phase 2a trial, volunteers with CUD were randomized to two ascending-dose cohorts (0.06 mg, n = 14; 1 mg, n = 15). AEF0117 significantly reduced cannabis' positive subjective effects (primary outcome measurement, assessed by visual analog scales) by 19% (0.06 mg) and 38% (1 mg) compared to placebo (P < 0.04). AEF0117 (1 mg) also reduced cannabis self-administration (P < 0.05). In volunteers with CUD, AEF0117 was well tolerated and did not precipitate cannabis withdrawal. These data suggest that AEF0117 is a safe and potentially efficacious treatment for CUD.ClinicalTrials.gov identifiers: NCT03325595 , NCT03443895 and NCT03717272 .

Cistracurium Besylate 10 mg/mL Solution Compounded in a Hospital Pharmacy to Prevent Drug Shortages: A Stability Study Involving Four Degradation Products.

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.

Encouraging outcomes of stemless ceramic head anatomic shoulder arthroplasty in severe primary osteoarthritis (Walch type B glenoids).

Background: We report the radiological and functional outcomes at five years in patients with severe osteoarthritis of the glenohumeral joint and a Walch type B glenoid who have undergone stemless anatomic total shoulder replacement. Methods: A retrospective analysis of case notes, computed tomography scans and plain radiographs of patients undergoing anatomic total shoulder replacement for primary glenohumeral osteoarthritis were performed. Patients were grouped by the severity of their osteoarthritis using the modified Walch classification, glenoid retroversion and posterior humeral head subluxation. An evaluation was made using modern planning software. Functional outcomes were assessed using the American shoulder and elbow surgeons score, shoulder pain and disability index and visual analogue scale. Annual Lazarus scores were reviewed as regard to glenoid loosening. Results: Thirty patients were reviewed at 5 years. Analysis of all patient-reported outcome measures demonstrated significant improvement at 5-year review, American shoulder and elbow surgeons (p = <0.0001), shoulder pain and disability index (p = 0.0001), visual analogue scale (p = 0.0001). Radiological associations between Walch scores and Lazarus scores were not statistically significant (p = 0.1251) at 5 years. There were no associations between features of glenohumeral osteoarthritis and patient-reported outcome measures. Discussion: The severity of osteoarthritis did not show any association with glenoid component survivorship or with patient-reported outcome measures at 5 years review. Level of evidence: IV.

Unintentional poisoning from decanted toxic household chemicals.

BACKGROUND: 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. MATERIALS AND METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Perception, knowledge, practices and training regarding the risk of exposure to antineoplastic drugs in three French compounding units.

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.

Adverse drug reactions in geriatric psychiatry-retrospective cohort study of a 6-year period.

OBJECTIVE: To investigate the frequency and characteristics of adverse drug reactions (ADRs) that occurred on the gerontopsychiatric ward of Hannover Medical School over a 6-year period. DESIGN: Retrospective monocentric cohort study. RESULTS: Six hundred thirty-four patient cases (mean age 76.6 ± 7.1 years; 67.2% female) were analysed. In total, 92 ADRs in 56 patient cases were registered in the study population. The overall ADR prevalence, the ADR prevalence upon hospital admission, and the ADR prevalence during hospitalisation were 8.8%, 6.3%, and 4.9%, respectively. The most frequent ADRs were extrapyramidal symptoms, alterations in blood pressure or heart rate, and electrolyte disturbances. Of note, two cases of asystole and one case of obstructive airway symptoms related to general anaesthesia in the context of electroconvulsive therapy (ECT) were detected. The presence of coronary heart disease was associated with an increased risk of ADR occurrence (odds ratio (OR) 2.92, 95% confidence interval (CI) 1.37-6.22), while the presence of dementia was associated with a decreased risk of ADR development (OR 0.45, 95% CI 0.23-0.89). CONCLUSIONS: Type and prevalence of ADRs in the present study were largely in accordance with previous reports. By contrast, we did not observe a relationship between advanced age or female sex and ADR occurrence. We detected a risk signal for cardiopulmonary ADRs related to general anaesthesia in the context of ECT that warrants further investigation. Elderly psychiatric patients should be carefully screened for cardiopulmonary comorbidities before initiation of ECT.

Sodium Oxybate for Alcohol Dependence: A Network Meta-Regression Analysis Considering Population Severity at Baseline and Treatment Duration.

AIMS: The estimated effect of sodium oxybate (SMO) in the treatment of alcohol dependence is heterogeneous. Population severity and treatment duration have been identified as potential effect modifiers. Population severity distinguishes heavy drinking patients with <14 days of abstinence before treatment initiation (high-severity population) from other patients (mild-severity population). Treatment duration reflects the planned treatment duration. This study aimed to systematically investigate the effect of these potential effect moderators on SMO efficacy in alcohol-dependent patients. METHODS: Network meta-regression allows for testing potential effect modifiers. It was selected to investigate the effect of the above factors on SMO efficacy defined as continuous abstinence (abstinence rate) and the percentage of days abstinent (PDA). Randomized controlled trials for alcohol dependence with at least one SMO group conducted in high-severity and mild-severity populations were assigned to a high-severity and mild-severity group of studies, respectively. RESULTS: Eight studies (1082 patients) were retained: four in the high-severity group and four in the mild-severity group. The high-severity group was associated with larger SMO effect sizes than the mild-severity group: abstinence rate risk ratio (RR) 3.16, P = 0.004; PDA +26.9%, P < 0.001. For PDA, longer treatment duration was associated with larger SMO effect size: +11.3% per extra month, P < 0.001. In the high-severity group, SMO showed benefit: abstinence rate RR 2.91, P = 0.03; PDA +16.9%, P < 0.001. In the mild-severity group, SMO showed benefit only in PDA for longer treatment duration: +23.9%, P < 0.001. CONCLUSIONS: In the retained studies with alcohol-dependent patients, high-severity population and longer treatment duration were associated with larger SMO effect sizes.

Four-year follow-up of surface contamination by antineoplastic drugs in a compounding unit.

OBJECTIVES: This study aimed to monitor the contamination by antineoplastic drugs on work surfaces in a compounding unit 4 years after its implementation. METHODS: This descriptive study was done in a unit performing on average 45 000 preparations per year. Surface sampling points (N=23) were monitored monthly in the frame of routine activity from the opening of an anticancer drug compounding unit. Contamination with nine antineoplastic drugs (cyclophosphamide, ifosfamide, dacarbazine, 5-fluorouracil, methotrexate, gemcitabine, cytarabine, irinotecan and doxorubicin) was assessed on wipes with a local liquid chromatography coupled with a tandem mass spectrometer analysis. The contamination rate (CR, %) was prospectively monitored every month during the entire study period. The occurrence of critical incidents was also registered. The effect of each safety measure implemented during this period was also analysed. RESULTS: Based on the 1104 samples collected between March 2016 and March 2020, the CR was 18.5%. If three different critical incidents among a vial breakage that occurred were individually considered, this CR was slightly lower than that in the literature. Eight months after opening and taking different corrective actions, the overall CR dropped from 42.39% to 11.52% (p<0.001). Contamination was limited to the area that includes the compounding room and, more precisely, the welder and the QC-Prep+ sampling points. CONCLUSIONS: From the beginning of the study and from month to month, surface contamination was limited to the nearest sampling points to the compounding unit. This 4-year monitoring study allowed us to determine the intravenous conventional antineoplastic drugs and sampling points to be focused on.

Knowledge and practices about safe handling regarding the risk of exposure to antineoplastic drugs for caregivers in compounding units and in operating rooms performing HIPEC/PIPAC.

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 registrationStudy CONTACT, ref. 19-504.

The promising efficacy of a risk-based letermovir use strategy in CMV-positive allogeneic hematopoietic cell recipients.

Letermovir is the first approved drug for cytomegalovirus (CMV) infection prophylaxis in adult patients who are CMV positive undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Because CMV infection risk varies from patient to patient, we evaluated whether a risk-based strategy could be effective. In this single-center study, all consecutive adult patients who were CMV positive and underwent allo-HCT between 2015 and 2021 were included. During period 1 (2015-2017), letermovir was not used, whereas during period 2 (2018-2021), letermovir was used in patients at high risk but not in patients at low risk, except in those receiving corticosteroids. In patients at high risk, the incidence of clinically significant CMV infection (csCMVi) in period 2 was lower than that in period 1 (P < .001) by week 14 (10.5% vs 51.6%) and week 24 (16.9% vs 52.7%). In patients at low risk, although only 28.6% of patients received letermovir in period 2, csCMVi incidence was also significantly lower (P = .003) by week 14 (7.9% vs 29.0%) and week 24 (11.2% vs 33.3%). Among patients at low risk who did not receive letermovir (n = 45), 23 patients (51.1%) experienced transient positive CMV DNA without csCMVi, whereas 17 patients (37.8%) experienced negative results. In both risk groups, the 2 periods were comparable for CMV disease, overall survival, progression-free survival, relapse, and nonrelapse mortality. We concluded that a risk-based strategy for letermovir use is an effective strategy which maintains the high efficacy of letermovir in patients at high risk but allows some patients at low risk to not use letermovir.