Assessing the applicability and appropriateness of ChatGPT in answering clinical pharmacy questions.

OBJECTIVES: Clinical pharmacists rely on different scientific references to ensure appropriate, safe, and cost-effective drug use. Tools based on artificial intelligence (AI) such as ChatGPT (Generative Pre-trained Transformer) could offer valuable support. The objective of this study was to assess ChatGPT's capacity to correctly respond to clinical pharmacy questions asked by healthcare professionals in our university hospital. MATERIAL AND METHODS: ChatGPT's capacity to respond correctly to the last 100 consecutive questions recorded in our clinical pharmacy database was assessed. Questions were copied from our FileMaker Pro database and pasted into ChatGPT March 14 version online platform. The generated answers were then copied verbatim into an Excel file. Two blinded clinical pharmacists reviewed all the questions and the answers given by the software. In case of disagreements, a third blinded pharmacist intervened to decide. RESULTS: Documentation-related issues (n=36) and drug administration mode (n=30) were preponderantly recorded. Among 69 applicable questions, the rate of correct answers varied from 30 to 57.1% depending on questions type with a global rate of 44.9%. Regarding inappropriate answers (n=38), 20 were incorrect, 18 gave no answers and 8 were incomplete with 8 answers belonging to 2 different categories. No better answers than the pharmacists were observed. CONCLUSIONS: ChatGPT demonstrated a mitigated performance in answering clinical pharmacy questions. It should not replace human expertise as a high rate of inappropriate answers was highlighted. Future studies should focus on the optimization of ChatGPT for specific clinical pharmacy questions and explore the potential benefits and limitations of integrating this technology into clinical practice.

Description and analysis of hospital pharmacies in Madagascar.

OBJECTIVE: Madagascar's health care system has operated without formal hospital pharmacies for more than two decades. The gradual integration of pharmacists in public hospitals since 2012 will allow the structuring of this field. This study was conducted to characterize the current situation regarding all aspects relating to the general functioning of hospital pharmacies and the services provided. METHODS: This qualitative research used semi-structured interviews. Interviewees' perceptions about the general organization and functioning of hospital pharmacies and details on services provided were collected. The 16 interviewees were Ministry of Health staff members involved in hospital pharmacy, hospital directors, medical staff members and hospital pharmacy managers. Interviews were recorded, translated into French if conducted in Malagasy, and fully transcribed. Verbatim transcripts were coded according to the themes of hospital pharmacy and topical content analysis was performed. RESULTS: The principal issue perceived by interviewees was the heterogeneity of the system in terms of technical and financing management, with a main impact on the restocking of pharmaceutical products. The drug supply chain is not under control: no internal procedure has been established for the selection of pharmaceutical products, the quantification of needs is complex, stock management is difficult to supervise, a standard prescription protocol is lacking, dispensing is performed by unqualified staff, no pharmaceutical preparation is manufactured in the hospitals and administration occurs without pharmaceutical support. CONCLUSIONS: Progressive structuring of efficient hospital pharmacy services using the Basel statements for the future of hospital pharmacy is urgently needed to improve health care in Madagascar.

Impact of Real-Time Therapeutic Drug Monitoring on the Prescription of Antibiotics in Burn Patients Requiring Admission to the Intensive Care Unit.

As pharmacokinetics after burn trauma are difficult to predict, we conducted a 3-year prospective, monocentric, randomized, controlled trial to determine the extent of under- and overdosing of antibiotics and further evaluate the impact of systematic therapeutic drug monitoring (TDM) with same-day real-time dose adaptation to reach and maintain antibiotic concentrations within the therapeutic range. Forty-five consecutive burn patients treated with antibiotics were prospectively screened. Forty fulfilled the inclusion criteria; after one patient refused to participate and one withdrew consent, 19 were randomly assigned to an intervention group (patients with real-time antibiotic concentration determination and subsequent adaptations) and 19 were randomly assigned to a standard-of-care group (patients with antibiotic administration at the physician's discretion without real-time TDM). Seventy-three infection episodes were analyzed. Before the intervention, only 46/82 (56%) initial trough concentrations fell within the range. There was no difference between groups in the initial trough concentrations (adjusted hazard ratio = 1.39 [95% confidence interval {CI}, 0.81 to 2.39], P = 0.227) or the time to reach the target. However, thanks to real-time dose adjustments, the trough concentrations of the intervention group remained more within the predefined range (57/77 [74.0%] versus 48/85 [56.5%]; adjusted odd ratio [OR] = 2.34 [95% CI, 1.17 to 4.81], P = 0.018), more days were spent within the target range (193 days/297 days on antibiotics [65.0%] versus 171 days/311 days in antibiotics [55.0%]; adjusted OR = 1.64 [95% CI, 1.16 to 2.32], P = 0.005), and fewer results were below the target trough concentrations (25/118 [21.2%] versus 44/126 [34.9%]; adjusted OR = 0.47 [95% CI, 0.26 to 0.87], P = 0.015). No difference in infection outcomes was observed between the study groups. Systematic TDM with same-day real-time dose adaptation was effective in reaching and maintaining therapeutic antibiotic concentrations in infected burn patients, which prevented both over- and underdosing. A larger multicentric study is needed to further evaluate the impact of this strategy on infection outcomes and the emergence of antibiotic resistance during long-term burn treatment. (This study was registered with the ClinicalTrials.gov platform under registration no. NCT01965340 on 27 September 2013.).

Does the type of parenteral lipids matter? A clinical hint in critical illness.

BACKGROUND & AIMS: An altered lipid profile is common among intensive care unit (ICU) patients, but evidence regarding the impact of different fatty acid (FA) emulsions administered to patients requiring parenteral nutrition (PN) is scarce. This study aimed to compare the plasma triglycerides (TG) response to two types of commercial lipid emulsions: a structured mixture of long- and medium-chain triglycerides (LCT/MCT) or LCTs with n-9 FA (LCT+) in ICU patients. METHODS: In this retrospective observational study conducted in a multidisciplinary ICU: two groups were defined by the type of emulsion used. Inclusion criteria were: consecutive patients on PN staying ≥4 days with one TG determination before commencing PN and at least one during PN. Recorded variables included energy intake, amount and type of nutritional lipids, propofol dose, glucose and protein intake, laboratory parameters, and all drugs received. Hypertriglyceridemia (hyperTG) was defined as TG >2 mmol/L. RESULTS: The dynamic impact of the emulsion was analyzed in 187/757 patients completing the inclusion criteria (112 LCT/MCT and 75 LCT+). The demographic variables, severity indices, diagnostic categories, and outcomes did not differ between the two groups. Seventy-seven patients (41%) presented hyperTG. Both groups received similar daily energy (1604 versus 1511 kcal/day), lipids (60 versus 61 g/day), and glucose intake (233 versus 197 g/day). There was no increase of TG concentration in those receiving the LCT/MCT emulsion compared to those receiving the LCT+ emulsion (0 and 0.2 mmol/L, respectively, p < 0.05). CONCLUSION: LCT/MCT emulsions are associated with a less pronounced increase of plasma TG levels than LCT+ emulsions.

Staphylococcus aureus carriage at admission predicts early-onset pneumonia after burn trauma.

Early-onset pneumonia (EOP) is frequent after burn trauma, increasing morbidity in the critical resuscitation phase, which may preclude early aggressive management of burn wounds. Currently, however, preemptive treatment is not recommended. The aim of this study was to identify predictive factors for EOP that may justify early empirical antibiotic treatment. Data for all burn patients requiring ≥4 h mechanical ventilation (MV) who were admitted between January 2001 and October 2012 were extracted from the hospital's computerized information system. We reviewed EOP episodes (≤7 days) among patients who underwent endotracheal aspiration (ETA) within 5 days after admission. Univariate and multivariate analyses were performed to identify independent factors associated with EOP. Logistic regression was used to identify factors predicting EOP development. During the study period, 396 burn patients were admitted. ETA was performed within 5 days in 204/290 patients receiving ≥4 h MV. One hundred and eight patients developed EOP; 47 cases were caused by Staphylococcus aureus, 37 by Haemophilus influenzae, and 23 by Streptococcus pneumoniae. Among the 33 patients showing S. aureus positivity on ETA samples, 16 (48.5 %) developed S. aureus EOP. Among the 156 S. aureus non-carriers, 16 (10.2 %) developed EOP. Staphylococcus aureus carriage independently predicted EOP (p < 0.0001). We identified S. aureus carriage as an independent and strong predictor of EOP. As rapid point-of-care testing for S. aureus is readily available, we recommend testing of all patients at admission for burn trauma and the consideration of early preemptive treatment in all positive patients. Further studies are needed to evaluate this new strategy.

Chemical contamination during the preparation of cytotoxics: validation protocol for operators in hospital pharmacies.

BACKGROUND AND OBJECTIVES: The chemical contamination during the preparation of cytotoxics remains a serious problem in hospital pharmacies and the operators could contribute to this risk during their manipulations. A validation protocol was developed using a non-toxic, highly detectable tracer, quinine dihydrochloride. METHOD: Further, a method for a high recovery extraction and quantification of this marker, and a protocol covering the critical operations of cytotoxic preparation, was developed and validated. Various devices were used to fill the syringes and perfusion bags. All the filled containers and used materials were collected at the end of the protocol and the tracer was extracted in water. The contaminated water was analyzed by fluorimetry. The number of spots on the working pads was counted under ultraviolet light. During a total of 28 sessions, the procedure was applied by 20 different operators. RESULTS: The mean cumulated quantities of contamination were 6.2 µL (0.6-23.8) and >10 spots (0-20), which was considered as high. No correlation was observed between the contamination rate and the operator's experience. CONCLUSION: This validation protocol facilitates controlling the operators' working 'cleanliness' and helps to improve the initial and continuing training. This simple test presents an effective answer for the important issue of the chemical safety of operators.

Use of a systematic risk analysis method to improve safety in the production of paediatric parenteral nutrition solutions.

BACKGROUND: Until recently, the preparation of paediatric parenteral nutrition formulations in our institution included re-transcription and manual compounding of the mixture. Although no significant clinical problems have occurred, re-engineering of this high risk activity was undertaken to improve its safety. Several changes have been implemented including new prescription software, direct recording on a server, automatic printing of the labels, and creation of a file used to pilot a BAXA MM 12 automatic compounder. The objectives of this study were to compare the risks associated with the old and new processes, to quantify the improved safety with the new process, and to identify the major residual risks. METHODS: A failure modes, effects, and criticality analysis (FMECA) was performed by a multidisciplinary team. A cause-effect diagram was built, the failure modes were defined, and the criticality index (CI) was determined for each of them on the basis of the likelihood of occurrence, the severity of the potential effect, and the detection probability. The CIs for each failure mode were compared for the old and new processes and the risk reduction was quantified. RESULTS: The sum of the CIs of all 18 identified failure modes was 3415 for the old process and 1397 for the new (reduction of 59%). The new process reduced the CIs of the different failure modes by a mean factor of 7. The CI was smaller with the new process for 15 failure modes, unchanged for two, and slightly increased for one. The greatest reduction (by a factor of 36) concerned re-transcription errors, followed by readability problems (by a factor of 30) and chemical cross contamination (by a factor of 10). The most critical steps in the new process were labelling mistakes (CI 315, maximum 810), failure to detect a dosage or product mistake (CI 288), failure to detect a typing error during the prescription (CI 175), and microbial contamination (CI 126). CONCLUSIONS: Modification of the process resulted in a significant risk reduction as shown by risk analysis. Residual failure opportunities were also quantified, allowing additional actions to be taken to reduce the risk of labelling mistakes. This study illustrates the usefulness of prospective risk analysis methods in healthcare processes. More systematic use of risk analysis is needed to guide continuous safety improvement of high risk activities.

Sterility validity period of vials after multiple sampling under vertical laminar airflow hood.

STUDY OBJECTIVES: The aim of this study is to validate the sterility period of vials after multiple sampling under Grade A vertical laminar airflow hood. METHODS: Vials filled aseptically with a sterile culture medium have been sampled with syringes three times a week over one month under Grade A vertical laminar airflow hood and in the mean-while, keeping the vials out of the laminar airflow hoods. RESULTS: No microbial growth has been observed. On the basis of these results, it has been decided to modify our standard operating procedures, to allow keeping the vials for two weeks in a box out of the laminar airflow hoods (ambient temperature Grade B) or any controlled environment (under refrigeration). CONCLUSIONS: This study validates the multiple use of vials of small to large volumes (5-100 mL), to simplify handling and to reduce the costs in centralized cytostatic reconstitution units in hospital pharmacies, with no microbial risk.

2C-B: a new psychoactive phenylethylamine recently discovered in Ecstasy tablets sold on the Swiss black market.

This study sought to identify, by means of several analytical methods (GC-MS, HPLC-DAD, CE-DAD, FTIR, and NMR), 4-bromo-2,5-dimethoxyphenethylamine (2C-B), which was found in two sets of tablets obtained from the Swiss black market. Unequivocal identification of 2C-B was only achieved by a combination of mass spectrometric and NMR analysis. Quantitation of 2C-B was performed by HPLC-DAD and CE-DAD. The amounts of 2C-B found in the tablets (3-8 mg) were in the range of the minimum quantity required to induce the effects characteristic of this drug.

Automated on-line dialysis and liquid chromatography of methylenedioxylated amphetamines in plasma and serum samples.

An automated on-line dialysis coupled to a trace enrichment method has been developed for the separation and quantification of four methylenedioxylated amphetamines in serum and plasma, using liquid chromatography coupled to a fluorimetric detector. The on-line dialysis method was optimized and validated on fresh human serum and plasma samples. This sample preparation method allowed the quantification of methylenedioxylated amphetamines in serum or plasma, at concentrations as low as ca. 10 ng ml-1, with good repeatability, reproducibility and accuracy. The automated on-line dialysis method took less than 30 min. This method was applied to seven toxicological cases and results showed that the concentration of methylenedioxylated amphetamines in blood was in the range of 20-484 ng ml-1.

Sensitive and selective determination of methylenedioxylated amphetamines by high-performance liquid chromatography with fluorimetric detection.

A rapid, sensitive and selective liquid chromatographic method with fluorimetric detection was developed for the separation and quantification of four methylenedioxylated amphetamines without interference of other drugs of abuse and common substances found in illicit tablets. The method was validated by examining linearity, precision and accuracy as well as detection and quantification limits. Methylenedioxylated amphetamines were quantified in eight tablets from illicit drug seizures and results were quantitatively compared to HPLC-UV analyses. To demonstrate the better sensitivity of the fluorimetric detection, methylenedioxylated amphetamines were analyzed in serum after a liquid-liquid extraction procedure and results were also compared to HPLC-UV analyses.

[Ecstasy--the status in French-speaking Switzerland. Composition of seized drugs, analysis of biological specimens and short review of its pharmacological action and toxicity]. / Ecstasy--la situation en Suisse romande. Composition des saisies, analyse des échantillons biologiques et brève revue de son action pharmacologique et de sa toxicité.

Methylenedioxy-N-methylamphetamine (MDMA, "Ecstasy") and other related phenylethylamines are nowadays used extensively in Western Switzerland at dance clubs and raves. There is a widely held belief among teenagers and misusers that ecstasy is safe. In the last years however, an increasing number of reports of MDMA-related deaths has been reported. Acute clinical toxicity problems following MDMA ingestion include hyperthermia, convulsions and arrhythmias. There is also growing concern that these phenylethylamines are neurotoxic and cause long-term damage to serotonineric nerve terminals in animal brains. Qualitative analyses by GC-MS of street samples of ecstasy showed that only a part of them contain MDMA or related phenylethylamines (MDA, MDEA, MBDB and 2C-B). Most of them were mixed with caffeine and an excipient (sugars or polyols [e.g. mannitol]). Amphetamine cut with caffeine and other drugs (e.g. testosterone), stimulants (e.g. pseudoephedrine) and other drugs unrelated to stimulants and phenylethylamines (e.g. LSD, chloroquine, vasodilators) were also detected. Quantitative determinations performed by HPLC-DAD or EC-DAD reveal huge fluctuations in the amount of active substance(s) per tablet. MDMA and related compounds display unique psychoactive properties, acting as a stimulant and inducing feelings of empathy. The effects of MDMA intake are very likely the results of the large release of serotonin (5-HT) in the synaptic cleft, of the inhibition of the re-uptake inactivation of 5-HT and of the inhibition of a key-enzyme involved in the biosynthesis of 5-HT. Forensic investigations performed at our institute showed significant blood levels of MDMA, MDEA and MDA in samples drawn from people suspected of driving under the influence of psychoactive drugs. Up to now, no death could be attributed to MDMA intoxication only because our analyses always revealed the additional presence of toxic amounts of other psychoactive drugs (e.g. opiates, cocaine). Our study shows that because of the variable composition of ecstasy tablets, unpredictable types and amounts of drugs may be taken by MDMA misusers. Moreover, there is considerable concern that traffic accidents may be caused by MDMA-abusers. MDMA intake could result in severe intoxication and even death, especially when combined with other types of drugs.