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ObjectivesThe emergence of artificial intelligence (AI) is catching the interest of hospital pharmacists. A massive collection of health data is now available to train AI models and hold the promise of disrupting codes and practices. The objective of this systematic review was to examine the state of the art of machine learning or deep learning models that detect inappropriate hospital medication orders.MethodsA systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. MEDLINE and Embase databases were searched from inception to May 2023. Studies were included if they reported and described an AI model intended for use by clinical pharmacists in hospitals. Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST).Results13 articles were selected after review: 12 studies were judged to have high risk of bias; 11 studies were published between 2020 and 2023; 8 were conducted in North America and Asia; 6 analysed orders and detected inappropriate prescriptions according to patient profiles and medication orders; and 7 detected specific inappropriate prescriptions, such as detecting antibiotic resistance, dosage abnormality in prescriptions, high alert drugs errors from prescriptions or predicting the risk of adverse drug events. Various AI models were used, mainly supervised learning techniques. The training datasets used were very heterogeneous; the length of study varied from 2 weeks to 7 years and the number of prescription orders analysed went from 31 to 5 804 192.ConclusionsThis systematic review points out that, to date, few original research studies report AI tools based on machine or deep learning in the field of hospital clinical pharmacy. However, these original articles, while preliminary, highlighted the potential value of integrating AI into clinical hospital pharmacy practice.

Switching antipsychotic medication must be done carefully to ensure patient safety and a successful response. Here, we present two major psychotic decompensations that occurred following a switch to aripiprazole in two patients with schizophrenia. Mr. X was treated with paliperidone and experienced residual anxiety. Thus, a switch to aripiprazole was planned with risperidone and a gradual decrease in paliperidone. Initially, an increase in aripiprazole resulted in remission of his residual symptoms. However, two weeks later, he presented an anxiety relapse with persecutory ideas which required hospitalization. Mr. Y, who was treated for many years with risperidone, presented with a treatment resistant psychotic episode. A switch to aripiprazole enhanced his clinical condition. Despite the initial improvement, soon after discharge from the hospital, the patient presented psychotic symptoms requiring home intervention. Ultimately, the patient in the midst of a delusional recrudescence, had killed himself when the health care team arrived. A strong dopamine antagonist may lead to the development of dopaminergic upregulation. The addition of a partial agonist to these hypersensitive neurotransmitter pathways could explain these episodes. We agree with previous reports and recommend careful management when switching from strong dopamine antagonists to aripiprazole.

The importance of clinical psychopharmacological knowledge for modern psychiatric care is both well-established and underdeveloped. Although psychiatric pharmacists are identified as experts in psychopharmacotherapy based on pharmacists’ overall expertise in pharmacotherapy, in real-life health settings, such is not necessarily the case. As a matter of fact, (1) pharmacists’ real expertise in pharmacotherapy is mainly seen as useful to patients (as part of therapeutic education), (2) pharmacists’ practice methods are usually circumscribed to the framework of quality processes (e.g. comprehensive medication management) which are not particularly useful to clinicians who have a greater need for pharmacotherapeutic skills, (3) the difficulties in terms of collaboration between pharmacists and physicians are well-known. We describe here the implementation of an alternative system of pharmacotherapy counselling inspired by case by cases in which the remote expertise of pharmacists in psychopharmacology guided prescribers towards the implementation of recommendations from the literature. This shared decision-making process integrates both the clinical elements provided by the psychiatrist and the pharmacotherapeutic information provided by the clinical psychopharmacist, to promote evidence-based medicine (algorithmic data in recommendations) and tailor-made solutions (drug-drug and drug-disease interactions) for patients. In our experience, the success of such an initiative is likely to promote the development of clinical psychopharmacology in psychiatric settings. Importantly, within this framework, the pharmacovigilance unit and psychopharmacologist are useful resources to guide the decision-making process of the pharmacist-psychiatrist duo.

ObjectiveThe aims of this study were to describe prescribing practices of lopinavir/ritonavir, hydroxychloroquine and azithromycin during the COVID-19 epidemic crisis (primary endpoint), then to characterise pharmaceutical interventions (PIs) targeted to these medications and evaluate the impact of these PIs on prescribers’ practices (secondary end-points).MethodsThis retrospective observational study was carried out at the University Hospital of Strasbourg (France) from March to April 2020. The analysed population excluded patients from intensive care units but included all other adult patients with COVID-19 who received at least one dose of lopinavir/ritonavir combination, hydroxychloroquine or azithromycin, while inpatients. Analyses were performed by using data extracted from electronic medical records.ResultDuring the study period, 278 patients were included. A rapid decrease in lopinavir/ritonavir prescriptions was observed. This was accompanied by an increase in hydroxychloroquine and azithromycin prescriptions until the end of March, followed by a decrease leading to the disappearance of these two medications in April. The pharmaceutical analysis of the prescriptions resulted in 59 PIs of which 21 were associated with lopinavir/ritonavir, 32 with hydroxychloroquine and 6 with azithromycin. Regarding the medication-related problems, the most frequent ones were incorrect treatment durations (n=32 (54.2%)), drug interactions with potential torsadogenic reactions (n=14 (23.7%)) and incorrect dosing (n=6 (10.2%)). From the 59 PIs, 48 (81.4%) were accepted and physicians adjusted the medication regimens in a timely manner.ConclusionThis study demonstrated the value—even more meaningful in a crisis situation—of a strong synergy between physicians and pharmacists for patient-safety focused practices.

ObjectiveAccording to current guidelines on atrial fibrillation (AF), the addition of an antiplatelet therapy to an anticoagulant for a stable vascular disease does not decrease the ischaemic hazard but increases the risk of bleeding. The aim of the study was to assess compliance of practices with existing clinical guidelines concerning the use of anticoagulant-antiplatelet combined therapy in patients 75 years and over with AF.MethodsThis prospective observational study was carried out at the University Hospital of Strasbourg (France) between August 2016 and January 2017 with data collection on 1 day of every month. To be included, the patient had to be 75 years and over with AF and treated with anticoagulant-antiplatelet therapy. The population included all the patients admitted at the hospital excluding those from the Gynaecology-Obstetrics and Paediatrics departments. With regard to clinical ongoing guidelines (French, European, American and Canadian), the patients were sorted into three groups. Group 1: combined therapy in compliance with recommendations; Group 2: combined therapy debatable as to benefit-risk ratio; and Group 3: combined therapy not compliant with recommendations.ResultNinety-three out of 3307 patients 75 years and over received anticoagulant-antiplatelet combined therapy prior to their hospital admission. Thirty-two patients (34.4% – Group 1) had experienced an acute event and/or revascularisation within the past year. Twenty-four patients (25.8% – Group 2) had not experienced recent revascularisation and had stable coronary disease but were suffering from peripheral artery disease. Group 3 consisted of 37 patients (39.8%), none of which had experienced recent revascularisation or had unstable coronary disease. For all groups, the main dual therapy was acetylsalicylic acid + fluindione (59.1%).ConclusionIn our study, 37 antiplatelet (39.8%) treatments could have been stopped. These results should spur prescribers into regular reassessment of combination antithrombotic therapy since it contributes to polypharmacy and increases the risk of adverse events.

Adsorption heat pumps offer a clean, zero-emission technology for universally applicable cooling or heating utilizing water as a refrigerant and waste or renewable heat as driving energy instead of electricity. Despite their attractive environmentally friendly prospects, the broader application of such classes of heat pumps has not yet been possible, mainly because of the low power density of adsorption heat exchangers and the corresponding large size and high cost of the adsorption heat pumps. We report an inexpensive route for the fabrication of zeolite coatings with high adsorption power density based on the bottom-up assembly of colloids directed by magnetic and capillary forces. Such an assembly process relies on the chaining of oil droplets under an external magnetic field during deposition of the coating, followed by the formation of a percolating network of bridged adsorbent particles upon drying. This results in vertically open channels and thermal bridges that facilitate directed mass and heat transport across the structured zeolite coating during sorption cycles. By reaching up to 3.3-fold higher performance than their unstructured counterparts using readily available zeolite as an adsorbent material, the architectured coatings produced through this facile, upscalable approach hold great potential for next-generation adsorption heat pumps.

ABSTRACTThis study's aims were: 1) to extract a comprehensive overview of the knowledge, experience and opinions of both community pharmacists and hospital pharmacists regarding biosimilar medicines in France; and 2) to identify the perceived problems and solutions to promoting their prescription. A 2015 web-based survey was conducted by the Observatoire des Médicaments, des Dispositifs Médicaux et de l'Innovation Thérapeutique of Alsace. A total of 802 pharmacists responded to the survey. Many (536, 66.8%, [95% confidence interval (CI) 63.6–70.1]) indicated that they were not familiar with biosimilars. Half of community pharmacists (95% CI 42.7–57.3) stated that they were not at all informed about biosimilar drugs, compared with 15.7% (95% CI 12.9–18.6) of hospital pharmacists. Almost all respondents (781, 97.4%, [95% CI 96.3–98.5]) had at least one pending question on biosimilars. Most of the questions were related to the manufacturing process, safety, substitution rules and the international non-proprietary name prescription. At the time of the study, 467 pharmacists (58.2%, [95% CI 54.8–61.6]) had already validated a prescription for a biosimilar drug, mainly for filgrastim. These latter were more comfortable in explaining the benefit of biosimilar medicines to the patient. Pharmacists were rather favorable to biosimilar drugs, and about 9 of 10 quoted healthcare cost savings as incentives to their prescription. However, many did not agree with allowing biosimilar substitution. “Patients' wishes to be treated with the originator” and “indication extrapolation” were the two main constraints identified. The survey highlighted the need to provide French pharmacists with accurate and comprehensive information regarding biosimilar medicines.

Quetiapine is an atypical antipsychotic with a good safety profile permitting its administration beyond the maximum dose of 800 mg/day. We report the case of a patient with a resistant schizophrenia treated with high doses of quetiapine (up to 2000 mg/day) combined with drug monitoring and with favourable therapeutic response and tolerance.

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The economic burden linked to rheumatoid arthritis (RA) has greatly increased since the inclusion of biotherapies in the therapeutic arsenal. This study aimed first to look at the breakdown of the rheumatoid arthritis patients on biotherapy in Alsace, France, in 2012, then to evaluate the annual cost per treated patient for each management pathway: inpatient care with intravenous biotherapies and/or outpatient care through the use of subcutaneous drugs, and finally to conduct a cost comparison with a focus on infliximab, adalimumab and etanercept. This observational study was conducted in Alsace using 2012 health claims data from the DCIR (Données de Consommation Inter Régime) and PMSI (Programme de Médicalisation des Systèmes d’Information) databases, taking into account direct medical and non-medical costs in a real-life setting and from a National Health Insurance perspective. There were 5702 RA patients, i.e. 0.31 % of the Alsace population in 2012, including 1075 subjects (18.85 %) receiving biotherapy treatment. The most frequently prescribed biotherapies were etanercept and adalimumab. The estimated overall cost of care of these 5702 patients was €30.3 million, with about 50 % for the care of the 18.85 % patients on biotherapy. Average costs for inpatient, outpatient and mixed care ranged from €14,197 to €16,873 per patient per year. Annual average cost for management of a single RA patient with infliximab was significantly higher than with adalimumab and etanercept: €16,480 versus €14,116 and €14,338, respectively. These findings confirm the trends of initial modelling approaches and quantify the cost difference between various biotherapy management pathways.

Orthoptera are infected by about 60 species of gregarines assigned to the genus GregarinaDufour, 1828. Among these species, Gregarina garnhamiCanning, 1956 from Schistocerca gregaria(Forsskål, 1775) was considered by Lipa et al. in 1996 to be synonymous with Gregarina acridiorum(Léger 1893), a parasite of several orthopteran species including Locusta migratoria(Linné, 1758). Here, a morphological study and molecular analyses of the SSU rDNA marker demonstrate that specimens of S. gregariaand specimens of L. migratoriaare infected by two distinct Gregarinaspecies, G. garnhamiand G. acridiorum,respectively. Validation of the species confirms that molecular analyses provide useful taxonomical information. Phenotypic plasticity was clearly observed in the case of G. garnhami: the morphology of its trophozoites, gamonts and syzygies varied according to the geographical location of S. gregariaand the subspecies infected.

Deux études menées en parallèle de mai à juin 2009 ont été proposées en Alsace afin d’analyser les pratiques de prescriptions hospitalières relatives à 6 médicaments facturés en sus des groupes homogènes de séjours (GHS) : bevacizumab, gemcitabine, trastuzumab, étanercept, adalimumab et infliximab. La 1reétude, menée dans 9 établissements, a permis le recueil de 343 situations de prescription. La 2eapproche, basée sur l’extraction des données programme de médicalisation des systèmes d’information (PMSI) issues des résumés de séjours des mêmes établissements, a permis l’exploitation de 771 situations de prescription. Les données recueillies sur site et à partir du PMSI ont respectivement mis en évidence 86,3 % et 73,0 % de prescriptions conformes aux référentiels. Aucune situation non acceptable n’a été relevée. L’écart entre les approches s’explique par la proportion importante de situations inclassables extraites à partir du PMSI. Ces approches apportent des éclairages complémentaires et permettent à l’Observatoire du médicament, des dispositifs médicaux et de l’innovation thérapeutique (OMEDIT) d’Alsace de se positionner dans ses missions d’expertise et de suivi des innovations thérapeutiques.

The article presents questions and answers related to a Dana 44 axle for Sport utility vehicles (SUV) such as General Motors Chevrolet S-10 Blazer, Danhard heaters for Ford's Bronco and using an A618 transmission for Dodge's Ramcharger.

We use microfluidic chips to detect the biologically important cytokine tumor necrosis factor α TNF-α with picomolar sensitivity using sub-microliter volumes of samples and reagents. The chips comprise a number of independent capillary systems CSs, each of which is composed of a filling port, an appended microchannel, and a capillary pump. Each CS fills spontaneously by capillary forces and includes a self-regulating mechanism that prevents adventitious drainage of the microchannels. Thus, interactive control of the flow in each CS is easily achieved viacollective control of the evaporation in all CSs by means of two Peltier elements that can independently heat and cool. Long incubation times are crucial for high sensitivity assays and can be conveniently obtained by adjusting the evaporation rate to have low flow rates of ∼30 nL min−1. The assay is a sandwich fluorescence immunoassay and takes place on the surface of a polydimethylsiloxane PDMS slab placed across the microchannels. We precoat PDMS with capture antibodies Abs, localize the capture of analyte molecules using a chip, then bind the captured analyte molecules with fluorescently-tagged detection Abs using a second chip. The assay results in a mosaic of fluorescence signals on the PDMS surface which are measured using a fluorescence scanner. We show that PDMS is a compatible material for high sensitivity fluorescence assays, provided that detection antibodies with long excitation wavelength fluorophores ≥580 nm are employed. The chip design, long incubation times, proper choice of fluorophores, and optimization of the detection Ab concentration all combine to achieve high-sensitivity assays. This is exemplified by an experiment with 170 assay sites, occupying an area of ∼0.6 mm2on PDMS to detect TNF-α in 600 nL of a dendritic cell DC culture medium with a sensitivity of ∼20 pg mL−11.14 pM.

No Abstract Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2002/z18619_s.pdf or from the author.

Image analysis tools and statistical procedures have been developed to quantify particle shape. Three copper sulfate crystallization processes have been carried out and the effects of process operating parameters upon crystal morphology have been studied as well as the relationships between morphology and powder end use properties. Both aspects give the capability to master end‐use properties by the process parameters. It is also shown that size distribution without morphology is deficient to globally characterize a powder and to describe its behaviour.

Bradykinin (BK) and analogs acting preferentially at kinin B1or B2receptors were tested on the rat isolated perfused kidney. Kidneys were perfused in an open circuit with Tyrode's solution. Kidneys preconstricted with prostaglandin F2αwere used for the analysis of vasodilator responses.BK induced a concentration‐dependent renal relaxation (pD2=8.9±0.4); this vasodilator response was reproduced by a selective B2receptor agonist, Tyr(Me)8‐BK (pD2=9.0±0.1) with a higher maximum effect (Emax=78.9±6.6 and 55.8±4.3% of ACh‐induced relaxation respectively, n=6 and 19, P<0.02). Icatibant (10 nM), a selective B2receptor antagonist, abolished BK‐elicited relaxation. Tachyphylaxis of kinin B2receptors appeared when repeatedly stimulated at 10 min intervals.Des‐Arg9‐BK, a selective B1receptor agonist, induced concentration‐dependent vasoconstriction at micromolar concentration. Maximum response was enhanced in the presence of lisinopril (1 μM) and inhibited by R 715 (8 μM), a selective B1receptor antagonist. Des‐Arg9‐[Leu8]‐BK behaved as an agonist.A contractile response to des‐Arg9‐BK occurred after 1 h of perfusion and increased with time by a factor of about three over a 3 h perfusion. This post‐isolation sensitization to des‐Arg9‐BK was abolished by dexamethasone (DEX, 30 mg kg−1i.p., 3 h before the start of the experiment and 10 μMin perfusate) and actinomycin D (2 μM). Acute exposure to DEX (10 μM) had no effect on sensitized des‐Arg9‐BK response, in contrast to indomethacin (30 μM) that abolished it. DEX pretreatment however had no effect on BK‐induced renal vasodilation.Present results indicate that the main renal vascular response to BK consists of relaxation linked to the activation of kinin B2receptors which rapidly desensitize. Renal B1receptors are also present and are time‐dependently sensitized during the in vitroperfusion of the rat kidneys.

The performances of two image analysis methods for the classification of some randomly selected KCl crystals from a crystallization experiment into four two‐dimensional classes (nearly circular, square, rectangular and irregular) are compared. The first method uses the first 15 Fourier descriptors of the angular bend as a function of arc length of the periphery of the particles, whereas the second method is based on a combination of seven geometrical and morphological parameters of the crystals using a commercially available image analysis system (Visilog, Noesis, Orsay, France). The feedforward neural network with back‐propagation learning algorithm and discriminant factorial analysis (STATlab, SLP, Ivry sur Seine. France) were found to classify the crystals with similar success.

Recent evidence suggests that tissue generation of angiotensins I and II depends on the level of the plasma components of the renin-angiotensin system and on tissue-specific processes. The present study was undertaken to clarify the possible relationship between plasma renin activity (PRA) and tissue angiotensin converting enzyme (ACE) activity in the heart, lung, kidney cortex and kidney medulla of Wistar-Kyoto rats. In the kidney cortex particular attention was focused on renal brush-border ACE.

Les effets anticholinergiques sont bien connus des prescripteurs, notamment en psychiatrie, à la fois comme des stratégies thérapeutiques pour les syndromes extrapyramidaux, mais également comme une source d’effets indésirables. Nous proposons ici une revue narrative de la littérature décrivant successivement : (i) la pharmacologie cholinergique et les effets anticholinergiques, (ii) l’importance des effets anticholinergiques en psychiatrie, (iii) les échelles anticholinergiques existantes avec la pertinence et les limites de leur usage en psychiatrie et, enfin, (iv) une mise à jour de l’échelle d’imprégnation anticholinergique, développée pour la psychiatrie française. Les effets anticholinergiques peuvent se manifester autant au niveau périphérique, qu’au niveau central. Schématiquement, les effets anticholinergiques/antimuscariniques sont aisément attribués parmi les psychotropes : à certains antipsychotiques, aux traitements correcteurs qualifiés d’anticholinergiques, et aux antidépresseurs tricycliques. Afin d’évaluer la charge anticholinergique, des outils appelés des échelles d’évaluation des effets anticholinergiques ont été développés au cours des deux dernières décennies (13 échelles répertoriées en 2021), mais trois seulement bénéficient d’une utilisation réellement importante : l’Anticholinergic Drug Scale(ADS), l’Anticholinergic Risk Scale(ARS) et l’Anticholinergic Cognitive Burden scale(ACB). Ces échelles présentent plusieurs limites : une faible concordance entre elles, une difficulté à prédire les effets centraux en raison de classements ne différenciant pas, ou mal, la capacité des traitements à passer à la barrière hémato-encéphalique, enfin, un manque de pondération de la puissance des effets anticholinergiques par la posologie. Nous proposons à l’issue de cette revue une mise à jour de l’échelle d’imprégnation anticholinergique développée spécifiquement pour la psychiatrie française.

Implantable technologies are becoming more widespread for biomedical applications that include physical identification, health diagnosis, monitoring, recording, and treatment of human physiological traits. However, energy harvesting and power generation beneath the human tissue are still a major challenge. In this regard, self‐powered implantable devices that scavenge energy from the human body are attractive for long‐term monitoring of human physiological traits. Thanks to advancements in material science and nanotechnology, energy harvesting techniques that rely on piezoelectricity, thermoelectricity, biofuel, and radio frequency power transfer are emerging. However, all these techniques suffer from limitations that include low power output, bulky size, or low efficiency. Photovoltaic (PV) energy conversion is one of the most promising candidates for implantable applications due to their higher‐power conversion efficiencies and small footprint. Herein, the latest implantable energy harvesting technologies are surveyed. A comparison between the different state‐of‐the‐art power harvesting methods is also provided. Finally, recommendations are provided regarding the feasibility of PV cells as an in vivo energy harvester, with an emphasis on skin penetration, fabrication, encapsulation, durability, biocompatibility, and power management. This report describes the state‐of‐the‐art energy harvesting technologies for implantable devices with a comparison between different power harvesting methods. It offers recommendations regarding the feasibility of photovoltaic cells as an in vivo energy harvester, with an emphasis on skin penetration, fabrication, encapsulation, durability, biocompatibility, and power management.

• Nine cases of superficial pemphigus that were treated by dapsone as the initial mode of therapy are reported. Five patients, all having low or negative serum anti-intercellular cement substance antibody titers, responded dramatically, while the other four patients, showing high titers of anti-intercellular cement substance antibodies, did not respond to this treatment. Complications of therapy were observed in three cases.(Arch Dermatol 1987;123:783-785)

Aripiprazole is reported to be a good clinical safety profile antipsychotic. However, recent data suggest that the risk of tardive dyskinesia could be higher than initially thought. We report the case of aripiprazole-induced tardive dyskinesia with dramatic evolution in a patient with several risk factors, including older age and exposure to antipsychotic over a period longer than six months. This case and its dramatic evolution, associated with other cases recently published, suggest reconsidering the real risk of tardive dyskinesia associated with aripiprazole, particularly in the elderly.