Therapeutic Inefficiency Research Articles

GSH-responsive prodrug-based nanodrugs for augmenting chemo-photodynamic synergistic therapy against tumors

Malignant tumors are a serious threat to human health, and chemotherapy (CT) is one of the most commonly used strategies in cancer treatment. However, CT often suffers from severe side effects and therapeutic inefficiency, due to poor targeting of antitumor drugs and drug resistance with long-term use. Herein, we developed a GSH-responsive prodrug-based nanodrugs, which was internally encapsulated with the mitomycin C (MMC) prodrug and the photosensitizer Chlorin e6 (Ce6), and with surface-modified aptamers specifically targeting tumors. The nanodrugs not only promoted GSH-responsive CT drug release at the tumor site, but also enhanced the efficacy of Ce6-based photodynamic therapy (PDT) due to the severe redox imbalance in the tumor caused by GSH depletion, thereby improving the chemo- photodynamic synergistic treatment of the tumor. In vivo studies confirmed that the nanodrugs exhibited excellent tumor-targeting capabilities and significant anti-tumor therapeutic effects, offers a promising approach for clinical cancer treatment.

Integration of phosphoinositide 3-kinase (PI3K) and transforming growth factor β1 (TGF-β1) signaling cascades: role in the therapeutic inefficiency of tamoxifen

Growth factors signaling cascades and their interaction with the central regulatory targets of tumor cells and estrogens are considered as the main mechanisms of hormonal resistance in breast cancer. The integration of the transforming growth factor β1 (TGF-β1) and PI3K (phosphoinositide 3-kinase)/Akt (protein kinase B)/mTOR (mammalian target of rapamycin) signaling pathway may result in the activation of proliferation and, as a result, the development of an in-effective response to therapy and disease progression. The review summarizes a systematic analysis of the literature data on the role of TGF-β1 signaling in the mechanisms of tamoxifen resistance to in the aspect of interaction with the PI3K/Akt/mTOR. The interaction between the estrogen receptors α signaling and tamoxifen, the mechanisms of regulatory activation of TGF-β1 and PI3K/Akt/mTOR, as well as their contribution to the tamoxifen response are considered. The direct involvement of TGF-β1/PI3K in the mechanisms of tamoxifen resistance to determines the prospects for studying the effector of these cascades as molecular targets. The knowledge accumulated to date allows considering the TGF-β1/PI3K signaling pathway as a potential molecular tool for the search for effective strategies for blocking the resistance of tumor cells to tamoxifen.

La modernización del hospital y la educación médica. El caso de España en perspectiva histórica

IntroductionIn Spain, hospital underwent a long and tortuous transformation from a charitable establishment aimed at the poor where the therapeutic inefficiency and death reigned, into a scientific institution with the following functions: healthcare, teaching and research. This new conception of hospital, linked to the birth of the clinic (to follow the analyses by Foucault and Ackerknecht) and to the development of hospitals as spaces of medicalization, led to the consolidation of the idea that hospital was the right place to enact the ideal of a physician based on the new way of training of medical professionals. MethodsThe article identifies historical factors that, in the period ranging from the late eighteenth to the mid-twentieth century, led to the emergence of modern, rationalized hospital in Spain and to the consolidation of the new conception of hospital as a scientific institution, in which medical training was one of the main aims. ResultsThe Spanish case shows a number of specific patterns. First and foremost, the hospital reform emerged and consolidated later than in many countries in Europe and North America. ConclusionsIn Spain, the process of reform and modernization of hospitals and of medical training did not occur systematically until the 1960s. This article focuses on the precedents and on the first stages of the process in the period from the end of the eighteenth- to the early twentieth century.

Penetrating Micelle for Reversing Immunosuppression and Drug Resistance in Pancreatic Cancer Treatment.

Pancreatic ductal adenocarcinoma (PDAC) is on of the most lethal malignant tumors with relatively poor prognosis, characterized with insufficient drug penetration, low immune response and obvious drug resistances. The therapeutic inefficiency is multifactorially related to its specific tumor microenvironment (TME), which is representatively featured as rich stroma and immunosuppression. In this work, a versatile drug delivery system is developed that can coencapsulate two prodrugs modified from gemcitabine (GEM) and a signal transducer and activator of transcription 3 (STAT3) inhibitor (HJC0152), and the gradient pH variation is further sensed in the TME of PDAC to achieve a higher penetration by reversing its surficial charges. The escorted prodrugs can release GEM intracellularly, and respond to the hypoxic condition to yield the parental STAT3 inhibitor HJC0152, respectively. By inhibiting STAT3, the tumor immunosuppression microenvironment can be re-educated through the reversion of M2-like tumor associated macrophages (M2-TAMs), recruitment of cytotoxic T lymphocytes and downregulation of regulatory T cells (Treg s). Furthermore, cytidine deaminase (CDA) and α-smooth muscle actin (α-SMA) expression can be downregulated, plus the lipid modification of GEM, the drug resistance of GEM can be greatly relieved. Based on the above design, a synergetic therapeutic efficacy in PDAC treatment can be achieved to provide more opportunity for clinical applications.

The role of the clinical pharmacist in guiding adjuvant hormonal therapy in patients with breast cancer.

Breast cancer is the most prevalent type of cancer among women, affecting about 2.1 million worldwide and is responsible for the highest number of cancer-related deaths among women. Approximately 80% of breast cancers express on the surface of hormone receptor cells, such as progesterone and estrogen. In these cases, Adjuvant Hormonal Therapy (AHT) is indicated for a period of five to ten years and consists of taking a daily oral pill. The two most used drugs in AHT are tamoxifen and Aromatase Inhibitors. One of the issues most faced by individuals who are subjected to long periods of treatment is the lack of medication adherence and, consequently, therapeutic inefficiency. It is believed that the monitoring by the pharmacist can contribute to the reduction of errors inherent to the medication, making the treatment more effective and improving the patient's quality of life. The present study aimed to know the perception of patients who live with breast cancer and who do AHT in relation to the educational performance of the clinical pharmacist. This is a qualitative, descriptive and exploratory study, carried out from March to October 2020, with 15 women undergoing treatment at the oncology unit of a tertiary-care hospital in south of Brazil. The data were obtained through a semi-structured interview using an instrument composed of two parts, one referring to the characterization of the participants and the other with the guiding question of the research: "How do you perceive the role of the pharmacist in relation to the guidelines for the use of adjuvant hormonal therapy?". The method of theoretical saturation was used to perform the sample closure and the thematic analysis was used to analyze the data. The participants were between 32 and 74 years old, seven were on tamoxifen therapy and eight on anastrozole, ten were on the first year of treatment, two on the second and three on the third year. The themes that emerged were: pharmacist-patient interaction as a safety factor in hormone therapy; role of the pharmacist in the development of strategies for self-management of the patients during hormone therapy; and, challenges for the pharmacist in relation to hormone therapy through continued guidance. It was evident that the pharmacist's educational action encouraged the participants to carry out the treatment in a more confident and assertive manner according to their particularities and beliefs.

Formulation and invitro evaluation of delayed release multiple unit pellets of Lansoprazole in capsules

The present research was aimed to formulate and evaluate Lansoprazole delayed release multiple unit pellets in capsules. Lansoprazole degrades in the acidic environment of the stomach. It is also unstable under conditions of high temperature and high humidity which leads to therapeutic inefficiency. Hence it is important to bypass the acidic pH of the stomach. Protection of drug from acidic environment is done by coating the drug with enteric polymer. In the present study, successive layers of drug layer, barrier layer and enteric layer was coated on the inert sugar spheres by using solution/suspension layering technique in Fluidized bed processor (FBP). The prepared drug layered and barrier layered pellets were evaluated for % yield. The prepared lubricated pellets were evaluated for flow properties i.e., bulk density, tapped density, compressibility index and hausner’s ratio. Lubricated pellets filled into size ‘1’ capsules and evaluated for drug content, drug content resisted in acid, invitro drug release studies and compared with the marketed product. The dissimilarity and similarity factors for the optimized and marketed formulations were found to be 84.29. Accelerated Stability Testing (AST) was performed as per the ICH guidelines at 40±5°C/75±5% RH for 6 months and found satisfactory.

Copper-mediated synergistic catalytic titanium dioxide nanofilm with nitric oxide generation and anti-protein fouling for enhanced hemocompatibility and inflammatory modulation

Nitric oxide (NO) has become a highly compelling therapeutic gas for treating vascular diseases due to its versatile functions to vascular responses. Currently, NO biomimetic materials are successfully established through loading catalyst (i.e., Se, Cu) with the vehicle to decompose endogenous NO donors in blood continuously. However, current NO biomimetic materials are susceptible to the non-specific protein fouling, resulting in undesired therapeutic inefficiency with the observation of attenuated or even blocked NO catalytic activities. Herein, we produced a multifunctional nanofilm with dual catalysis based on the vascular stent platform via simply doping one kind of metal (Cu) as cocatalyst into anatase TiO2 crystal. Beneficial synergistic interactions between two kinds of catalysis are reported in this work. The nanofilm surface is endowed with photoinduced super hydrophilic conversion and controlled NO catalytic release simultaneously. The super hydrophilic surface shows the excellent self-cleaning ability to resist protein fouling. Importantly, the maintenance of the protein-resistant surface can effectively improve the NO catalytic release and reduce inflammatory stimuli, contributing to enhanced hemocompatibility. The optimum doping amount of Cu (TiO2@Cu1, 0.77 wt.%) is determined through the characterization of adjustable photoinduced hydrophilic conversion and appropriate NO catalytic generation within the effective physiological concentration. After vascular implantation in rats, the TiO2@Cu1 nanofilms achieved elevated performances on antithrombosis, reducing the intima hyperplasia area and promoting rapid reendothelialization at 4 weeks. This study provides a valuable guideline for NO-biomimetic materials used for blood contact devices and paves the way for the surface modification for vascular implants.

Okra-Thioglycolic Acid Conjugate—Synthesis, Characterization, and Evaluation as a Mucoadhesive Polymer

The success of mucoadhesive drug delivery systems relies on the type of polymer used, which becomes adhesive naturally upon hydration. Intended polymers should be able to maintain prolonged contact with biological membranes, and to protect or cater the drug to a prolonged period. Most of the hydro polymers form weak non-covalent bonds, that hinder localization of dosage forms at specific sites resulting in therapeutic inefficiency. This can be overcome by the thiol functionalization of natural polymers. In the present study, natural okra gum (OG) was extracted, followed by thiolation (TOG) and evaluated for mucoadhesion property and its role in enhancing the efficacy of repaglinide as a model drug (short-acting Type II antidiabetic drug). The thiol functionalization of OG (TOG) was confirmed by a Fourier-transform infrared spectroscopy (FTIR) study that showed a polyhedral to a spherical shape that had a rougher surface. Differential scanning calorimetry (DSC) and X-Ray Diffraction (XRD) studies of TOG indicated a decline in endothermic transition temperature and high crystallinity, respectively, in comparison to OG. CSFR (Crushing Strength: Friability Ratio), weight and thickness variations of repaglinidetablets formulated using TOG were >80% and <2.5% respectively. The highest swelling index (107.89 ± 1.99%) and strong mucoadhesion due to high disulfide bonds were observed for repaglinide TOG tablets in comparison to RG OG tablets. In-vitro release studies indicated a controlled drug release from thiolated formulations proportional to the concentration of thiomers that have a good correlation with in-vivo studies. Pharmacokinetic studies indicated higher AUC (area under the curve), longer t1/2 with thiomers. and Level A IVIV (in vitro in vivo) correlation was established from the bioavailability and dissolution data. Consequently, all the obtained results suggest that thiomers based formulations can be promising drug delivery systems, even in targeting onerous mucosal surfaces like nasal, ocular or vaginal.

Nuclear shape, protrusive behaviour and in vivo retention of human bone marrow mesenchymal stromal cells is controlled by Lamin-A/C expression

Culture expanded mesenchymal stromal cells (MSCs) are being extensively studied for therapeutic applications, including treatment of graft-versus-host disease, osteogenesis imperfecta and for enhancing engraftment of hematopoietic stem cells after transplantation. Thus far, clinical trials have shown that the therapeutic efficiency of MSCs is variable, which may in part be due to inefficient cell migration. Here we demonstrate that human MSCs display remarkable low migratory behaviour compared to other mesodermal-derived primary human cell types. We reveal that specifically in MSCs the nucleus is irregularly shaped and nuclear lamina are prone to wrinkling. In addition, we show that expression of Lamin A/C is relatively high in MSCs. We further demonstrate that in vitro MSC migration through confined pores is limited by their nuclei, a property that might correlate to the therapeutic inefficiency of administered MSC in vivo. Silencing expression of Lamin A/C in MSCs improves nuclear envelope morphology, promotes the protrusive activity of MSCs through confined pores and enhances their retention in the lung after intravenous administration in vivo. Our findings suggest that the intrinsic nuclear lamina properties of MSCs underlie their limited capacity to migrate, and that strategies that target the nuclear lamina might alter MSC-based cellular therapies.

Nanotherapeutic approaches targeting angiogenesis and immune dysfunction in tumor microenvironment.

Tumor microenvironment (TME) comprising cellular and non-cellular components is a major source of cancer hallmarks. Notably, angiogenesis responsible for normal physiological remodeling process can otherwise harness vessel abnormalities during tumorigenesis eliciting severe therapeutic inefficiency. Currently, FDA approved antiangiogenic drugs have only shown modest clinical success owing to tumor hypoxia, antiangiogenic therapeutic resistance, and limited knowledge in understanding TME. In order to overcome these limitations, targeting angiogenesis combined with immunosuppressive TME could offer potential therapeutic opportunities. Indeed, these therapeutic approaches can be further revisited with the advent of nanotechnology that can target the key cellular components of TME and tumor cells more precisely. Synergetic targeting without eliciting systemic toxicity achieved by integration of antiangiogenic and immunotherapy in a single nanoplatform is vital for therapeutic success. In this review, we will discuss the most promising nanotechnological advancements oriented to modulate the immunosuppressive TME in association with antiangiogenic therapy that has gained immense popularity in cancer treatment.

Ergosterol isolated from the basidiomycete Pleurotus salmoneostramineus affects Trypanosoma cruzi plasma membrane and mitochondria

BackgroundMajor drawbacks of the available treatment against Chagas disease (American trypanosomiasis) include its toxicity and therapeutic inefficiency in the chronic phase of the infection, which makes it a concern among neglected diseases. Therefore, the discovery of alternative drugs for treating chronic Chagas disease requires immediate action. In this work, we evaluated the mushroom Pleurotus salmoneostramineus in the search for potential antiparasitic compounds.MethodsFruit bodies of the basidiomycete Pleurotus salmoneostramineus were triturated and submitted to organic solvent extraction. After liquid-liquid partition of the crude extract, three fractions were obtained and the bioguided fractionation study was conducted to isolate the active metabolites. The elucidation of the chemical structure was performed using GC-MS and NMR techniques. The biological assays for antiparasitic activity were carried out using trypomastigotes of Trypanosoma cruzi and murine macrophages for mammalian cytotoxicity. The mechanism of action of the isolated compound used different fluorescent probes to evaluate the plasma membrane permeability, the potential of the mitochondrial membrane and the intracellular levels of reactive oxygen species (ROS).ResultsThe most abundant fraction showing the antiparasitic activity was isolated and chemically elucidated, confirming the presence of ergosterol. It showed anti-Trypanosoma cruzi activity against trypomastigotes, with an IC50 value of 51.3 μg/mL. The compound demonstrated no cytotoxicity against mammalian cells to the maximal tested concentration of 200 μg/mL. The mechanism of action of ergosterol in Trypanosoma cruzi trypomastigotes resulted in permeabilization of the plasma membrane, as well as depolarization of mitochondrial membrane potential, leading to parasite death. Nevertheless, no increase in ROS levels could be observed, suggesting damages to plasma membrane rather than an induction of oxidative stress in the parasite.ConclusionsThe selection of naturally antiparasitic secondary metabolites in basidiomycetes, such as ergosterol, may provide potential scaffolds for drug design studies against neglected diseases.

Kalirin and CHD7: novel endothelial dysfunction indicators in circulating extracellular vesicles from hypertensive patients with albuminuria.

Despite of the great advances in anti-hypertensive therapies, many patients under Renin-Angiotensin- System (RAS) suppression develop albuminuria, which is a clear indicator of therapeutic inefficiency. Hence, indicators of vascular function are needed to assess patients’ condition and help deciding future therapies.Proteomic analysis of circulating extracellular vesicles (EVs) showed two proteins, kalirin and chromodomain-helicase-DNA-binding protein 7 (CHD7), increased in albuminuric patients. A positive correlation of both with the expression of the endothelial activation marker E-selectin was found in EVs. In vitro analysis using TNFα-treated adult human endothelial cells proved their involvement in endothelial cell activation.Hence, we propose protein levels of kalirin and CHD7 in circulating EVs as novel endothelial dysfunction markers to monitor vascular condition in hypertensive patients with albuminuria.

Quality and Competences Ateuropean Standardsin the Area of Medicine-food Interactionsfor the Students Following a Study Programme in Pharmacy, Nutrition and Dietetics

The training of future specialists in the area of health enabling them to face the practical reality can only be ensured by high quality university education offering the students the possibility to be trained through the most performing means. The increased incidence of pathologies specific to the modern society require urgent competitive and high quality training of specialists, whose role should be to ensure improvement and preservation of public health. A better training of the students specialising in Pharmacy, as well as in Nutrition and Dietetics can be achieved by developing a module on “Medicine-Food Interactions”. The university training of future pharmacists puts a significant focus on the interactions between medicines, while the interactions between medicine and food, medicine and food supplementsare less considered, although it is of major importance that the pharmacist and the dietician know them. This could avoid phenomena of therapeutic inefficiency, toxic adverse events and even self-medication, which is often the case for food supplements. The absence of this subject in the curricula, as well as the social and economic needs, the strategies in the health area, the requirements on the labour market, the need for pertinenttherapeutic and nutritional advice for the sick population,and the training of human resources in these areas in the European Union impose a more complex training of the students in the area of medicine-food interactions.

Évaluation des erreurs d’administration des médicaments injectables en néonatologie

Use of injectable drugs in newborns represents more than 90% of prescriptions and requires special precautions in order to ensure more safety and efficiency. The aim of this study is to gather errors relating to the administration of injectable drugs and to suggest corrective actions. This descriptive and transversal study has evaluated 300 injectable drug administrations in a neonatology unit. Two hundred and sixty-one administrations have contained an error. Data are collected by direct observations of administrative act. Errors observed are: an inappropriate mixture (2.6% of cases); an incorrect delivery rate (33.7% of cases); incorrect dilutions (26.7% of cases); error in calculation of the dose to be injected (16.7% of cases); error while sampling small volumes (6.3% of cases); error or omission of administration schedule (1% of cases). These data have enabled us to evaluate administration of injectable drugs in neonatology. Different types of errors observed could be a source of therapeutic inefficiency, extended lengths of stay or iatrogenic drug. Following these observations, corrective actions have been undertaken by pharmacists and consist of: organizing training sessions for nursing; developing an explanatory guide for dilution and administration of injectable medicines, which was made available to the clinical service. Collaborative strategies doctor-nurse-pharmacist can help to reduce errors in the medication process especially during his administration. It permits improvement of injectable drugs use, offering more security and better efficiency and contribute to guarantee ideal therapy for patients.

Cancer stem cells are new vistas for predicting the course of breast cancer

Despite progress in treating breast cancer (BC) using a combined approach in view of morphological findings, distant metastases may develop in 30–90 % of patients with primary BC even at its early stages. The cancer stem cell (CSC) theory is one of the versions that could at least partially explain therapeutic inefficiency. This theory suggests that cancer may occur and arise from a small proportion of stem cells that are able to induce tumor growth and to affect resistance to chemoand radiotherapy. CSCs were identified in different malignant tumors, including BC, cancer of the prostate, colon, pancreas, head and neck, melanoma, and multiple myelomas. This investigation analyzed aldehyde dehydrogenase type 1 (ALDH1) expression in patients with BC. Moreover, the investigators examined the relationship between this marker and the clinical and pathological features of BC. The investigation enrolled 83 locally advanced BC (T1–4N0–3M0) patients treated in 2005 to 2009. To detect CSCs, 83 histological specimens obtained at biopsy in BC patients treated at the Russian Research Center for Radiology and Surgical Technologies underwent immunohistochemical examination for ALDH1 according to the developed protocol. Analysis of a relationship between time to metastases and ALDH1 expression showed a statistically significant decrease in time to disease progression in BC patients with high ALDH1 expression versus those with low ALDH1 expression. The similar trend was observed in overall survival. The survival of patients with less than 1 % ALDH1 expression in the cancer cells was statistically higher than that in the patients with high ALDH1 expression (more than 1 %).

Caffeine Medication Error in Newborn Inducing Therapeutic Inefficiency: A Case Report

Caffeine citrate is commonly used for prophylaxis and treatment of apnea in preterm babies [1,2]. Its pharmaceutical form is presented as a solution used intravenously and orally. In clinical use, caffeine citrate needs generally a dilution protocol to be administrated in newborns. Such calculating may increase the risk of medication errors and so the risk of toxic side effects or therapeutic inefficiency. Medication errors inducing toxicity are frequently reported in pediatric inpatients [3,4] but therapeutic inefficiency seems to be not described.

How effective is therapy for childhood stuttering? Dissecting and reinterpreting the evidence in light of spontaneous recovery rates

Similar positive results (e.g. immediate decreases in stuttering frequency and a 60-80% recovery rate from stuttering) have been reported for numerous therapeutic protocols for treating childhood stuttering, many of which have been diametrically opposite in their orientations and implementations. For example, Johnson advocated indirect treatments that simply advocated refraining from drawing any negative attention to childhood disfluencies as persistent and chronic stuttering was thought to progress via negative parental reactions to normal disfluencies. In contrast, direct interventionists sought immediately to eliminate stuttered speech patterns by training 'corrected' speech models that usually involved some form of prolonged speech. However, reports from speech and language therapists around North Carolina, USA, suggest much lower recovery rates in the children they treat (i.e. 13.9% over a median therapeutic period of 3 years, which to the present authors is an indicator of therapeutic inefficiency and ineffectiveness). The discrepancy between these recovery rates calls for a re-examination of the efficacy of stuttering therapy for children, especially in light of recent statements from some therapies suggesting that therapy might be curative in nature. Spontaneous and complete recovery (removing all overt and covert markers of the pathology) occurs in 60-80% of all children who display incipient stuttering behaviours. As such, it appears that many claims of therapeutic success in children who stutter are confounded by the possibility of spontaneous recovery during the testing and intervention period. Simply put, it is impossible to discriminate between recovery that would occur naturally over time, and what may have been simply accelerated via therapy. Based on stable prevalence rates and the data in the present paper, it is suggested that therapy does little to boost recovery rates from incipient stuttering. Therapy can provide 'inhibitory' symptomatic relief with varying degrees of success with respect to decreasing stuttering severity and the need for continued therapy. However, it must be made clear that curing stuttering is not a likely outcome of therapy, although successful management can decrease the severity of the problem. It is argued that all forms of stuttering inhibition, including those at work during spontaneous recovery, are all mediated by the degree of mirror neuron engagement in the brain. It is proposed that in children who stutter, the best source of relief from stuttering is in the effective and efficient engagement of mirror neurons via methods that best replicate choral speech. In order to induce natural sounding, fluent speech, it is suggested that one uses primarily derivations of choral speech such as altered auditory feedback. Motoric techniques might also be used synergistically to provide supplementary sources of mirror neuron engagement.

Impact of long-term therapy with eprosartan on the structural and functional state of the heart and large vessels and on the autonomic regulation of circulation in patients with arterial hypertension

To examine the effects of eprosartan on the remodelling of the heart and large vessels, on endothelial dysfunction and autonomic circulatory regulation in patients with hypertensive disease, thirteen patients were included into the study: Doppler echocardiographic study and evaluation of left ventricular diastolic function were performed on a Vingmed CFM800 apparatus: the thickness of the carotid intima-media complex and the diameter of the brachial artery were determined on the same apparatus using a 7.5-MHz transducer in the reactive hyperemia test. Automatic balance was evaluated by the spectral assay of cardiac rhythm variations. The cardiopulmonary component of baroreflex was also tested. Blood pressure normalized in 3 patients following 24 weeks of therapy with eprosartan in a daily dose of 600 mg. Two patients were excluded due to therapeutic inefficiency. In the remaining patients, the antihypertensive effect was incomplete. The mass of the left myocardial myocardium decreased by 10.8%. there was an increase in brachial arterial dilatation in the reactive hyperemia test. The variations of cardiac rhythm were not significantly changed, the baroreflex tended to be decreased. Thus, long-term eprosartan therapy improves the structural and functional state of the heart and vessels and fails to affect the autonomic regulation of circulation.

Impact of a Medication Card on Compliance in Older People

Medication compliance is often poor amongst older people, and this can contribute to adverse drug reactions, therapeutic inefficiency and associated increase in morbidity. This study was conducted among outpatients to assess the impact of a medication card as a counselling aid to increase knowledge about medications and increase drug compliance. Patients were randomly assigned to Group A, which received counselling only, from a pharmacist, or to Group B, which received both counselling and a medication card from the pharmacist. Knowledge improvement for patients in Group B was significant, compared with patients in Group A, t = 9.82, p < 0.001. The compliance of patients in Group A and in Group B, were respectively, (mean ± S.D) 87.5 ± 15.1 v 92.5 ± 11.9, t = 1.76, p = 0.082. The results of this study show that a medication card can increase medication knowledge and may aid compliance.

La règle du consentement éclairé et ses impasses en psychiatrie*

Every medical intervention is submitted to the rule of informed consent. Over the years, criteria of consent validity and exception situations have been defined. After a discussion of the difficult application of the informed consent rule in psychiatry, this article suggests an analysis of the motivations of a refusal of neuroleptic medication in 20 psychotic patients of a psychiatric hospital. The irrational motivations of refusal (particularly, denial and delusional ideation) have been evoked much more often then rational motivations (therapeutic inefficiency, secondary effects). The authors question the denial as a sufficient reason to declare a psychotic patient incompetent to consent. The consequences of the refusal of the neuroleptic treatment in some patients, mainly the risk of criminalization, are discussed.