From 'molecules of life' to new therapeutic approaches, an evolution marked by the advent of artificial intelligence: the cases of chronic pain and neuropathic disorders.

The large families of the molecules of life are at the origin of the discovery of new compounds with which to treat disease. The arrival of artificial intelligence (AI) has considerably modified the search for innovative bioactive drugs and their therapeutic applications. Conventional approaches at different organizational research levels have emerged and, thus, AI associated with gene and cell therapies could supplant conventional pharmacotherapy and facilitate the diagnosis of pathologies. Using the examples of chronic pain and neuropathic disorders, which affect a large number of patients, I illustrate here how AI could generate new therapeutic approaches, why some compounds are seen as recreational drugs and others as medicinal drugs, and why, in some countries, psychedelic drugs are considered as potential therapeutic drugs but not in others.

Results of a UK National Cancer Research Institute Phase II study of brentuximab vedotin using a response-adapted design in the first-line treatment of patients with classical Hodgkin lymphoma unsuitable for chemotherapy due to age, frailty or comorbidity (BREVITY).

Standard treatment for classical Hodgkin lymphoma (cHL) is poorly tolerated in older patients and results disappointing. We assessed safety and efficacy of brentuximab vedotin (BV), in previously untreated patients with cHL unfit for standard treatment due to age, frailty or comorbidity. The primary outcome was complete metabolic response (CMR) by positron emission tomography/computed tomography after four BV cycles (PET4). The secondary outcomes included progression-free survival (PFS), overall survival (OS), and toxicity. In all, 35 patients with a median age of 77 years and median total Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score of 6 were evaluable for toxicity and 31 for response. A median of four cycles were given (range one-16). In all, 14 patients required dose reduction due to toxicity and 11 patients stopped treatment due to adverse events (AEs). A total of 716 AEs were reported, of which 626 (88%) were Grade 1/2 and 27 (77%) patients had at least one AE Grade ≥3. At PET4, CMR was 25·8% [95% confidence interval (CI) 13·7-42.2%] and objective response rate 83·9% (95% CI 63·7-90·8%). Median PFS was 7·3 months (95% CI 5·2-9·0), and OS 19·5 months. Our results suggest that BV monotherapy is tolerable but suboptimal in the front-line therapy of elderly or comorbid patients with cHL. Combining BV with other agents may be more effective. Trial Registration: Clinicaltrials.gov identifier: NCT02567851.

Riesgo de medicamentos en el embarazo: un problema de transferencia del conocimiento con repercusiones éticas / Risk of medicines in pregnancy: a problem of knowledge transfer with ethical implications

El uso de fármacos durante el embarazo es esencial y beneficioso, pero resulta imprescindible consultar su seguridad. La evidencia científica disponible resulta pobre y de difícil interpretación. Las clasificaciones de riesgo (FDA, ADEC) han resultado demasiado simples y categóricas; conducen a percepciones imprecisas del riesgo y decisiones desafortunadas, como el abandono de la medicación o el aborto. Esto se ha puesto de manifiesto con los antidepresivos o el antirretroviral efavirenz. Si bien el aborto no está justificado, la desinformación contribuye aún más a aumentar el problema. La información tiende a obviar que no todo riesgo en embarazo es de tipo teratógeno, que la existencia de riesgo no implica probabilidad elevada, y que la naturaleza y probabilidad del riesgo varían según la etapa del desarrollo del embrión o feto. Existen situaciones especiales, como el uso de antineoplásicos, donde se necesita información muy adecuada para actuar a favor de la madre y del hijo. Con las clasificaciones categóricas en regresión, son necesarias innovaciones informativas, que deberían incluir: tipo de daño, si es agudo o crónico y si es reversible; probabilidad de que aparezca, riesgo según período del embarazo y nivel de evidencia. Las carencias de información sobre medicamentos en embarazo agravan la amenaza eugenésica sobre la vida de los no nacidos y las familias, y añaden riesgos para la salud de la mujer. Resulta un área de gran interés para la innovación en servicios y fuentes de información mejorados

Drug use in pregnancy is essential and beneficial, but it is needed to check their safety. Available scientific evidence is poor and difficult to interpret. Risk classifications (FDA, ADEC) have shown to be too simple and categorical; they lead to inaccurate perceptions of risk and unfortunate decisions, such as interrumption of medication, or abortion. This has become clear with antidepressants or the antiretroviral efavirenz. Although abortion is not justified, misinformation contributes even more to the problem. Information tends to obviate that not every risk in pregnancy is teratogenic, that the existence of risk does not imply high probability, and that the nature and probability of the risk vary according to the stage of development of the embryo or fetus. There are special situations, such as the use of antineoplastics, where very precise information is needed to act on behalf of the mother and the child. With categorical classifications in regression, informative innovations are necessary, which should include: type of damage, whether it is acute or chronic, reversible or irreversible; probability of occurrence, risk according to pregnancy period and level of evidence. The lack of information on medicines in pregnancy aggravates the eugenic threat on the lives of the unborn and families, and adds risks to women’s health. It is an area of great interest for innovation in services and improved information sources

Honoring the Moral Concerns of Caregivers Afraid of Giving Morphine.

: Updated several times a week with posts by a wide variety of authors, AJN's blog Off the Charts allows us to provide more timely-and often more personal-perspectives on professional, policy, and clinical issues. Best of the Blog will be a regular column to draw the attention of AJN readers to posts we think deserve a wider audience. To read more, please visit: www.ajnoffthecharts.com.

Surrogate decision making of chemotherapy consent: do we really provide informed consent of chemotherapy for patients?

BACKGROUND/AIMS: Despite increased demand for cancer patient's to make their own decisions based on an adequate understanding of what is involved in chemotherapy, the primary signing agent and the reasons for surrogate signing have not been appropriately evaluated. METHODS: The ethics committee of the palliative medicine subgroup of the Korean Cancer Study Group designed this study and solid cancer patients to whom chemotherapy was offered, from seven institutions, were evaluated. The details relating to surrogate's signing of chemotherapy consent were evaluated. Then, we analyzed the factors associated with surrogate's signing according to patient's demographics and characteristics related to chemotherapy consent. RESULTS: Surrogate's signing was noted for 20.7% (84/405) of patient and over half of surrogate signings were performed by the patients' son or daughter (60.7%). Two main reasons for surrogate signing were patient's incapacity (34.5%) and taking over authorization from patients (33.3%). The factors associated with more frequent surrogate's signing were absence of spouse, lower education level, outpatient, and when residents played a role as a principle provider of chemotherapy consent. CONCLUSION: This study suggests the lack of patients' own decision making for chemotherapy in some situations. This ethical dilemma must be considered for adequately informed decision making for chemotherapy while ensuring the patients' autonomy is maintained.

Effect of an Educational Intervention on Knowledge and Perception Regarding Rational Medicine Use and Self-medication.

BACKGROUND: Rational use of medicines is important for safe and cost-effective pharmacotherapy. However, nearly half of the medicines available in the market may be used irrationally. The present study assessed the perceptions and knowledge about rational medicine use and responsible self-medication among participants before and after an educational intervention at KIST Medical College, Lalitpur. METHODS: An educational module was conducted among healthcare professionals, media personnel and female community health volunteers. The questionnaire was administered before and immediately after the module. The areas addressed were rational medicine use, ethical prescribing, rational drug use situation in Nepal, pharmaceutical promotion, rational self-medication, safe use of antibiotics, and drug use problems in Nepal. RESULTS: Among healthcare professionals, the rational drug use situation in Nepal and the total score significantly increased post-intervention (p<0.05). Among media personnel the mean scores increased significantly in pharmaceutical promotion and drug use problems in Nepal areas but there was a significant decrease in safe use of antibiotics. The pre-intervention pharmaceutical promotion score was significantly higher among healthcare professionals compared to media personnel while the rational self-medication scores were highest among female community health volunteers, safe use of antibiotics scores were highest among the media personnel. Post-intervention the mean pharmaceutical promotion scores was highest among healthcare professionals, rational self-medication scores among female community health volunteers, safe use of antibiotics, drug use problems in Nepal and total scores were highest among the media personnel. CONCLUSIONS: There were differences in the mean pre-intervention scores among different subgroups. A single session may not be enough to bring about significant changes in knowledge and perception. The retention of knowledge could be measured in future studies.

La agresividad terapéutica y la oncología líquida / Therapeutic aggressiveness and liquid oncology

Los criterios de agresividad terapéutica publicados hace una década proporcionan un juicio de calidad y son una referencia en la atención de pacientes con cáncer avanzado, pero su utilización no está generalizada en la evaluación de los Servicios de Oncología. En este trabajo analizamos la agresividad terapéutica, según los criterios estándar, en 1.001 pacientes con cáncer avanzado fallecidos en el Complejo Hospitalario Universitario de Santiago de Compostela, entre los años 2010 y 2013. Los resultados parecen demostrar que la agresividad terapéutica al final de la vida en nuestro medio hospitalario está presente con más frecuencia de lo recomendado, ya que el 25% de los pacientes cumple al menos un criterio de agresividad. Este resultado podría explicarse por la presencia de una Oncología líquida que no prioriza al paciente como sujeto moral del encuentro clínico. Los cuidados se dirigen a la atención de las necesidades y deben estar articulados en modelos centrados en la comunicación y en la dignidad. Su aplicación mediante la Planificación Anticipada de los Cuidados, la consideración de los valores y preferencias del paciente y la Limitación del Esfuerzo Terapéutico, son formas de disminuir esta agresividad y mejorar la práctica clínica al final de la vida. Necesitamos plantear actitudes sinérgicas y proactivas, sumando lo mejor de la investigación oncológica con el mejor cuidado y atención clínica en beneficio del ser humano, sujeto moral y finalidad última de la Medicina

Aggressiveness criteria proposed in the scientific literature a decade ago provide a quality judgment and are a reference in the care of patients with advanced cancer, but their use is not generalized in the evaluation of Oncology Services. In this paper we analyze the therapeutic aggressiveness, according to standard criteria, in 1.001 patients with advanced cancer who died in our Institution between 2010 and 2013. The results seem to show that aggressiveness at the end of life is present more frequently than experts recommend. About 25% of patients fulfill at least one criterion of aggressiveness. This result could be explained by a liquid Oncology which does not prioritize the patient as a moral subject in the clinical appointment. Medical care is oriented to necessities and must be articulated in a model focused on dignity and communication. Its implementation through Advanced Care Planning, consideration of patient’s values and preferences, and Limitation of therapeutic effort are ways to reduce aggressiveness and improve clinical practice at the end of life. We need to encourage synergic and proactive attitudes, adding the best of cancer research with the best clinical care for the benefit of human being, moral subject and main goal of Medicine

Segunda opinión, uso compasivo y ensayo clínico / Second opinion, compasive use and clinical trial

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Comentario al caso: segunda opinión, uso compasivo y ensayo clínico / Commentary on the case: second opinion, compassionate use, and clinical trial

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Can covert administration of medicines be in a patient's best interests?

In this article Richard Griffith considers whether it is ever in a patient's best interests to be given medicine by covert means, such as disguising it in food.

Health and Ethical Consequences of Outsourcing Pivotal Clinical Trials to Latin America: A Cross-Sectional, Descriptive Study.

INTRODUCTION: The implications of conducting clinical trials in low and middle income countries on the financial accessibility and safety of the pharmaceutical products available in those markets have not been studied. Regulatory practices and ethical declarations lead to the commercialization of the new products, referred to as New Molecular Entities (NMEs), in the countries where tested as soon as they are approved in high surveillance countries. Patients and patients' associations use the Latin American courts to access new and expensive treatments, regardless of their safety profile and therapeutic value. DESIGN AND OBJECTIVES: Cross-sectional, descriptive study. To determine the therapeutic value and safety profile of the NMEs approved by the Food and Drug Administration (FDA) in 2011 and 2012 that had been tested in Latin America, and the implications of their market approval for the pharmaceutical budgets in the countries where tested. SETTING: Latin America. MEASURES: To assess the therapeutic value and safety of the NMEs commercialized in the different countries we used f independent drug bulletins. The prices of the NMEs for the consumers were obtained from the pharmaceutical price observatories of the countries were the medicines had been tested. If the price was not available in the observatories, it was obtained from pharmaceutical distributors. We used the countries' minimum wage and per capita income to calculate the financial accessibility of a course of treatment with the NMEs. RESULTS: We found that 33 NMEs approved by the FDA in 2011 and 2012 have been tested in Latin America. Of these, 26 had been evaluated by independent drug bulletins and only five were found to add some value to a subset of patients and had significant side-effects. The pharmaceutical prices were very high, varied widely across countries and were unrelated to the countries' income per capita or minimum wage. CONCLUSION: The implementation of clinical trials in Latin America results in the commercialization of medicines with questionable safety profiles and limited therapeutic value, putting patients at risk and causing budgetary strains in pharmaceutical budgets.

Minors and Contested Medical-Surgical Treatment.

Use of the best-interests test as the legal standard to justify medical treatment (or its cessation) in respect to legally incompetent adults or minors has come under sustained critique over the years. "Best interests" has variously been alleged to be indeterminate as well as susceptible to majoritarian ideology and inherent bias. It has also been alleged to be inferior to rights-based approaches. Against the background of several particularly hard cases involving minors discussed by Gillett in a prior article in this journal, this article considers some of these critiques. It concludes that these critical accounts make significant contributions to enabling a more procedurally and substantively robust consideration of what might be in a child's best interests. However, it is argued that none of these accounts alone provide a superior framework that would justify jettisoning the concept of best interests. Further, it is suggested that best interests still has an important role in achieving patient-centered decisionmaking in this context. It concludes by suggesting a taxonomy of considerations when determining best interests.

Impacto de la Intervención Farmacéutica en el tratamiento del paciente mayor pluripatológico / The impact of Pharmacy Intervention on the treatment of elderly multi-pathological patients

Objetivo: analizar el impacto de la Intervención Farmacéutica (IF), dentro del equipo asistencial que atiende al paciente mayor pluripatológico, en la evolución de los Problemas Relacionados con la Medicación (PRM) y los Resultados Negativos asociados con la Medicación (RNM). Estimar la prevalencia de PRM, RMN y Prescripciones Potencialmente Inadecuadas (PPI), y fármacos implicados, considerando las características de su ubicación asistencial. Método: estudio multicéntrico, prospectivo, de intervención, en pacientes mayores de 65 años pluripatológicos, institucionalizados u hospitalizados. El farmacéutico revisó la medicación crónica del paciente para detectar PRM y RNM y emitió recomendaciones al médico responsable del paciente, valorando posteriormente el efecto de dicha intervención. Los PRM y los RNM se clasificaron según el Tercer Consenso de Granada. Para la detección de PPI se utilizaron los Criterios STOPP/START. Las variables principales fueron: número IF realizadas y aceptadas por el médico. Resultados: se incluyeron 338 pacientes, presentando 326 (96,4%) algún PRM. Se detectaron 1.089 PRM, proponiéndose para su resolución 933 IF y aceptándose 651(69,9%). Las IF resolvieron 58,9% de los PRM, encontrándose asociación entre la IF y la resolución del PRM (p<0.001). Las IF fueron más aceptadas en pacientes institucionalizados que en hospitalizados (p=0,002), por médicos con mayor especialización (p<0,001) y cuando implicaban RNM de seguridad cuantitativa (p = 0,042). Los criterios STOPP/START detectaron el 65% de las PPI, encontrándose más PPI no relacionadas con estos criterios en institucionalizados que en hospitalizados (p<0,001). Conclusiones: la IF en el equipo interdisciplinar logra resolver de forma significativa los PRM y RNM en el paciente mayor pluripatológico, contribuyendo a mejorar la calidad de su farmacoterapia. Es el primer estudio multicéntrico de estas características realizado en España (AU)

Objective: to analyze the impact of Pharmacy Intervention (PI), within the healthcare team who manages elderly multi-pathological patients, regarding the evolution of Drug Related Problems (DRPs) and Negative Outcomes Associated with Medication (NOMs). To estimate the prevalence of DRPs, NOMs, and Potentially Inappropriate Prescriptions (PIPs), and the drugs involved, considering the characteristics of their healthcare location. Method: multicenter, prospective study, on >65-year-old patients with multiple pathologies, either institutionalized or hospitalized. The Pharmacist reviewed the chronic medication of the patient in order to detect DRPs and NOMs, and issued recommendations to the physician responsible for the patient, and this intervention was subsequently evaluated. DRPs and NOMs were classified according to the Third Consensus of Granada. The STOPP/START Criteria were used for PIP detection. The primary variables were: number of PIs conducted and accepted by the physician. Outcomes: 338 patients were included, and 326 (96.4%) presented some DRP. 1089 DRPs were detected, with 983 PIs suggested for their solution, and 651 (69.9%) of these were accepted. PIs solved 58.9% of DRPs, and an association was found between PI and the solution for the DRP (p<0.001). PIs were more accepted in institutionalized than in hospitalized patients (p=0.002), by physicians with a higher specialization (p<0.001) and when they involved quantitative safety NOMs (p=0.042). The STOPP/START Criteria detected 65% of PIPs, and more PIPs not associated with these criteria were found in institutionalized than in hospitalized patients (p<0.001). Conclusions: pharmacy Intervention within the multidisciplinary team can solve in a significant way both DRPs and NOMs in elderly multi-pathological patients, and thus help to improve the quality of their pharmacological therapy. This is the first multicenter clinical trial with these characteristics that has been conducted in Spain (AU)

[Current issues in psychiatric ethics]. / A pszichiátriai etika aktuális kérdései.

The article analyzes some ethical problems in psychiatry that have been emerging in recent years. It deals with the ongoing intensive debates about the DSM-5 before its publication, and with some of the criticisms of the DSM-5 itself. Then it goes on to analyze the use of placebo. This is followed by the ethical problems of the treatment of ADHD with stimulant drugs, among which one is the question of authenticity, namely whether the pre-treatment or the post-treatment personality is the real, authentic self of the patient. This question has been raised not only in the case of the ADHD, but also in relation with the antidepressant treatment of depression earlier, and in relation with deep brain stimulation and dopamine replacement therapy now, all of which causes changes in the treated patient's personality and motivations. Finally the article describes some ethical problems of informed consent in the case of antidepressant medication, together with the necessity to involve psychiatric nurses and rating scales in the assessment of the patient's decision making capacity.

To What did They Consent? Understanding Consent Among Low Literacy Participants in a Microbicide Feasibility Study in Mazabuka, Zambia.

We conducted a study to review the consenting process in a vaginal microbicide feasibility study conducted in Mazabuka, Zambia. Participants were drawn from those participating in the microbicide study. A questionnaire and focus group discussion were used to collect information on participants' understanding of study aims, risks and benefits. Altogether, 200 participants took part in this study. The results of the study showed that while all participants signed or endorsed their thumbprints to the consent forms, full informed consent was not attained from most of the participants since 77% (n = 154) of the participants had numerous questions about the study and 34% (n = 68) did not know who to get in touch with concerning the study. Study objectives were not fully understood by over 61% of the participants. Sixty four percent of the participants were not sure of the risks of taking part in the microbicide study. A significant number thought the study was all about determining their HIV status. Some participants were concerned that their partners were not on the trial as they were convinced that being on the study meant that that they had a lifetime protection from HIV infection. The process of obtaining consent was inadequate as various phases of the study were not fully understood. We recommend the need for researchers to reinforce the consenting process in all studies and more so when studies are conducted in low literacy populations.

The medicalization of love.

Pharmaceuticals or other emerging technologies could be used to enhance (or diminish) feelings of lust, attraction, and attachment in adult romantic partnerships. Although such interventions could conceivably be used to promote individual (and couple) well-being, their widespread development and/or adoption might lead to the 'medicalization' of human love and heartache--for some, a source of a serious concern. In this essay, we argue that the medicalization of love need not necessarily be problematic, on balance, but could plausibly be expected to have either good or bad consequences depending upon how it unfolds. By anticipating some of the specific ways in which these technologies could yield unwanted outcomes, bioethicists and others can help to direct the course of love's medicalization--should it happen to occur--more toward the 'good' side than the 'bad.'

Caso clínico de seguimiento farmacoterapéutico a paciente con dolor crónico / No disponible

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