Infection control in long term care institutions for the elderly: A reflection document on the situation in Spain.

A progressively increasing percentage of the elderly live during the last years of their lives in nursing homes. Although these institutions are intended to mimic life at home as much as possible, they have characteristics that make them quite similar to a "nosocomiun", i.e. an establishment for the treatment of the sick. The very coexistence among the elderly, the fact of sharing caregivers and the very significant exposure to third parties, together with the frequent predisposing diseases to infection in this population, make infection frequent among residents and also easily transmissible. This leads us to ask what can be done to prevent infection in this environment and more specifically what is the state of the art of the matter in a Western European nation such as ours. The Board of Trustees of the Health Sciences Foundation has asked itself a series of questions on the subject of infection prevention in Nursing Homes, the structure of procedures, the legislation available, compliance with the measures indicated, the best indicators of the processes and therefore, the need to promote in Spain a document of recommendations to avoid infections in this poplation whose morbidity and mortality need not be highlighted. To this end, a multidisciplinary group of experts in different aspects of this problem has been convened and asked the proposed questions. The questions were discussed by the group as a whole and led to a series of conclusions agreed upon by the participants. The results of the meeting are reported below.

Impact of the COVID-19 pandemic on the mental health of the general population and health care workers.

The Health Sciences Foundation has assembled a multidisciplinary group around a series of questions about the impact of the COVID-19 pandemic on the mental health of the general population and specific groups within that population, particularly healthcare workers. In the general population, the most prevalent mental disorders have been anxiety, sleep disorders and affective disorders, primarily depression. There has been a considerable increase in suicidal behavior, especially in young women and men over 70 years of age. There has been an increase in alcohol abuse and nicotine, cannabis and cocaine use. In contrast, the use of synthetic stimulants during periods of confinement has decreased. With regard to non-substance addictions, gambling was very limited, pornography consumption increased significantly and there was an increase in compulsive shopping and the use of video games. Particularly vulnerable groups include adolescents and patients with autism spectrum disorders. Healthcare workers suffered an increase in depression, anxiety and post-traumatic stress, especially those who were exposed during the early stages of the pandemic. Female sex, being a nurse, proximity to patients with COVID-19, working in a rural environment and having previous psychiatric or organic illnesses were some of the most frequently repeated factors in various studies in this population group. The media have shown a good degree of knowledge about these problems and have dealt with them frequently and from the point of view of ethics, crisis situations, such as the one experienced, have triggered not only physical but also moral claudications.

Impact of the COVID-19 pandemic on the diagnosis and treatment of onco-hematologic patients: a discussion paper.

We do not know the precise figure for solid organ tumors diagnosed each year in Spain and it is therefore difficult to calculate whether there has been a decrease in cancer diagnoses as a consequence of the pandemic. Some indirect data suggest that the pandemic has worsened the stage at which some non-hematological neoplasms are diagnosed. Despite the lack of robust evidence, oncology patients seem more likely to have a poor outcome when they contract COVID-19. The antibody response to infection in cancer patients will be fundamentally conditioned by the type of neoplasia present, the treatment received and the time of its administration. In patients with hematological malignancies, the incidence of infection is probably similar or lower than in the general population, due to the better protective measures adopted by the patients and their environment. The severity and mortality of COVID-19 in patients with hematologic malignancies is clearly higher than the general population. Since the immune response to vaccination in hematologic patients is generally worse than in comparable populations, alternative methods of prevention must be established in these patients, as well as actions for earlier diagnosis and treatment. Campaigns for the early diagnosis of malignant neoplasms must be urgently resumed, post-COVID manifestations should be monitored, collaboration with patient associations is indisputable and it is urgent to draw the right conclusions to improve our preparedness to fight against possible future catastrophes.

Air pollution and health prevention: A document of reflection.

Ambient air quality, pollution and its implication on health is a topic of enormous importance that is normally dealt with by major specialists in their particular areas of interest. In general, it is not discussed from multidisciplinary approaches or with a language that can reach everyone. For this reason, the Health Sciences Foundation, from its prevention area, has formulated a series of questions to people with very varied competences in the area of ambient air quality in order to obtain a global panorama of the problem and its elements of measurement and control. The answers have been produced by specialists in each subject and have been subjected to a general discussion that has allowed conclusions to be reached on each point. The subject was divided into three main blocks: external ambient air, internal ambient air, mainly in the workplace, and hospital ambient air and the consequences of its poor control. Along with the definitions of each area and the indicators of good and bad quality, some necessary solutions have been pointed out. We have tried to know the current legislation on this problem and the competences of the different administrations on it. Despite its enormous importance, ambient air quality and health is not usually a topic of frequent presence in the general media and we have asked about the causes of this. Finally, the paper addresses a series of reflections from the perspective of ethics and very particularly in the light of the events that the present pandemic raises. This work aims to provide objective data and opinions that will enable non-specialists in the field to gain a better understanding of this worrying reality.

Past and future of HIV infection. A document based on expert opinion.

HIV infection is now almost 40 years old. In this time, along with the catastrophe and tragedy that it has entailed, it has also represented the capacity of modern society to take on a challenge of this magnitude and to transform an almost uniformly lethal disease into a chronic illness, compatible with a practically normal personal and relationship life. This anniversary seemed an ideal moment to pause and reflect on the future of HIV infection, the challenges that remain to be addressed and the prospects for the immediate future. This reflection has to go beyond merely technical approaches, by specialized professionals, to also address social and ethical aspects. For this reason, the Health Sciences Foundation convened a group of experts in different aspects of this disease to discuss a series of questions that seemed pertinent to all those present. Each question was presented by one of the participants and discussed by the group. The document we offer is the result of this reflection.

Overview of virus and cancer relationships. Position paper.

The role of certain viruses in the etiology of some tumors is today indisputable, but there is a lack, however, of annoverview of the relationship between viruses and cancer with amultidisciplinary approach. For this reason, the Health Sciences Foundation has convened a group of professionals from different areas of knowledge to discuss the relationship between viruses and cancer, and the present document is the result of these deliberations. Although viruses cause only 10-15% of cancers, advances in oncology research are largely due to the work done during the last century on tumor viruses. The clearest cancer-inducing viruses are: HPV, HBV, HCV, EBV and, depending on the geographical area, HHV-8, HTLV-1 and HIV. HPVs, for example, are considered to be the causative agents of cervical carcinomas and, more recently, of a proportion of other cancers. Among the Herpes viruses, the association with the development of neoplasms is well established for EBV and HHV-8. Viruses can also be therapeutic agents in certain neoplasms and, thus, some oncolytic viruses with selective tropism for tumor cells have been approved for clinical use in humans. It is estimated that the prophylaxis or treatment of viral infections could prevent at least 1.5 million cancer deaths per year.

The situation of infection in the elderly in Spain: a multidisciplinary opinion document.

Infection in the elderly is a huge issue whose treatment usually has partial and specific approaches. It is, moreover, one of the areas where intervention can have the most success in improving the quality of life of older patients. In an attempt to give the widest possible focus to this issue, the Health Sciences Foundation has convened experts from different areas to produce this position paper on Infection in the Elderly, so as to compare the opinions of expert doctors and nurses, pharmacists, journalists, representatives of elderly associations and concluding with the ethical aspects raised by the issue. The format is that of discussion of a series of pre-formulated questions that were discussed by all those present. We begin by discussing the concept of the elderly, the reasons for their predisposition to infection, the most frequent infections and their causes, and the workload and economic burden they place on society. We also considered whether we had the data to estimate the proportion of these infections that could be reduced by specific programmes, including vaccination programmes. In this context, the limited presence of this issue in the media, the position of scientific societies and patient associations on the issue and the ethical aspects raised by all this were discussed.

Chronic obstructive pulmonary disease (COPD) in Spain and the different aspects of its social impact: a multidisciplinary opinion document.

Chronic obstructive pulmonary disease (COPD) is one of the most prevalent diseases in the World, and one of the most important causes of mortality and morbidity. In adults 40 years and older, it affects more than 10% of the population and has enormous personal, family and social burden. Tobacco smoking is its main cause, but not the only one, and there is probably a genetic predisposition that increases the risk in some patients. The paradigm of this disease is changing in Spain, with an increase of women that has occurred in recent years. Many of the physio pathological mechanisms of this condition are well known, but the psychological alterations to which it leads, the impact of COPD on relatives and caregivers, the limitation of daily life observed in these patients, and the economic and societal burden that they represent for the health system, are not so well-known. A major problem is the high under-diagnosis, mainly due to difficulties for obtaining, in a systematic way, spirometries in hospitals and health-care centers. For this reason, the Fundación de Ciencias de la Salud and the Spanish National Network Center for Research in Respiratory Diseases (CIBERES) have brought together experts in COPD, patients and their organizations, clinical psychologists, experts in health economics, nurses and journalists to obtain their opinion about COPD in Spain. They also discussed the scientific bibliometrics on COPD that is being carried out from the CIBERES and speculated on the future of this condition. The format of the meeting consisted in the discussion of a series of questions that were addressed by different speakers and discussed until a consensus conclusion was reached.

The situation of vaccines for the prevention of infections in adults: An opinion paper on the situation in Spain.

The childhood immunization schedule is well known and generally well implemented in developed countries. For various reasons, the same is not true of vaccines aimed at preventing infections in adults, in which vaccination coverage is incomplete and generally very deficient. In order to assess the situation of adult vaccination in Spain, the Fundación de Ciencias de la Salud has brought together a series of experts in different fields, including doctors, nurses, representatives of patient associations, health managers and economists, health authorities and journalists to deal with this issue. The format was that of a round table in which a series of questions previously formulated by the coordinators were to be answered and debated. The document presented is not an exhaustive review of the topic, nor is it intended to make recommendations, but only to give a multidisciplinary opinion on topics that could be particularly debatable or controversial. The paper reviews the main vaccine-preventable adult diseases, their clinical and economic impact, the possibilities of reducing them with vaccination programmes and the difficulties in carrying them out. The role of nursing, pharmacy services, patient associations and the health administration itself in changing the current situation was discussed. Prospects for new vaccines were discussed and we speculated on the future in this field. Finally, particularly relevant ethical aspects in decision-making regarding vaccination were discussed, which must be faced by both individuals and states. We have tried to summarize, at the end of the presentation of each question, the environment of opinion that was agreed with all the members of the table.

Information on nosocomial infections in the mainstream media: an opinion document.

This paper seeks to explore the reasons for the low impact of nosocomial infection in the mainstream media and the responsibilities of physicians and journalists in terms of this situation. To this end, a small group of 13 experts met for round-table discussions, including physicians with expertise in nosocomial infection, medical lawsuits and ethics, as well as journalists from major mainstream Spanish media outlets. The various participants were asked a series of questions prior to the meeting, which were answered in writing by one of the speakers and discussed during the meeting by the whole group, the aim being to obtain consensual conclusions for each of them. The document was subsequently reviewed, edited and forwarded to all co-authors for their agreement. The opinions expressed are the personal opinions of the participants and not necessarily those of the institutions in which they work or with which they collaborate.

Antidiarrheal activity of extracts from Maytenus gonoclada and inhibition of Dengue virus by lupeol.

Diarrhea is an infectious disease caused by bacterial, virus, or protozoan, and dengue is caused by virus, included among the neglected diseases in several underdeveloped and developing countries, with an urgent demand for new drugs. Considering the antidiarrheal potential of species of Maytenus genus, a phytochemical investigation followed by antibacterial activity test with extracts of branches and heartwood and bark of roots from Maytenus gonoclada were conducted. Moreover, due the frequency of isolation of lupeol from Maytenus genus the antiviral activity against Dengue virus and cytotoxicity of lupeol and its complex with ß-cyclodextrins were also tested. The results indicated the bioactivity of ethyl acetate extract from branches and ethanol extract from heartwood of roots of M. gonoclada against diarrheagenic bacteria. The lupeol showed potent activity against Dengue virus and low cytotoxicity in LLC-MK2 cells, but its complex with ß-cyclodextrin was inactive. Considering the importance of novel and selective antiviral drug candidates the results seem to be promising.

Antidiarrheal activity of extracts from Maytenus gonoclada and inhibition of Dengue virus by lupeol

ABSTRACT Diarrhea is an infectious disease caused by bacterial, virus, or protozoan, and dengue is caused by virus, included among the neglected diseases in several underdeveloped and developing countries, with an urgent demand for new drugs. Considering the antidiarrheal potential of species of Maytenus genus, a phytochemical investigation followed by antibacterial activity test with extracts of branches and heartwood and bark of roots from Maytenus gonoclada were conducted. Moreover, due the frequency of isolation of lupeol from Maytenus genus the antiviral activity against Dengue virus and cytotoxicity of lupeol and its complex with β-cyclodextrins were also tested. The results indicated the bioactivity of ethyl acetate extract from branches and ethanol extract from heartwood of roots of M. gonoclada against diarrheagenic bacteria. The lupeol showed potent activity against Dengue virus and low cytotoxicity in LLC-MK2 cells, but its complex with β-cyclodextrin was inactive. Considering the importance of novel and selective antiviral drug candidates the results seem to be promising.

Maytenus distichophylla and Salacia crassifolia: source of products with potential acetylcholinesterase inhibition

ABSTRACT The phytochemical study of the extract leaves from Maytenus distichophylla Mart. and Salacia crassifolia (Mart. ex Schult.) G. Don, Celastraceae, resulted in the isolation of 3-oxofriedelane, 3β-hydroxyfriedelane, 3β,24-dihydroxyfriedelane, 3-oxo-28,29-dihydroxyfriedelane, two mixtures of pentacyclic triterpenes (α-amyrin with β-amyrin and 3β-stearyloxy-urs-12-ene with 3β-stearyloxy-olean-12-ene), 3β-palmityloxy-urs-12-ene, the steroid β-sitosterol and its glycosylated derivative β-glucosyl-β-sitosterol, tritriacontanoic acid and the natural polymer gutta percha. The chemical structures of these constituents were established by IR, 1H and 13C NMR spectral data. Crude extracts, the mixtures of triterpenes and the isolated constituents were subjected to in vitro acetylcholinesterase inhibitory evaluation. Acetylcholinesterase inhibitory effect was observed for crude chloroform extract leaves from M. distichophylla (100%) and S. crassifolia (97.93 ± 5.63%) and for the triterpenes 3β,24-dihydroxyfriedelane (99.05 ± 1.12%), 3-oxo-28,29-dihydroxyfriedelane (90.59 ± 3.76%) and 3β-palmityloxy-urs-12-ene (97.93 ± 1.47%). The percent inhibitions induced by these natural products were very similar to those produced by physostigmine (93.94 ± 2.10%) a standard acetylcholinesterase inhibitor. Therefore, these results open perspectives for the use of these species as source of compounds with similar physostigmine pharmacological effect.

Effect of constituents from samaras of Austroplenckia populnea (Celastraceae) on human cancer cells.

BACKGROUND: Aiming the continuity of the studies of Austroplenckia populnea, Brazilian species of the Celastraceae family, in the present study, it was investigated the effect of crude extracts obtained with ethanol, ethyl acetate and chloroform and two purified constituents, proanthocyanidin A and 4'-O-methylepigallocatechin, both isolated from its samaras, on cancer cell proliferation assays. MATERIALS AND METHODS: The human cancer cells lines MCF-7 (ductal breast carcinoma), A549 (lung cancer), HS578T (ductal breast carcinoma) and non-cancer HEK293 (embryonic kidney cells) were treated with different concentrations of extracts and constituents and the effect was observed through the acid phosphatase method. The chemical structures of the purified compounds were identified by the respective IR and (1)H and (13)C nuclear magnetic resonance spectral data. RESULTS: While crude extracts from samaras of the folk medicine A. populnea can trigger cell proliferative effects in human cell lines, the purified compounds (proanthocyanidin A and 4'-O-methyl-epigallocatechin) isolated from the same extracts can have an opposite (anti-proliferative) effect. CONCLUSION: Based on the results, it was possible to suggest that extracts from samaras of A. populnea should be further investigated for possible cancer-promoting activities; and the active extracts can also represent a source of compounds that have anti-cancer properties.

El equívoco terapéutico en los ensayos clínicos: combatirlo y convivir con él / Therapeutic misconception in clinical trials: fighting against it and living with it

Un ensayo clínico busca obtener datos para el beneficio de futuros pacientes y no necesariamente para los que participan en él. Sin embargo, hay pacientes que creen que obtendrán un beneficio terapéutico directo por participar en un ensayo clínico: es el denominado «equívoco terapéutico». En este artículo se describe la naturaleza y la extensión del equívoco terapéutico, que también pueden presentar los investigadores. Su presencia es especialmente relevante en ensayos con grupo placebo y en los de fase 1 de oncología. Para intentar limitar su aparición hay que asegurar que las hojas de información para los participantes estén bien redactadas, y que los investigadores establezcan una conversación efectiva y transparente en el proceso de obtención del consentimiento informado, de forma que el paciente conozca todos los matices de su participación en la investigación y valore lo que esto significa (AU)

A clinical trial seeks information for the benefit of future patients and not necessarily for those who participate in the study. However, there are patients who believe that they will receive a direct therapeutic benefit by participating in a clinical trial, the so-called «therapeutic misconception». In this article, we describe the nature and extent of therapeutic misconception, which researchers can also experience. Its presence is especially important in phase 1 oncology trials and those with placebo group. To limit its occurrence, investigators have to ensure that participant information sheet are well written and to establish an effective and transparent discussion during the process of obtaining informed consent so that patients understand all aspects of their participation in the research and appreciate what this participation entails (AU)

Therapeutic misconception in clinical trials: fighting against it and living with it. / El equívoco terapéutico en los ensayos clínicos: combatirlo y convivir con él.

A clinical trial seeks information for the benefit of future patients and not necessarily for those who participate in the study. However, there are patients who believe that they will receive a direct therapeutic benefit by participating in a clinical trial, the so-called «therapeutic misconception¼. In this article, we describe the nature and extent of therapeutic misconception, which researchers can also experience. Its presence is especially important in phase 1 oncology trials and those with placebo group. To limit its occurrence, investigators have to ensure that participant information sheet are well written and to establish an effective and transparent discussion during the process of obtaining informed consent so that patients understand all aspects of their participation in the research and appreciate what this participation entails.

Craneoplastia con vendaje. nuevas formas de limitación del tratamiento de soporte vital y donación de órganos / Cranioplasty with bandaging. new forms of limitation of life support and organ donation

La mayoría de los órganos trasplantados proceden de donantes fallecidos en muerte encefálica (ME). En pacientes neurocríticos con lesiones catastróficas y craniectomía descompresiva (CD) que tienen una pésima evolución a pesar de todo el tratamiento, la CD puede llegar a ser una medida fútil que impida la evolución natural hacia la ME. Planteamos si realizar un vendaje compresivo pericraneal (craneoplastia con vendaje) puede ser una práctica éticamente correcta y comparable a otras formas habituales de limitación del tratamiento de soporte vital (LTSV).A partir de un caso clínico, realizamos una consulta al Comité de Ética Asistencial y a expertos bioéticos, formulando las siguientes cuestiones: 1) En pacientes que se decide la LTSV ¿es éticamente correcto realizar una craneoplastia con vendaje? 2) ¿Es preferible esta opción considerando una posible donación de órganos? Conclusiones 1) La craneoplastia con vendaje puede ser considerada una forma de LTSV éticamente aceptable y similar a otros procedimientos 2) Facilita la donación de órganos para trasplante, lo que aporta valor añadido por el bien social correspondiente 3) En estos casos, es necesario conocer las instrucciones previas del paciente y en su ausencia, obtener el consentimiento familiar por delegación tras un informe detallado del procedimiento (AU)

Most of transplanted organs are obtained from brain death (BD) donors. In neurocritical patients with catastrophic injuries and decompressive craniectomy (DC), which show a dreadful development in spite of this treatment, DC could be a futile tool to avoid natural progress to BD. We propose if cranial compressive bandage (cranioplasty with bandage) could be an ethically correct practice, similar to other life-sustaining treatment limitation (LSTL) common methods. Based on a clinical case, we contacted with the Assistance Ethics Committee and some bioethics professionals asking them two questions: 1) Is ethically correct to perform acranioplasty with bandage in those patients with LSTL indication? 2) Thinking in organ donation possibility, is this option preferable? Conclusions 1) Cranioplasty with bandage could be considered an ethically acceptable LSTL practice, similar to other procedures. 2) It facilitates organ donation for transplant, which provides value-added because of its own social good. 3) In these cases, it is necessary to know previous patient's will or, in absentia, to obtain family consent after a detailed procedure report (AU)

Cranioplasty with bandaging. New forms of limitation of life support and organ donation.

Most of transplanted organs are obtained from brain death (BD) donors. In neurocritical patients with catastrophic injuries and decompressive craniectomy (DC), which show a dreadful development in spite of this treatment, DC could be a futile tool to avoid natural progress to BD. We propose if cranial compressive bandage (cranioplasty with bandage) could be an ethically correct practice, similar to other life-sustaining treatment limitation (LSTL) common methods. Based on a clinical case, we contacted with the Assistance Ethics Committee and some bioethics professionals asking them two questions: 1) Is ethically correct to perform a cranioplasty with bandage in those patients with LSTL indication? 2) Thinking in organ donation possibility, is this option preferable? Conclusions 1) Cranioplasty with bandage could be considered an ethically acceptable LSTL practice, similar to other procedures. 2) It facilitates organ donation for transplant, which provides value-added because of its own social good. 3) In these cases, it is necessary to know previous patient's will or, in absentia, to obtain family consent after a detailed procedure report.

New triterpenes from Maytenus robusta: structural elucidation based on NMR experimental data and theoretical calculations.

Leaves of Maytenus robusta (Celastraceae) were subjected to phytochemical investigation mainly directed at the isolation of pentacyclic triterpenes. The compounds friedelin (1), β-friedelinol (2), 3-oxo-21β-H-hop-22(29)-ene (7), 3,4-seco-friedelan-3,11β-olide (8), 3β-hydroxy-21β-H-hop-22(29)-ene (9), 3,4-seco-21β-H-hop-22(29)-en-3-oic acid (10), 3,4-seco-friedelan-3-oic acid (11), and sitosterol were identified in the hexane extract of M. robusta leaves. Compounds 8 and 9 are described herein for the first time. The structure and stereochemistry of both compounds were experimentally established by IR, HRLC-MS, and 1D (1H, 13C, and DEPT 135) and 2D (HSQC, HMBC and COSY) NMR data and supported by correlations with carbon chemical shifts calculated using the DFT method (BLYP/6-31G* level). Compounds 7 and 10 are also described for the first time, and their chemical structures were established by comparison with NMR data of similar structures described in the literature and correlations with BLYP/6-31G* calculated carbon chemical shifts. Compound 9, a mixture of 11 and sitosterol, and 3β,11β-dihydroxyfriedelane (4) were evaluated by the Ellman’s method and all these compounds showed acethylcholinesterase inhibitory properties.

Mesoscopic model for free-energy-landscape analysis of DNA sequences.

A mesoscopic model which allows us to identify and quantify the strength of binding sites in DNA sequences is proposed. The model is based on the Peyrard-Bishop-Dauxois model for the DNA chain coupled to a Brownian particle which explores the sequence interacting more importantly with open base pairs of the DNA chain. We apply the model to promoter sequences of different organisms. The free energy landscape obtained for these promoters shows a complex structure that is strongly connected to their biological behavior. The analysis method used is able to quantify free energy differences of sites within genome sequences.