Old ideas from a new philosophical model: levels and means of human life extension

Since 2000, the possibility of extending human lifespan has been a highly debated topic by both biomedical scientists (de Grey and Rae, 2007; Olshansky & Carnes, 2002) and philosophers (Agar, 2010; Overall, 2003). One kind of attempt to find middle ground in this debate has been efforts to distinguish two kinds of life extension: moderate and radical (Agar, 2013; Glannon 2002; Lucke et al, 2006). Although, there are three reasons for rejecting this distinction: 1. The difference between moderate and radical life extension cannot be explained only by a quantitative measurement but also by a qualitative distinction. Jeanne Calment's age is not a maximum lifespan (imaginable) and I propose the concept of Uncertainty Threshold of Longevity to debate whether there is a limit in our species. 2. The question of whether a therapy will be considered in a Weak Sense or in a Strong Sense. It still does not exist, save (or with the exception of) caloric restriction, many promising researches on aging. How to evaluate whether a treatment will add more years or more health or how to know the best way to live 200 years? 3. A thought experiment named Peter Pan Drug suggests that a healthspan extension, in a radical sense, allows us to re-think about a lifestyle totally different from now. Example: a life extended to 120 years but maintaining physical and mental condition all the time, is it moderate kind? I propose an alternative model for resolving this debate. This model builds upon the distinctions that Juengst (et al, 2003) and Wareham (2016) make about different levels and means to control human senescence, to propose the following conceptual categories: (a) Compression of Morbidity; (b) Slowed Aging; (c) Negligible Aging or SENS; (d) Arrested Aging; (e) Escaping Aging. In addition, I have to add several concepts which are relevant for my purpose: indefinite life, virtual sort of immortality or (true) immortality.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

A new framework for thinking about life extension

I propose an alternative framework for resolving the debate about life extension. This model builds upon the distinctions that Juengst (et al. 2003) and Wareham (2016) make about different levels and means to control human senescence, to propose the following conceptual categories: (a) Compression of Morbidity; (b) Slowed Aging; (c) Negligible Aging or SENS; (d) Arrested Aging; (e) Escaping Aging. In addition, I have to add several concepts which are relevant for my purpose: indefinite life, virtual sort of immortality or (true) immortality.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Longer Lives?: Understanding the Human Life Extension Possibilities

Over the last few years, ethical and social issues related to life extension have gathered much attention among biologists, medical doctors and philosophers. However, despite the general agreement on the importance of life extension both for biogerontology and philosophy of medicine, a satisfactory definition of life extension has not been provided yet. In order to mediate with all the knowledge, in this paper I will present a conceptual model of human life extension: (1) to offer a general definition and some biomedical aspects; (2) to present the origin of the ethical mistake; (3) to introduce two levels: moderate human life extension and radical life extension (4) to comment successful aging idea.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Sobre la extensión de la vida humana: bases para crear un sistema

En esta comunicación pretendo arrojar algo de luz al debate en torno al concepto de extensión de la vida humana. Para ello, ofreceré una definición ajustada de qué se puede considerar en general como extensión de la vida humana y, a continuación, analizaré cómo es posible crear un sistema que englobe las tres formas distintas de extensión que concibo.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

La filosofía de la biología como disciplina autónoma

En la presente conferencia tengo la intención de seguir la siguiente estructura: 1. Exponer una introducción sobre qué es la filosofía de la biología. 2. Argumentar y justificar la interdisciplinariedad de la filosofía de la biología. 3. Sugerir cuáles pueden ser los nuevos enfoques y temas que se abordarán en un futuro próximo en filosofía de la biología.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Is aging a disease? The theoretical definition of aging in the light of the philosophy of medicine

In this talk, I attempt to shed light on the philosophical debate about the theoretical definition of aging from the discussion of the notion of disease in the philosophy of medicine. As a result, I introduce a concrete approach -- the pragmatist approach to aging -- to account for the theoretical relationship between the notions of disease and aging, as they are addressed in the philosophy of aging. To that end, the structure of this work is as follows: first, in section 2, I analyze the discussion between the two major positions in this debate, and introduce the influential accounts of authors such as Hayflick, Schramme, Caplan, Murphy, and Callahan & Topinkova. I will show that in this discussion it is being assumed by some authors that the definition of disease is univocal and corresponds to what some of these authors understand as a "non-natural state". The motivation of this is straightforward: in order to decide if aging should be defined as a disease we need to clarify first what a disease is and what implies to characterize something as such. In section 3, I will show that the disagreement between those who argue that aging is a disease and those who claim that it is not is ultimately based on an assumption of different notions of disease. In addition, I will also turn to the debate on disease in the philosophy of medicine to analyze the proposals of Callahan & Topinkova and Murphy. These authors advocate avoiding the question of whether or not aging is a disease for pragmatic reasons. The important thing would not be to define aging as a disease but to medically treat it as such. I propose to reformulate this proposal of pragmatic motivation to frame it in an approach to the concept of disease, which I call "pragmatist", that has advocated philosophers of medicine such as Cooper or Hofmann. I think that this pragmatist approach addresses the issue of medical categorization of aging in a more scientific and philosophical fruitful way.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Spontaneous Breathing in Early Acute Respiratory Distress Syndrome: Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study

OBJECTIVES: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. DESIGN: Planned secondary analysis of a prospective, observational, multicentre cohort study. SETTING: International sample of 459 ICUs from 50 countries. PATIENTS: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. INTERVENTIONS: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92-1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93-1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0-22] vs 8 [0-20]; p = 0.014) and shorter duration of ICU stay (11 [6-20] vs 12 [7-22]; p = 0.04). CONCLUSIONS: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013