Due to evidence that traumatic experience impacts the brain, the body (concerning sensory sensitivity), and the mind, a recent study that attempted to answer the question of whether the effects of CSA can be reversed by using a multidisciplinary approach consisting of dual treatments: hyperbaric & psychotherapy, was conducted. Its results showed that in addition to improvement of brain functionality, symptoms of distress were significantly reduced. The current paper aims to present the process as experienced by the 40 female (...) childhood sexual abuse survivor participants. Data included participants’ daily journals and drawings, and participants’ summaries presented verbally and written, 6-months after the study ended. A phenomenological analysis was used. Results showed three phases, the initial phase – remembering the trauma from both physical and cognitive aspects, the second phase - physiological relaxation as well as positive memories emerge; and, the third phase – bouncing back to life. The results are discussed in light of the study theoretical model and Lev-Wiesel (2014) childhood sexual abuse conceptualization. (shrink)

BackgroundThe prognosis of hypertensive intracerebral hemorrhage is poor at high altitudes. The objective of this study was to explore whether hyperbaric oxygen can improve the results of computed tomography perfusion imaging and the neurological function of patients with HICH, and influence the hemoglobin concentration.MethodThe patients with HICH were treated with puncture and drainage. Twenty-one patients were treated with HBO after the operation, and the other patients received conventional treatment. CTP was performed twice, and all indices were measured. (...) Scatter plots were used to determine the effect of hemoglobin concentration on CTP imaging. Receiver operating characteristic curves were plotted to analyze the effects of hemoglobin concentration and hematoma volume on recovery results. The patients were followed up for 6 months.ResultsForty-one patients with HICH were treated with puncture and drainage. In total, 21 were treated with HBO after the operation, and 20 received conventional treatment as the control group. No significant differences in the CBV and CBF values of the two groups were noted before treatment. After 10 days, the values of CBV and CBF in the HBO group were significantly higher than those in the control group. A scatter diagram showed there was no significant in the HBO group, but significant correlation for the CBV and CBF values in the control group’s hematoma center and margin. The ROC curves showed that hematoma volume had an influence on prognosis of the control group. The Glasgow Coma Scale scores of the HBO group were significantly higher than those of the control group.ConclusionsHBO therapy can improve the postoperative CBV and CBF values of patients with HICH and ameliorate their prognoses. There was no significant correlation between HBO group and hemoglobin concentration on admission. (shrink)

Hyperbaric oxygen (HBO) therapy still lacks proper interpretations of its many actions. This hypothesis is based on reports of temporarily elevated peripheral vascular resistance (PVR) during HBO sessions. Besides that, during HBO sessions, hyperoxygenated tissues can reduce their perfusion so much that CO2 can accumulate in them. Tissue perfusion depends on vascular innervation and on the balance between systemic constrictors and local dilators. During an HBO session, increased tissue oxygen levels suppress dilatory mechanisms. Tissue hyperoxygenation increases PVR, (...) suggesting that the HBO action on an edematous tissue may be caused by an oxygen‐induced disbalance among Starling capillary forces. The presented hypothesis is that oxygen‐caused arteriolar constriction reduces the hydrostatic pressure in downstream capillaries. Thus, more tissue fluid is absorbed in vascular capillaries, under the condition that the plasma colloid osmotic pressure remains unaltered during the HBO session. Among several known mechanisms behind the HBO actions, the vasoconstriction has been listed as a therapeutic modality for the reduction of the tissue edema, for a crush injury, for burns (in an acute phase), and for the compartment syndrome. The Bell's palsy is among often listed indications for the HBO treatment, although evidence is poor and reports of randomized trials are scarce. (shrink)

Most studies have examined the outcomes of patients supported by extracorporeal membrane oxygenation as a life-sustaining treatment. It is unclear whether significant social events are associated with the use of life-sustaining treatment. This study aimed to compare the trend of extracorporeal membrane oxygenation use in Taiwan with that in the world, and to examine the influence of significant social events on the trend of extracorporeal membrane oxygenation use in Taiwan.

Extra-corporeal membrane oxygenation has been introduced to clinical practice for several decades. It is unclear how internet and newspapers portray the use of extra-corporeal membrane oxygenation. This study were: (1) to quantify the coverage of extra-corporeal membrane oxygenation use in newspapers and on the Internet; (2) to describe the characteristics of extra-corporeal membrane oxygenation users presented in newspaper articles and the Internet web pages in comparison with those shown in extra-corporeal membrane oxygenation studies in Taiwan; and (3) to examine the (...) survival rates of extra-corporeal membrane oxygenation users presented in newspaper articles and the Internet web pages in comparison with those in Taiwan and in the Extracorporeal Life Support Registry Report International Summary for January 2014. (shrink)

Neonatal extracorporeal membrane oxygenation (ECMO), a technology for the treatment of respiratory failure in newborns, is used as a case study to examine statistical and ethical aspects of clinical trials and to illustrate a proposed 'ethics of evidence', an approach to medical uncertainty within the context of contemporary biomedical ethics. Discussion includes the twofold aim of the ethics of evidence: to clarify the role of uncertainty and scientific evidence in medical decision-making, and to call attention to the need to (...) confront the irreducible nature of uncertainty. (shrink)

The Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT) has been the focal point of many different criticisms regarding the ethics of the study ever since publication of the trial's findings in 2010 and 2012. In this article, we focus on a concern that the technical design and implementation details of the study were ethically flawed. While the federal Office Human Research Protections focused on the consent form, rather than on the study design and implementation, OHRP's critiques of the consent (...) form reveal views about the study design and implementation that we believe are fundamentally flawed. These criticisms about the design and implementation of SUPPORT, if generalized, become relevant concerns about these aspects of many comparative effectiveness research studies.Our analytical approach will be to use SUPPORT as a prime example of comparative effectiveness research and show why it challenges some prevailing assumptions about the riskiness of research. We will address five aspects of the study design and implementation: 1) randomization, 2) treatment by protocol, 3) choice of endpoints, 4) lack of a “standard care” control group, and 5) the use of altered oximeters. Examining these aspects will allow us to answer two specific central questions. The first is a methodological question with ethical implications: was the study designed in such a way as to answer the primary study question? The second question is whether the study design added or decreased risk to the babies enrolled in the study compared to babies who were not in the study. (shrink)

PurposeThe acute-on-chronic exacerbations of end-stage respiratory diseases often result in prolonged hospital stays, relating these events to ethical conflicts in the fields of medical futility and distributive justice. This study aimed to understand patients’ preferences for life-sustaining treatments when clinically stable and during regular follow-up visits, and to determine the factors that can influence these preferences.ProcedureThis was a prospective, observational, exploratory study using convenience sampling. Over a three-year period, the study enrolled 106 adult outpatients with end-stage pulmonary disease on long-term (...) oxygen treatment with/without noninvasive mechanical ventilation with dyspnoea scores of 6 or more in the modified Borg dyspnoea scale and one of the following: Gold stage IV, diffusing capacity <40%, heart failure ) stage III/IV, or systolic pulmonary artery... (shrink)

In recent years, precise high flow oxygen therapy as a new type of oxygen therapy machine has gradually attracted people’s attention and has been widely used in hospital emergency and clinical treatment of respiratory diseases; especially in recent years, severe coronavirus disease has played an important role in the treatment of patients. This paper presents a new type of precise high flow oxygen therapy machine with electromagnetic pneumatic flow valve as the core control element. A (...) sliding mode control strategy based on the system is proposed to realize the accurate control of oxygen concentration and output flow of oxygen therapy mixture. The physical equipment of the precision high flow system is established, and its working performance is verified through the test platform. The optimization design goal of the precision high flow equipment is achieved. (shrink)

Objectives: Treatment decisions in ethically complex situations are known to depend on a physician's personal characteristics and medical experience. We sought to study variability in decisions to withdraw or withhold specific life-supporting treatments in terminal care and to evaluate the association between decisions and such background factors.Design: Readiness to withdraw or withhold treatment options was studied using a terminal cancer patient scenario with alternatives. Physicians were asked about their attitudes, life values, experience, and training; sociodemographic data were also (...) collected.Setting: Finnish physicians, postal survey.Survey sample: Five hundred general practitioners, 300 surgeons, 300 internists, and 82 oncologists.Results: Treatments most often forgone were blood transfusion and thrombosis prophylaxis . Least willingly abandoned were intravenous hydration and supplementary oxygen . Female doctors were less likely to discontinue thrombosis prophylaxis and supplementary oxygen , but more readily x ray and laboratory examinations. Young doctors were more likely to continue antibiotics , thrombosis prophylaxis , supplementary oxygen and laboratory tests . Oncologists comprised the specialty most ready to forgo all studied treatments except antibiotics and blood transfusion. The family's wishes significantly increased treatment activity. Young and female practitioners and oncologists were most influenced by family appeal. Advance directives made decisions significantly more reserved and uniform. Different factors in the physician's background were found to predict decisions to withdraw antibiotics or IV hydration.Conclusion: The considerable variation observed in doctors' decisions to forgo specific life-sustaining treatments was seen to depend on their personal background factors. Experience, supervision, and postgraduate education seemed to be associated with more reserved treatment decisions. To increase the objectivity of end of life decisions, training, and research are of prime significance in this ethically complex area of medicine. (shrink)

River water pollution by wastewater can cause significant negative impact on the aquatic sustainability. Hence, accurate modeling of this complicated system and its cost-effective treatment and reuse decision is very important because this optimization process is related to economic expenditure, societal health, and environmental deterioration. In order to optimize this complex system, we may consider three treatment or reuse options such as microscreening filtration, nitrification, and fertilization-oriented irrigation on top of two existing options such as settling and biological (...) oxidation. The objective of this environmental optimization is to minimize the economic expenditure of life cycle costs while satisfying the public health standard in terms of groundwater quality and the environmental standard in terms of river water quality. Particularly, this study improves existing optimization model by pinpointing the critical deficit location of dissolved oxygen sag curve by using analytic differentiation. Also, the proposed formulation considers more practical constraints such as maximal size of irrigation area and minimal amount of filtration treatment process. The results obtained by using an evolutionary algorithm, named a parameter-setting-free harmony search algorithm, show that the proposed model successfully finds optimal solutions while conveniently locating the critical deficit point. (shrink)

The relationships between age and the life-supporting treatments use, and between gender and the life-supporting treatments use are still controversial. Using extracorporeal membrane oxygenation as an example of life-supporting treatments, the objectives of this study were: to examine the relationship between age and the extracorporeal membrane oxygenation use; to examine the relationship between age and the extracorporeal membrane oxygenation use; and to deliberate the ethical and societal implications of age and gender disparities in the initiation of extracorporeal membrane oxygenation. This (...) is a population-based, retrospective cohort study. Taiwan’s extracorporeal membrane oxygenation cases from 2000 to 2010 were collected. The annual incidence rate of extracorporeal membrane oxygenation use adjusting for both age and gender distribution for each year from 2000 to 2010 was derived using the population of 2000 as the reference population. The trend of extracorporeal membrane oxygenation use was examined using time-series linear regression analysis. We conducted joinpoint regression for estimating the trend change of extracorporeal membrane oxygenation use. The trends of extracorporeal membrane oxygenation use both for different gender groups, and for different age groups have been significantly increasing over time. Men were more likely to be supported by extracorporeal membrane oxygenation than women. Women’s perspectives toward life and death, and women’s perception of well-being may be associated with the phenomenon. In addition, the patients at the age of 65 or older were more likely to be supported by extracorporeal membrane oxygenation than those younger than 65. Family autonomy/family-determination, and the Confucian tradition of filial piety and respecting elders may account for this phenomenon. This study showed gender and age disparities in the initiation of extracorporeal membrane oxygenation use in Taiwan, which may be accounted for by the cultural and societal values in Taiwan. For a healthcare professional who deals with patients’/family members’ medical decision-making to initiate life-supporting treatments, he/she should be sensitive not only to the legality, but also the societal and ethical issues involved. (shrink)

Coronavirus disease 2019 can lead to respiratory failure. Some patients require extracorporeal membrane oxygenation support. During the current pandemic, health care resources in some cities have been overwhelmed, and doctors have faced complex decisions about resource allocation. We present a case in which a pediatric hospital caring for both children and adults seeks to establish guidelines for the use of extracorporeal membrane oxygenation if there are not enough resources to treat every patient. Experts in critical care, end-of-life care, bioethics, and (...) health policy discuss if age should guide rationing decisions. (shrink)

At the time of this writing, a widely publicized, waived-consent trial is underway. Sponsored by Northfield Laboratories, Inc. (Evanston, IL) the trial is intended to evaluate the emergency use of PolyHeme®, an oxygen-carrying resuscitative fluid that might prevent deaths from uncontrolled bleeding. The protocol allows patients in hemorrhagic shock to be randomized between PolyHeme® and saline in the field and, still without consent, randomized between PolyHeme® and blood after arrival at an emergency department. The Federal regulations that govern the (...) waiver of consent restrict its applicability to circumstances where proven, satisfactory treatments are unavailable. Blood - the standard treatment for hemorrhagic shock - is not available in ambulances but is available in hospitals. The authors argue that the in-hospital stage of the study fails to meet ethical and regulatory standards. (shrink)

Healthcare professionals are currently working under extreme pressure as they respond to the pandemic outbreak of COVID-19. At the time of writing, there is currently no effective vaccine or anti-viral treatment. The pandemic is fast-moving, relatively unpredictable and of uncertain duration. In many countries, it is placing an enormous stress on healthcare resources and providing care to existing standards is proving difficult. Unfortunately, in some countries, health services have been overwhelmed. The impact of the pandemic on resource-poor countries is (...) of particular concern. This extraordinary situation is raising, or has the potential to raise, many ethical challenges for doctors delivering care to patients. It is possible, for example, that there may be points in this pandemic where decisions need to be made about who should have access to finite specialised intensive care beds, drugs and equipment. This has happened in some countries and, despite efforts by the UK Government to reduce demand and increase supply, it is still possible that this could happen in the UK. Some hospital trusts in the UK are already reporting concerningly low supplies of oxygen and vital medicines such as propofol and alfentanil.1 In these circumstances, where not everyone can be treated, difficult ethical decisions will have to made. For example, can some patients be prioritised over others? How should a doctor decide on which patients to treat? Can treatment be withdrawn from patients who are currently being treated, but are not responding, in order to offer treatment to those who may have a better chance of benefiting? The UK is also reporting concerningly low supplies of vital personal protective equipment for frontline workers, raising the question - what are a doctor’s obligations to treat patients, in circumstances that present a high …. (shrink)

This Essay examines the elegantly simple idea that consent to medical treatment or participation in human research must be “informed” to be valid. It does so by using as a case study the controversial clinical research trial known as the Surfactant, Positive Pressure, and Oxygenation Randomized Trial. The Essay begins by charting, through case law and the adoption of the common rule, the evolution of duties to secure fully informed consent in both research and treatment. The Essay then (...) utilizes the SUPPORT study, which sought to pinpoint the level of saturated oxygen that should be provided to extremely low birth weight infants to demonstrate modern complexities and shortcomings of the duty to secure informed consent. This Essay shows how the duty is measured by foreseeability of risks and benefits in human research and why federal regulators believed the tradeoffs in risk and benefits from differing oxygen levels administered in the support study were foreseeable. It then explores the contours of the duty to secure informed consent when applied to researchers who also serve as treating physicians, highlighting how common law duties differ in jurisdictions that apply the professional standard and those that apply the patient-centered material risk standard. This Essay provides new insight into what the law must do to make real the notion that [e]very human being of adult years and sound mind has a right to determine what shall be done with his body.”. (shrink)

In a recent paper in this journal, John Worrall (2008) used the example of a series of trials involving extracorporeal membrane oxygenation (ECMO), a technology for the treatment of respiratory failure in newborns, to illustrate the relationship between ethics and epistemology in medical research. One of the issues considered was whether or not it was ethical to perform a particular clinical trial at all, and he showed clearly that the answer was intimately related to epistemological judgments about the weight (...) to be given existing evidence concerning treatment effectiveness. In the case of ECMO, a trial was initiated at the University of Michigan (Bartlett et al. 1985), despite the fact that the researchers had .. (shrink)

BACKGROUND: Although placing patients with acute respiratory failure in a prone (face down) position improves their oxygenation 60 to 70 percent of the time, the effect on survival is not known. METHODS: In a multicenter, randomized trial, we compared conventional treatment (in the supine position) of patients with acute lung injury or the acute respiratory distress syndrome with a predefined strategy of placing patients in a prone position for six or more hours daily for 10 days. We enrolled 304 (...) patients, 152 in each group. RESULTS: The mortality rate was 23.0 percent during the 10-day study period, 49.3 percent at the time of discharge from the intensive care unit, and 60.5 percent at 6 months. The relative risk of death in the prone group as compared with the supine group was 0.84 at the end of the study period (95 percent confidence interval, 0.56 to 1.27), 1.05 at the time of discharge from the intensive care unit (95 percent confidence interval, 0.84 to 1.32), and 1.06 at six months (95 percent confidence interval, 0.88 to 1.28). During the study period the mean (+/-SD) increase in the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen, measured each morning while patients were supine, was greater in the prone than the supine group (63.0+/-66.8 vs. 44.6+/-68.2, P=0.02). The incidence of complications related to positioning (such as pressure sores and accidental extubation) was similar in the two groups. CONCLUSIONS: Although placing patients with acute respiratory failure in a prone position improves their oxygenation, it does not improve survival. (shrink)

The scenario is all too common: the elderly woman with end-stage dementia readmitted to the hospital for the fourth time in three months for anorexia, now static cancer progressing despite all proven chemotherapy now pursuing a toxic experimental treatment, or the patient with a rampant infection leading to multiple organ failure who requires machines, medications, and devices to filter the blood, pump the heart, exchange oxygen, facilitate clotting, and provide nutrition. Modern medical science is adept at sustaining life. (...) The field of bioethics has, since its earliest days, debated end-of-life issues; yet American society more broadly remains ill equipped for the experience of dying. This can be .. (shrink)

Medical researchers must continue to develop and test non-blood oxygen-transport products. Resources provided by the Jehovah's Witness Hospital Assistance Line must be consulted. Sickle cell researchers must continue to test non-blood treatment. Information about non-blood treatments must be disbursed. Ways to enhance parental comport as the laws further and further support children's best interest must be provided. Information regarding cultural diversity must be disseminated. Hospitals and healthcare agencies that have not done so must institute the use of ethics (...) consulting or ethics committees. Nurse ethicists must continue development of the role of educating staff; mediation, arbitration and negotiation; problem solving; obtaining legal opinion; providing patient, family, or staff advocacy; and helping to reduce suffering on the part of the providers. Difficult ethical decisions should continue to be debated.Were the staff at X Med Center correct in overriding parental wishes and breaking tenets of their faith? In the doctor's, nurse's lawyer's, and judge's view they were. The child, now eight years old, is alive and well. The stroke resolved, and imminent death averted. The parents' and child's views are not presently available. Whether the family is suffering from the child's loss of his relationship with God, or are secretly relieved in their hearts that they are not, like Rita Swan, mourning their dead son, is unknown. What is known, is that this was a difficult case for all involved, and that such cases will continue to present themselves in the future. (shrink)

In this article, I distinguish between 4 models for thinking about how to balance the interests of parents, families, and a sick child: (1) the oxygen mask model; (2) the wide interests model; (3) the family interests model; and (4) the direct model. The oxygen mask model – which takes its name from flight attendants' directives to parents to put on their own oxygen mask before putting on their child's – says that parents should consider their own (...) interests only insofar as doing so is, ultimately, good for the sick child. The wide interests model suggests that in doing well by my child I am at the very same time doing well by myself. My interests can, and plausibly do, encompass the interests of others; they are, to that extent, wide. There is, then, no sharp separation between the interests of the sick child and the interests of other family members. In the family interests model, families themselves are seen as having interests that are neither identical to the sum, nor a simple function, of the interests of individual family members. The family has goals, values, and aspirations that are essentially corporate rather than individual. According to this model, these family interests can explain why sacrifices can sometimes be demanded of some family members for the sake of others in a medical setting. Finally, the direct model takes a simpler view of family members' interests; it claims that these interests matter simply on their own and should be taken into account in making treatment decisions for a sick child. This model openly considers the competing interests that parents and other family members often have when caring for a sick child, and advocates for weighing those interests when making decisions for and about the sick child. While there is room for all four models at the bedside, I argue that the direct model should be highlighted in clinical decision-making. (shrink)

RD, a 32-year-old male, was admitted to the hospital with hypoxic COVID pneumonia–a potentially life-threatening condition characterized by dangerously low levels of oxygen in the body- during one of the pandemic’s surges. While RD’s age gave the clinical team hope for his prognosis, his ability to recover was complicated by his being unvaccinated and having multiple comorbidities, including diabetes and obesity. His condition worsened to the point that he required extracorporeal membrane oxygenation (ECMO), a machine that maintains the functioning (...) of a person’s heart and lungs. -/- Given its scarcity–only 264 of the over 6,000 hospitals in the United States offer ECMO, according to the Extracorporeal Life Support Organization–as well as its high cost and the inadequate supply of staff required to maintain it, ECMO primarily serves as a bridge to support critically ill patients until they can receive an organ transplant or implanted medical device. For RD, ECMO was started to support him until he could be evaluated for, and possibly receive, a bilateral lung transplant. Despite its intended use as a treatment of last resort, some patients can remain on ECMO for weeks or months. And some are awake, alert, and capable of medical decision-making. -/- RD was one such patient. However, the transplant evaluation committee ruled out RD’s candidacy for bilateral lung transplantation, based on his poor potential for recovery and a lack of family and friends to provide post-transplant support. This determination raised the prospect of continued ECMO treatment being a bridge to nowhere. But RD was comfortable on ECMO and wanted to remain in the ICU. The ICU intensivist contacted the ethics consult service with questions about whether continued ECMO support was medically and ethically inappropriate. (shrink)

At the time of this writing, a widely publicized, waived-consent trial is underway. Sponsored by Northfield Laboratories, Inc. (Evanston, IL) the trial is intended to evaluate the emergency use of PolyHeme®, an oxygen-carrying resuscitative fluid that might prevent deaths from uncontrolled bleeding. The protocol allows patients in hemorrhagic shock to be randomized between PolyHeme® and saline in the field and, still without consent, randomized between PolyHeme® and blood after arrival at an emergency department. The Federal regulations that govern the (...) waiver of consent restrict its applicability to circumstances where proven, satisfactory treatments are unavailable. Blood—the standard treatment for hemorrhagic shock—is not available in ambulances but is available in hospitals. The authors argue that the in-hospital stage of the study fails to meet ethical and regulatory standards. (shrink)

LANGUAGE NOTE | Document text in Chinese; abstract also in English. ECMO是一項高風險、高創傷、高消耗的創新技術，它能夠為新冠病毒肺炎重症患者提供挽救性治療°ECMO的治療目標是幫助患者恢復心肺功能，或者橋接最終治療，包括器械植入，或者器官移植等。然而，容易被忽視的 事實是，ECMO挽救了一些患者的生命，但也可能讓那些沒有康復機會的患者陷入醫療困境。於是，ECMO的臨床應用不得不面對一些反對意見，包括嚴重併發症危害患者生命安全、無效治療導致技術失敗，以及大量佔用資 源損害醫療公平等。ECMO技術的臨床應用應該在尊重生命價值和患者意願的基礎上，合理設置治療目標、確立可接受退出標準、妥善處理患者意願與ECMO設備撤除困境之間的倫理衝突，建立適度倫理框架以合理控制醫療 干預的邊界。 Characterized by high risk, high trauma and high consumption, Extra-Corporeal Membrane Oxygenation (ECMO) is an innovative technology that can be used as salvage therapy for COVID-19 patients. ECMO treatment can help restore patients' cardiopulmonary function or can bridge their final treatment, including device implantation or organ transplantation. However, although ECMO saves some patients' lives, it can also leave those with no chance of recovery in a medical (...) dilemma. ECMO is thus controversial: it is criticized for technical failures and ineffective treatments, and its use raises questions about medical equity. This paper argues that the clinical application of ECMO technology should be based on a respect for the value of life and the will of patients, reasonably set therapeutic goals, acceptable withdrawal criteria, proper management of the conflict between patients' desires and the medical dilemma, and the establishment of an ethical framework to control the limits of medical intervention. (shrink)

AimsThis study evaluates a protocol for early, routine ethics consultation for patients on extracorporeal membrane oxygenation to support decision-making in the context of clinical uncertainty with the aim of mitigating ethical conflict and moral distress.MethodsWe conducted a single-site qualitative analysis of EC documentation for all patients receiving ECMO support from 15 August 2018 to 15 May 2019. Detailed analysis of 20 ethically complex cases with protracted ethics involvement identifies four key ethical domains: limits of prognostication, bridge to nowhere, burden of (...) treatment and system-level concerns. There are three subthemes: relevant contextual factors, the role of EC and observed outcomes. Content analysis of transcripts from interviews with 20 members of the multidisciplinary ECMO team yields supplemental data on providers’ perceptions of the impact of the early intervention protocol.ResultsLimited outcome data for ECMO, unclear indications for withdrawal, adverse effects of treatment and an obligation to attend to programme metrics present significant ethical challenges in the care of this patient population. Upstream EC mitigates ethical conflict by setting clear expectations about ECMO as a time limited trial, promoting consistent messaging among multiple services and supporting surrogate decision-makers. When ECMO becomes a ‘bridge to nowhere’, EC facilitates decision-making that respects patient values yet successfully sets limits on non-beneficial use of this novel therapy.ConclusionData from this study support the conclusion that ECMO poses unique ethical challenges that necessitate a standardised protocol for early, routine EC—at least while this medical technology is in its nascent stages. (shrink)

SUPPORT, a study involving approximately 1,300 premature infants who were randomly assigned to treatment protocols that differed in whether they offered higher or lower levels of oxygen saturation, was purportedly an example of comparative effectiveness research performed in the intensive care unit. However, SUPPORT became highly controversial. One source of controversy involved the proper determination of “reasonably foreseeable risks.” Commentators debated whether randomization to contrasting restrictive strategies that are within existing standard‐of‐care treatments imposed additional “reasonably foreseeable risks” greater (...) than what study participants would have received outside of the research. A second controversial issue had to do with disclosures in informed consent documents. This article explores these issues.We argue that randomization to contrasting restrictive interventions lying at the outer ends of “standard‐of‐care” practices differs in important ways from unrestricted “standard‐of‐care” practices available outside of a proposed study; that research involving such randomization might pose additional “reasonably foreseeable risks” from what occurs in “standard‐of‐care” practices; and that for trials whose study designs are similar to the SUPPORT study, respect for persons requires the disclosure of information about the nature of the experimental procedures and their risks. (shrink)

Robert Truog describes the controversial randomized controlled trials (RCTs) of extracorporeal membrane oxygenation (ECMO) therapy in newborns. Because early results with ECMO indicated that it might be a great advance, saving many lives, Truog argues that ECMO should not have been tested using RCTs, but that a long-term, large-scale observational study of actual clinical practice should have been conducted instead. Central to Truog’s argument, however, is the idea that ECMO is an unusual case. Thus, it is an open question whether (...) Truog’s conclusions can be extended to other areas of medical research. In this paper, I look at epistemological and ethical issues arising in the care of patients with chronic diseases, using ECMO as a starting point. Both the similarities and the dissimilarities of these two cases highlight important issues in biomedical research and support a conclusion similar to Truog’s. Observational studies of clinical practice provide the best evidence to inform the treatment of patients with chronic disease. (shrink)

Imagine your body is populated by billions of respirocytes capable of delivering 236 times more oxygen than your natural red blood cells. These mechanical, micron sized spheres are appropriately programmed by your physician to meet your personal requirements, be it the treatment of anemia or the enhancement of your physical abilities. Robert Freitas’ vision of such artificial blood cells comprised of nanometer-scale components was published in 1998 in a peer-reviewed medical journal, and was the first medical nanorobot design (...) paper to be published.The fact that this proposal for a future blood substitute was accepted as worthy of publication in a scientific journal, despite the inventor's explicit statement that such a device could not be built at the time, clouds the criteria upon which an informed opinion about the feasibility of such devices could be formed. In that respect, the idea of respirocytes formidably testifies to the current “blurring of fact and fiction” occurring in the field of nanotechnology. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Living with Blindness and Fibromyalgia while Occupying AgingKatherine SchneiderI’m blind from birth and in middle age developed fibromyalgia. I’ve retired from a thirty year career as a clinical psychologist and am working on my third book tentatively titled “Occupying Aging: Delights, Disabilities and Daily Life.” My relationship with medical professionals includes gratitude (without good care I would not be alive) and also frustration for assumptions often made about my (...) abilities. I write from the perspectives of an impatient patient, woman living in the United States, former provider of mental health services, person with both invisible and visible disabilities, and boomer moving into the world of the aged. My stories are mine of course, but when I swap medical stories with blind friends, similar happenings abound.When my mom fell down the stairs at a friend’s house, five months pregnant with me, she was told to go to bed for the next four months to save the pregnancy. Thus began the impact of health care professionals on me. I was born a month premature and spent my first month in an incubator. In 1949 it wasn’t known that the enriched oxygen atmosphere in an incubator would cause blindness. At least one lawsuit was filed against physicians and a hospital by a person blinded in this way. A large out–of–court settlement was received. The way I look at it, the health care community did the best they knew and without enough oxygen, I would have died.Early in my life, my parents took me to several ophthalmologists to see what could be done for my vision. Family folklore has it that I could smell a hospital as we entered and would begin howling. These early traumatic experiences may have led to my current healthy lifestyle so I don’t have to go to doctors much now. By about age five, it was clear that nothing could be done about my vision. For the next twenty years my forays into the health care system were for tonsillitis, sprains, and the usual childhood ills.In my early twenties, I developed acute glaucoma in one eye—caused, I’m convinced, by birth control pills. In seeking treatment for this condition, I encountered the first truly insensitive physician I’d met, who said, “Your eyes aren’t doing you any good; let’s take them out.” I was horrified! They were my eyes. I was attached to them, psychologically as well as physically. It turned out that a simple operation relieved the pressure and allowed me to keep my eyes. True, they are not the best looking big brown eyes around, but they did come with the package.Life with blindness seemed quite straightforward until my early forties, when I developed extreme fatigue and pain all over. I was worried. I knew a blind woman who had developed multiple sclerosis and I admired her, but I did not want to walk in her brave footsteps. Then a college student came to see me with the same symptoms and said that she had recently been diagnosed with fibromyalgia. I am often very empathetic with people’s concerns, but this time she complimented me by saying, “You’re great! You seem to know just how I feel.” I sagely counseled her about portioning out her energy carefully, prioritizing, using short cuts, and taking elevators when possible. Being an adult [End Page 216] student used to overachieving, she did not like what I was saying, but said she’d try to follow my advice because she could no longer do it all.What finally broke through my own denial was the day coiling up a hose and dragging it to the basement for the winter took me an hour. It left me totally exhausted and I figured that even being middle aged couldn’t account for feeling that awful.After a thorough physical and plenty of blood work to rule out Lyme disease and multiple sclerosis, I was diagnosed with fibromyalgia and placed on low doses of antidepressants to help me sleep through the night. The medication worked and I began to feel like myself again. My battle to accept that... (shrink)

The study of cellular senescence and proliferative lifespan is becoming increasingly important because of the promises of autologous cell therapy, the need for model systems for tissue disease and the implication of senescent cell phenotypes in organismal disease states such as sarcopenia, diabetes and various cancers, among others. Here, we explain the concepts of proliferative cellular lifespan and cellular senescence, and we present factors that have been shown to mediate cellular lifespan positively or negatively. We review much recent literature and (...) present potential molecular mechanisms by which lifespan mediation occurs, drawing from the fields of telomere biology, metabolism, NAD+ and sirtuin biology, growth factor signaling and oxygen and antioxidants. We conclude that cellular lifespan and senescence are complex concepts that are governed by multiple independent and interdependent pathways, and that greater understanding of these pathways, their interactions and their convergence upon specific cellular phenotypes may lead to viable therapies for tissue regeneration and treatment of age‐related pathologies, which are caused by or exacerbated by senescent cells in vivo. (shrink)

The debate about the ethics of the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT) often focuses on the assumptions made by the different parties involved, failing to note the lack of a necessary connection between those assumptions and the main criticism of the study—that the parents appear to have been poorly informed. The fact that the target ranges of oxygen saturation (SpO2) used in SUPPORT were within the range recommended as an appropriate “standard of care” does not mean (...) that the infants randomized to one of two restricted SpO2 ranges received the same treatment they would have received outside of the trial. The corresponding observation that randomization altered the potential harms to which an individual infant was exposed does not mean that the risks of being in SUPPORT were greater than or in addition to the risks associated with usual care. The argument that parents should have been better informed about these potential harms does not entail the (incorrect) assumption that neonatal clinicians make individualized treatment decisions rather than follow a standardized protocol when adjusting the level of oxygen a preterm infant receives. The fact that parents are unaware of the trade‐off clinicians make between these potential harms when establishing such a protocol does not justify the failure to adequately inform parents about the purpose of SUPPORT and the risks and harms that were involved. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Stories of Families with Chronically Ill Pediatric Patients during the War in UkraineVita VoloshchukFebruary 24th was a day that has left a mark in the memory and on the lives of every Ukrainian person. My husband and I work together [End Page E5] in a hospital. He had gone into work early to conduct a kidney transplant that had been scheduled for that day. Suddenly, whilst on my way (...) to work that morning, I heard a strange sound—it was an air-raid siren. Before that, I had never heard such a sound. I went through all the possible options of what it could be. Of course, watching the morning news had never been a habit either. The next thing that astonished me was that the taxi I had ordered was taking an unnaturally long time to turn up. When I got into the taxi, I noticed that the taxi driver was really upset and silent for half of the journey. He then said, “A war has begun...”“War? So? The war has been going on since 2014.”“You don’t understand,” he said. “Russia is launching missile attacks all over the territory of Ukraine; Russian troops are coming from the east and north of Ukraine. They want to capture the capital of Ukraine.” (Kyiv).Arriving at the hospital, I saw confused faces everywhere. The morning meeting began with a discussion of how we were to act in any possible situation that may occur. We were to discharge patients from the hospital, as many as possible. The arrangement of a bomb shelter began (although I didn’t even think that such a thing existed in our hospital), along with the strengthening of the hospital’s windows, and the increase of supplies such as medicine and food. Of course, the boy who expected a kidney transplant did not receive it because no one knew what to expect at any second or where a hostile Russian missile might hit, as Russian missiles hit not only military objects but residential buildings, hospitals, and memorials as well.Children who had to continue therapy remained in the hospital. As soon as we heard the sound of an air-raid siren, we had to go down into the bomb shelter. This happened 5-10 times per day. Families with palliative and chronically ill children began to call and ask for advice on how to proceed in such a situation. As many children were on artificial respiration devices, others needed oxygen therapy, and sputum of mucus from the upper respiratory tract. All this required uninterrupted power supplies and appropriate equipment. Later that day, a doctor from Poland called me and asked if our pediatric patients needed help, saying it would be better if they were moved to Poland, where they would be safer and have the correct equipment. We started organizing evacuations for chronically ill and palliative patients.Seven days after the war began, parents from other regions, where the situation was more dangerous, began calling, asking for help evacuating. The hospital began to work intensively round the clock. Some patients moved in, and others were evacuated abroad. Some did not want to go. They continued treatment in the hospital, which turned into a hub for patients who had come from more dangerous, occupied territories; patients who were forced to leave their motherland to continue treatment.Since the beginning of the war, I have been responsible for transferring palliative patients and other patients with gastrointestinal diseases abroad. After the massive invasion, everything changed in our country. It is important to say that during the war, Lviv is safer than any other Ukrainian city, still air-raid sirens often go off, and everyone needs to run immediately to shelters for their safety. Palliative patients need special care. It is very difficult to run with patients several times per day during an air-raid siren or live with these children for a long time (2-3 weeks) in shelters because of the explosions occurring around them.It is impossible to move some patients to safety because they need appropriate medical equipment or mechanical ventilation is necessary. In shelters, there are crowds, and the high risk of... (shrink)

My aim is to suggest that there is a case for using a randomised consent design in some neonatal trials. As an example I use the trials of extracorporeal membrane oxygenation (ECMO) in neonates suffering pulmonary hypertension. In some trials the process of obtaining consent has the potential to harm the subject, for example, by disappointing those who end in the control group and by creating additional anxiety at times of acute illness. An example of such were the trials of (...) extracorporeal membrane oxygenation (ECMO) in neonates suffering pulmonary hypertension. Pre-randomised consent could avoid or lessen these harms. However, a number of ethical objections are made to these research designs. They involve denial of information, using people, denial of choice, and "overselling" of allocated treatment. Furthermore, they are the wrong response; better communication might be the answer, for example. I argue that these objections are not completely persuasive. However, they are enough to suggest caution in the use of such designs. (shrink)

Following the introduction of do-not-resuscitate orders in the 1970s, there was widespread misinterpretation of the term among healthcare professionals. In this brief report, we present findings from a survey of healthcare professionals. Our aim was to examine current understanding of the term do-not-attempt-resuscitate, decision-making surrounding DNAR and awareness of current guidelines. The survey was distributed to doctors and nurses in a university teaching hospital and affiliated primary care physicians in Dublin via email and by hard copy at educational meetings from (...) July to December 2014. A total of 519 completed the survey. The response rate in the hospital doctors group was 35.5%, 19.8% in the nurses group but 68.8% in the specialist nurses group and 40% in the primary care physician group.Alarmingly, our results demonstrate that 26.8% of staff nurses and 30% of primary care physicians surveyed believed that a patient with a DNAR order could not receive any/at least one of a list of simple treatments including antibiotics, physiotherapy, intravenous fluids, pain relief, oxygen, nasogastric feeding or airway suctioning, which were higher percentages compared to the other hospital doctors and experienced nurses groups with statistically significant differences. Furthermore, a higher percentage of staff nurses and primary care physicians believed that a patient with a DNAR order could not be referred to hospital from home/a nursing home, when compared with other healthcare groups. Our findings highlight continued misunderstanding and over-interpretation of DNAR orders. Further collaboration and information is required for meaningful Advance Care Plans. (shrink)

From 1991 to 1994 the Dutch Health Insurance Council financed research on Extracorporeal Membrane Oxygenation . This is a technique for providing cardiopulmonary bypass to patients with pulmonary and/or cardiac failure. Most often, these patients are premature neonates. During ECMO, blood is drained from the right atrium, pumped along a membrane where gas exchange takes place, and then redirected to the aorta. To prevent blood clotting, heparin is added. However, with the heparin added, the risk of hemorrhage is considerably increased. (...) Therefore, both the chance of surviving and the chance of severe disability are higher with ECMO than with conventional treatment. (shrink)

Much of the ethical discourse concerning the coronavirus pandemic has focused on the allocation of scarce resources, be it potentially beneficial new treatments, ventilators, intensive care beds, or oxygen. Somewhat ironically, the more important ethical issues may lie elsewhere, just as the more important medical issues do not concern intensive care or treatment for COVID‐19 patients, but rather the diversion towards these modes of care at the expense of non‐Covid patients and treatment. In this article I explore (...) how ethicists can and should prioritize which ethical issues to deal with, and develop a method of triage for identification and prioritization of ethical issues both in the next public health emergency and in bioethics more widely. (shrink)

Widespread expression of the transcription factor, nuclear factor (erythroid‐derived 2)‐like 2 (NRF2), which maintains redox homeostasis, has recently been identified in the hair follicle (HF). Small molecule activators of NRF2 may therefore be useful in the management of HF pathologies associated with redox imbalance, ranging from HF greying and HF ageing via androgenetic alopecia and alopecia areata to chemotherapy‐induced hair loss. Indeed, NRF2 activation has been shown to prevent peroxide‐induced hair growth inhibition. Multiple parameters can increase the levels of reactive (...) oxygen species in the HF, for example melanogenesis, depilation‐induced trauma, neurogenic and autoimmune inflammation, toxic drugs, environmental stressors such as UV irradiation, genetic defects and aging‐associated mitochondrial dysfunction. In this review, the potential mechanisms whereby NRF2 activation could prove beneficial in treatment of redox‐associated HF disorders are therefore discussed. (shrink)

Richard, a sixty‐seven‐year‐old man, has been admitted to Midtown University Center for difficulty breathing. He has a significant medical history that includes pulmonary fibrosis and subsequent heart failure, and he depends on supplemental oxygen to breathe. Upon admission and after discussing his prognosis with his family and doctors, Richard decided to sign a do‐not‐resuscitate order stating that if his heart stops or he stops breathing, he does not want to undergo cardiopulmonary resuscitation or other life‐sustaining measures. On his third (...) day in the hospital, the nurse practitioner who is caring for Richard notices that his breathing is becoming more labored and that his blood pressure is steadily dropping. She thinks he requires closer observation and treatment in the cardiac intensive care unit. Dr. P, the physician in the intensive care unit at the time, Dr. P does not want to accept Richard into the CICU because of his prognosis and his DNR order. He believes that Richard should be cared for on a regular hospital floor, and that the last bed in the CICU should be held for its intended user—a patient suffering a life‐threatening heart attack who requires intensive care. Should Richard be admitted to the CICU? (shrink)

ObjectiveTo explore the effect of independently developed transcranial pulsed current stimulation on alleviating athlete’s mental fatigue.MethodsA total of 60 college athletes were randomly divided into the active stimulation group and the sham stimulation group. Subjective questionnaires, behavior test, and functional near-infrared spectroscopy test were conducted before and after the experiment. Two-way ANOVA with repeated measures was used to compare the differences in mental fatigue indexes before and after the two experimental conditions.ResultsAfter 7 days of exercise training, there was a significant (...) difference in the main effect of the time factor in all indexes of the two groups. The scores of rated perceived exertion scale, positive and negative affect schedule, critical flicker frequency, and reaction time, in the tPCS treatment group, were better than those in the sham stimulation group. After 7 days of exercise training, all the subjects had different degrees of athlete’s mental fatigue; the subjects in the active stimulation group have a good evaluation of the tPCS developed by the research group without adverse actions.ConclusiontPCS intervention can improve emotional state, reduce the subjective evaluation of fatigue, improve behavioral levels such as attention and reaction time and increase cerebral prefrontal blood flow and oxygen supply. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Moral Distress for the Physician AssistantSharyn L. KurtzMy morning rounds as an inpatient medical oncology physician assistant began as usual. I arrived at the hospital early to receive 7 a.m. sign out from the covering resident. The overnight report began favorably. All patients remained stable. Even my patient, whom I will call Mrs. Walker,* had a quiet night. However, given her tenuous admission presentation, including altered mental status, hypercalcemia (...) (high levels of calcium in the blood), atrial fibrillation with rapid ventricular response (irregular, rapid heart function), widespread metastatic lung cancer, and recent neurosurgery to stabilize her spine, I decided to prioritize Mrs. Walker’s morning evaluation.Examining her medical chart proved reassuring. Her tachycardia (rapid heart rate) had been better controlled over the past two days. Her hypercalcemia had been treated, such that she was no longer somnolent. In fact, she was now arousable, conversant, and able to offer some input regarding her healthcare wishes. However, because she was experiencing intermittent delirium, her husband continued to act as her primary medical decision–maker.As her health care proxy, Mr. Walker had experienced conflict with the medical team during his wife’s prior hospital admission. However, even though Mr. Walker lived greater than 45 minutes from the hospital and was not able to visit regularly, he and I spoke daily by phone, which allowed me the opportunity to offer regular medical updates. Mr. Walker felt overwhelmed with his wife’s condition, but he was comfortable with the care the medical team had provided thus far. He was encouraged by the small improvements we had noted since her hospital admission five days prior.Mr. Walker stated on hospital admission that he wished for DNR/I orders to be placed, since this cohered with his wife’s previously stated wishes. However, he still wanted “everything else done” in terms of treating his wife’s medical conditions, including treatment of her atrial fibrillation, pain, and electrolyte anomalies. Most of all, he hoped Mrs. Walker would soon have increased mobility, which he felt would grant his wife the best quality of life possible. He was adamant that “being active” was what Mrs. Walker wished for, and that she had never wanted to be confined to bed.Mr. Walker’s requests seemed reasonable. Although Mrs. Walker’s lung cancer was widespread, and although many on the medical team felt she would not improve to the point where palliative chemotherapy could be considered, [End Page E13] she had stabilized. Her recent spine surgery had been successful, and she was healing adequately. The neurosurgeons had cleared Mrs. Walker for increased activity out of bed as soon as she could be fitted with a lumbar brace. The pain and palliative care specialists felt that Mrs. Walker’s residual back pain and delirium could be well managed with oral medications.Prior to my entering Mrs. Walker’s room to begin her physical evaluation, I was met by her seasoned nurse, whom I will call Amy. “Sharyn,” Amy warned, “Mrs. Walker’s heart rate is 150 and she is complaining of chest pain.” I entered Mrs. Walker’s room, and she was notably uncomfortable, grasping her chest. The monitor showed that Mrs. Walker’s heart rate was in fact in the 150’s. She was pale, short of breath, and wheezing. “Mrs. Walker,” I asked, “how severe is your chest pain on a scale from 1 to 10?” Mrs. Walker replied, “Nine.” I asked Amy to obtain an EKG, to provide oxygen, and to administer an IV medication that would slow Mrs. Walker’s heart rate. I stepped out of the room to place the computer orders, and I paged my attending physician to let him know about Mrs. Walker’s change in status. After hearing the update, my attending physician, whom I will call Dr. Clark, stated that he agreed with all of my treatment decisions thus far. He was on his way into the hospital. I planned out my next steps with him on the phone and returned to the patient’s room.The monitor gave evidence that Mrs. Walker’s heart rate was improving. Mrs. Walker reported that her pain was now “4 out of... (shrink)

Pain is the single most common reason patients seek care in the emergency department. Given the prevalence of pain as a presenting complaint, one might expect emergency physicians to assign its treatment a high priority; however, pain is often seemingly invisible to the emergency physician. Multiple research studies have documented that the undertreatment of pain, or oligoanalgesia, is a frequent occurrence. Pain that is not acknowledged and managed appropriately causes dissatisfaction with medical care, hostility toward the physician, unscheduled returns (...) to the emergency department, delayed return to full function, and potentially, an increased risk of litigation. Failure to recognize and treat pain may result in anxiety, depression, sleep disturbances, increased oxygen demands with the potential for end organ ischemia, and decreased movement with an increased risk of venous thrombosis. (shrink)

Richard, a sixty‐seven‐year‐old man, has been admitted to Midtown University Center for difficulty breathing. He has a significant medical history that includes pulmonary fibrosis and subsequent heart failure, and he depends on supplemental oxygen to breathe. Upon admission and after discussing his prognosis with his family and doctors, Richard decided to sign a do‐not‐resuscitate order stating that if his heart stops or he stops breathing, he does not want to undergo cardiopulmonary resuscitation or other life‐sustaining measures. On his third (...) day in the hospital, the nurse practitioner who is caring for Richard notices that his breathing is becoming more labored and that his blood pressure is steadily dropping. She thinks he requires closer observation and treatment in the cardiac intensive care unit. Dr. P, the physician in the intensive care unit at the time, Dr. P does not want to accept Richard into the CICU because of his prognosis and his DNR order. He believes that Richard should be cared for on a regular hospital floor, and that the last bed in the CICU should be held for its intended user—a patient suffering a life‐threatening heart attack who requires intensive care. Should Richard be admitted to the CICU? (shrink)

From 1991 to 1994 the Dutch Health Insurance Council financed research on Extracorporeal Membrane Oxygenation (ECMO). This is a technique for providing cardiopulmonary bypass to patients with pulmonary and/or cardiac failure. Most often, these patients are premature neonates. During ECMO, blood is drained from the right atrium, pumped along a membrane where gas exchange takes place, and then redirected to the aorta. To prevent blood clotting, heparin is added. However, with the heparin added, the risk of hemorrhage is considerably increased. (...) Therefore, both the chance of surviving and the chance of severe disability are higher with ECMO than with conventional treatment (i.e., ventilator support). (shrink)

Previous studies have shown that zinc deficiency leads to apoptosis of neuronal precursor cells in vivo and in vitro. In addition to the role of p53 as a nuclear transcription factor in zinc deficient cultured human neuronal precursors (NT-2), we have now identified the translocation of phosphorylated p53 to the mitochondria and p53-dependent increases in the pro-apoptotic mitochondrial protein BAX leading to a loss of mitochondrial membrane potential as demonstrated by a 25% decrease in JC-1 red:green fluorescence ratio. Disruption of (...) mitochondrial membrane integrity was accompanied by efflux of the apoptosis inducing factor (AIF) from the mitochondria and translocation to the nucleus with a significant increase in reactive oxygen species (ROS) after 24 h of zinc deficiency. Measurement of caspase cleavage, mRNA, and treatment with caspase inhibitors revealed the involvement of caspases 2, 3, 6, and 7 in zinc deficiency-mediated apoptosis. Down-stream targets of caspase activation, including the nuclear structure protein lamin and polyADP ribose polymerase (PARP), which participates in DNA repair, were also cleaved. Transfection with a dominant-negative p53 construct and use of the p53 inhibitor, pifithrin- ␮, established that these alterations were largely dependent on p53. Together these data identify a cascade of events involving mitochondrial p53 as well as p53-dependent caspase-mediated mechanisms leading to apoptosis during zinc deficiency. (shrink)

Two articles in this issue of the Hastings Center Report address the continuing controversy over the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT). This controversy is part of a larger discussion about the appropriate regulatory framework for protecting human research participants in comparative effectiveness research (CER), a group of studies that aims to compare two “usual” or “standard” treatments in order to provide evidence of which treatment is most effective.

Pain is the single most common reason patients seek care in the emergency department. Given the prevalence of pain as a presenting complaint, one might expect emergency physicians to assign its treatment a high priority; however, pain is often seemingly invisible to the emergency physician. Multiple research studies have documented that the undertreatment of pain, or oligoanalgesia, is a frequent occurrence. Pain that is not acknowledged and managed appropriately causes dissatisfaction with medical care, hostility toward the physician, unscheduled returns (...) to the emergency department, delayed return to full function, and potentially, an increased risk of litigation. Failure to recognize and treat pain may result in anxiety, depression, sleep disturbances, increased oxygen demands with the potential for end organ ischemia, and decreased movement with an increased risk of venous thrombosis. (shrink)