Joseph L. Verheijde

Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial

BACKGROUND Minocycline has anti-apoptotic and anti-inflammatory effects in vitro, and extends survival in mouse models of some neurological conditions. Several trials are planned or are in progress to assess whether minocycline slows human neurodegeneration. We aimed to test the efficacy of minocycline as a treatment for amyotrophic lateral sclerosis (ALS). METHODS We did a multicentre, randomised placebo-controlled phase III trial. After a 4-month lead-in phase, 412 patients were randomly assigned to receive placebo or minocycline in escalating doses of up to 400 mg/day for 9 months. The primary outcome measure was the difference in rate of change in the revised ALS functional rating scale (ALSFRS-R). Secondary outcome measures were forced vital capacity (FVC), manual muscle testing (MMT), quality of life, survival, and safety. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00047723. FINDINGS ALSFRS-R score deterioration was faster in the minocycline group than in the placebo group (-1.30 vs -1.04 units/month, 95% CI for difference -0.44 to -0.08; p=0.005). Patients on minocycline also had non-significant tendencies towards faster decline in FVC (-3.48 vs -3.01, -1.03 to 0.11; p=0.11) and MMT score (-0.30 vs -0.26, -0.08 to 0.01; p=0.11), and greater mortality during the 9-month treatment phase (hazard ratio=1.32, 95% CI 0.83 to 2.10; p=0.23) than did patients on placebo. Quality-of-life scores did not differ between the treatment groups. Non-serious gastrointestinal and neurological adverse events were more common in the minocycline group than in the placebo group, but these events were not significantly related to the decline in ALSFRS-R score. INTERPRETATION Our finding that minocycline has a harmful effect on patients with ALS has implications for trials of minocycline in patients with other neurological disorders, and for how potential neuroprotective agents are screened for use in patients with ALS.

Determinants of moral distress in medical and surgical nurses at an adult acute tertiary care hospital

AIM To determine the prevalence and contributing factors of moral distress in medical and surgical nurses. BACKGROUND Moral distress from ethical conflicts in the work environment is associated with burnout and job turnovers in nurses. METHOD A prospective cross-sectional survey using the Moral Distress Scale tool was administered to medical and surgical nurses at an adult acute tertiary care hospital. RESULTS The survey was completed by 260 nurses (92% response rate). The intensity of moral distress was uniformly high to situations related to physician practice, nursing practice, institutional factors, futile care, deception and euthanasia. Encounter frequencies for situations associated with futile care and deceptions were particularly high. Encounter frequencies increased with years of nursing experience and caring for oncology and transplant patients. CONCLUSION Moral distress is common among nurses in acute medical and surgical units and can be elicited from different types of situations encountered in the work environment. Nursing experience exacerbated the intensity and frequency of moral distress. IMPLICATIONS FOR NURSING MANAGEMENT Strategies aimed to minimize exposure to situations of moral distress and augment mechanisms mitigating its effect on nurses are necessary to enhance job satisfaction and retention.

Use of the exercise treadmill to measure baseline functional status and surgical outcome in patients with severe lumbar spinal stenosis.

Study Design. A prospective study of exercise tolerance on the treadmill before and after decompressive laminectomy in patients with severe lumbar spinal stenosis. Objectives. To determine whether treadmill testing provides useful information about baseline functional status and surgical outcome. Summary of Background Data. Historically, criteria for selecting patients for surgery and assessing postoperative outcome have been variable. Functional testing has not been used in a systematic fashion. Methods. Fifty patients with severe lumbar spinal stenosis underwent decompressive laminectomy. Preoperatively and 3 months postoperatively, functional capacity was assessed on an exercise treadmill. Time to first symptoms and total ambulation time were recorded. The examination was stopped at the onset of severe symptoms or after 15 minutes. Results. In the preoperative trial, mean time to first symptoms (± standard deviation) was 1.82 minutes (median, 0.58), and mean total ambulation time was 6.91 minutes (median, 5.22). In the postoperative trial mean time to first symptoms increased to 11.93 minutes (median, 15) and mean total ambulation time increased to 13.26 minutes (median, 15). There was significant improvement after surgery in both time to first symptoms (P < 0.001) and total ambulation time (P < 0.001). Conclusion. Exercise stress testing on a treadmill is a safe, easily administered, and quantifiable means of assessing baseline functional status and surgical outcome in patients with neurogenic claudication due to lumbar spinal stenosis. Treadmill testing provides objective evidence that surgery is beneficial in most cases and is helpful in guiding subsequent management of patients with residual symptoms.

Recovery of transplantable organs after cardiac or circulatory death: Transforming the paradigm for the ethics of organ donation

Organ donation after cardiac or circulatory death (DCD) has been introduced to increase the supply of transplantable organs. In this paper, we argue that the recovery of viable organs useful for transplantation in DCD is not compatible with the dead donor rule and we explain the consequential ethical and legal ramifications. We also outline serious deficiencies in the current consent process for DCD with respect to disclosure of necessary elements for voluntary informed decision making and respect for the donors autonomy. We compare two alternative proposals for increasing organ donation consent in society: presumed consent and mandated choice. We conclude that proceeding with the recovery of transplantable organs from decedents requires a paradigm change in the ethics of organ donation. The paradigm change to ensure the legitimacy of DCD practice must include: (1) societal agreement on abandonment of the dead donor rule, (2) legislative revisions reflecting abandonment of the dead donor rule, and (3) requirement of mandated choice to facilitate individual participation in organ donation and to ensure that decisions to participate are made in compliance with the societal values of respect for autonomy and self-determination.

Continuous Deep Sedation Until Death: Palliation or Physician-Assisted Death?

Published literature have not discerned end-of-life palliative versus life-shortening effects of pharmacologically maintaining continuous deep sedation until death (ie, dying in deep sleep) compared with common sedation practices relieving distress in the final conscious phase of dying. Continuous deep sedation predictably suppresses brainstem vital centers and shortens life. Continuous deep sedation remains controversial as palliation for existential suffering and in elective death requests by discontinuation of chronic ventilation or circulatory support with mechanical devices. Continuous deep sedation contravenes the double-effect principle because: (1) it induces permanent coma (intent of action) for the contingency relief of suffering and for social isolation (desired outcomes) and (2) because of its predictable and proportional life-shortening effect. Continuous deep sedation should be distinguished from common sedation practices for palliation and characterized instead as physician-assisted death.

Scientific, legal, and ethical challenges of end-of-life organ procurement in emergency medicine

AIM We review (1) scientific evidence questioning the validity of declaring death and procuring organs in heart-beating (i.e., neurological standard of death) and non-heart-beating (i.e., circulatory-respiratory standard of death) donation; (2) consequences of collaborative programs realigning hospital policies to maximize access of procurement coordinators to critically and terminally ill patients as potential donors on arrival in emergency departments; and (3) ethical and legal ramifications of current practices of organ procurement on patients and their families. DATA SOURCES Relevant publications in peer-reviewed journals and government websites. RESULTS Scientific evidence undermines the biological criteria of death that underpin the definition of death in heart-beating (i.e., neurological standard) and non-heart-beating (i.e., circulatory-respiratory standard) donation. Philosophical reinterpretation of the neurological and circulatory-respiratory standards in the death statute, to avoid the appearance of organ procurement as an active life-ending intervention, lacks public and medical consensus. Collaborative programs bundle procurement coordinators together with hospital staff for a team-huddle and implement a quality improvement tool for a Rapid Assessment of Hospital Procurement Barriers in Donation. Procurement coordinators have access to critically ill patients during the course of medical treatment with no donation consent and with family or surrogates unaware of their roles. How these programs affect the medical care of these patients has not been studied. CONCLUSIONS Policies enforcing end-of-life organ procurement can have unintended consequences: (1) erosion of care in the patients best interests, (2) lack of transparency, and (3) ethical and legal ramifications of flawed standards of declaring death.

Organ procurement organizations Internet enrollment for organ donation: Abandoning informed consent

BackgroundRequirements for organ donation after cardiac or imminent death have been introduced to address the transplantable organs shortage in the United States. Organ procurement organizations (OPOs) increasingly use the Internet for organ donation consent.MethodsAn analysis of OPO Web sites available to the public for enrollment and consent for organ donation. The Web sites and consent forms were examined for the minimal information recommended by the United States Department of Health and Human Services for informed consent. Content scores were calculated as percentages of data elements in four information categories: donor knowledge, donor consent reinforcement, donation promotion, and informed consent.ResultsThere were 60 Web sites for organ donation enrollment serving the 52 states. The median percent (10 percentile-90 percentile) content scores of the Web sites for donor knowledge, donor consent reinforcement, and donation promotion were 33% (20–47), 79% (57–86), and 75% (50–100), respectively. The informed consent score was 0% (0–33). The content scores for donor knowledge and informed consent were significantly lower than donor consent reinforcement and donation promotion for all Web sites (P < .05). The content scores for the four categories were similar among the 11 regions of the United Network for Organ Sharing.ConclusionThe Web sites and consent forms for public enrollment in organ donation do not fulfill the necessary requirements for informed consent. The Web sites predominantly provide positive reinforcement and promotional information rather than the transparent disclosure of organ donation process. Independent regulatory oversight is essential to ensure that Internet enrollment for organ donation complies with legal and ethical standards for informed consent.

Islam and End-of-Life Practices in Organ Donation for Transplantation: New Questions and Serious Sociocultural Consequences

Advances in knowledge about human biological processes bring into question whether either brain (heart-beating) or circulatory (non-heartbeating) criteria of death ensure that donors are really dead before organ procurement. The utility of conflating the “prognosis” (incipiently dying or destined to die) with the “diagnosis” of death (really dead) to justify organ donation has been morally defended in both the medical and the ethics literature. Major religions emphasize the sanctity of human life but permit organ donation if it is performed after death. Thus, the moral justification of end-of-life practices in organ donation poses serious ethical and religious challenges. Legislation has been introduced in several countries, including the United States, to permit the administration of life support systems for organ preservation without prior consent for organ donation. Such administration of life support systems for organ preservation interrupts traditional Islamic practices about the care of the dying and the deceased. We conclude that: 1) many practical aspects of end-of-life organ donation conflict with the Islamic faith’s core principles of care for the dying and their families; 2) defining the societal role of transplantation medicine is not uniquely a matter of accounting for technical capabilities and expertise, but must include the recognition of cultural, social, and religious values that constitute morality and guide best scientific evidence; 3) Muslim scholars should critically evaluate new evidence about end-of-life practices in organ donation, their effects on the care of terminally ill patients and their families

Organ Procurement After Cardiocirculatory Death: A Critical Analysis

To shorten the transplantation waiting time in the United States, federal regulations have been introduced requiring hospitals to develop policies for organ donation after cardiac (or circulatory) death (DCD). The practice of DCD is invoked based on the validity of the University of Pittsburgh Medical Center (UPMC) protocol and relies on the accuracy of the University of Wisconsin (UW) evaluation tool to appropriately identify organ donors. There is little evidence to support the position that the criteria for organ procurement adopted from the UPMC protocol complies with the dead donor rule. A high false-positive rate of the UW evaluation tool can expose many dying patients to unnecessary perimortem interventions because of donation failure. The medications and/or interventions for the sole purpose of maintaining organ viability can have unintended negative consequences on the timing and quality of end-of-life care offered to organ donors. It is essential to address and manage the evolving conflict between optimal end-of-life care and the necessary sacrifices for the procurement of transplantable organs from the terminally ill. The recipients of marginal organs recovered from DCD can also suffer higher mortality and morbidity than recipients of other types of donated organs. Finally, transparent disclosure to the public of the risks involved to both organ donors and recipients may contribute to open societal debate on the ethical acceptability of DCD.

Mass media campaigns and organ donation: managing conflicting messages and interests

Mass media campaigns are widely and successfully used to change health decisions and behaviors for better or for worse in society. In the United States, media campaigns have been launched at local offices of the states’ department of motor vehicles to promote citizens’ willingness to organ donation and donor registration. We analyze interventional studies of multimedia communication campaigns to encourage organ-donor registration at local offices of states’ department of motor vehicles. The media campaigns include the use of multifaceted communication tools and provide training to desk clerks in the use of scripted messages for the purpose of optimizing enrollment in organ-donor registries. Scripted messages are communicated to customers through mass audiovisual entertainment media, print materials and interpersonal interaction at the offices of departments of motor vehicles. These campaigns give rise to three serious concerns: (1) bias in communicating information with scripted messages without verification of the scientific accuracy of information, (2) the provision of misinformation to future donors that may result in them suffering unintended consequences from consenting to medical procedures before death (e.g, organ preservation and suitability for transplantation), and (3) the unmanaged conflict of interests for organizations charged with implementing these campaigns, (i.e, dual advocacy for transplant recipients and donors). We conclude the following: (1) media campaigns about healthcare should communicate accurate information to the general public and disclose factual materials with the least amount of bias; (2) conflicting interests in media campaigns should be managed with full public transparency; (3) media campaigns should disclose the practical implications of procurement as well as acknowledge the medical, legal, and religious controversies of determining death in organ donation; (4) organ-donor registration must satisfy the criteria of informed consent; (5) media campaigns should serve as a means of public education about organ donation and should not be a form of propaganda.