Acute myocardial infarction (AMI) is a common disease in the Western world and has been the topic of much research. Conducting clinical trials with patients in the acute phase of a myocardial infarction, however, poses an ethical challenge. As patients are often under extreme stress and require urgent medical attention, the process of informed consent is severely constrained. Furthermore, the very procedure of informed consent, which is supposed to protect eligible patients, may be a (...) cause of harm in itself due to the delay in the provision of therapy which it causes. This paper describes how physicians have dealt with the informed consent process in various AMI trials and summarizes the results from empirical studies of the consent process of such trials. Finally, the ethical issues and their implications for future trials involving this particular group of patients are discussed. (shrink)

This study aimed to investigate the status and risk factors of post-traumatic stress disorder in patients with acute myocardial infarction after emergency percutaneous coronary intervention in acute and convalescence phases. A longitudinal study design was used. Two questionnaire surveys were conducted in the acute stage of hospitalization, and 3 months after onset in patients. Logistic regression was used to analyze the risk factors for PTSD in AMI patients. The incidence of PTSD was 33.1 and 20.4% (...) in acute and convalescent patients, respectively. The risk factors related to PTSD were door-to-balloon time, left ventricular ejection fraction, smoking, anxiety, and depression. AMI patients after PCI had PTSD in the acute and convalescent stage. The findings indicate that tailored measures should be developed and carried out to prevent PTSD and improve the mental health of patients with AMI after undergoing PCI. (shrink)

Clinical trials for acute conditions such as myocardial infarction and stroke pose challenges related to informed consent due to time limitations, stress, and severe illness. Consent processes shou...

Definition of the problemA myocardial infarction is often a vitally and emotionally threatening situation for the affected. Unconscious coping mechanisms in dealing with the heart disease may result in, for example, complete denial or emotional decompensation.ArgumentAn understanding of myocardial infarction as a borderline situation may provide theoretical enrichment for clinicians and point to a third coping avenue, described as “posttraumatic growth”. Affected individuals often refer to the event as a “wake-up call”. Clinical knowledge of these different (...) coping mechanisms may in turn lead to a relativization of primarily subjectivist positions and substantively hedonistic or preferentialist notions of good life or “quality of life”. Such a position would in turn be compatible with the deliberative model of physician–patient communication.ConsequencesIn the light of such a broader understanding of disease coping, the task of (psychosomatic) physicians would thus to accompany persons with heart disease, to be aware of the teachable moment and to enable a process of development for the patients. (shrink)

The present work is aimed at investigating the effects of myocardial infarction and ischemia on induction of ventricular fibrillation. Electrophysiologic effects of global and local ischemia (variation of the dispersion of refractory periods as well as conduction velocity) on initiation of reentry mechanisms was studied by means of computer simulations based on a cellular automata model of propagation of activation wave through a ventricular surface element. A local area of ischemia where effects of the dispersion of refractory periods (...) are investigated is then simulated. This is made using a Gaussian distribution characterized by its mean and standard deviation. These simulations show that ischemia is capable of initiating reentry phenomena which propagate through the whole ventricle; they are responsible for ventricular fibrillation which causes sudden cardiac death, even when ischemia only involves limited parts of the myocardium. Statistical study of the probability of reentries as a function of both of the size of ischemic zones and the rate of dispersion of refractory periods shows that the latter parameter is of primary importance in triggering cardiac reentries. (shrink)

Coping after myocardial infarction. The mediational effects of positive and negative emotions The aim of the study was to examine mediational effects of positive and negative emotions on the relationship between cognitive appraisal and coping after myocardial infarction. Subjects were 163 patients assessed a few days after their first MI episode for cognitive appraisal using the Situation Appraisal Questionnaire developed by Wrześniewski and based on the Lazarus theory. The participants' current emotional state and coping strategies were (...) evaluated with Polish versions of the PANAS and CISS-S, respectively. The data were analyzed using the boostrapping procedure. Resultant models turned out to be similar for threat and loss appraisal, where PEs mediated task-oriented coping, while NEs were found to mediate emotion-oriented coping. A different relationship was found for challenge. Due to a significant intercorrelation among appraisals, mediational models for threat and loss were re-analyzed when controlling for challenge. Nevertheless, even if a situation is perceived as highly stressful, both positive and negative emotions can emerge, resulting in strategies that serve different functions to meet external and internal demands. (shrink)

How physicians approach patients and the problems they present is much influenced by the conceptual models around which their knowledge is organized. In this paper the implications of the biopsychosocial model for the study and care of a patient with an acute myocardial infarction are presented and contrasted with approaches used by adherents of the more traditional biomedical model. CiteULike Connotea Del.icio.us What's this?

Increasingly, clinical research is evaluated on the quality of its statistical analysis. Traditionally, statistical analyses in clinical research have been carried out from a ‘frequentist’ perspective. The presence of an alternative paradigm – the Bayesian paradigm – has been relatively unknown in clinical research until recently. There is currently a growing interest in the use of Bayesian statistics in health care research. This is due both to a growing realization of the limitations of frequentist methods and to the ability of (...) Bayesian methods explicitly to incorporate prior expert knowledge and belief into the analyses. This is in contrast to frequentist methods, where prior experience and beliefs tend to be incorporated into the analyses in an ad hoc fashion. This paper outlines the frequentist and Bayesian paradigms. Acute myocardial infarction mortality data are then analysed from both a Bayesian and a frequentist perspective. In some analyses, the two methods are seen to produce comparable results; in others, they produce different results. It is noted that in this example, there are clinically relevant questions that are more easily addressed from a Bayesian perspective. Finally, areas in clinical research where Bayesian ideas are increasingly common are highlighted. (shrink)

Using dimensional analysis, we demonstrate that it is possible to quantify changes in the topological structure of cardiac dynamics over long periods of time. A method was developed to calculate a dimension-like measure (referred to here as apparent dimension) from a correlation algorithm within a data window of 500 heart beats which is moved in equidistant steps over the time series of the RR intervals over 24 hours. The correspondence between the apparent dimension and the correlation dimension was tested using (...) artificial data sequences. Furthermore 24 hour electrocardiographic recordings of two healthy subjects and of a patient with acute myocardial infarction were examined. The reliability of the analysis could be demonstrated and changes in dimension reflecting physiological as well as pathophysiological changes were observed. (shrink)

The article presents the results of research on the relationship between social support and self-care of people with myocardial infarction. 127 patients treated in a rehabilitation centre participated in the study. The Inventory of Socially Supportive Behaviours and the Self-care Questionnaire developed by the author, were used. The findings suggest that persons receiving little support are characterised by lower level of self-care than people with medium and high level of support. No such difference was noted between people with (...) medium and high support level. This suggests that social support is of considerable importance for the changes in the level of self-care only in the case of people previously receiving little support. The research also indicates that informational support is related to higher level of self-care whereas instrumental support is related to lower level of self-care. Emotional support was significant only for the care for social functioning. (shrink)

Definition of the problem: In 1997, Percutaneous Transluminal Coronary Angioplasty (PTCA) was performed in 138.001 cases in Germany. The standard indications, single vessel disease and badly controlled angina, are more and more extended to multivessel disease with and without severe angina, unstable or preinfarction angina, and acute myocardial infarction (AMI) itself. Dilating asymptomatic stenoses of more than 70–80% is a widely used indication, intending prophylaxis of complete occlusion and AMI. Actually there is no generally accepted guideline for (...) the different new indications, conservative versus invasive treatment schedule. It is difficult for the patient to get appropriate information before his decision between mechanical procedures and conservative methods; authentic informed consent actually seems to be in a very bad position. In 1992 the working group called ”Arbeitsgemeinschaft leitender kardiologischer Krankenhausärzte (ALKK)” decided to start a registry of all PTCA procedures, in order to gain knowledge about the present status of PTCA in Germany. Up to March 1999, 198.608 PTCA are logged.Arguments: Each PTCA was included on an intention-to-treat basis. The registry succeeded in a nearly complete recording with 98,6% of all PTCA procedures complete on March 17th, 1999. 93,5% of stenosed and 72,2% of the total occluded vessels were successfully dilated. In 4.729 cases (2,63%) the PTCA caused severe complications. The overall in-hospital mortality was only 0,5%, if the procedures done for AMI were excluded (including AMI it was 1,1%). The calculation of complications should be an essential part of the patients informed consent.Conclusion: Complete recording of all PTCA procedures is feasible even on a nationwide basis. Some results of the registry, as the indication control and the complication rate may help to realize a better doctor-patient-conversation on risks and benefits of either concept. The trend of many CHD patients is ”modern”: It should be done what can be done (mechanically), with results at once. Although said somehow paternalistic, this point of view cannot be tolerated: Proper informed consent today includes the realistic alternative of modern medicaments, especially those with an aggressive cholesterol lowering potency. (shrink)

BackgroundAcute myocardial infarction (AMI) research is challenging as it requires enrollment of acutely ill patients. Patients are generally in a suboptimal state for providing informed consent. Patients’ understanding to verbal assents have not been previously examined in AMI research. Patients Acceptance and Comprehension to Written and Verbal Consent (PAC–VC) compared patients’ understanding and attitudes to verbal and written consents in AMI RCTs.MethodsPAC–VC recruited patients from 3 AMI trials using both verbal N = 12 and written N = 6 (...) consents. We compared patients’ understanding using two survey questionnaires. The first questionnaire used open-ended questions with multiple choice answers. The second questionnaire used a 5-point Likert scale to measure patients understanding and attitudes to the consent process. Overall answers average scores were categorized into three groups: Adequate understanding (71–100) %, Partial understanding (41–70)% and Inadequate understanding (0–40)%.ResultsResponses showed patients with verbal assent had adequate understanding to most components of informed consent, close to those of written consent. Most patients did not read written information entirely and believed that it is not important to make a final decision. Patients favoured to have written information be part of the consent but not necessarily presented during the initial consent process. Patients felt less pressured in the verbal assent arm than those of written consent.ConclusionPatients had adequate understanding to most components of verbal assent and comparable to those of written consent. Utilizing verbal assents in the acute care setting should be further assessed in larger trials. (shrink)

Advances in medicine are closely linked to clinical research, but certain study procedures may be in conflict with the fundamental principles of ethics and codes of conduct in medicine. Following an analysis of two studies involving treatments for acute myocardial infarction (AMI), the admissibility of continuing a study was questioned after the initial results for two types of treatment showed that one was significantly better than the other. Also considered doubtful was the information provided to patients with (...) the object of obtaining their informed consent. (shrink)

Clinical trials give rise to ethical dilemmas, especially in the acutely ill, but we take issue with two points raised in a recent comment on a specific acute myocardial infarction (AMI) trial. The commentators judged that the trial most likely could, and therefore should, have been terminated much earlier. By analysing the problem statistically we arrive at results that go against their intuitive judgment—they also see it as mandatory to update the patient Information sheet as trial results (...) accrue and trends begin to emerge. In our view, interpreting subtle trends and borderline p-values must rest with data monitoring boards, not patients. Moreover, patients with AMI or in other medical emergencies need very simple instructions. Empirical studies of the consent process confirm that the idea of a genuinely informed consent is problematic in such cases. (shrink)

This study is a continuation of the work of Professor Kazimierz Wrześniewski. It concerns the role of curiositytrait in the dynamics of changes in coping and quality of life after a heart attack. The study was attended by 222 people after a heart attack, of whom 140 participated in the three stages of the study: at the beginning and at the end of cardiac rehabilitation and a year after leaving the resort. The participants aged 24-64 years. Curiosity-trait was measured by (...) Spielberger and Wrześniewski’s STPI questionnaire. To assess coping strategies a modified version of the COPE by Carver et al., was used. The specific and general quality of life were measured by the Polish adaptations of MacNew and NHP questionnaires. The level of curiosity-trait significantly differentiated changes in the dynamics of positive reinterpretation, problem solving and resignation, but did not affect the change in quality of life within the year after a heart attack. (shrink)

The Supreme Court has ruled in the case of Y that there is no requirement to seek the approval of the Court of Protection in decisions to withdraw clinically assisted nutrition and hydration from patients in a prolonged disorder of consciousness.1 Mr Y was 52-year-old man who suffered a cardiac arrest after a myocardial infarction as a result of coronary artery disease. It was not possible to resuscitate him for well over 10 min, resulting in severe cerebral hypoxia (...) which caused extensive brain damage. Mr Y’s family and the NHS Trust treating him agreed that Mr Y would not want to be kept alive through the provision of CANH given his poor prognosis. They sought a declaration that it was not mandatory for applications of withdrawal of CANH to come before the court, which was granted by Mrs Justice O’Farrell in the first instance.2 Permission was granted for the appeal to ‘leapfrog’ the Court of Appeal and to proceed to the Supreme Court for consideration. In the interim, Mr Y died after contracting acute respiratory sepsis, but the Supreme Court determined that the appeal should go ahead in light of the general importance of the issues raised. In delivering the opinion of the Supreme Court on 30 July 2018, Lady Justice Black rejected the historical distinction that had been drawn between patients in PDOC and non-PDOC patients, in a way that had justified judicial involvement for patients in PDOC but not for others.3 She was clear that the correct approach to all cases involving CANH was to make a decision based on what was in the best interests of the patient. She further outlined that: > The documentation supplied to us shows that the difficulty that there is in assessing the patient and in …. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The Limits of Our ObligationsRyan C. MavesDisclaimers. No funding was utilized for this manuscript. Dr. Maves is a retired U.S. Navy officer, and the opinions contained herein are his own. The opinions in this manuscript do not reflect the official opinion of the Department of the Navy, Department of Defense, nor of the U.S. Government.In 2012, I was a commander in the United States Navy, deployed to the NATO (...) Role 3 Multinational Medical Unit in Kandahar Airfield (KAF), Afghanistan. The KAF Role 3 began as a tent hospital under Canadian command, built along the flight line at Ahmad Shah Baba International Airport as [End Page 176] part of an expanding NATO base. By the time of my arrival, it was a small but capable brick-and-mortar building under U.S. Navy command, with four operating rooms, two CT scanners, and a busy intensive care unit (ICU).Not long before my deployment, the KAF Role 3 was described as one of the busiest trauma hospitals in the world. Casualties arrived every day, usually by helicopter. Blast injuries from improvised explosive devices (IEDs) were common, ranging in severity from concussions in passengers in armored vehicles, to multiple amputations from blast injuries with concomitant thoracic, abdominal, and pelvic trauma. KAF had a daytime population of over 30,000 in 2012, and our hospital was effectively the referral center for the region, so patients with non-surgical diagnoses were similarly common: myocardial infarctions, seizures, pulmonary emboli, and endemic infections, to name a few.As an infectious disease (I.D.) specialist, I functioned mainly as a hospitalist, managing patients postoperatively, but I also provided any consultative support when needed. During mass casualty events, the intensivists and I would act as backups in the trauma bay, freeing up the surgeons for the most acutely injured patients. It turned out that an I.D. doctor’s skillset lent itself well to acute trauma evaluations; we are well known for having an eye for fine details, combined with low-grade paranoia. These traits served me well during what I came to describe as “my involuntary trauma fellowship.”Our patients could be divided into five key groups: Afghan National Security Forces (ANSF, including the army and national police), non-Afghan coalition military (mostly U.S. and other NATO members), Afghan civilians, NATO civilian contract staff, and the Taliban. Our approach to each of these groups was different. For all patient groups, we would provide the same emergency care, including acute resuscitation and immediate life-saving surgery. It was after this emergency care period that our management plans diverged.For coalition forces, our next priority after acute resuscitation and stabilization was to assess whether a patient could remain in theater. Stable patients with relatively minor injuries could often undergo rehabilitation at KAF; many personnel could subsequently return to combat duty with their units. More seriously-injured patients would be transported out of Afghanistan within 24-48 hours (if not faster). Usually, this would involve stops at Bagram Airfield near Kabul and then Landstuhl Regional Medical Center in Germany before reaching a military hospital in their home countries. There were few limits on whom could be transported. Dedicated critical care air transport teams (CCATT) included intensivists, respiratory therapists, and critical care nurses, who could manage the most unstable patients on board what was effectively a flying ICU. The “lung team” in Landstuhl could fly to KAF to start patients with severe respiratory failure on extracorporeal membrane oxygenation (ECMO) and then fly them out on maximal support.NATO civilian contractors would receive comparable care, although the exact details of how they would be transported out of theater would depend on their home countries and the nature of their contract. We cared for one civilian contractor with newly-diagnosed HIV infection whom we were able to stabilize on the ventilator, get him extubated, start on initial antiretroviral therapy, and transport him home with a referral to his local HIV care program.Afghan soldiers were part of the coalition, but there was no distant home country where we could transport them. They were home. After their resuscitations and surgeries, we would arrange transfer to the Kandahar Regional... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:To Be or Not to Be:Waiving Informed Consent in Emergency ResearchCharles R. McCarthy (bio)The requirements for prior, legally authorized informed consent constitute a necessary condition for recruiting subjects into biomedical or behavioral research. However, informed consent requirements pose a serious problem for most research conducted in emergency care settings. For this reason, the Food and Drug Administration's (FDA) regulations governing investigational devices and the Department of Health and Human (...) Services' (HHS) regulations for the protection of human subjects allow narrow exceptions to the general requirements of informed consent. In a joint effort to clarify the applicability of the current FDA regulations and to better understand the intent of the HHS regulations as they apply to emergency research, the FDA and the National Institutes of Health (NIH) cosponsored a public forum on the ethical conduct of emergency research in January 1995.Although the forum was not designed as a consensus conference and participants vigorously disagreed on some of the details, a broad consensus emerged on several major points: (1) both HHS and FDA regulations should, in the immediate future, be interpreted to allow for randomized clinical trials in emergency situations so long as the subjects are carefully protected; and (2) consideration should be given to producing new, closely harmonized regulations from both agencies that will provide greater clarity concerning what kinds of emergency research may be allowed without obtaining prior informed consent.The FDA-NIH forum in January was occasioned primarily by controversy about the hypothermia research protocol described below, but it is obvious that many other kinds of emergency research also await the outcome of deliberations concerning waiver of informed consent in emergency situations. These include research into the care and treatment of: occlusive stroke; subarachnoid hemorrhage due to intracranial aneurysm; metabolic coma; status epilepticus; cardiac arrest; myocardial infarction; cardiac arrhythmia; hemorrhagic shock; pulmonary embolism; acute asthmatic attack; and poisoning. All of these conditions [End Page 155] are encountered in emergency settings where obtaining informed consent from the patient-subjects to participate in research is seldom possible, and obtaining consent from legally authorized representatives of the subjects is either not feasible, or, if obtained, is of doubtful validity.The Hypothermia Research Case and HHS RegulationsA $7.2 million grant for research on the use of hypothermia in the treatment of severe head trauma, the largest award ever made to the University of Texas Health Sciences Center at Houston, is in danger of expiring before the study is completed. The protocol, which involves the use of cooling blankets to induce hypothermia in patients suffering from severe head injuries, is designed to test the hypothesis that: "Early lowering of the body temperature of patients suffering from severe head trauma to approximately 91 degrees Fahrenheit will slow patients' metabolism and will/will not, as a consequence, reduce the rates of both morbidity and mortality in these patients." The protocol was approved by seven Institutional Review Boards (IRBs), each of which waived the requirement to obtain informed consent from research subjects in accordance with Sec. 46. 116(d) of the HHS Regulations for the Protection of Human Subjects.1However, NIH's Office for Protection from Research Risks (OPRR), which is responsible for assuring compliance with the HHS regulations, has taken a controversial regulatory position by requiring informed consent from a legally authorized representative of each subject to be entered in the hypothermia trial. Because the obtaining of surrogate consent has proved to be very difficult, OPRR's position has slowed the research to a point where it may have to be terminated.At issue in the controversy is a fundamental question of ethics and public policy. Is it ever permissible to involve incompetent subjects in research without either their consent, or the consent of their legally authorized representatives? Pertinent HHS regulations for the protection of human subjects seem to answer the question affirmatively by allowing local IRBs to waive some or all of the elements of informed consent under carefully limited circumstances (45 CFR 46 116(d)). Nevertheless, OPRR has signalled the research community that use of the informed consent waiver provision for the Houston hypothermia study is not permitted under the regulations. OPRR judged that the risks... (shrink)

Background and purposeThis study aimed to analyze the feasibility and safety of endovascular therapy (EVT) in patients with acute posterior circulation stroke and vertebrobasilar dolichoectasia (VBD).Materials and methodsBASILAR was a national prospective registry of consecutive patients with symptomatic and imaging-confirmed acute stroke in the posterior circulation within 24 h of symptom onset. We evaluated EVT feasibility and safety in patients with VBD. Primary outcomes included improvement in modified Rankin Scale scores (mRS) at 90 days and mortality within 90 (...) days. The secondary outcome was the rate of favorable functional outcome, defined as mRS ≤ 3 (indicating independent ambulation) at 90 days. Safety outcomes included surgery-related complications and other serious adverse events.ResultsA total of 534 cases were included: 159 with VBD and 375 controls. No significant difference in mRS at 90 days was found between groups, but patients with VBD had a higher baseline National Institutes of Health Stroke Scale (NIHSS) score [30 (19–33) vs. 25 (15–32)] and were older [65 (59–74) vs. 63 (55–72) year]. After propensity score matching, there were no significant differences in baseline NIHSS score between the two groups, and the efficacy and safety of EVT were similar between patients with or without VBD. Furthermore, the prognostic effect of puncture-to-recanalization time on the probability of mortality within 90 days in EVT-treated patients with VBD was significant {adjusted odds ratio, 1.008 [95% confidence interval (1.001–1.015)]}.ConclusionEndovascular therapy is safe and feasible in patients with acute posterior circulation stroke and VBD. The puncture-to-recanalization time is important for predicting the prognosis of EVT-treated patients with VBD. (shrink)

Ischemic stroke involves numerous and complex pathophysiological mechanisms including blood flow reduction, ionic exchanges, spreading depressions and cell death through necrosis or apoptosis. We used a mathematical model based on these phenomena to study the influences of intensity and duration of ischemia on the final size of the infarcted area. This model relies on a set of ordinary and partial differential equations. After a sensibility study, the model was used to carry out in silico experiments in various ischemic conditions. The (...) simulation results show that the proportion of apoptotic cells increases when the intensity of ischemia decreases, which contributes to the model validation. The simulation results also show that the influence of ischemia duration on the infarct size is more complicated. They suggest that reperfusion is beneficial when performed in the early stroke but may be either inefficacious or even deleterious when performed later after the stroke onset. This aggravation could be explained by the depolarisation waves which might continue to spread ischemic damage and by the speeding up of the apoptotic process leading to cell death. The effect of reperfusion on cell death through these two phenomena needs to be further studied in order to develop new therapeutic strategies for stroke patients. (shrink)

In the past decade, the availability of genetically modified animals has enabled the discovery of interesting roles for phosphatidylinositol 3‐kinase‐γ (PI3Kγ) and ‐δ (PI3Kδ) in different cell types orchestrating innate and adaptive immune responses. Therefore, these PI3K isoforms appear to be attractive drug targets for the treatment of diseases caused by unrestrained immune reactions. Currently, pharmacological targeting of PI3Kγ and/or PI3Kδ represents one of the most promising challenges for companies interested in the development of novel safe treatments for inflammatory diseases. (...) In this review we provide a general outline of PI3Kγ‐ and PI3Kδ‐specific functions in distinct subsets of inflammatory cells. We also discuss the therapeutic impact of novel compounds targeting PI3Kγ, PI3Kδ or both, in mouse models of autoimmune disorders (systemic lupus erythematosus (SLE) and rheumatoid arthritis), respiratory diseases (allergic asthma and chronic obstructive pulmonary disease) and cardiovascular dysfunctions (atherosclerosis and myocardial infarction). (shrink)

Boorse’s biostatistical theory states that diseases should be defined in ways that reflect disturbances of biological function and that are objective and value free. We use three examples from contemporary medicine that demonstrate the complex issues that arise when defining the boundaries of disease: polycystic ovary syndrome, chronic kidney disease, and myocardial infarction. We argue that the biostatistical theory fails to provide sufficient guidance on where the boundaries of disease should be drawn, contains ambiguities relating to choice of (...) reference class, and is out of step with medical processes for identifying disease boundaries. Although proponents of the biostatistical theory might regard these practical issues as irrelevant to the aim of providing a theoretical account of disease, we take them to indicate the need for a theoretical account that is adequate for current needs—including limiting new forms of medicalization that are driven by the identification of disease based on dysfunction. Our processes for determining the boundaries for disease need to recognize that there is no value-free method for making these decisions. (shrink)

The new class of anti-inflammatory drugs, the COX-2 inhibitors, have been commercially successful to the point of market dominance within a short time of their launch. They attract a price premium on the basis that they are associated with fewer adverse gastric events than traditional anti-inflammatory drugs. This marketing continues even though a pivotal safety study with one of the COX-2 inhibitors, rofecoxib, showed a significant increase in myocardial infarction with rofecoxib use compared with a traditional anti-inflammatory drug. (...) This finding has led to a series of publications containing pooled analyses of existing data that both support and refute the possibility of increased cardiovascular risk with COX-2 inhibitors.These medical journal publications have served to obfuscate rather than provide guidance for medical practitioners. Consideration of a research ethics committee approach to this issue suggests that it would deal with the controversy in a straightforward manner—namely, it would simply inform research participants of the trial results with rofecoxib. The certainty of this research ethics committee approach raises the issue of whether it should be applied in normal medical practice outside of the research environment. A consideration of the legal tests for disclosure of information suggests that therapeutic medical practice should mirror that within the research environment, in this case. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 11.2 (2001) 165-168 [Access article in PDF] UPMC Presbyterian Policy and Procedure Manual Guidelines for Disclosure and Discussion of Conditions and Events with Patients, Families and Guardians* I. Introduction and Background In the course of hospital care, an extensive amount of clinical information is generated. It includes diagnostic findings, treatment options, responses to interventions, and professional opinions. The information can be positive or negative. (...) Clinical events may or may not be caused by clinicians and consequently may be iatrogenic (caused by medical treatment), nosocomial (occurring in the hospital) or natural events.In accordance with the informed consent policy (#4011), Patients' Bill of Rights (# 0154, Section II H), and the Guidelines on Forgoing Life Sustaining Treatment (#4007), patients have the right to information regarding their condition and care. Physicians and other caregivers are obligated to provide accurate information as expeditiously as possible. While it is usually easy to provide positive information, negative information is more difficult to disclose, especially when the cause is iatrogenic."Therapeutic privilege" has been invoked to explain why certain negative information might be withheld. By invoking therapeutic privilege, the physician refrains from full disclosure to protect the patient from the effects of receiving the information itself. The use of therapeutic privilege is increasingly being called into question because it decreases patient autonomy and reduces trust.The following recommendations are provided to clinicians to help guide delivery of sensitive information, positive and negative. Specific recommendations [End Page 165] are provided for situations where the information is about an unfavorable or adverse event, or where the information might best be characterized as "bad news." II. Definitions Unfavorable event or unfavorable condition. For the purposes of these guidelines, an unfavorable condition is an occurrence or diagnosis that results in or is likely to result in a significant negative outcome, and/or a significant alteration in the care plan.An unfavorable event in this context is not the same as a sentinel event, which in policy #4025 is defined as, "a serious, unexpected, adverse patient event which has resulted in, or if repeated would have a significant probability of resulting in, loss of life or serious physical or psychological injury, that is judged to be a warning of an underlying problem involving hospital facilities, policies, procedures, systems or personnel."Adverse Event. An unfavorable event for the purposes of these guidelines is also distinguished from the FDA definition of the term "adverse event", which is a reportable negative effect of a drug or device potentially resulting in death, hospitalization, or medical or surgical intervention. (See policy #4022 Safe Medical Device Act.)Examples of unfavorable events or conditions for the purpose of these guidelines include a new diagnosis of cancer, a perioperative myocardial infarction, or unintended delivery of an incorrect medication that results in clinical change.Examples of events not covered by these guidelines are intravenous saline infiltration and medication dosing errors that have no clinical impact on care.Iatrogenic. Event caused by the treatment of a healthcare provider. III. Guidelines and Principles It is appropriate that UPMC Presbyterian support basic principles for patient and family notification regarding all clinical events and conditions, including unfavorable ones. Physicians must be honest because that is a cornerstone of the patient-physician relationship, and because it fosters patient autonomy.UPMC Presbyterian supports the following AMA position regarding patient information: [End Page 166] It is a fundamental ethical requirement that a physician should at all times deal honestly and openly with patients. Patients have a right to know their past and present medical status and to be free of any mistaken beliefs concerning their conditions. Situations occasionally occur in which a patient suffers significant medical complications that may have resulted from the physician's mistake or judgement. In these situations, the physician is ethically required to inform the patient of all the facts necessary to ensure understanding of what has occurred. Only through full disclosure is a patient able to make informed decisions regarding future medical care. Ethical responsibility includes informing patients of changes in their diagnoses... (shrink)

A non-inferiority design accepts the possibility of some efficacy loss, as part of a “successful”, statistically significant result. That loss may be excessive when the non-inferiority threshold is lenient. However, even stringent significance thresholds and safety monitoring may fail to adequately protect study participants when the primary outcome is death. The OPTIMAAL trial, a large randomized clinical trial performed in high-risk patients, is discussed as an example, using the Belmont Report principles as an ethical frame of reference. OPTIMAAL compared losartan, (...) a new drug, to captopril, a drug known to reduce the risk of death in patients with heart failure after a myocardial infarction. Serious ethical challenges occurred in that study. Firstly, subjects had to tolerate captopril to participate, meaning that participation implied the possibility of higher risk of death if randomized to the losartan arm, as compared to the standard of care. Additionally, the stopping rules had to ensure enough powe... (shrink)

Health and disease are core concepts in health care and have attracted substantial interest and controversy. In recent and interesting contributions to the debate it has been argued that the challenges with the concept of disease can be resolved by a prototype concept of disease. As a robin is a more prototypical of a bird than a penguin, some diseases are more prototypical than others. If disease is a prototype concept, it would change nosology, but also health care and the (...) study of health and disease. However, the statement that “disease is a prototype concept” forms an empirically testable hypothesis. Therefore, this study aims to test the hypothesis that health professionals have a prototype concept of disease. Two hundred twenty-three health care professionals in Norway were invited to participate in a survey where they were asked to rank a wide range of diseases according to how typical they considered them to be as diseases. Results were analysed with descriptive statistics. The response rate was 90%. Lung cancer, leukemia, colon cancer, myocardial infarction, and AIDS are the diseases ranged to be most typical, while homosexuality, pregnancy, drapetomania, dissidence, and nostalgia are considered to be the least typical diseases. The results also show that the answers to how typical various diseases are vary greatly, even amongst a relatively homogenous group of health professionals. This study falsifies the hypothesis that disease is a prototype concept for health professionals. This has implications for the debate on core concepts for health care. If health professionals do not have a prototype concept of disease, it is unlikely that there is a prototype concept of disease in general. Consequently, nosologies should not be based on prototypes. (shrink)

Background:The theoretical framework of Jϋrgen Habermas suggests that effective communication requires competent participants with an objective attitude that complies with the rules and worlds designated as objective, social and subjective. This situation determines communicative action, which stimulates the search for mutual understanding and results in a process of interaction that promotes self-determination.Objectives:In this study, the discharge letters of patients with myocardial infarction were explored regarding the provision of information. The patient’s right to information and the duty of informing (...) were analysed according to the perspective of Jϋrgen Habermas.Research design:This was a cross-sectional analysis of all discharge letters that were directly related to nursing interventions regarding the provision of information to 106 patients. In this major study, the difficulties faced by patients who experienced a myocardial infarction and the changes in their lifestyles were analysed based on the type of information received.Ethical considerations:The hospital Ethics Committee approved the study, which complied with ethical principles and required informed consent.Findings:In the nursing letters, interventions related to the provision of information were conducted at an average of 3.59 interventions per patient. For 8.5% of the patients, however, no interventions related to the provision of information were performed. The most common area of information during hospitalisation was related to the management of signs and symptoms and applied to 90.6% patients.Discussion:The nursing interventions did not cover patient education, transition processes or awareness of the disease. Thus, the right to information can be questioned.Conclusion:Information is a right, and communication is extremely important. Health professionals should be aware of this importance regarding both care management and the satisfaction guarantee. The sharing of information by health professionals based on their competency is essential for patients to exercise their right to self-determination and decision-making. (shrink)

We explored differences in the course of physiological functions and in the subjective evaluations in response to listening to a 7-min recording of the sound of a chainsaw and to the sounds of a forest. A Biofeedback 2000x-pert apparatus was used for continual recording of the following physiological functions in 50 examined persons: abdominal and thoracic respiration and their amplitude and frequency, electrodermal activity, finger skin temperature, heart rate and heart rate variability. The group of 25 subjects listening to the (...) sound of a chainsaw exhibited significantly lower values of blood volume pulse amplitude, lower values in peak alpha frequency HRV and higher values in peak high-frequency HRV. In the time interval from 80 s to 209 s, in which the two groups showed the greatest differences, lower values of blood volume pulse were also recorded while listening to the sound of a chainsaw. Listening to the sound of a chainsaw is associated with a greater feeling of fatigue and higher tension, while listening to the sounds of a forest is even considered to elicit feelings of improved learning abilities. The assumption that listening to the sound of a chainsaw results in higher defense arousal was confirmed. The greater variability which is exhibited by a majority of physiological functions while listening to the forest sounds may also be an innovative finding. It seems that there are two types of arousal following from correlations between physiological functions and subjective assessment. Low values of blood volume pulse amplitude are especially important from the health perspective. They correspond to the amount of vasoconstriction which occurs in the endothelial dysfunction related to increased mortality, incidence of myocardial infarction, leg atherosclerosis and topically to COVID-19. (shrink)

The contemporary epistemic status of mental health disciplines does not allow the cross validation of mental disorders among various genetic markers, biochemical pathway or mechanisms, and clinical assessments in neuroscience explanations. We attempt to provide a meta-empirical analysis of the contemporary status of the cross-disciplinary issues existing between neuro-biology and psychopathology. Our case studies take as an established medical mode an example cross validation between biological sciences and clinical cardiology in the case of myocardial infarction. This is then (...) contrasted with the incoherence between neuroscience and psychiatry in the case of bipolar disorders. We examine some methodological problems arising from the neuro-imaging studies, specifically the experimental paradigm introduced by the team of Wayne Drevets. Several theoretical objections are raised: temporal discordance, state independence, and queries about the reliability and specificity, and failure of convergent validity of the inter-disciplinary attempt. Both modern neuroscience and clinical psychology taken as separate fields have failed to reveal the explanatory mechanisms underlying mental disorders. The data acquired inside the mono-disciplinary matrices of neurobiology and psychopathology are deeply insufficient concerning their validity, reliability, and utility. Further, there haven’t been developed any effective trans-disciplinary connections between them. It raises the requirement for development of explanatory significant multi-disciplinary “meta-language” in psychiatry (Berrios, 2006, 2008). We attempt to provide a novel conceptual model for an integrative dialogue between psychiatry and neuroscience that actually includes criteria for cross-validation of the common used psychiatric categories and the different assessment methods. The major goal of our proactive program is the foundation of complementary “bridging” connections of neuroscience and psychopathology which may stabilize the cognitive meta-structure of the mental health knowledge. This entails bringing into synergy the disparate discourses of clinical psychology and neuroscience. One possible model accomplishment of this goal would be the synergistic (or at least compatible) integration of the knowledge under trans-disciplinary convergent cross-validation of the commonly used methods and notions. (shrink)

This paper discusses two proposals to the US President’s Council on Bioethics that try to overcome the issue of killing embryos in embryonic stem cell research and argues that neither of them can hold good as a compromise solution. The author argues that the groups of people for which the compromises are intended neither need nor want the two compromises, the US government and other governments of countries with restrictive regulation on ES cell research have not provided a clear and (...) sound justification to take into account minority views on the protection of human life to such a considerable extent as to constrain the freedom of research in the area of stem cell research, and the best way to deal with these issues is to accept that many people and most governments adopt a gradualist and variable viewpoint on the human embryo which implies that embryos can be sacrificed for good reasons and to try to find other, less constraining, ways to take into account minority views on the embryo. Finally, another more efficient and time and money sparing compromise will be proposed for those who accept IVF, a majority in most societies.STEM CELL RESEARCHStem cells are widely believed to represent one of the greatest promises for medicine and biomedical research in the coming century with hopes raised for treatments for common diseases and conditions, including neurological disease or injury, diabetes, and myocardial infarct. At present there are three main lines of stem cell research, namely on stem cells originating from early in vitro embryos, left over from infertility treatment, or especially created for research through in vitro fertilisation or cell nuclear transfer cells), on cord blood derived stem cells, and on stem cells from more developed tissues or organs from foetuses …. (shrink)

Elective surgery can be cancelled when resources are overwhelmed by emergency cases. We hypothesized that such cancellations, on psychological grounds, are followed also by inferior clinical results and we conducted a retrospective survey of patients following joint replacement surgery. Sixty patients having suffered from administrative cancellation prior to their operation during an 18-month period and with six months follow-up were identified and compared with another 60 matched patients after having the same type of surgery but without prior cancellation. All patients (...) received questionnaires on complications and on visual analogue scale (VAS) assessment on subjective wellbeing and quality of life (QoL) at follow-up. The study group reported 50 complications versus 33 for controls (P < 0.03). A borderline significant difference was found for myocardial infarction, 4 versus 0 (P < 0.05). There was no difference in VAS registration and QoL measurements did not quite reach statistical significance (P = 0.06). Cancellations (postponements) of elective surgery for administrative reasons may be followed by inferior clinical results, and this merits further prospective study. (shrink)

A brief poll of my scientific colleagues confirmed that, to a person, they regard addiction as a disease, whereas most non-science acquaintances consider it to be a failure of willpower. Reconciliation of these polarized views seems difficult and rather than finding a middle path, such as suggested by Foddy and Savulescu. I am an entrenched supporter of the view that addiction can be a disease. I first should declare my position as a card-carrying biologist, holding the view that behavior emanates (...) from the brain and, accordingly, that behavior and emotions result from brain function. This brain function also produces addiction and related behaviors, whereas Foddy and Savulescu seem to credit humans with a greater capacity to choose than biological evidence suggests. The second problem relates to definitions of disease: I argue that there are at least three ways addiction might be considered a disease. 1.? ? ? Addiction is a disease because it results in pathology. For example, hypertension is a disease. Hypertension per se does not cause dysfunction, but leads to pathologically definable conditions such as stroke and myocardial infarction. Smoking, like hypertension, can result in pathologies such as emphysema and cancer. The problem is not smoking per se, or even addiction to nicotine, rather it is the consequent diseases caused by tobacco. Nevertheless, if hypertension is a disease, so is smoking. The question of “choosing‘ to persist with smoking has no bearing on whether it is disease. Whether a person chooses to care for their hypertension or ignore it does not alter the fact that they have hypertension; it is still a disease and it will still harm them. Whether addiction affects the capacity to choose is not relevant because it does not alter the fact that smoking causes pathology and hence is a disease. 2.? ? ? Foddy and Savulescu argue that addiction leaves no tell-tale pathology to set it aside from. (shrink)

Insulin is well known for its essential role in carbohydrate metabolism: insulin deficiency results in the development of diabetes mellitus. It has been known for many years that people with diabetes mellitus are predisposed to develop thrombotic diseases including myocardial infarction. It was thought that the thrombus formation was the consequence of impaired carbohydrate metabolism. In recent years, it has become apparent that insulin is capable of ameliorating several pathophysiological events, leading to the inhibition and dissolution of the (...) formed thrombus in the system. These insulin‐induced events include inhibition of platelet aggregation by prompting the synthesis of NO in platelet and prostacyclin in endothelial cells. Furthermore, insulin upregulates prostacyclin receptors and downregulates α2 adrenergic receptor in platelets, thereby amplifying the inhibition of platelet aggregation. Insulin also releases tissue plasminogen activator, a potent thrombolytic enzyme, from the platelet membrane which dissolves the formed thrombus leading to the resumption of normal blood circulation. In effect, insulin could be an essential tool in the control of thrombotic disorders. BioEssays 26:91–98, 2004. © 2003 Wiley Periodicals, Inc. (shrink)