The Nocebo Effect: A Bias in Clinical Practice-An Ethical Approach.

BACKGROUND: The nocebo effect is often disregarded in medical practice and is certainly much less known than the placebo effect, although, in reality, both can influence therapeutic decision making and the quality of life of patients. However, the nocebo effect raises a number of issues not only of a practical nature related to clinical activity but also ethical dilemmas related to the observance of the patient's autonomy, nonmaleficence, or informed consent and the information on which it is based. AREAS OF UNCERTAINTY: The ethical dilemmas raised by the nocebo effect revolve around how informed consent can be achieved, the accuracy and volume of information that is transmitted to the patient, and how to report negative side effects of therapeutic treatment. DATA SOURCES: In September 2023, a narrative analysis of the literature was conducted using a combination of keywords such as nocebo, placebo, ethics, therapeutic relationship from PubMed, Scopus, Google Scholar, and so on, as well as from official documents developed at an international level (World Health Organization), for a period of 10 years (2012-2021). RESULTS: Analyzing the articles that remarked upon the significant impact of ethics in nocebo research or in the therapeutic relationship, we can state that the existence of several relevant issues of interest have been detected regarding the ethical use of nocebo and its impact in research or in clinics and thus the need for proper knowledge and management of the impact of nocebo effects. The ethical paradox of obtaining informed consent with the 2 goals, first, the need for complete information and second, the preservation of the autonomy of the patient, respectively, that of "primum non-nocere" and of avoiding unnecessary harm by revealing probable adverse effects is a point of interest for numerous studies. The potential for a nocebo effect is present when we inform patients about the risks and benefits of treatment, there being a clear link between the moral and ethical duty to inform patients and the need to avoid situations that increase the nocebo impact on how the disease or the adverse effects of the treatment are perceived. Adapting information about the side effects of medicines should focus on ensuring a balance between transparency and caution, especially in patients with a high potential for nocebo effect. CONCLUSIONS: The nocebo effect had for a long time been unknown or denied, although it can interfere with the results of the treatment used. As the nocebo phenomenon becomes increasingly known in medical practice, the clinical and ethical implications are identified by medical staff, and nocebo's adverse responses are no longer ignored.

Early Evaluation and Monitoring of Critical Patients with Acute Respiratory Distress Syndrome (ARDS) Using Specific Genetic Polymorphisms.

A high percentage of critical patients are found to develop acute respiratory distress syndrome (ARDS). Several studies have reported high mortality rates in these cases which are most frequently associated with multiple organ dysfunctions syndrome. Lately, many efforts have been made to evaluate and monitor ARDS in critical patients. In this regard, the assessment of genetic polymorphisms responsible for developing ARDS present as a challenge and are considered future biomarkers. Early detection of the specific polymorphic gene responsible for ARDS in critically ill patients can prove to be a useful tool in the future, able to help decrease the mortality rates in these cases. Moreover, identifying the genetic polymorphism in these patients can help in the implementation of a personalized intensive therapy scheme for every type of patient, based on its genotype.

Using the Expression of Damage-Associated Molecular Pattern (DAMP) for the Evaluation and Monitoring of the Critically Ill Polytrauma Patient.

BACKGROUND: The critically ill polytrauma patient continues to be one of the most complex cases in the intensive care unit (ICU). The molecular damage is closely connected with the severe, specific pathophysiological imbalances, such as severe inflammation, infections, hypermetabolism, oxidative stress, and ultimately multiple organ dysfunction syndrome (MODS). METHODS: The literature available on PubMed and Scopus was analysed for this study. The key words used in the search were "biomarkers in critically ill patients", "molecular damage", "sepsis biomarkers", "miRNAs biomarkers", and "oxidative stress". RESULTS: After reviewing the available literature, 133 science articles were selected. According to recent studies, the gold goal in the management of the critically ill patient is the optimization of intensive care therapy dependent on the molecular damage. CONCLUSIONS: Furthermore, evaluation, monitoring, and therapy adaptation in this type of patient is closely related to the biochemical and molecular disorders.

The Use of Lipid Peroxidation Expression as a Biomarker for the Molecular Damage in the Critically Ill Polytrauma Patient.

BACKGROUND: The critically ill polytrauma patient, apart from the primary, traumatic injuries and the secondary, port-traumatic injuries, presents with a series of molecular disasters. Dysfunctions of the biochemical pathways and molecular damage add to the worsening of the clinical status of these patients, one of the most well-known molecular phenomena being oxidative stress (OS), responsible for an escalation of the inflammatory status, multiple infections, and multiple organ dysfunction syndrome (MODS). METHODS: For this study was analysed the literature available on PubMed and Scopus. The key words used in the search were "oxidative stress", "lipid peroxidation", "critically ill", "polytrauma patients", and "biomarkers oxidative stress". RESULTS: For the study we selected 47 science articles. The oxidative attack on lipids is responsible for the biosynthesis of an increased quantity of free radicals (FR), which further intensifies and aggravates the redox status in these patients. CONCLUSIONS: One of the most aggressive redox mechanisms related to lipid molecules is known as lipid peroxidation (LPOX).

Modulation of the Redox Expression and Inflammation Response in the Critically Ill Polytrauma Patient with Thoracic Injury. Statistical Correlations between Antioxidant Therapy.

BACKGROUND: One of the major causes of mortality in the world is represented by multiple traumas. Thoracic trauma is commonly associated with polytraumas. A series of physiopathological complications follow polytraumas, leading to a significant decrease in the survival rate. As a result of injuries, significant quantities of free radicals (FR) are produced, responsible for oxidative stress (OS). To minimize the effects of OS, we recommend the administration of antioxidant substances. In this study we want to highlight statistically significant correlations between antioxidant therapy and a series of clinical variables. METHODS: This retrospective study included 132 polytrauma patients admitted to the ICU-CA between January 2013 and December 2014. The selection criteria were: injury severity score (ISS) ≥ 16, ≥ 18 years, presence of thoracic trauma (abbreviated injury scale, AIS ≥ 3). Eligible patients (n = 82) were divided into two groups: Group 1 (n = 32, antioxidant free, patients from 2013) and Group 2 (n = 50 antioxidant therapy, patients from 2014). Antioxidant therapy consisted in the administration of vitamin C (i.v.), vitamin B1 (i.v.), and N-acetylcysteine (i.v.). Clinical and biological tests were repeated until discharge from ICU-CA or death. RESULTS: Between Group 1 and Group 2 statistically significant differences were highlighted regarding the ISS score (p = 0.0030). 66% of patients from Group 2 were admitted at more than 24 hours after the trauma, in contrast to the patients from Group 1, where 62.5% were directly admitted to the ICU (p = 0.0114). Compared with the patients from Group 1, patients who received antioxidant therapy show improved parameters: leukocytes (p < 0.0001), platelets (p = 0.0489), urea (p = 0.0199), total bilirubin (p = 0.0111), alanine transaminase (p = 0.0010), lactat dehydrogenase (p < 0.0001). Between the two groups there were no statistically significant differences regarding the length of stay in the ICU-CA (p = 0.4697) and mortality (p = 0.1865). CONCLUSIONS: Following the study, we can affirm that due to the administration of antioxidant substances, posttraumatic complications are greatly reduced. Moreover, the administration of high dose of antioxidants remarkably improves the clinical status of the critical patient.

Genetic Expression in Cystic Fibrosis Related Bone Disease. An Observational, Transversal, Cross-Sectional Study.

BACKGROUND: Cystic fibrosis (CF) is the most frequent monogenic genetic disease with autosomal recessive transmission and characterized by important clinical polymorphism and significant lethal prospective. CF related bone disease occurs frequently in adults with CF. Childhood is the period of bone formation, and therefore, children are more susceptible to low bone density. Several factors like pancreatic insufficiency, hormone imbalance, and physical inactivity contribute to CF bone disease development. Revealing this would be important for prophylactic treatment against bone disease occurrence. The study was observational, transversal, with a cross-sectional design. METHODS: The study included 68 children with cystic fibrosis, genotyped and monitored in the National CF Centre. At the annual assessment, besides clinical examination, biochemical evaluation for pancreatic insufficiency, and diabetes, they were evaluated for bone mineral density using dual energy X-ray absorptiometry (DXA). RESULTS: Twenty-six patients, aged over 10 years were diagnosed with CF bone disease, without significant gender gap. Bone disease was frequent in patients aged over 10 years with exocrine pancreatic insufficiency, carriers of severe mutations, and CF liver disease. CONCLUSIONS: CF carriers of a severe genotype which associates pancreatic insufficiency and CF liver disease, are more likely predisposed to low bone mineral density. Further studies should discover other significant influences in order to prevent the development of CF bone disease and an improved quality of life in cystic fibrosis children.

Functional improvement between brain death declaration and organ harvesting.

INTRODUCTION: The quality of harvested organs is crucial for graft survival and for posttransplant evolution. This study sought to investigate the evolution of the functional status of brain death (BD) patients during the period between declaration and organ harvesting (BD duration). MATERIALS AND METHODS: The study included all BD patients who underwent organ harvesting between January 2006 and June 2009. We compared the functional status regarding hemodynamics, respiration, kidney and liver function, coagulation, water, electrolytes, and acid-base balance evaluated at the moment of BD declaration (P1) and just before organ harvesting (P2). The results of the comparison were expressed as improvement, stable, or aggravation. We calculated mean values of the functional parameters in P1 and P2 and the statistical significance of the differences. RESULTS: Twelve BD patients were included in the study. The time interval between P1 and P2 was 16.08 +/- 8.54 hours (range, 6-32). The number of patients with vasopressor support was 9/12 at P1 and 0/12 at P2, oxygenation disturbances 1/12 in P1 and 0/12 in P2, renal dysfunction 9/12 in P1 and 2/12 in P2, liver dysfunction 7/12 in P1 and 1/12 in P2, coagulopathy 4/12 in P1 and 0/12 in P2, hypernatremia 8/12 in P1 and 3/12 in P2, and metabolic acidosis 9/12 in P1 and 1/12 in P2. The overall assessment showed improvement in all patients. The most statistically significant improvement was registered in the cardiovascular, respiratory, renal, liver, and acid-base status (P < .05). CONCLUSION: With early, aggressive, protocolized donor management, functional improvement may be achieved during BD duration.

Presumed consent for organ donation: is Romania prepared for it?

INTRODUCTION: In November 2007, a legislative initiative regarding the presumed consent for organ donation was proposed for parliamentary debate in Romania and was followed by public debate. The study aimed to asses public opinions expressed in the Romanian media. MATERIALS AND METHODS: An Internet search was made. The pro and con reasons, the affiliation of parts involved in the debate and suggested future direction of action were identified. RESULTS: The Internet search had 8572 results. The parts involved in the pro and con debate consisted of governmental structures, physicians, ethicists, politicians, media, religious authorities, nongovernmental associations, and lay persons. The main pros were the low rate of organ donation and the long waiting lists, enhancement of organ procurement, avoidance of wasting valuable organs, avoiding responsibility, and the stress imposed to the family in giving the donation consent, humanitarian purposes (saving lives), going along with the scientific progress, and less bureaucracy. The main cons were an unethical issue, violation of human rights, denial of brain death, unethical advantage of public ignorance, unethical use of underprivileged people, little results in terms of organ procurement, but huge negative effects on public opinion, public mistrust in transplant programs and impossibility of refusal identification due to particularities of the Romanian medical system. CONCLUSION: The con opinions prevailed. For the moment, Romania seems to be unprepared to accept presumed consent. A future change in public perception regarding organ transplantation may modify the terms of a public debate.

The rate of organ and tissue donation after brain death: causes of donation failure in a Romanian university city.

AIM: To evaluate the rate of organ donation after brain death in 2 tertiary care medical centers of a Romanian city, the reasons for donation exclusion (donors or organs), and identification of potential strategies for improvement. MATERIAL AND METHODS: The study retrospectively evaluated potential organ donors with brain death (BD) who were identified between January 2006 and June 2009 in an university city of Romania. The potential donors were considered patients with severe intracranial pathology and clinical signs of brain death who were reported to the regional transplant team. The BD declaration was completed according to the Law of Transplant Procurement and Management in Romania: clinical signs of brain stem death, apnea test, and flat EEG, criteria that must be fulfilled twice at a 6 hour interval. According to Romanian law, family consent is mandatory for organ harvesting. RESULTS: The study included 35 potential donors, of whom 22 had a declaration of BD. Failure of potential donors to be declared BD was caused by positive viral serology (n = 7), improvement in clinical status (n = 2), sudden cardiac arrest (n = 2), and refusal of physician in charge (n = 2). Among the 22 with a BD declaration, organ harvesting was performed in only 12 cases due to family refusal (n = 10). In 4 cases the planned organ harvesting was aborted owing to unexpected intraoperative findings. DISCUSSION: Factors that generate the low rate of organ procurement include local organizational particularities, a high rate of viral infections, poor education, (both of lay persons and of medical personnel), restrictive criteria for BD declaration and the mandatory need for family approval. CONCLUSION: The rate of donation in this university city of Romania is still low. Several strategies have been identified to improve the rate: better identification of potential donors, better management, and education of the public and of health care personnel.