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.

Pharmacological Management of Cholera: A Century of Expert Opinions in Cecil Textbook of Medicine.

BACKGROUND: Cholera is a potentially lethal diarrheal disease produced by Vibrio cholerae serotypes O1 El Tor and O139. Known since antiquity, the condition causes epidemics in many areas, particularly in Asia, Africa, and South America. Left untreated, the mortality may reach 50%. The crucial therapeutic intervention is intravenous or oral rehydration and correction of acidosis, dyselectrolytemia, and renal impairment. Antibiotic use represents the main pharmacological intervention. STUDY QUESTION: What are the milestones of the antibiotics use recommended by experts for the pharmacological management of cholera in the past century? STUDY DESIGN: To determine the changes in the experts' approach to the management of cholera and particularly the use of antibiotics as presented in a widely used textbook in the United States. DATA SOURCES: The chapters describing the management of cholera in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. RESULTS: Sulfonamides were recommended in 1947, followed by the introduction of tetracyclines, chloramphenicol, and furazolidone in 1955. The options were restricted in 2000 to doxycycline. In the past decade, patients infected with strains known to have a degree a resistance to tetracyclines were treated with azithromycin or ciprofloxacin. Antibiotic use decreases the volume of stool and the duration of diarrhea but has not been considered lifesaving. Drugs with antimotility, antiemetic, or antisecretory properties are not useful. CONCLUSIONS: The utility of antibiotic use in cholera has been endorsed by experts, but only as an adjunct to rapid and complete fluid and electrolyte replacement.

Bed Rest After Acute Myocardial Infarction: A Century of Expert Opinions in Cecil Textbook of Medicine.

BACKGROUND: Complete bed rest has been a component of the management of acute myocardial infarction, which was first diagnosed in the United States in 1912. The prescribed duration of bed rest has been progressively shortened in the past century. STUDY QUESTION: What are the milestones of the changes in the expert approach to the duration of bed rest for patients with acute myocardial infarction? STUDY DESIGN: To determine the changes in the experts' approach to the duration of bed rest after a diagnosis of acute myocardial infarction, as presented in a widely used textbook in the United States. DATA SOURCES: The chapters presenting the management of myocardial infarction in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. RESULTS: Complete rest for 2-6 weeks was recommended by the Cecil's experts from 1927 through 1967. The practice was questioned since the early 1950s, but the recommended duration of bed rest was decreased to 3-4 days only in 1971, after most US hospitals opened coronary care units. The required time in bed was further decreased to 1 day in 1992 and to 12 hours in 2004. By 2007, the literature contained data from 15 trials with a total of 1471 patients kept in bed "longer" and 1487 patients who had been prescribed bed rest for "shorter" periods after an acute uncomplicate myocardial infarction and there was no difference between the groups regarding reinfarction, cardiac mortality, or all-cause mortality. CONCLUSIONS: The duration of bed rest after acute myocardial infarction recommended by experts in the United States has had a downward trend with an inflection point in the early 1970s. The change reflected experts' opinion, rather than evidence produced by randomized controlled trials.

Prehospital Care of Coronary Artery Disease and Its Major Risk Factors in Geropsychiatric Inpatients.

BACKGROUND: Older adults with serious mental illness have a high prevalence of coronary artery disease and of its major risk factors, that is, arterial hypertension, dyslipidemia, and diabetes mellitus. The prevalence and clinical control of these conditions have not been compared in geropsychiatric inpatients with dementia versus those with mood or psychotic disorders. STUDY QUESTION: What is the prevalence and acuity of coronary artery disease, arterial hypertension, dyslipidemia, and diabetes mellitus among patients with dementia, mood, and psychotic disorders admitted for geropsychiatric care? STUDY DESIGN: Patients 65 years of age or older were identified in a cohort of 1000 patients consecutively admitted over a 3-year period to the geropsychiatric unit of a 200-bed mental health hospital in suburban New York. All patients had a structured clinical and laboratory evaluation within 72 hours of admission. DATA SOURCES: Primary psychiatric diagnoses, medical history, the frequency of poorly controlled cardiometabolic comorbidity requiring an immediate change in the management plan, and the Charlson Comorbidity Index (CCI). RESULTS: The 65 years and older patient sample (N = 689) had a mean age of 74.8 years, and 58.8% of the subjects were women. The 205 patients with dementia were older ( P < 0.001) than the 337 patients with mood disorders and the 147 patients with psychotic syndromes. The numbers of medical conditions and the CCI after exclusion of dementia were similar in patients with dementia versus patients without dementia. A substantial number of patients had poorly controlled arterial hypertension (51.2%), dyslipidemia (25.4%), diabetes (24.2%), and coronary artery disease (15.4%). Patients with dementia had a lower prevalence of poorly controlled dyslipidemia ( P = 0.0006), diabetes ( P = 0.0089), and coronary artery disease ( P = 0.045). CONCLUSIONS: Compared with mood or psychotic disorder, a diagnosis of dementia with behavioral disturbance seemed to be associated with better control of coronary artery disease, dyslipidemia, and diabetes mellitus in geropsychiatric inpatients.

Self-Medicating for Pain: A Public Health Perspective.

BACKGROUND: Pain is one of the symptoms for which any man is willing not only to go to the doctor but also to resort to any means, including self-medication, to "get rid" of it. Self-medication is not only a current practice but also a public health problem, under the circumstances that it can influence the way in which a disease is diagnosed and/or treated in a timely manner, and, consequently, repercussions may occur on the cost of treatment, in the case of severe forms. Pain is a vital symptom, and the diminution until the disappearance of pain is a fundamental right of each individual; the analysis of ethical issues in the case of self-administration of analgesic medication has not been a major concern. AREAS OF UNCERTAINTY: Understanding the problem is important to realize whether self-medicating for pain is a necessity or an abuse, and in this respect, we review scientific articles from international databases: PubMed and ProQuest. DATA SOURCES: The study is based on the consultation of scientific articles from international databases-PubMed and ProQuest, the main keywords in the search being pain and self-medication, to which a stigma or public health is sequentially added. RESULTS: Pain is becoming more and more a global problem and the extent of its spread can substantiate our assertion about pathology with pandemic impact. Under the pressure of patient associations, of the media, and of nonmedical authorities, the opinion about the need for a stoic approach to pain has long become an outdated theory, and chronic pain, beyond a multidimensional approach, is increasingly considered not only a useless element but also even a destructive one. CONCLUSIONS: Pain and self-medication must be addressed, including in medical practice, starting from their multidimensionality from the following perspectives: medicobiological, sociocultural, instructive-educational, legal-political, and especially ethical. They are not only individual health problems but also become, when connected with a stigma, a public health problem.

Therapeutic Interventions for Adjustment Disorder: A Systematic Review.

BACKGROUND: Adjustment disorder requires therapeutic intervention because of its complications, which include a significant risk of suicide, but evidence-based therapeutic guidelines are not available. AREAS OF UNCERTAINTY: The main problem is related to answer to the following question: What is the optimal therapeutic approach to adjustment disorder? In this respect we review all randomized controlled trials that aimed to investigate therapeutic interventions for adjustment disorder in adult populations. DATA SOURCES: Comprehensive search of the electronic database PubMed (January 1980-June 2019). The review included clinical trials that aimed to investigate a psychological or pharmacological treatment for adjustment disorder in adult population and reported outcome data for therapeutic interventions. RESULTS: The search identified 23 studies that fulfilled the inclusion criteria for this review. Pharmacotherapy interventions were the focus of 11 studies that used various medications and dosages including viloxazine, lormetazepam, S-adenosylmethionine, pivagabine, trazodone, clorazepate, etifoxine, lorazepam, diazepam, afobazole, and plant extracts (Kava-kava, Euphytose, and Ginkgo biloba) on a total number of 1020 patients. Psychotherapy interventions were identified in 12 studies that used mirror therapy, short-term dynamic psychotherapy, yoga meditation, body-mind-spirit technique, mindfulness, bibliotherapy (self-help manual), humor training, and cognitive behavioral therapy. CONCLUSIONS: Psychotherapy seems indicated for mildly symptomatic adjustment disorder. Given the fact that adjustment disorder with severe symptoms is associated with a high risk of suicidal ideation and suicide attempts, clinicians must consider the potential benefit of using psychotropic agents such as benzodiazepines, antidepressants, or etifoxine.

Multiple Drug-Intolerant Hypertension.

CLINICAL FEATURES: The term multiple drug intolerance (MDI) is attributed to patients who experience adverse drug reactions to more than 3 different classes of medication without a known immunological mechanism. A special attention should be given to multiple drug-intolerant hypertension (MDI-HTN) that is a cause of drop out from treatment and consequent poor blood pressure control. Patients with MDIs account for 2%-5% of all population. The patient we present is a 63-year-old man with third-degree hypertension identified with intolerance to drugs from 4 major classes of antihypertensive medication. THERAPEUTIC CHALLENGE: Patients with MDIs are difficult to treat. They frequently also have numerous comorbidities and high cardiovascular risk. It is recognized that guidelines for the management of hypertension do not include an algorithm of action in situations of MDIs to medication. SOLUTION: We chose to use a recently proposed four-step algorithm for the management of MDI-HTN. A 1-month follow-up program was established. Weekly visits were scheduled to elicit about side effects and measure blood pressure . Ambulatory blood pressure monitoring was performed after a month. The strategy was first to reuse medication from classes the patient was intolerant to, but in smaller doses and in combinations. Among same class members, we have chosen those with less adverse effects. Not all steps within the algorithm were followed since our patient did not need alternative formulation as liquid or transdermal ones. Anxiety medication was prescribed as nonlicensed antihypertensive medication. At the end of the follow-up month, blood pressure control was satisfactory, 24-hour ambulatory blood pressure monitoring was 135.5/83.0 mm Hg, and the patient did not claim any adverse drug reactions.

Bioethical dilemmas in using animal in medical research. Challenges and opportunities.

PURPOSE: The study aims to present the main ethical dilemmas that research on animals raised for anyone involved in this process, starting from the idea that there are rights of animals to be known and respected. BACKGROUND: The evolution of medicine is inextricably linked to the production of new drugs, the occurrence of surgical techniques; none of these can be possible without the study of experimental animals, in vivo experimentation being part of the process of medical research. CONTENT: The article analyzes the main ethical dilemmas related to the use of animals in medical research, in the current legislative context and historical perspective of achieving such studies. DISCUSSION AND CONCLUSIONS: The use of animals in medical research must be conducted in accordance with clearly established moral rules, which facilitate reducing to the maximum the negative effects on the animals, avoiding unnecessary suffering to them and especially to facilitate progress achievement with the minimum possible animals sacrificed.