An Ethical Analysis Regarding the COVID-19 Pandemic Impact on Oral Healthcare in Patients with Mental Disorders.

During the COVID-19 pandemic, restrictive measures were imposed that significantly impacted the healthcare system in general, and the dental healthcare system in particular. The literature cites a possible association between mental and oral health, as psychiatric patients have decreased awareness of their oral health and, therefore, poor dental status. Moreover, several studies have found a positive association between SARS-CoV-2 infection and oral health conditions, as well as between SARS-CoV-2 infection and mental health status. This context generated multiple ethical dilemmas in the case of persons with mental health disorders who require dental treatment because they are more vulnerable in this respect. This article aims to analyze the ethical issues in dental care for patients with mental disorders concerning the COVID-19 restrictive measures. The ethical aspects involved here are the basic principles of bioethics and the related elements of accessibility, equity, consent, and confidentiality.

Dignity as a Central Issue in Treating Patients with Dementia Associated with COVID-19 Infection.

COVID-19 was initially considered a primary respiratory disorder associated with various short- and long-term complications, affecting many patients and imposing a significant burden. Patients who have dementia are especially vulnerable to the SARS-CoV2 infection, which is associated with an increased risk for neuropsychiatric complications. These patients need a unique approach to managing ethical issues related to the COVID-19 pandemic, including autonomy, veracity, non-maleficence, justice, compassion, and dignity. The latter is one of the most elusive and misunderstood concepts in medical ethics and is extremely important in debates surrounding the proper management of patients with dementia. However, it is often left out of ethical analysis, as most clinicians, when debating issues associated with clinical practice, often evaluate only the "classical" principles of biomedical ethics. In this article, we aim to assess the unique features of dignity in treating this group of patients during the COVID-19 pandemic. We will briefly analyze dignity as a bioethical concept. We will further explore its principal axes, namely compassion, creating a humane and purposeful environment, employing persuasion to meet the person's essential needs, exerting a certain degree of mild restraint to meet the person's critical needs, minimizing harm in terminal care, and justice, through the lens of people who had dementia during the COVID-19 pandemic. Applying this principle in clinical practice requires significant commitment from all healthcare workers. New approaches to the analysis of dignity, such as through the Ring Theory of Personhood, may facilitate its understanding by practitioners and aid its implementation in populations with multiple vulnerabilities, such as dementia patients, during an infectious outbreak that generates significant social and medical changes.

From Monastic Benevolence to Medical Beneficence: The Inception of Medical Ethics in Wallachia and Moldavia before the Second Half of the 19th Century.

In Middle Ages, in Moldavia and Wallachia, the healthcare system was almost non-existent, medical practice being the attribute of old women, midwives, charmers, and later monastic personnel. The first elements of medical ethics are identifiable in written texts from the 17th century, associated with a process of laicization of medicine and the appearance of the first combined civil and penal codes (Vasile Lupu's Law from 1646 and Matei Basarab's Law from 1652). In the next 150 years, elements of medical ethics were rarely identified, usually in legal regulations, personal letters, or literary works. Starting with the end of the 18th century, associated with the emergence of the position of public physician, detailed regulations regarding the healthcare system associated with an increased number of ethical norms began to emerge. The purpose of this article is to increase awareness to an international audience about the history of Romanian medical deontology and the roots of concepts appertaining to medical ethics in the territories of Moldavia and Wallachia.

Hereditary Hemorrhagic Telangiectasia Associating Neuropsychiatric Manifestations with a Significant Impact on Disease Management-Case Report and Literature Review.

(1) Background: Genetic hereditary hemorrhagic telangiectasia (HHT) is clinically diagnosed. The clinical manifestations and lack of curative therapeutic interventions may lead to mental illnesses, mainly from the depression-anxiety spectrum. (2) Methods: We report the case of a 69-year-old patient diagnosed with HHT and associated psychiatric disorders; a comprehensive literature review was performed based on relevant keywords. (3) Results: Curaçao diagnostic criteria based the HHT diagnosis in our patient case at 63 years old around the surgical interventions for a basal cell carcinoma, after multiple episodes of epistaxis beginning in childhood, but with a long symptom-free period between 20 and 45 years of age. The anxiety-depressive disorder associated with nosocomephobia resulted in a delayed diagnosis and low adherence to medical monitoring. A comprehensive literature review revealed the scarcity of publications analyzing the impact of psychiatric disorders linked to this rare condition, frequently associating behavioral disengagement as a coping strategy, psychological distress, anxiety, depression, and hopelessness. (4) Conclusions: As patients with HHT face traumatic experiences from disease-related causes as well as recurring emergency hospital visits, active monitoring for mental illnesses and psychological support should be considered as part of the initial medical approach and throughout the continuum of care.

COVID-19-related psychiatric manifestations requiring hospitalization: Analysis in older vs. younger patients.

The complex manifestations of COVID-19 include psychiatric symptoms, having multifaceted profiles with varying severity during the acute phase and further during the recovery period. Limited data exist which have analyzed whether there are any age-related differences. A study lot of 89 COVID-19 patients with mild-to-moderate SARS-CoV-2 infection requiring hospitalization for mental issues provided comparative data from two age groups below and above 60 years. The majority of patients had new onset of a mental issue during COVID-19, 24.7% of the total lot being diagnosed with depressive disorder. The senior patient set had a significantly higher prevalence of sleep disorder vs. the younger study group (53.3 vs. 28.8%), depression (33.3 vs. 10.2%) and cognitive impairment (26.7 vs. 8.5%), while patients <60 years of age had a higher prevalence of hallucinations, delirium and bizarre behavior. Psychiatric manifestations are an important part of the symptomatology of COVID-19, sometimes requiring hospitalization. Age-related neuropsychiatric substrate could explain some of these differences between the two study subgroups. Further data are needed to complete the acute and long-term distinctive profiles of COVID-19-related mental illness in older and younger patients.

Mouthwash Use and the Risk of Oral, Pharyngeal, and Laryngeal Cancer. A Meta-Analysis.

OBJECTIVE: The main aim of this study was to test whether the use of mouthwash is associated with subtypes of squamous cell carcinoma of the head and neck (SCCHN) and to test the potential risk of SCCHN depending on the mouthwash use duration, frequency, or alcoholic content. MATERIALS AND METHODS: We performed a meta-analysis using Web of Science and Scopus databases to detect the risk change associated with mouthwash use depending on the alcohol content, duration and frequency of use, and anatomical location. We used a random-effects model with the Sidik-Jonkman estimator for effect size model measures. RESULTS: We included 17 studies in the meta-analysis containing 17,085 cases and 20,032 controls. The risk difference for SCCHN between mouthwash users and non-users was minimal, with a value of -0.02 [-0.05, 0.01]. Alcoholic mouthwash use was associated with a minimal decrease in risk (of -0.01 [-0.07, 0.05]). Frequent usage of mouthwash was associated with a statistically significant risk increase for SCCHN but the risk increase was marginal (0.04, [0.01, 0.06]). CONCLUSIONS: Overall, our study failed to show a statistically significant correlation between mouthwash use and the risk of SCCHN. The only statistically significant correlation that we could identify was between frequent usage and SCCHN, potentially caused by prolonged contact between some constituents of mouthwash (possibly alcohol) and the oral epithelium.

Age in the Time of COVID-19: An Ethical Analysis.

Despite using a myriad of methods to combat the spread of COVID-19, the healthcare systems (especially the intensive care units) have been overwhelmed, showing an outpaced capacity of available beds and ventilators. Choosing the right criteria to allocate the scarce ICU seems very challenging, being necessary a rapid, uncomplicated and universally accepted tool for patients' triage regarding access to lifesaving resources; one such criterion, which generates intense debates, is age. Under certain circumstances, it might seem appropriate to choose to treat a young over an old patient. The main advantage of this approach is the potential for long-term survival, implying an equal right to reach an advanced age. Many authors have given moral reasons to support it, mainly based on utilitarian ethics or on distributive justice. However, there are numerous counterarguments to this approach, which we will summarize in this article. We will show that age should never be used as a unique criterion for withholding/not initiating life-saving procedures, even in pandemics or cases in which healthcare resources are extremely scarce. This approach is based on fundamental Codes of Ethics, such as the WMA Code of Ethics or the Oath of Hippocrates and all physicians treating patients should obey them.

The moral status of cerebral organoids.

Organoids are 3D biological structures constructed from stem cells in vitro. They partially mimic the function of real organs. Although the number of articles detailing this technology has increased in recent years, papers debating their ethical issues are few. In addition, many of such articles outline a mere summary of potential ethical concerns associated with organoids, although some have focused on consciousness assessment or organoid use in cystic fibrosis treatment. This article seeks to evaluate the moral status of cerebral organoids and to determine under which conditions their use should be allowed from a bioethical standpoint. We will present an overview of recent steps in developing highly advanced cerebral organoids, followed by an analysis of their ethics based on three factors: human origin, a specific biological threshold (which, once crossed, grants an entity moral status), and the potential to generate human beings. We will also make practical recommendations for researchers working in this biological field.

Corrigendum: The Association of Unfavorable Traffic Events and Cannabis Usage: A Meta-Analysis.

[This corrects the article on p. 99 in vol. 9, PMID: 29487531.].

Cardiac telocytes. From basic science to cardiac diseases. I. Atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is nowadays considered to be one of the most important causes of heart failure, stroke, cognitive decline, vascular dementia, sudden death and overall cardiovascular morbidity. Recently were published a few articles suggesting a possible involvement of telocytes in the development of atrial fibrillation. The purpose of this article is to analyze the results obtained in the field systematically, and to see if there is enough data to support a possible involvement of telocytes in arrhythmogenesis. MATERIALS AND METHODS: To this end, we performed a systematic review of the relevant scientific literature, indexed in PubMed, Web of Science, and Scopus. RESULTS AND DISCUSSIONS: Our systematic review of the published data identified five articles containing original data, based on which the association between telocytes and atrial fibrillation was inferred in later studies. We analyzed the usefulness of the information contained in the original articles to support this association, showing a lack of definite proofs correlating telocytes with atrial fibrillation. CONCLUSIONS: Even if a few articles implied a potential association between AF and telocytes, the current data is not enough to support it. Moreover, even an association between the morphology, characteristics, or density of the telocytes in the atrium/pulmonary veins and AF is potentially speculative, and more studies should be performed before implying it with a reasonable degree of certainty.

The Association of Unfavorable Traffic Events and Cannabis Usage: A Meta-Analysis.

Background: In the last years were published many epidemiological articles aiming to link driving under the influence of cannabis (DUIC) with the risk of various unfavorable traffic events (UTEs), with sometimes contradictory results. Aim: The primary objective of this study was to analyze whether there is a significant association between DUIC and UTEs. Materials and Methods: We used two meta-analytical methods to assess the statistical significance of the effect size: random-effects model and inverse variance heterogeneity model. Results: Twenty-four studies were included in the meta-analysis. We obtained significant increases in the effect size for DUIC tested through blood analysis, with an odds ratio (OR) of 1.97 and a confidence interval (CI) between 1.35 and 2.87; [corrected] death as an outcome, with an OR of 1.56 and a CI between 1.16 and 2.09; and case-control as the type of study, with an OR of 1.99 and a CI between 1.05 and 3.80. Publication bias was very high. Conclusion: Our analysis suggests that the overall effect size for DUIC on UTEs is not statistically significant, but there are significant differences obtained through subgroup analysis. This result might be caused by either methodological flaws (which are often encountered in articles on this topic), the indiscriminate employment of the term "cannabis use," or an actual absence of an adverse effect. When a driver is found, in traffic, with a positive reaction suggesting cannabis use, the result should be corroborated by either objective data regarding marijuana usage (like blood analyses, with clear cut-off values), or a clinical assessment of the impairment, before establishing his/her fitness to drive.

Testing decision-making competency of schizophrenia participants in clinical trials. A meta-analysis and meta-regression.

BACKGROUND: The process of assessing the decision-making capacity of potential subjects before their inclusion in clinical trials is a legal requirement and a moral obligation, as it is essential for respecting their autonomy. This issue is especially important in psychiatry patients (such as those diagnosed with schizophrenia). The primary purpose of this article was to evaluate the degree of impairment in each dimension of decision-making capacity in schizophrenia patients compared to non-mentally-ill controls, as quantified by the (MacCAT-CR) instrument. Secondary objectives were (1) to see whether enhanced consent forms are associated with a significant increase in decision-making capacity in schizophrenia patients, and (2) if decision-making capacity in schizophrenia subjects is dependent on the age, gender, or the inpatient status of the subjects. METHODS: We systematically reviewed the results obtained from three databases: ISI Web of Science, Pubmed, Scopus. Each database was scrutinised using the following keywords: "MacCAT-CR + schizophrenia", "decision-making capacity + schizophrenia", and "informed consent + schizophrenia." RESULTS: We included 13 studies in the analysis. The effect size between the schizophrenia and the control group was significant, with a difference in means of -4.43 (-5.76; -3.1, p < 0.001) for understanding, -1.17 (-1.49, -0.84, p < 0.001) for appreciation, -1.29 (-1.79, -0.79, p < 0.001) for reasoning, and -0.05 (-0.9, -0.01, p = 0.022) for expressing a choice. CONCLUSIONS: Even if schizophrenia patients have a significantly decreased decision-making capacity compared to non-mentally-ill controls, they should be considered as competent unless very severe changes are identifiable during clinical examination. Enhanced informed consent forms decrease the differences between schizophrenia patients and non-mentally-ill controls (except for the reasoning dimension) and should be used whenever the investigators want to include more ill patients in their clinical trials. Increased age, men gender and an increased percentage of inpatients might increase the differential of decision-making incompetence compared to non-mentally-ill subjects in various dimensions of the decision-making competence as analysed by the MacCAT-CR scale, but the small number of subjects did not allow us (except for one instance) to reach statistical significance.

GSK-3 Inhibitors and Tooth Repair: An Ethical Analysis.

Tideglusib®, a GSK-3 inhibitor, was initially tested for the treatment of Alzheimer's disease. However, a recent report has suggested its potential off-label use for the treatment of dental cavities. Even if this effect is not yet confirmed, this off-label use can have significant public/dental health consequences, mainly because of the large number of patients with cavities. The purpose of this mini-review is to perform an ethical analysis of the use of Tideglusib in dentistry. The ethical analysis identified three main areas in which ethical breaches could be significant: 1) respect for the autonomy of the patient, 2) issues raised by horizontal shifts in the translational research process, and 3) the conflict between dental beneficence and general non-maleficence. In conclusion, the use of Tideglusib in dentistry should respect the same strict ethical and regulatory criteria from clinical medicine. A translation of the potential risks should be done only after large-scale, phase-III/IV clinical trials, explicitly designed to test the usefulness of this drug in dental medicine.

Placebo in Surgical Research: A Case-Based Ethical Analysis and Practical Consequences.

Placebo is a form of simulated medical treatment intended to deceive the patient/subject who believes that he/she received an active therapy. In clinical medicine, the use of placebo is allowed in particular circumstances to assure a patient that he is taken care of and that he/she receives an active drug, even if this is not the case. In clinical research placebo is widely used, as it allows a baseline comparison for the active intervention. If the use of placebo is highly regulated in pharmacological trials, surgery studies have a series of particularities that make its use extremely problematic and regarded less favorably. The purpose of this paper is to present three famous cases of placebo use in surgical trials and to perform an ethical analysis of their acceptability using the Declaration of Helsinki as a main regulatory source.

Shake the Disease. Georges Marinesco, Paul Blocq and the Pathogenesis of Parkinsonism, 1893.

James Parkinson, in his "Essay on the Shaking Palsy" from 1817 described for the first time the disease that later on carried his name. Its anatomical substrate remained controversial for over 100 years. The first case that suggested the association between Parkinson's disease and substantia nigra was published in 1893 Blocq and Marinesco, two scientists who worked at Salpêtrière. The article described a 38 years-old man, with tuberculosis, who was admitted to the Charcot's neurological ward because he also showed signs of unilateral Parkinsonism. During the autopsy, the investigators found a tubercle that destroyed the right substantia nigra. As the patient had overactive reflexes on the left side and the symptomatology matched exactly the localization of the tumor, Blocq and Marinesco suggested the Parkinsonism to be more likely a complication of tuberculosis and not an incidental finding. In this article, we will discuss the contribution of these two authors to the elucidation of the pathology of Parkinson's disease, and highlight how even a single case report may play an essential role in the development of knowledge in biomedical sciences.

Cognitive impairment in manic bipolar patients: important, understated, significant aspects.

BACKGROUND: Bipolar disorder is a chronic mood disorder with episodic progress and high relapse rate. Growing evidence suggests that individuals with bipolar disorder display cognitive impairment which persists even throughout periods of symptom's remission. METHOD: 137 bipolar patients met the inclusion criteria (depressive episode: DSM-IV-TR criteria for major depressive episode, HAMD score ≥17; manic/hypomanic episode: DSM-IV-TR criteria for manic/hypomanic episode, YMRS score ≥12, euthymic: 6 months of remission, HAMD score ≤8, YMRS score ≤6; and mixed: DSM-IV-TR criteria for mixed episode, HAMD score >8 and YMRS score >6) and were therefore enrolled in the study. Patients were free of psychotic symptoms (hallucinations/delusions) at the moment of testing. Control group consisted of 62 healthy subjects without history of neurological and/or psychiatric disorder. Cognitive battery has been applied in order to assess verbal memory, working memory, psychomotor speed, verbal fluency, attention and speed of information processing, and executive function. Following data were collected: demographics, psychiatric history, age of illness onset; current and previous treatment (including hospitalizations). Cognitive deficits were assessed in bipolar patients experiencing manic, depressive, mixed episodes or who were euthymic in mood. Results were compared between the subgroups and with healthy individuals. The association of impaired cognition with illness course was analyzed. RESULTS: Bipolar patients showed cognitive deficits in all evaluated domains when compared to controls. The lowest scores were obtained for the verbal fluency test. After adjusting for current episode, manic subgroup showed greater cognitive impairment in verbal and working memory, executive function/reasoning and problem solving, compared to depressive, mixed, and euthymic subgroup. Low-neurocognitive performance was directly associated with a predominance of manic episodes and severe course of bipolar illness. An increased number of past manic episodes was the strongest correlated event with the poorest outcomes in verbal memory testing. Other factors correlated with poor verbal memory scores in manic subgroup were age at illness onset (positive correlation), illness length, and hospitalizations (negative correlations). CONCLUSIONS: Bipolar patients showed cognitive deficits regardless of the phase of illness. Subjects experiencing a manic episode displayed higher deficits in verbal and working memory, executive function/reasoning, and problem solving. Severe course of illness also showed significant contribution in terms of cognitive impairment.