Anti-vascular endothelial growth factor therapy has revolutionised the treatment of a variety of ophthalmic conditions and has become the first-line therapy for a range of retinal diseases. Bevacizumab, a VEGF inhibitor first approved for the treatment of colorectal cancer, has been shown to be nearly or virtually as effective and safe as other anti-VEGF therapies in the treatment of certain retinal diseases but is not approved or registered by the Food and Drug Administration or European Medicines (...) Agency. While other anti-VEGF options are approved and registered, they are generally more expensive and less accessible. Accordingly, despite its off-label status, bevacizumab is frequently used for a variety of disabling retinal diseases. Indeed, bevacizumab is included on the World Health Organization’s list of essential medicines. However, its use in some parts of the world remains restricted due to its off-label status. How, then, should healthcare authorities approach this situation? What are the ethical and societal implications of adhering to a standard and generally effective evaluation and approval system while restricting access to a potentially cost-saving therapy? In countries where its use is not restricted, how should providers approach off-label treatment with bevacizumab? By examining the evidence behind bevacizumab’s efficacy and safety and evaluating the individual and societal implications of off-label use and restriction, this paper illustrates the ethical factors providers and policy makers must consider in the off-label use of bevacizumab and ultimately argues for increased access to bevacizumab in the treatment of retinal disease. (shrink)

The present review highlights an association between autism, Alzheimer disease , and fragile X syndrome . We propose a conceptual framework involving the amyloid-beta peptide , Abeta precursor protein , and fragile X mental retardation protein based on experimental evidence. The anabolic effect of the secreted alpha form of the amyloid-beta precursor protein may contribute to the state of brain overgrowth implicated in autism and FXS. Our previous report demonstrated that higher plasma sAPPalpha levels associate with more severe symptoms (...) of autism, including aggression. This molecular effect could contribute to intellectual disability due to repression of cell-cell adhesion, promotion of dense, long, thin dendritic spines, and the potential for disorganized brain structure as a result of disrupted neurogenesis and migration. At the molecular level, APP and FMRP are linked via the metabotropic glutamate receptor 5 . Specifically, mGluR5 activation releases FMRP repression of APP mRNA translation and stimulates sAPP secretion. The relatively lower sAPPalpha level in AD may contribute to AD symptoms that significantly contrast with those of FXS and autism. Low sAPPalpha and production of insoluble Abeta would favor a degenerative process, with the brain atrophy seen in AD. Treatment with mGluR antagonists may help repress APP mRNA translation and reduce secretion of sAPP in FXS and perhaps autism. (shrink)

This chapter contains sections titled: Is There a Right to Health Care? What Does a Right to Health Care Include? Choice or Consent and the Exercise of our Right to Health Care References.

In lieu of an abstract, here is a brief excerpt of the content:The Road to Understanding and Acceptance of the Late Effects of Pediatric Brain Tumors and TreatmentJeanne CarlsonWe had little warning or time to adjust to our daughter’s diagnosis. A call from her third grade teacher reporting that Sarah seemed to be having vision problems rapidly led to eye exams, an MRI, and the discovery of a Germinoma brain tumor in the suprastellar region of Sarah’s brain. We were terrified (...) but began treatment feeling optimistic about the outlook for Sarah’s recovery. Luckily, Sarah’s treatment was relatively non–invasive and quick, chemotherapy and radiation, five months start to finish. We were thrilled to have Sarah’s treatment behind us.As any parent of a child with a life–threatening illness knows, family life is seriously disrupted by the countless doctor, lab, and hospital visits, the worry, and the financial strain that are suddenly added to the demands of everyday life. We did our best to balance our focus on both of our children as Sarah is a twin and we didn’t want her brother Will to suffer as a result of his sister’s illness. It wasn’t easy but we found a way to schedule Will’s usual play dates, baseball practice, and family time. We were all happy and relieved when Sarah’s treatment was completed, yet we would later learn that we had been incredibly naïve in two ways; we thought that our brain tumor journey was over after Sarah’s treatment was completed and we thought that we’d brought Will through the process without effect. We had a lot to learn.At the time of diagnosis we knew that Sarah’s memory and ability to express emotion had already been impacted by the tumor but we didn’t yet know what that would mean to her quality of life. We were virtually unaware however that at age nine the chemotherapy and radiation treatments that Sarah received would result in profound late effects. Following treatment Sarah successfully completed 3rd grade and even received excellent STAR test scores (California state standardized tests). In 4th grade however, Sarah’s performance began to diverge from that of her peers and she found herself struggling in school and unable to make friends. We began looking for ways to help our daughter.What followed was a five year long journey through testing, evaluations, individualized education plans (IEPs), and therapies, which, in the end, left our family needing to accept the fact that although Sarah remains intelligent and artistically talented, she suffers from a constellation of late effects that will always affect her ability to function in the world. As a result of Sarah’s tumor and treatment she struggles with Auditory Processing Disorder, word finding problems, poor executive function, inability to recognize how she feels, significant difficulty making decisions, inability to read social cues, poor memory, slow processing, an emotional age of about nine, and lots of anxiety. She is also panhypopituitary, meaning that she has no remaining pituitary function and must take replacement medications by pill and injection, has hypothalamic obesity (HO), which is primarily controlled by more medication, and Raynaud’s Disease. The HO is an ongoing challenge because if Sarah does gain weight she can’t lose it again and exercise is not an easy solution because, like many pediatric brain tumor survivors, Sarah is easily fatigued. Finally, although Sarah’s vision improved after treatment her vision loss is significant enough to prevent her from driving. We pieced together this understanding of Sarah’s challenges and disabilities slowly so it wasn’t until the end of our children’s middle school years that we finally accepted the magnitude of the damage caused by the tumor and treatment. Thereafter we changed our focus from what Sarah might achieve in life to how to support [End Page 21] her in the activities at which she still excels and how to keep her active, interested in life, and feeling good about herself.It would have been a huge gift if we had been provided with information about the possible late effects that can result from treating the brain of a 9–year–old... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Autonomy, Well-Being, Disease, and DisabilityJulian Savulescu (bio)Keywordsautonomy, well-being, mental disorder, psychiatric disease, disability, welfare, body integrity identity disorderVarelius seeks to redefine what constitutes mental disorder or mental illness. (I use these terms interchangeably.) "According to this account, 'a person is mentally disordered when her psychological capacity for autonomy is diminished as compared with that of a typical member of our species of her age-group" (Varelius 2009). (...) This is a stimulating and important paper. Varelius describes fruitfully the relationship between mental illness and autonomy, specifically the ways in which mental disorder can undermine autonomy. This is valuable in understanding the impact of mental illness on the lives of people who suffer from it, which is a serious issue in practical ethics. But is it what constitutes mental disorder or illness? There are logical, conceptual reasons why we should not redefine mental illness in this way.Incomplete Account of Mental DisorderThere are a family of related concepts: disease, injury, disorder, illness, disability. There are old and entrenched disputes about how we should define these concepts. Varelius' paper is a contribution to the definition of mental disorder and illness.The primary classificatory category that defines medical practice is that of health and disease. Disease, broadly construed, involves the presence of pathology. Pathology can result from processes primarily or predominantly internal to the organism, such as genetic disease (although external factors affect their expression), or from processes primarily or predominantly external to the organism, such as injuries.The concepts of disorder and illness relate to the concept of disease. Disorder could be defined in terms of the functional effect of pathology. Illness could be defined in terms of the experiential impact of disease.1 How these terms are precisely defined and related need not concern us at the present. What matters is that the primary category is disease.Psychiatry has evolved in its use of terminology. What used to be called psychiatric diseases are now often called mental disorders. I now claim, for the purposes of illustration of the argument (though it does not require this claim), that the dominant category is disease. Indeed, what are called mental disorders appear in the International Classification of Diseases.Disease can be divided into the mental and physical. I believe that the mental will one day be [End Page 59] shown to be shown to be entirely a subset of the physical. That is, that brain pathology will be a cause, if not the only cause, of mental disease. But others may believe the sets of mental and physical disease are intersecting but not coextensive.What matters is that mental disease is a subcategory of the more general category of disease. It must have the same definitional features as "disease" plus some extra ones specific to the "mental," or mind. (The same points apply if you use "disorder" as the dominant category rather than "disease.")One problem for Varelius is this: how does this autonomy account of "mental disease" relate to an account of "physical disease," and "disease" in general? If mental disease is defined in terms of its impact on the psychological capacities necessary for autonomy, how is "disease" in general, or physical disease, to be defined? One obvious response is to define these related concepts in a similar way:Disease: "a person is diseased when her capacity for autonomy is diminished as compared to that of a typical member of our species of her age-group." Physical disease: "a person is physically disordered when her physical capacity for autonomy is diminished as compared to that of a typical member of our species of her age-group."This interpretation is suggested by the following passage from Varelius:As contrasted with the actual condition of being autonomous, as a capacity of an individual autonomy means that a person has the psychological and bodily abilities that being autonomous... requires.(2009)It would be radical to define disease in general in terms of capacity for autonomy. There is no doubt that disease affects our autonomy, and that is morally significant, but these seem clearly separable concepts. Varelius could respond that he is not defining mental disease but rather the mental component... (shrink)

Definitions of health and disease are of more than theoretical interest. Understanding what it means to be healthy has implications for choices in medical treatment, for ethically sound informed consent, and for accurate assessment of policies or programs. This deeper understanding can help us create more effective public policy for health and medicine. It is notable that such contentious legal initiatives as the Americans with Disability Act and the Patients' Bill of Rights fail to define adequately (...) the medical terms on which their effectiveness depends. In Ethics and the Metaphysics of Medicine, Kenneth Richman develops an "embedded instrumentalist" theory of health and applies it to practical problems in health care and medicine, addressing topics that range from the philosophy of science to knee surgery."Embedded instrumentalist" theories hold that health is a match between one's goals and one's ability to reach those goals, and that the relevant goals may vary from individual to individual. This captures the normative implications of the term health while avoiding problematic relativism. Richman's embedded instrumentalism differs from other theories of health in drawing a distinction between the health of individuals as biological organisms and the health of individuals as moral agents. This distinction illuminates many difficulties in patient-provider communication and helps us understand conflicts between promoting health and promoting ethically permissible behavior. After exploring, expanding, and defending this theory in the first part of the book, Richman examines its ethical implications, discussing such concerns as the connection between medical beneficence and respect for autonomy, patient-provider communication, living wills, and clinical education. (shrink)

The issue of wrongful disability arises when parents face the choice whether to produce a child whose life will be unavoidably flawed by a serious disease or disorder (Down syndrome, for example, or Huntington’s disease) yet clearly worth living. The authors of From Chance to Choice claim, with certain restrictions, that the choice to produce such a child is morally wrong. They then argue that an intuitive moral approach––a “person-affecting” approach that pins wrongdoing to the harming of (...) some existing or future person––cannot account for that wrong since the choice to produce such a child cannot, under the logic of the nonidentity problem, harm that child. The authors propose that we supplement the person-affecting approach with an “impersonal” principle that takes the form of their well-known principle N. In this paper, I argue that the authors are mistaken to suppose that a plausibly articulated person-affecting approach cannot account for the wrong of wrongful disability. We can retain an intuitive, comparative, “worse for” account of harm and still identify serious harms imposed by the choice of wrongful disability. In particular, I argue that harm, both to the impaired child and to others, comes not in the form of that procreative choice’s procreative effect but rather in the form of its many distributive effects. I also argue that the rare, residual case in which a person-affecting approach would approve of the choice of wrongful disability does not function as a counterexample to that approach. As a separate matter, I address legal claims for wrongful disability, which are closely akin to claims for wrongful life. The legal claim is brought by the impaired child, not against the parents, but rather against health care providers whose negligent failure to diagnose or inform parents of an increased risk of a genetic or congenital impairment results in the birth of the impaired child. The authors’ treatment of the moral wrong that is done as impersonal in nature suggests that courts are correct to dismiss any such claim. Once we identify harm, however, the person-affecting approach can identify a clear foundation in the law for the wrongful disability claim. (shrink)

The success of deep brain stimulation (DBS) for movement disorders and the improved understanding of the neurobiologic and neuroanatomic bases of psychiatric diseases have led to proposals to expand current DBS applications. Recent preclinical and clinical work with Alzheimer's disease and obsessive-compulsive disorder, for example, supports the safety of stimulating regions in the hypothalamus and nucleus accumbens in humans. These regions are known to be involved in addiction and overeating associated with obesity. However, the use of DBS targeting these (...) areas as a treatment modality raises common ethical considerations, which include informed consent, coercion, enhancement, threat to personhood, and manipulation of the reward center. Pilot studies for both of these conditions are currently investigational. If these studies show promise, then there is a need to address the ethical concerns related to the initiation of clinical trials including the reliability of preclinical evidence, patient selection, study design, compensation for participation and injury, cost-effectiveness, and the need for long-term follow-up. Multidisciplinary teams are necessary for the ethical execution of such studies. In addition to establishing safety and efficacy, the consideration of these ethical issues is vital to the adoption of DBS as a treatment for these conditions. We offer suggestions about the pursuit of future clinical trials of DBS for the treatment of addiction and overeating associated with obesity and provide a framework for addressing ethical concerns related to treatment. (shrink)

Introduction Hundreds of thousands of premature neonates born in low-income countries are implicitly denied treatment each year. Studies from India show that treatment is rationed even for neonates born at 32 gestational age weeks (GAW), and multiple external factors influence treatment decisions. Is withholding of life-saving treatment for children born between 28 and 32 GAW acceptable from an ethical perspective? Method A seven-step impartial ethical analysis, including outcome analysis of four accepted priority criteria: severity of (...) class='Hi'>disease, treatment effect, cost effectiveness and evidence for neonates born at 28 and 32 GAW. Results The ethical analysis sketches out two possibilities: (a) It is not ethically permissible to limit treatment to neonates below 32 GAW when assigning high weight to health maximisation and overall health equality. Neonates below 32 GAW score high on severity of disease and efficiency and cost-effectiveness of treatment if one gives full weight to early years of a newborn life. It is in the child's best interest to be treated. (b) It can be considered ethically permissible if high weight is assigned to reducing inequality of welfare and maximising overall welfare and/or not granting full weight to early years of newborns is considered acceptable. From an equity-motivated health and welfare perspective, we would not accept (b), as it relies on accepting the lack of proper welfare policies for the poor and disabled in India. Conclusion Explicit priority processes in India for financing neonatal care are needed. If premature neonates are perceived as worth less than other patient groups, the reasons should be explored among a broad range of stakeholders. (shrink)

This chapter argues that standard accounts of health are ill-suited to constructing a plausible theory of health justice, particularly a sufficientarian theory. The problem in these accounts is revealed by their treatment of disability. Theorists of health justice need to define “health” more narrowly to capture the legitimate claims of people with disabilities. Following Ronald Amundson and Peter Hucklenbroich, this chapter proposes such a definition. Health, as defined in this chapter, is the absence of conditions that directly cause, (...) or threaten to directly cause, certain kinds of bodily harm, such as pain and premature death. It is concluded that on a plausible sufficientarian theory of health justice, a society that achieves health justice is one that ensures that none of its members face too much of those kinds of bodily harm. (shrink)

Chronic migraine is a difficult disease to diagnose, and its pathophysiology remains undefined. Its symptoms affect the quality of life and daily living tasks of the affected person, leading to momentary disability. This is a pilot, randomized, controlled, double-blind clinical trial study with female patients between 18 and 65 years old with chronic migraine. The patients underwent twelve mindfulness sessions paired with anodal transcranial direct-current stimulation over the left dorsolateral prefrontal cortex, with current intensity of 2 mA applied (...) for 20 min, three times a week for 4 weeks. In addition, 20 min of mindfulness home practices were performed by guided meditation audio files. A total of 30 participants were evaluated after the treatment, and these were subdivided into two groups—active tDCS and sham tDCS, both set to mindfulness practice. The FFMQ-BR, MIDAS, and HIT-6 questionnaires were used to evaluate the outcomes. After the treatment, the active mindfulness and tDCS group showed better results in all outcomes. The sham group also showed improvements, but with smaller effect sizes compared to the active group. The only significant difference in the intergroup analysis was the outcome evaluated by HIT-6 in the post treatment result. Our results provide the first therapeutic evidence of mindfulness practices associated with left DLPFC anodal tDCS with a consequent increase in the level of full attention and analgesic benefits in the clinical symptoms of patients with chronic migraine. (shrink)

Providing care for a baby born at 24 weeks of gestation in a neonatal intensive care unit is one of the most expensive medical treatments in the United States today. The cost can easily run over $300,000 for one baby. Furthermore, many extremely premature babies who survive are left with chronic diseases or disabilities that require further medical expenses and other specialized services throughout childhood or throughout life. When all these expenditures are totaled up, it can seem that neonatal intensive (...) care is just not worth it.Concerns about the cost-effectiveness of NICUs have led to persistent critical scrutiny of these specialized units by physicians, economists, and epidemiologists. These analysts have examined NICUs and the patients in them in order to determine whether there are subpopulations of babies for whom neonatal intensive care is so demonstrably ineffective or so costly that it should not be provided. Such examinations have been carried out in many different countries, at many times over the last 30 years, and have analyzed outcomes for babies by gestational age, birthweight, and illness severity. (shrink)

Belief in destiny is one of the principles of faith. Although the belief in fate is not explicitly mentioned in the Qur’an, there are many verses that indicate this belief. There are many hadiths about fate that have reached us from the Prophet. Although there are schools that deny destiny, Ahl al-Sunnah schools Ash‘aris and Maturidis accept the existence of belief in destiny. The definitions of destiny of these schools are expressed with words that can be used interchangeably. However, fate (...) should not be evaluated in a single category. It also has varieties. If destiny is perceived as only one kind of Forced destiny, it is inevitable to cause misunderstandings. Forced fate; it is destiny that does not give freedom to beings; It happens with the knowledge, will, power and creation of Allah. Some destinies of inanimate substances, plants, animals and humans are of this type. Jabr and responsibility are incompatible. Although some actions take place in their own bodies, people are not responsible for their forced destiny. Man is a freely created being within certain limits. The ability of intellect, will, power, and carrying out actions has been granted to them. By using them, a person performs his acts of will, and as a result, he becomes responsible for his actions. Having free will and freedom distinguishes humans from other living things. Where there is no human freedom, there is no responsibility. Human life is not uniform, it is in a state of constant change and transformation. In addition to these two types of fate, there is also a type of fate that turns into willful fate, although it was forced in the beginning. In addition to this, there are some actions that start with the will of man and later turn into forced fate. There are also types of disability that we have examined in connection with the belief in destiny and its types. Allah has sent humans to the world to be tested. Illness and disability are also part of the test. Diseases; they may be due to genetic, environmental factors, and food-related. Congenital diseases and disabilities can sometimes cause the world test to be difficult. The biological rules set by Allah are also valid for humans. Genetic hereditary diseases and disabilities occur when the genes carried by the parents are passed on to the child. While some genes are recessive, some genes are dominant. Genes that cause hereditary diseases and disabilities show an uneven distribution depending on their geographical habitats, sharing the same environment in the historical process, and the extent of intermingling of their lineages through marriages. While recessive genes can be passed on from generation to generation, dominant genes that cause death generally do not have the opportunity to pass on to the next generation. In today’s context, the diagnosis of genetic diseases and disabilities is attainable, enabling the implementation of necessary precautions accordingly; furthermore, partial or even complete treatment opportunities can be available depending on the circumstances. In this respect, all of the congenital diseases and disabilities due to genes are a forced fate that is not in the hands of man. As for those diseases and disabilities for which treatment opportunities exist, they fall under the category of fate that transitions from forced fate to willful destiny. Some genetic diseases and disabilities of people may appear in later ages. However, non-genetic diseases and disabilities are also facts of life. Every individual can become ill and experience disability during certain periods of their life. Diseases and disabilities can occur with a number of factors that do not depend on an individual's will, actions, or behaviors. Such diseases are also within the scope of forced fate. A person can also be disabled due to one’s own mistakes and negligence. However, it is a behavior befitting a Muslim to be treated in cases of all kinds of diseases and disabilities. The treatment of diseases for which there is a cure is a willed destiny. Diseases and obstacles that cannot be cured are forced fate. (shrink)

Tremor of the upper extremity is a significant cause of disability in some patients with multiple sclerosis. The MS tremor is complex because it contains an ataxic intentional tremor component due to the involvement of the cerebellum and cerebellar outflow pathways by MS plaques, which makes the MS tremor, in general, less responsive to medications or deep brain stimulation than those associated with essential tremor or Parkinson's disease. The cerebellar component has been thought to be the main reason (...) for making DBS less effective, although it is not clear whether it is due to the lack of suppression of the ataxic tremor by DBS or else. The goal of this study was to clarify the effect of DBS on cerebellar tremor compared to non-cerebellar tremor in a patient with MS. By wearing an accelerometer on the index finger of each hand, we were able to quantitatively characterize kinetic tremor by frequency and amplitude, with cerebellar ataxia component on one hand and that without cerebellar component on the other hand, at the beginning and end of the hand movement approaching a target at DBS Off and On status. We found that cerebellar tremor surprisingly had as good a response to DBS as the tremor without a cerebellar component, but the function control on cerebellar tremor was not as good due to its distal oscillation, which made the amplitude of tremor increasingly greater as it approached the target. This explains why cerebellar tremor or MS tremor with cerebellar component has a poor functional transformation even with a good percentage of tremor control. This case study provides a better understanding of the effect of DBS on cerebellar tremor and MS tremor by using a wearable device, which could help future studies improve patient selection and outcome prediction for DBS treatment of this disabling tremor. (shrink)

With the development of artificial intelligence technologies, it is possible to use computer to read digital medical images. Because Alzheimer’s disease has the characteristics of high incidence and high disability, it has attracted the attention of many scholars, and its diagnosis and treatment have gradually become a hot topic. In this paper, a multimodal diagnosis method for AD based on three-dimensional shufflenet and principal component analysis network is proposed. First, the data on structural magnetic resonance imaging and (...) functional magnetic resonance imaging are preprocessed to remove the influence resulting from the differences in image size and shape of different individuals, head movement, noise, and so on. Then, the original two-dimensional ShuffleNet is developed three-dimensional, which is more suitable for 3D sMRI data to extract the features. In addition, the PCANet network is applied to the brain function connection analysis, and the features on fMRI data are obtained. Next, kernel canonical correlation analysis is used to fuse the features coming from sMRI and fMRI, respectively. Finally, a good classification effect is obtained through the support vector machines method classifier, which proves the feasibility and effectiveness of the proposed method. (shrink)

It is widely recognized that prioritizing health care resources by their relative cost-effectiveness can result in lower priority for the treatment of disabled persons than otherwise similar non-disabled persons. I distinguish six different ways in which this discrimination against the disabled can occur. I then spell out and evaluate the following moral objections to this discrimination, most of which capture an aspect of its unethical character: it implies that disabled persons' lives are of lesser value than those of non-disabled (...) persons; it constitutes “double jeopardy” or violates Frances Kamm's non-linkage principle; it conflicts with equality of opportunity; it conflicts with fairness, which requires ignoring (some/most) differential impacts of treatment; it wrongly gives lower priority to disabled persons for equally effective treatment; it conflicts with giving all persons an equal chance to reach their full potential; and, it is in conflict with giving priority to the worse off. (shrink)

Schooling fish, swarms of starlings, plodding wildebeest, and musicians all display impressive synchronization. To what extent do they use acoustic cues to achieve these feats? Could the acoustic cues used in movement synchronization be relevant to the treatment of movement disorders such as Parkinson's disease in humans? In this article, we build on the emerging view in evolutionary biology that the ability to synchronize movement evolved long before language, in part due to acoustic advantages. We use this insight (...) to explore potential mechanisms that explain why music therapy has beneficial effects for PD patients. We hypothesize that rhythmic auditory cues, particularly music, can stimulate neuronal and behavioral processes that ease the symptoms and potentially the causes of PD because the neural circuits used in auditory entrainment at individual and group levels are associated with dopamine production. We summarize current treatment of PD and outline how new insights from an evolutionary perspective could improve understanding and eventual treatment of movement disorders in humans. (shrink)

The effective provision of psychotherapy services to individuals with intellectual disability requires consideration of ethical issues related to clinical competence, access to services, obligations to multiple parties, guardianship, and appropriate assessment practices. This article provides an overview of major ethical considerations with guidance for clarifying and resolving common ethical concerns. Psychologists are encouraged to expand access to psychotherapy services for this population while maintaining awareness of potential modifications, training needs, and boundaries of professional competence. The authors provide recommendations (...) and resources for effective and ethical treatment of psychotherapy clients with intellectual disabilities. (shrink)

BackgroundAt present, adherence to antipsychotic treatment is often poor, leading to the recurrence of symptoms. This increases the likelihood of the patient experiencing disability and thus increases the disease burden for the patient, their family, and society as a whole. However, to date, there is no clear evidence regarding the effect of medication adherence interventions on outcomes for patients with schizophrenia. Moreover, the traditional intervention methods are limited by manpower and resources in low- and middle-income countries. Recent (...) studies have demonstrated that increasing a patient’s level of self-compassion may improve their treatment adherence. Online mental health care interventions have advantages in terms of feasibility and acceptability for patients with schizophrenia. In this regard, a WeChat-based self-compassion training protocol to improve patient treatment adherence was designed in this study and will be evaluated in the future to determine its impact on patients with schizophrenia.MethodsThe protocol for the randomized controlled trial is based on the SPIRIT 2013 statement. This parallel RCT will aim to recruit 392 patients with schizophrenia who will be randomized at a 1:1 ratio into a 3-week intervention or control group. Both groups will receive routine care. The intervention group will also receive WeChat-based self-compassion training, which requires participants to complete three tasks every day, including a reading task, a meditation task, and a self-compassion journal task. The control group will receive WeChat-based psychological health education, which will only require participants to read positive articles about psychological health every day. Medication adherence, self-compassion, stigma, and social support will be measured at baseline, immediately after the intervention, and 3 weeks after the intervention. Program feasibility will be evaluated throughout the course of the study, and acceptability will be measured immediately after the intervention.Expected results:The intervention described here will address the barriers to accessing mental health care for people with schizophrenia, including patients’ desire for independent management, difficulty accessing providers, and concerns about privacy and stigma. The current study provides guidance for clinical nurses to carry out psychological intervention, with the ultimate aim of addressing the problems associated with a shortage of psychological professionals in low- and middle-income countries. (shrink)

In his paper, ‘Patients, doctors and risk attitudes’, Makins argues that doctors, when choosing a treatment for their patient, need to follow their risk profile.1 He presents a pair of fictitious diseases facing a patient who either has ‘exemplitis’, which requires no treatment or ‘caseopathy’, which is severe and disabling and for which there is a treatment with unpleasant side effects. The doctor needs to decide whether the patient should pursue the unpleasant treatment, just in case (...) he has caseopathy. Makins believes that rational-choice theory is a productive way to approach this problem. This theory frames all decisions as gambles. Each possible gamble (eg, not to pursue treatment) leads, probabilistically, to a set of outcomes (life with no disease and no side effects, but also, possibly, life with a disabling disease, since no treatment is taken). Utilities of these outcomes and probabilities that they will happen are combined to yield a number—expected utility. One is supposed to gamble—to make a choice—in a way that maximises this expected utility. Makins takes this framework for granted and is focused on an additional complication, the patient’s risk preference. He believes that, in his hypothetical example, even if expected utility were exactly the same, withholding treatment …. (shrink)

Patients with advanced Alzheimer's disease experience cognitive impairment and physical disabilities in daily life. Currently, there are no treatments available to slow down the course of the disease, and limited treatments exist only to treat symptoms. However, deep brain stimulation of the nucleus basalis of Meynert has been reported to improve cognitive function in individuals with AD. Here, we report the effects of NBM-DBS on cognitive function in a subject with severe AD. An 80-year-old male with severe AD (...) underwent surgery for bilateral NBM-DBS electrode placement. After 10 weeks of stimulation, Mini-Mental State Examination assessment improved from a score of 5 to 9 points, and assessment using the Alzheimer's Disease Assessment Scale–Cognitive Subscale showed a marked reduction in total score from 43 to 33 points, suggesting cognitive benefits from NBM-DBS. The patient's postoperative course was complicated by a subdural effusion that occurred several days after surgery, with complete recovery. Interestingly, the subject also displayed abnormal thermoregulation with stimulation initiation and stimulation parameter modifications. NBM-DBS may serve as a potential therapy for severe AD patients.Clinical Trial Registration: ChiCTR1900022324. (shrink)

In this article, I draw on my fieldwork creating protein models of hepatitis B at a biotech laboratory to think through how to approach the body and disease from ontological and phenomenological perspectives. I subsequently draw on Mariella Pandolfi’s work on how bodies can be made to suffer history and Paul Farmer’s work on global tuberculosis disparities to explore ways of analysing embodied activity as a means of identifying and clinically addressing enactments of social inequality and disease. I (...) also introduce Merleau-Ponty’s phenomenological concept of ‘flesh’ as a conceptual heuristic that allows us to understand the meaningful structuring of ontological worlds beyond our own. As I argue, bringing these perspectives together not only allows us to re-envision what an effective disease treatment should be in diverse medical contexts, but also how to better understand health disparities and the nature of disease itself. (shrink)

Cancer viewed as a programmed, evolutionarily conserved life‐form, rather than just a random series of disease‐causing mutations, answers the rarely asked question of what the cancer cell is for, provides meaning for its otherwise mysterious suite of attributes, and encourages a different type of thinking about treatment. The broad but consistent spectrum of traits, well‐recognized in all aggressive cancers, group naturally into three categories: taxonomy (“phylogenation”), atavism (“re‐primitivization”) and robustness (“adaptive resilience”). The parsimonious explanation is not convergent evolution, (...) but the release of an highly conserved survival program, honed by the exigencies of the Pre‐Cambrian, to which the cancer cell seems better adapted; and which is recreated within, and at great cost to, its host. Central to this program is the Warburg Effect, whose malign influence permeates well beyond aerobic glycolysis to include biomass interconversion and genomic heuristics. Warburg‐type metabolism and genomic instability are targets whose therapeutic disablement is a major priority. (shrink)

No cure yet exists for devastating Alzheimer's disease (AD), despite many years and humongous efforts to find efficacious pharmacological treatments. So far, neither designing drugs to disaggregate amyloid plaques nor tackling solely inflammation turned out to be decisive. Mesenchymal stem cells (MSCs) and, in particular, extracellular vesicles (EVs) originating from them could be proposed as an alternative, strategic approach to attack the pathology. Indeed, MSC‐EVs—owing to their ability to deliver lipids/proteins/enzymes/microRNAs endowed with anti‐inflammatory, amyloid‐β degrading, and neurotrophic activities—may be (...) exploited as therapeutic tools to restore synaptic function, prevent neuronal death, and slow down memory impairment in AD. Herein the results presented in the most recently published studies on this topic are critically evaluated, providing a strong rationale for possible employment of MSC‐EVs in AD. (shrink)

The Human Genome Project has allowed researchers to gain new insights into the genetic causes of health and disease. With this knowledge comes the potential to develop new genetic tests that are capable of predicting the risk of disease or disability among presently healthy individuals. This information is potentially beneficial in that it may allow individuals to develop strategies to reduce their risk of illness and may allow health providers to recognize and treat the early stages of (...) disease more effectively. As knowledge about genetic contributions to disease continues to grow and genetic testing technology becomes more widespread, there is a risk that personal genetic information could be used in ways potentially concerning to consumers. Genetic testing technology could potentially be used to discriminate against individuals in terms of their ability to obtain health, life, and disability insurance. Decreased access to insurance, in turn, significantly hinders access to health care and income for oneself and/or for one's dependent. (shrink)

In this paper I will discuss three areas in which advances in human reproductive technology could occur, their uses and abuses, and their effects on society. First is the potential to drastically increase the success rate and availability of in vitro fertilization and embryo freezing. Second is the ability to perform biopsies on embryos prior to the onset of pregnancy. Finally, I will consider the adding or altering of genes in embryos, commonly referred to as genetic engineering.As new reproductive technologies (...) pass from experimental models into the potential for medical utilization, I believe that it will be important for lawmakers everywhere to avoid the impulse to outlaw procedures that a society believes to be unnatural at a first glance. Rather, I would hope that they can respond thoughtfully with legislation that serves two purposes — to protect the rights of couples to overcome infertility or to reduce the risk of genetic disease in their children-to-be, and more importantly, to protect children-to-be from the abuses that could result from some of the practices that I will discuss. (shrink)

On the basis of the evidence that tumor development is suppressed by the embryonic microenvironment, some experiments using the factors taken from Zebrafish embryo at precise stages of cell differentiation were made. These experiments demonstrated a significant growth inhibition on different tumor cell lines in vitro. The observed mechanism of tumor growth inhibition is connected with the key-role cell cycle regulation molecules, such as p53 and pRb, which are modified by transcriptional or post-translational processes. Research on apoptosis and differentiation revealed (...) that treatment with these factors induces caspase-3 with a p73 apoptotic-dependent pathway activation and a concurrent significant normalization of e-cadherin and beta-catenin ratio. Other experiments found a synergistic effect on the colon cancer proliferation curve after the concurrent treatment with these factors and 5-fluorouracil. Finally, a product prepared for human therapy demonstrated 19.8% regression and 16% stable disease in an... (shrink)

Rare neuromuscular diseases are a group of pathologies characterized by a progressive loss of muscular strength, atrophy, fatigue, and other muscle-related symptoms, which affect quality of life levels. The low prevalence, high geographical dispersion and disability of these individuals involve difficulties in accessing health and social care services. Teleassistance is presented as a useful tool to perform psychosocial interventions in these situations. The main aim of this research is to assess the effects of a teleassistance psychosocial program on the (...) QoL levels of people with RNMDs who have different levels of disability. A sample of 73 participants was divided into an experimental group, which participated in the intervention, and a control wait list group. QoL was evaluated through the SIP and the SF-36, and disability through the WHO-DAS II. The participants with a moderate to severe level of disability were those who most benefited from the intervention. The results also revealed that the psychosocial teleassistance program was suitable to improve physical and psychosocial aspects of people suffering from a rare neuromuscular disease with a moderate level of disability, but just psychosocial aspects in those with a severe level of disability. (shrink)

Cost-effectiveness analysis is the standard analytical tool for evaluating the aggregate health benefits of treatments, interventions, or health programs. It works by comparing the ratio of costs and benefits of different alternatives. The lower the ratio, the more effective the treatment, intervention, or program. The use of cost-effectiveness analysis can ensure that scarce health care resources are allocated in a way that maximizes the satisfaction of health needs. According to a common objection, however, the use of cost-effectiveness analysis (...) for setting priorities in the allocation of health care resources may lead to unfair discrimination against people with disabilities.The aim of the first part of this .. (shrink)

Many existing biomedical vocabulary standards rest on incomplete, inconsistent or confused accounts of basic terms pertaining to diseases, diagnoses, and clinical phenotypes. Here we outline what we believe to be a logically and biologically coherent framework for the representation of such entities and of the relations between them. We defend a view of disease as involving in every case some physical basis within the organism that bears a disposition toward the execution of pathological processes. We present our view in (...) the form of a list of terms and definitions designed to provide a consistent starting point for the representation of both disease and diagnosis in information systems in the future. (shrink)

The question of whether medical and psychiatric judgements involve a normative or evaluative component has been a source of wide and vehement disagreement. But among those who think such a component is involved, there is considerable further disagreement as to its nature. In this article, I consider several versions of Aristotelian normativism, as propounded by Christopher Megone, Michael Thompson and Philippa Foot, and Martha Nussbaum. The first two, I claim, can be persuasively rebutted by different modes of liberal pluralist challenge (...) — respectively, pluralism about structures of social organisation and pluralism about biological forms. Nussbaum's version, by contrast, is alert to the need for pluralism; I argue, however, that the Aristotelian aspects of her theory hamper her pursuit of those pluralistic aims. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Philosophy, Psychiatry, & Psychology 10.3 (2003) 225-226 [Access article in PDF] Travelers in the Land of Sickness Eric J. Cassell THE PROBLEM OF knowing another person and the world in which that person lives, particularly someone with major mental illness, is addressed in this interesting and rich essay. The number of different metaphors and concepts Potter employs to describe the task of crossing into and then understanding the thoughts, (...) emotions, symptoms, constraints, context, and perspectives of another testifies to the difficulties involved.Yet, as I read the essay, it was not clear what the clinician world traveler, moral tourist, empathizer (and other categories) is supposed to do on the journey to another person. Why do we reach out to the sick person? What is it that we want to know or do that makes this trip necessary? Potter is primarily concerned with mental illness—the examples she cites are patients with schizophrenia—while my experience has in the main been with persons with physical illness, but for the moment, the differences are less important than the central lesson. The illness that the patient presents—the experience of the symptoms, the impairments, disability, and disruptions of the emotional and social existence that happen because of the disease result from an amalgam of the disease process with the specific nature of the sick person. There is no disease in pure form; there is no disease in abstract for clinicians. There is only this sick person. She correctly quotes me, because of all this, as pointing out the importance of integrating knowledge of this particular patient with the abstract knowledge of disease to understand the illness as it is expressed in this person. All to form a basis for the treatment of the patient and especially to help relieve suffering because suffering is always personal, particular, and individual. (It is important in thinking about this topic to remember that most serious diseases, psychiatric and otherwise, are chronic and take place over significant lived time. The acute schizophrenic symptoms or the acute infectious diseases, as dramatic as they are, distract attention from the importance of the place of the sick person.)In physical disease, our long (and continuing) history of separating human beings from nature and the body, and the importance medicine places on objectivity and the objective, have made the inevitable personalization of the disease and symptoms virtually invisible. After ages of explaining psychiatric diseases as the alienation of the person, and a long psychoanalytic period of finding their origins in the person, in the last 30 years these diseases have become increasingly objectified. The place of the person has been diminished as psychiatry has entered the DSM, neurotransmitter, and effective psychotropic drug era. For both physical and mental disease, however, and whatever the current ideology, the nature of person is crucial in determining the onset, diagnosis, course, treatment, and outcome of each illness. It is in order to have an impact on these crucial aspects of sickness that clinicians must come to know their patients to the degree possible. [End Page 225]But there is something more. Nancy Potter quotes a woman with schizophrenia as saying, "All that was my former self has crumbled and fallen together and a creature has emerged of whom I know nothing. She is a stranger to me... She is not real—she is not I... She is I—and because I still have myself on my hands, even if I am a maniac, I must deal with me somehow." (Potter, 2003, p. 215)Must she deal with this crazy self alone? Is that not what her doctors and caregivers are for? But how can they take care of her, protect her, keep what is left intact, and sustain her until she is (hopefully) better without knowing who she is? She makes clear in those few phrases that inside her there is a person with a past, a family, a world, a culture, a role(s) in life, relationships, a body, dreams for the future, things she does, and all the other things that make up a person. It is in... (shrink)

Free will has been the object of debate in the context of addiction given that addiction could compromise an individual’s ability to choose freely between alternative courses of action. Proponents of the brain-disease model of addiction have argued that a neuroscience perspective on addiction reduces the attribution of free will because it relocates the cause of the disorder to the brain rather than to the person, thereby diminishing the blame attributed to the person with an addiction. Others have worried (...) that such displacement of free will attribution would make the person with a drug addiction less responsible. Using the paradigmatic literature on the seductive allure of neuroscience explanations, we tested whether neuroscience information diminishes attributions of free will in the context of addiction and whether respondent characteristics influence these attributions and modulate the effect of neuroscience information. We performed a large-scale, web-based experiment with 2,378 German participants to explore how attributions of free will in the context of addiction to either alcohol or cocaine are affected by: (1) a text with a neurobiological explanation of addiction, (2) a neuroimage showing effects of addiction on the brain, and (3) a combination of a text and a neuroimage, in comparison to a control group that received no information. Belief in free will was measured using the FAD-Plus scale and was, subsequent to factor analysis, separated into two factors: responsibility and volition. The investigated respondent characteristics included gender, age, education, self-reported knowledge of neuroscience, substance-use disorder (SUD), and having a friend with SUD. We found that attributions of volition (in the cocaine-subsample) were reduced in the text and neuroimage-treatment compared to the control group. However, respondent characteristics such as education and self-reported knowledge of neuroscience were associated with lower attributions of responsibility for both substances, and education was associated with lower attribution of volition for the alcohol sub-sample. Interaction analyses showed that knowledge of neuroscience was found to generally decrease attribution of responsibility. Further research on attribution of free will should consider the effects of context and respondent characteristics, which appeared surprisingly larger than those induced by experimental treatments. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Introduction:The Heat of Mild Cognitive ImpairmentJulian C. Hughes (bio)Keywordsaging, explanation, mild cognitive impairment, understanding, valuesDebates about mild cognitive impairment (MCI) are generating heat, albeit civilized heat. But under the surface, as I think the papers in this special issue demonstrate, the civilized heat comes from a good deal of passion. One way in which philosophy can contribute to the debate is by making plain the sources of this passion, (...) so that the motivating forces are clearer.One motivating force is this: There will be people who do not have dementia but who have symptoms or signs that might predict dementia, which cause them concern, whom we might help by early intervention. The intervention might involve advice and support, or it might involve some form of drug treatment; and in the utopia of our dreams, it might involve prevention. All of this is very motivating for clinical scientists. It also offers a laudable motivation to pharmaceutical companies, who simultaneously must have regard to the possibility of profits for their shareholders.Here, however, is an alternative motivation: The effects of aging must not be ignored if help can be given, but older people must not be stigmatized by a medical process that thrusts disabling labels on them. People age, but they age differently, and it is better to recognize difference, both from a biological and from a philosophical perspective. Thus, a passionate commitment to the cause of individual agency in old age and a desire for authentic autonomy for older people provide strong motivation too.At root, then, the conflicting passions over MCI reflect the age-old struggle in the philosophy of psychiatry between the natural sciences (Naturwissenschaften) and the human or cultural sciences (Geisteswissenschaften): the tension is between a tendency to approach the problem with the aim of eliciting a scientific explanation and a tendency to try to achieve a human and cultural understanding of the phenomena (Phillips 2004). So, although MCI can be regarded as an explanatory diagnostic entity with some predictive value, it can also be regarded as a label that might cause harm or as a human phenomenon that requires understanding. Furthermore, MCI raises ontological questions about the nature of disease entities. And there is a wider issue as well about how aging itself should be regarded.From a biological perspective, it turns out there is no clear cutoff between what is normal and what [End Page 1] is not. Hence, in a number of ways, values seem to be as important as facts (Sadler 2005). Perhaps philosophy should content itself with saying no more than this: MCI ought not to be considered or debated as if it lies outside the realm of evaluative judgment. The very possibility of its existence as a clinical entity is a matter worthy of moral and social discourse.The direction of thought indicated here and in the papers that follow, however, is more radical than the easily won point that the "diagnosis" of MCI is not value free. On the back of the biological point, that there is a continuum between physiological and pathological aging, is the broader philosophical point that aging can neither be understood solely in terms of physiology nor in terms of pathology, nor even in terms of both. Ageing represents, inter alia, a social and cultural phenomenon manifest in the context of particular psychological and spiritual responses to a mixture of physiological adaptations and pathological predispositions. Without the broader picture, we tend to characterize old age, as Michael Bavidge has suggested elsewhere, in terms of deteriorations: "We should think of old age as offering alternative rather than impaired ways of experiencing life" (2006, 49). The difficulty is that any diagnosis seems to suggest impairment in one form or another. The radical suggestion, therefore, might be to commend descriptions that encourage shared understanding over and above the giving of names and labels.In a brief critique of the scientific approach to "banal memory disorders and MCI", Jean-Marie Léger, like Bavidge, regrets the extent to which people with cognitive impairment "are described in terms of what they have lost, with no regard for the wealth of faculties which are still present." Léger... (shrink)

Gene therapy and gene editing are revolutionising the treatment of genetic diseases, most notably haematological disorders. This paper evaluates the use of both techniques in hereditary blood disorders. Many studies have been conducted in this field, especially with gene therapy, with very promising results in diseases such as haemophilia, certain haemoglobinopathies and Fanconi anaemia. The application of these techniques in clinical practice and the foreseeable development of these approaches in the coming years suggest that it might be useful to (...) evaluate the results achieved thus far. It is also essential to reflect on the possible bioethical concerns raised by the use of both techniques, especially in terms of safety issues for patients, potential side effects, treatment duration, accessibility and cost of treatment, and the heritability of genetic changes produced if germline cells are used. (shrink)

Syphilis occupies a unique position in the history of U.S. medicine and medical ethics. Given its widespread prevalence and variable presentation, syphilis was a major professional concern among late nineteenth‐ and early twentieth‐century physicians. Syphilis was also at the center of perhaps the most famous example of medical racism in our history, the U.S. Public Health Service Syphilis Study at Tuskegee, in which officials followed the natural history of the disease in a cohort of black men for forty years (...) without offering treatment, even once penicillin became available. In this essay, I call attention to a less well‐known aspect of syphilis and its history. I examine one of the disease's most dreaded manifestations, neurosyphilis (also known as general paresis or general paralysis of the insane), and its treatment via malarial inoculation from the 1920s into the 1950s. The goal of this treatment, dramatic even to observers at the time, was to produce spiking fevers that would kill the syphilitic spirochete and arrest the disease process. My focus will be on developments at St. Elizabeths Hospital, a large‐scale federal psychiatric facility in the District of Columbia that served the city's residents and members of the U.S. military. Physicians at St. Elizabeths were the first in the United States to experiment with malarial fever therapy, treating their initial cohort of patients in December of 1922.Malarial fever therapy raised a host of ethical questions, rendered all the more complex from today's vantage point by efforts to understand them within the context of the time. What sorts of risks, both from malaria and via indirect exposure, might be deemed acceptable in the treatment of a devastating and almost invariably fatal disease? How ought researchers and clinicians to have approached the question of consent, itself an evolving concept in the early decades of the twentieth century, when the disease they were targeting impaired a patient's ability to reason effectively? Finally, at a time when segregated and inferior care for black Americans was the norm and when the black community bore a disproportionate burden of disease, who would have had access to malarial fever therapy, and at what cost? (shrink)

PurposeThe aim of this study was to investigate the effect of possible late effects of cancer treatment and of two job resources on future burnout complaints, among employees living 2–10 years beyond breast cancer diagnosis.MethodsData at T1 and at T2 were collected in 2018 and 2019. These data were part of a longitudinal study among Dutch speaking workers with a cancer diagnosis 2–10 years ago. All complaints and job resources were self-reported. Longitudinal multivariate regression analyses were executed, controlling for (...) years since diagnosis, living with cancer, and other chronic or severe diseases. Mediation by baseline burnout complaints was considered.ResultsA higher level of fatigue and cognitive complaints at baseline resulted in higher future burnout complaints, with partial mediation by baseline burnout complaints. No effect of physical complaints at T1 was observed. Higher levels of autonomy or a supportive leadership style resulted in lower burnout complaints, with full mediation by baseline burnout complaints. Buffering was observed by autonomy in the relationship of cognitive complaints with future burnout complaints. No moderation was observed by supportive leadership.ConclusionThe level of burnout complaints among employees 2–10 years beyond breast cancer diagnosis may be an effect of fatigue or cognitive complaints, and awareness of this effect is necessary. Interventions to stimulate supportive leadership and autonomy are advisable, the latter especially in the case of cognitive complaints. (shrink)

Reading difficulties that are not addressed at the primary level continue to exist at the secondary level with serious consequences. Thus, it is important to provide struggling students with specific reading support. In particular, many students with learning disabilities and emotional behavioral disorders demonstrate reading obstacles and are at risk for motivation loss. A multiple baseline design was used to evaluate the effects of a motivational reading racetrack as peer-tutoring on the word reading skills of secondary students with LD with (...) and without EBD. The intervention was conducted through 4–5 baseline and 16–18 reading units three times a week for 15 min over 8 weeks. The results showed positive effects indicating a highly effective treatment. In addition, follow-up results were also promising. Our findings indicate that this multicomponent intervention has a positive effect on the word fluidity of low-achieving students in secondary education with LD and/or EBD. (shrink)

Background: Treatment of psychotic disorders in pregnancy is often ethically and clinically challenging, especially when psychotic symptoms impair decision-making capacity. There are several competing ethical obligations to consider: the ethical obligation to maternal autonomy, the maternal and fetal beneficence-based obligations to treat peripartum psychosis, and the fetal beneficence-based obligation to minimize teratogenic exposure. Objective: This article outlines an ethical framework for clinical decision-making for the management of chronic psychosis in pregnancy, with an emphasis on special considerations in the previable (...) and periviable period. Case Presentation: A 31-year-old gravida 2, para 1 with intrauterine pregnancy at 12 weeks and 4 days gestation was brought to the emergency department by her husband seven months after delivering her first child, due to sudden onset of behavioral changes that included self-isolation, not eating, and not taking care of her child. Her past medical history included hypothyroidism and inflammatory bowel disease, but no prior psychiatric illness. After being admitted to the psychiatric hospital, she continued to have poor oral intake and weight loss despite initial inpatient treatment with antipsychotics, levothyroxine, and discontinuation of corticosteroids. Her pregnancy was also complicated by the diagnosis of multiple fetal anomalies at 20 weeks gestation, when the fetus was periviable. Conclusions: For previable or periviable pregnancies, the patient and/or surrogate should decide whether to pursue prenatal genetic screening and invasive diagnostic testing, as well as whether to continue or terminate the pregnancy. When the choice is made to continue the pregnancy, initiation of long-term psychiatric treatment (including medications with potential adverse fetal effects) should be based on shared decision-making between the physician and the patient and/or surrogate. Although some pharmacologic interventions may have potential adverse effects on the developing fetus, the use of psychotropic medications can be ethically justified, even if the patient herself does not have the capacity to consent and requires a surrogate, when the goal is to restore maternal autonomy and minimize the risks of maternal and fetal harm from untreated psychiatric illness. (shrink)

Deep brain stimulation is part of state-of-the-art treatment for medically refractory Parkinson’s disease, essential tremor or primary dystonia. However, there are multiple movement disorders that present after a static brain lesion and that are frequently refractory to medical treatment. Using Holmes tremor as an example, we discuss the effectiveness of currently available treatments and, performing simulations using a Markov Chain approach, propose that DBS with iterative parameter optimization is expected to be more effective than an approach (...) based on sequential trials of pharmacological agents. Since, in DBS studies for HT, the thalamus is a frequently chosen target, using data from previous studies of lesion connectivity mapping in HT, we compared the connectivity of thalamic and non-thalamic targets with a proxy of the HT network, and found a significantly higher connectivity of thalamic DBS targets in HT. The understanding of brain networks provided by analysis of functional connectivity may thus provide an informed framework for proper surgical targeting of individual patients. Based on these findings, we argue that there is an ethical imperative to at least consider surgical options in patients with uncommon movement disorders, while simultaneously providing consistent information regarding the expected effectiveness and risks, even in a scenario of surgical-risk aversion. An approach based on n-of-1 DBS trials may ultimately significantly improve outcomes while informing on optimal therapeutic targets and parameter settings for HT and other disabling and rare movement disorders. (shrink)

Rid and Wendler propose the development of a Patient Preference Predictor (PPP), an actuarial model for predicting incapacitated patient’s life-sustaining treatment preferences across a wide range of end-of-life scenarios. An actuarial approach to end-of-life decision making has enormous potential, but transferring the logic of actuarial prediction to end-of-life decision making raises several conceptual complexities and logistical problems that need further consideration. Actuarial models have proven effective in targeted prediction tasks, but no evidence supports their effectiveness in the kind (...) of broad spectrum prediction task that is the proposed goal of the PPP. We argue that a more focused approach, targeting specific medical conditions and generating treatment predictions based on the preferences of individuals with actual disease experience, is both more firmly grounded in past research and is a more prudent initial strategy for exploring the efficacy of actuarial prediction in end-of-life decision making. (shrink)

BackgroundChronic airway diseases are prevalent and costly conditions. Interdisciplinary rehabilitation programs that include Acceptance and Commitment-based components could be important to tackle the vicious circle linking progression of the disease, inactivity, and psychopathological symptoms.MethodsA retrospective evaluation of routinely collected data of an interdisciplinary rehabilitation program was performed. The program included group sessions including patient education, breathing exercise, occupational therapy and an ACT-based psychological treatment, and individual sessions of physical therapy. Demographic data, clinical characteristics of the patients and the (...) values of outcome variables before treatment, at discharge, at 3 months, and at 6 months were extracted from medical records. Multiple imputation was employed to address missing data. Linear mixed models were employed to assess changes over time. Multivariable logistic regression was performed to assess predictors of a minimum clinically important change of health status from baseline to the 6-months follow-up.ResultsData from 31 patients with chronic obstructive pulmonary disease and 12 patients with bronchiectasis were extracted. Health status improved from baseline to discharge to the 3 months follow-up, but not to the 6 months follow-up. Anxiety and depression improved across all the time points. Quality of life did not improve over time. Having a worse health status at baseline and fewer depressive symptoms were significantly associated with achieving a minimum clinically important change of health status at 6 months. The effects of the interdisciplinary program were not different for patients with COPD or with bronchiectasis.DiscussionInterdisciplinary programs including ACT-based components are promising treatments for the rehabilitation of patients with chronic airway diseases. (shrink)

Background: Thrombolytic drugs to treat an acute ischaemic stroke reduce the risk of death or major disability. The treatment is, however, also associated with an increased risk of potentially fatal intracranial bleeding. This confronts the patient with the dilemma of whether or not to take a risk of a serious side effect in order to increase the likelihood of a favourable outcome. Objective: To explore acute stroke patients’ perception of risk and willingness to accept risks associated with thrombolytic (...) drug treatment. Design: Eleven patients who had been informed about thrombolytic drug treatment and had been through the process of deciding whether or not to participate in a thrombolytic drug trial went through repeated qualitative, semistructured interviews. Results: Many patients showed a limited perception of the risks connected with thrombolytic drug treatment. Some perceived the risk as not relevant to them and were reluctant to accept that treatment could cause harm. Others seemed to be aware that treatment would mean exposure to risk. The patients’ willingness to take a risk also varied substantially. Several statements revealed ambiguity and confusion about being involved in a decision about treatment. The patients’ reasoning about risk was put into the context of their health-related experiences and life histories. Several patients wanted the doctor to be responsible for the decisions. Conclusion: Acute stroke patients’ difficulties in perceiving and processing information about risk may reduce their ability to be involved in clinical decisions where risks are involved. (shrink)

Background Little is known about the attitudes and practices of intensivists working in Lebanon regarding withholding and withdrawing life-sustaining treatments. The objectives of the study were to assess the points of view and practices of intensivists in Lebanon along with the opinions of medical, legal and religious leaders regarding withholding withdrawal of life-sustaining treatments in Lebanese intensive care units. Methods A web-based survey was conducted among intensivists working in Lebanese adult ICUs. Interviews were also done with Lebanese medical, legal and (...) religious leaders. Results Of the 229 survey recipients, 83 intensivists completed it, i.e. a response rate of. Most respondents were between 30 and 49 years old, Catholic Christians, anesthesiologists, working in Beirut. Ninety-two percent of them were familiar with the withholding and withdrawal concepts and 80% applied them. Poor prognosis of the acute and chronic disease and futile therapy were the main reasons to consider withholding and withdrawal of treatments. Ninety-five percent of intensivists agreed with the “Principle of Double Effect”. The main withheld therapies were vasopressors, respiratory assistance and CPR. Most of the respondents reported the decision was often to always multidisciplinary, involving the family, and the patient, or his advance directives or his surrogate and the nurses. The interviewees agreed there was a law governing withholding and withdrawal decisions/practices in Lebanon. Christians and Muslim Sunni leaders declared accepting those practices. Conclusion Withholding and withdrawal of LSTs in the ICU are known concepts among intensivists working in Lebanon and are being practiced. Our results could be used to inform and optimize therapeutic limitation in ICUs in the country. (shrink)

Race or ethnic identity, despite its imprecise categorization, is a useful means of identifying population differences in mechanisms of disease and treatment effects. Therefore, race and other arbitrary demographic and physiological variables have appropriately served as a helpful guide to clinical management and to clinical trial participation. The African-American Heart Failure Trial was carried out in African-Americans with heart failure because prior data had demonstrated a uniquely favorable effect in this subpopulation of the drug combination in BiDil. The (...) remarkable effect of the drug in reducing mortality in this study has illuminated an important new mechanism of therapy for heart failure. Application of these findings need not be confined to the population studied, but the observation highlights the need for more precise ways to identify individual responsiveness to therapy. (shrink)

The experience of the use of applied containerized biomedical software tools in cloud environment is summarized. The reproducibility of scientific computing in relation with modern technologies of scientific calculations is discussed. The main approaches to biomedical data preprocessing and integration in the framework of the intelligent analytical system are described. At the conditions of pandemic, the success of health care system depends significantly on the regular implementation of effective research tools and population monitoring. The earlier the risks of (...) class='Hi'>disease can be identified, the more effective process of preventive measures or treatments can be. This publication is about the creation of a prototype for such a tool within the project «Development of methods, algorithms and intelligent analytical system for processing and analysis of heterogeneous clinical and biomedical data to improve the diagnosis of complex diseases», implementted by the V.M. Glushkov Institute of Cybernetics, National Academy of Sciences of Ukraine, together with the United Institute of Informatics Problems, National Academy of Sciences of Belarus. The insurers, entering the market, can insure mostly low risks by facilitating more frequent changes of insurers by consumers and mixing the overall health insurance market. Socio-demographic variables can be risk adjusters. Since age and gender have a relatively small explanatory power, other socio-demographic variables were studied – marital status, retirement status, disability status, educational level, income level. Because insurers have an interest in beneficial diagnoses for their policyholders, they are also interested in the ability to interpret relevant information – upcoding: insurers can encourage their policyholders to consult with doctors more often to select as many diagnoses as possible. Many countries and health care systems use diagnostic information to determine the reimbursement to a service provider, revealing the necessary data. For processing and analysis of these data, software implementations of construction for classifiers, allocation of informative features, processing of heterogeneous medical and biological variables for carrying out scientific research in the field of clinical medicine are developed. The experience of the use of applied containerized biomedical software tools in cloud environment is summarized. The reproducibility of scientific computing in relation with modern technologies of scientific calculations is discussed. Particularly, attention is paid to containerization of biomedical applications, this permits to get reproducibility of the conditions in which the calculations took place, technologies of software pipelining of calculations, that allows to organize flow calculations, and technologies for parameterization of software environment, that allows to reproduce, if necessary, an identical computing environment. The main approaches to biomedical data preprocessing and integration in the framework of the intelligent analytical system are described. The experience of using the developed linear classifier, gained during its testing on artificial and real data, allows us to conclude about several advantages provided by the containerized form of the created application: it permits to provide access to real data located in cloud environment; it is possible to perform calculations to solve research problems on cloud resources both with the help of developed tools and with the help of cloud services; such a form of research organization makes numerical experiments reproducible, i.e. any other researcher can compare the results of their developments on specific data that have already been studied by others, in order to verify the conclusions and technical feasibility of new results; there exists a universal opportunity to use the developed tools on technical devices of various classes from a personal computer to powerful cluster. (shrink)

Just allocation of resources for control of infectious diseases can be profoundly influenced by the dynamics of those diseases. In this paper we discuss the use of antiviral drugs for treatment of pandemic influenza. While the primary effect of such drugs is to alleviate and shorten the duration of symptoms for treated individuals, they can have a secondary effect of reducing transmission in the community. However, existing stockpiles may be insufficient for all clinical cases. Here we use simple mathematical (...) models to present scenarios where the optimum policies to minimise morbidity and mortality, with a limited drug stockpile, are not always the most intuitively obvious and may conflict with theories of justice. We discuss ethical implications of these findings. (shrink)

The random]ized clinical trial is widely accepted as the optimal approach to evaluating the safety and efficacy of medical treatments. Resistance to randomized treatment assignment arises regularly, most commonly in situations where the disease is life-threatening and treatments are either unavailable or unsatisfactory. Historical control designs, in which all participants receive the experimental treatment with results compared to a prior cohort, are advocated by some as more ethical in such circumstances; however, such studies are often highly biased (...) in favor of the new treatment and frequently yield misleading results. Alternative controlled designs motivated by the desire to maximize the number of patients with the treatment ultimately determined to be superior have been proposed, but have been challenged on both methodological and ethical grounds. Debates about appropriate and ethical study designs recurred during the recent Ebola Virus Disease epidemic in West Africa. Despite its devastating nature, the EVD epidemic showed the ongoing necessity of conducting randomized trials to obtain convincing evidence of the safety and efficacy of therapeutic interventions. (shrink)