Abstract in English:Medical education is expensive. Its expense has led many stakeholders to speculate on how costs could be reduced. In an ideal world such decisions would be made on sound evidence; however this is impossible in the absence of evidence. Sometimes practice will be informed by policy, but policy will not always be evidence based. So how is policy in the field of cost and value in medical education actually developed? The foremost influence on policy in cost and value should be evidence-based knowledge. Unfortunately policy is sometimes influenced by what might at best be termed tradition and at worst inertia. Another influence on policy will be people - but some individuals may have more influence than others. A further influence on policy in this field is events, and mainly events that have gone wrong. One final influence on emerging policy in medical education cost analysis is that of the media.
Abstract in English:Introduction. A number of studies highlight the difficulty in forming a diagnosis for patients with disorders of consciousness when this is established merely on behavioral assessments. Background. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and electroencephalography combined with transcranial magnetic stimulation (TMS-EEG) techniques are promoting the clinical characterization of this challenging population. With such technology-based "objective" tools, patients are also differentially able to follow simple commands and in some cases even communicate through modified brain activity. Consequently, the vegetative state and minimally conscious state have been revised and new nosologies have been proposed, namely the unresponsive wakefulness syndrome, the minimally conscious state plus and minus, and the functional locked-in syndrome. Aim. To our mind, an integration of different technical modalities is important to gain a holistic vision of the underlying pathophysiology of disorders of consciousness in general and to promote single-patient medical management in particular.
Abstract in English:The directive 2001/20/UE and the research involving patients with docs. Research involving patients with disorders of consciousness (DOCs) deserves special ethical and legal attention because of its Janus-faced nature. On the one hand, it raises concerns about the risk to expose the involved subjects to disproportionate risks not respecting their individual dignity, particularly their right to be cared for; on the other hand, research is an essential tool in order to improve the clinical condition of patients with DOCs. The present paper concerns the ethical and legal dimensions of biomedical research involving patients with disorders of consciousness. In particular, it focuses on informed consent to experimental treatments, which is a challenging issue both from an ethical and legal point of view. The first part reads the Directive 2001/20/EU in the light of the experimentation of patients with DOCs, and suggests a revision in order to better assess the issue of informed consent. The particular case of informed consent for observational studies of non-communicative patients. The second part presents an informed consent form for studies through video-recording of patients unable to communicate their own consent. This form has been elaborated by the bioethics unit of the project "Review of the nosography of vegetative states: application of methods of behavioral analysis to individuals in coma or vegetative state" developed at the Italian National Institute of Health. Relevance of the suggested form. The paper describes the conceptual framework of the form for informed consent to studies through video-recoding, which is a relevant example of what issues should be included in an informed consent for any type of studies through video-recording of patients unable to express their own consent. The article has been sent on November the 7th 2013, before the adoption of the Regulation (EU) no. 536/2014 (and consequent abrogation of the Directive 2001/20/EU) and the release of the new edition of the Italian Code of Medical Ethics.
Abstract in English:Difficulties of behavioral assessment of consciousness. An astonishingly high rate of misdiagnosis between vegetative state/unresponsive wakefulness syndrome and minimally conscious state has been detected. This raises the issue of the adequacy of the consciousness' assessment in patients with disorders of consciousness. The behavioral assessment of consciousness could be not able to detect covert awareness, which is increasingly identified by the instrumental assessment. Ancillary methods. Neurotechnology, particularly neuroimaging, provides relevant data concerning the neurological underlying condition of patients with DOCs, but the instrumental approach has still to assess some technical issues. Ethical considerations. A correct diagnosis of a DOC is not only an instrumental issue, but also an ethically relevant demand to the scientific community. Finally, an integration between behavioral and instrumental assessments seems to be the most adequate strategy in order to decrease the rate of misdiagnosis.
Abstract in English:Introduction. The paper describes the evolution of knowledge concerning severe brain injury which determines the Vegetative State/Unresponsive Wakefulness Syndrome. Background. The term Vegetative State was proposed by Jennet and Plum in 1972. Later on, the Intensive Care Units progresses increased the survival of these patients and, contemporary, decreased their characteristic conditions of cachexia and severe dystonia. In 1994, the disease was conceived as a disconnection syndrome of the hemispheres from the brainstem, mainly due to a temporary or permanent deficit of the functions of the white matter. From 2005 on, the psychophysiological parameters relative to an emotional consciousness, albeit submerged, were described. Since then, it has been recognized that the brain of these patients was not only to be considered living but also working. Conclusion. The latest studies that have greatly improved the knowledge of the physiopathology of this particular state of consciousness. These new insights have led to the formation of a European Union Task Force, which has proposed in 2009 to change the name from a Vegetative State to Unresponsive Wakefulness Syndrome, outlining the character of syndrome and not that of state, as forms of even late recovery in consciousness levels have been observed and described.
Abstract in English:Brain damage of various aetiologies can lead to different disorders of consciousness (DOC), varying from coma to vegetative, to minimally conscious states. Each state is characterised by a different degree of wakefulness, awareness, pain sensitivity and is differentially handled with respect to treatment, ethical considerations and end-of-life decisions. Thus, its correct identification is crucial while devising or modulating appropriate treatment strategies. Actually, the main coma scales cannot always accurately determine the state of consciousness of an individual, while other tools (e.g. imaging techniques) present a certain degree of uncertainty. A complementary approach may be constituted by a 24-hour observation of patients, for a sufficient period of days, using an ad hoc behavioural scale, further correlated with physiological and pharmacological parameters measured on patients. The method herein described might help recognising the presence of consciousness of the different DOC patients, and thus discerning a vegetative from a minimally conscious state.
Abstract in English:An epistemological foundation for cultural psychology is essential to neuro- and behavioural sciences for the challenge psychological sciences must currently face: searching for an explanation of how a brain can become a mind and how individuals assign a sense to the world and their life. Biological systems are very likely determined by physical and chemical laws of spontaneous self-organization and endogenous constraints but, even if the major result of the Darwinian revolution is "the discovery that living species are their story", the modern synthesis of the evolution theory adopted only continuist and gradualist hypotheses. This nourished the analogy between the theory of natural selection and the theory of operant conditioning, thereby supporting empiricist associationism and the methodological positivism of behavioural and "classical" cognitive psychologists. Current scientific contributions provide evidence to the need for psychotherapy and psychopathology of a new epistemological approach in order to connect research stemming from animal models, up to the most abstract levels of personal meaning. The complex system oriented approach, here described, called "post-rationalism", shaped by a change initiated by evolutionary epistemology. The regulation of emotions initially develops within interpersonal relationships and evolves during both phylogeny and ontogeny, according to complex self-organization processes, leading to the acquisition of Self-organizing abilities and the construction of personal meaning. Endorsing the epistemological similarities of neo-Darwinism and behaviourism, and differentiating from this, the above mentioned approach, emphasises the fact that clinical and psycho-therapeutical practice must be founded on the laws of biological organisation: the ongoing activity of neurobiological systems, including the more abstract domains of thought and language.
Abstract in English:Objectives. Adverse effects of waste management represent a public health issue. Mortality meta-analysis in Italian National Priority Contaminated Sites (NPCSs) with industrial waste landfills or illegal dumps is presented. Methods. 24 NPCSs include industrial waste landfills or illegal dumps. Class 1 (10 NPCSs with industrial waste landfills) and Class 2 (14 NPCSs with illegal dumps) were categorized. Random-effects model meta-analyses of Standardized Mortality Ratios non-adjusted (SMRs) and adjusted for Deprivation (DI-SMRs) computed for each CS (1995-2002) were performed for overall 24 NPCSs and the two classes. The North-Southern gradient was considered. Results. 24 CSs pooled-SMRs are significantly increased in both genders for cancer of liver (men: SMR = 1.13; women: SMR = 1.18), bladder (men: SMR = 1.06; women: SMR = 1.11), and for cirrhosis (men: SMR = 1.09; women: SMR = 1.13). In Class 2 the increase is confirmed in both genders for liver and bladder cancers and for cirrhosis and in men only for lung cancer. Congenital anomalies and adverse perinatal conditions are not increased. Conclusion. The results are consistent with the hypothesis of adverse health effects of non-adequately managed hazardous waste. Causal interpretation is not allowed, but the meta-analytic approach provides more confidence in the findings.
Abstract in English:Background. Issues regarding cancer stem cell (CSC) movement are important in neurosphere biology as cell-cell or cell-environment interactions may have significant impacts on CSC differentiation and contribute to the heterogeneity of the neurosphere. Aims. Despite the growing body of literature data on the biology of brain tumor stem cells, floating CSC-derived neurospheres have been scarcely characterized from a morphological and ultrastructural point of view. Results. Here we report a morphological and ultrastructural characterization performed by live imaging and scanning electron microscopy. Glioblastoma multiforme (GBM) CSC-derived neurospheres are heterogeneous and are constituted by cells, morphologically different, capable of forming highly dynamic structures. These dynamic structures are regulated by not serendipitous cell-cell interactions, and they synchronously pulsate following a cyclic course made of "fast" and "slow" alternate phases. Autocrine/paracrine non canonical Wnt signalling appears to be correlated with the association status of neurospheres. Conclusions. The results obtained suggest that GBM CSCs can behave both as independents cells and as "social" cells, highly interactive with other members of its species, giving rise to a sort of "multicellular organism".
Abstract in English:Introduction. In industrialized countries, the availability of highly active antiretroviral therapy (HAART) caused a slow but substantial ageing of the AIDS epidemic mainly due to the longer survival of persons with HIV/AIDS which has turned HIV into a manageable, chronic disease. The number of older people with AIDS is growing in many European countries. We described the impact of AIDS among persons aged 50 years or more in Italy and compared the characteristics of these cases with those of persons diagnosed with AIDS at an age younger than 50. Methods. The source of data was the Italian AIDS Registry, from 1982 to 2011. We defined "older" persons those aged 50 years or more, and younger individuals those aged less than 50 years. We built two multivariate logistic regression models: the first one to identify factors associated with being older, and the second one to identify AIDS-defining diseases correlated with being older. Variables with a P value of < 0.05 were entered in the model. Results. Of the total AIDS cases, 10.5% were among persons older than 49 years. This proportion progressively increased from 0.0% in 1983 to 26.4% in 2011. Among older cases, the incidence of AIDS was 2.0 per 100 000 residents in 1996, then decreased to 1.4 per 100 000 in 2000 and levelled off around 1 per 100 000 residents until 2011. Compared to younger cases, older cases were more frequently males, Italians, diagnosed with AIDS in recent years, residing in Northern or Central Italy, non-injecting drug users, and late testers. Discussion. These findings stress the need for physicians to consider carefully the possibility of HIV infection among older individuals not to miss the opportunity to deliver prevention messages, offer HIV testing, and make an early diagnosis.
Abstract in English:Purpose. To determine if the use of combined HLA matched limbal stem cells allograft with amniotic membrane transplantation (AMT) is a safe and effective prophylactic surgical procedure to prevent corneal graft after penetrating keratoplasty (PK). Methods. We report the case of a 17 years old patient with a history of congenital glaucoma, trabeculectomy and multiple corneal graft rejections, presenting total limbal cell deficiency. To reduce the possibility of graft rejection in the left eye after a new PK, a two step procedure was performed. At first the patient underwent a combined HLA matched limbal stem cells allograft (LAT) and AMT and then, 10 months later, a new PK. Results. During 12 months of follow-up, the corneal graft remained stable and smooth, with no sign of graft rejection. Conclusions. In our patient, the prophylactic use of LAT from HLA-matched donors and AMT before PK, may result in a better prognosis of corneal graft survival.