During the process of neurogenesis, the stem cell committed to the neuronal cell fate starts a series of molecular and morphological changes. The understanding of the physio-pathology of mechanisms controlling the molecular and morphological changes occurring during neuronal differentiation is fundamental to the development of effective therapies for many neurologic diseases. Unfortunately, our knowledge of the biological events occurring in the cell during neuronal differentiation is still poor. In this study, we focus preliminarily on the relevance of the cytoskeletal rearrangements, which earlier drive the morphology of the neuronal precursors, and later the migrating/mature neurons. In fact, neuritogenesis, neurite branching, outgrowth and retraction are seminal to the development of a fully functional nervous system. With this in mind, we highlight the importance of iPSC technology to study the processes of cytoskeletal-driven morphological changes during neuronal differentiation. Glutathione is considered an antioxidant that protects the cells against oxidative stress. Glutathione (GSH) is a tripeptide thiol antioxidant molecule, present within cells at millimolar concentrations (1-10mM). In response to increased oxidation, glutathione becomes oxidized to its disulfide form (GSSG). The disulfide form, GSSG can be reduced back to GSH via glutathione reductase, at the expense of oxidation of NADPH. In the cytosol, the ratio of oxidized to reduced GSH is around 100:1, while in the ER, which has a more oxidizing environment to permit oxidative protein folding, the ratio of GSH/GSSG is around 3:1 . i. i123]. ntiation . This prin vitro into several cell types, including neurons and glial cells, allowing to follow their molecular, biochemical and morphological features during human neurogenesis/neuritogenesis in a dish. iPSCs have been compared to ESCs and many studies demonstrated that they present molecular and cellular properties very similar to ESCs [A systematic and integrated analysis will help us to understand MT, AF and IF functions and dynamics in the nervous system during development and disease. One possibility to deeply investigate the mechanisms of cytoskeletal rearrangements during neurogenesis is offered by iPSCs. In fact, iPSCs can be differentiated  to ESCs , 126. Un to ESCs -129. TheIn addition to the iPSC technology, the recently developed genome editing technique known as CRISPR/Cas9 offers great advantages to cellular reprogramming, and a great advancement to the reliability of iPSC model for human diseases and for its applications in translational medicine. The CRISPR/Cas9 technology for editing genomes, allows scientists to make changes in DNA. In particular, it offers the possibility to insert or remove genomic mutation in specific genes and to correct known mutations. Thus, the CRISPR/Cas9 technology allows to obtain isogenic control iPSCs, where the mutations present in the patients are reversed to the wild type sequence. Importantly, this technique allows to perform studies on iPSCs obtained from specific patients and on genetically corrected cells that have the same genetic background of the affected cells -132. Morin vivo environment account on in utero electroporation, which allows transfection of plasmid DNA into restricted areas of the brain and is performed on small embryos through electroporation. This helps to study in vivo processes like cell differentiation, cell migration and axon guidance [i.e. the mesenchymal cells) and therefore, the effects observed may result from the influence of different cell types on the developing neural tube. In addition to this, it can not be performed early in development  and this impedes the possibility that the gene of interest may have an effect very early in development. Moreover, it is limited to investigations in the murine/rodent models and it is possibile that it is not suitable to model several human neurologic disorders. For example, therapeutic approaches developed in Amyotrophic lateral sclerosis (ALS) animals with encouraging results were not successful in human clinical trials [Alternative techniques for studying the generation and differentiation of neurons in their guidance , 135, bul trials .in vitro, which resembles features of human cortical development and it has been used to model microcephaly due to CDK5RAP2 mutation [in vitro culture system has the great potential to model still poorly known human neurodevelopmental and neurological pathologies.In conclusion, a new methodology that allows to study neurogenesis in a 3D system is the cerebral organoid technology, that has been obtained from human iPSCs and allows to develop mini-brains mutation . Thus, tAn example on how several technologies can be integrated to establish a reliable human disease model based on the iPSC technology is offered by Chen et al. . In factIn light of the studies related to the discovery of human mutations leading to neurologic diseases and the new evidence on the cytoskeleton as an active player of cell fate determination, it is compulsory to deeply investigate the mechanisms regulating and regulated by the cytoskeleton. This may offer the opportunity to understand the physio-pathology of many human neurologic diseases and to pave the way for future therapeutic intervention.Moreover, recent advances in live imaging will allow to reveal the dynamics of cytoskeletal organization during neural development and the combination of these methodologies together with the iPSC technology will speed the pace for therapeutic intervention of many neurologic diseases [as reviewed in


Gravity is crucial for spatial perception, postural equilibrium, and movement generation. The vestibular apparatus is the main sensory system involved in monitoring gravity. Hair cells in the vestibular maculae respond to gravitoinertial forces, but they cannot distinguish between linear accelerations and changes of head orientation relative to gravity. The brain deals with this sensory ambiguity  by combining several cues with the otolith signals: angular velocity signals provided by the semicircular canals, proprioceptive signals from muscles and tendons, visceral signals related to gravity, and visual signals. In particular, vision provides both static and dynamic signals about body orientation relative to the vertical, but it poorly discriminates arbitrary accelerations of moving objects. However, we are able to visually detect the specific acceleration of gravity since early infancy. This ability depends on the fact that gravity effects are stored in brain regions which integrate visual, vestibular, and neck proprioceptive signals and combine this information with an internal model of gravity effects. All axons pieced together would cover the distance between the Earth and the Moon (about 400.000 km). One would assume that we are able to monitor gravity directly by means of our sensory systems, but this is not the case. As we shall review in this paper, gravity effects are only extrapolated indirectly by the brain by combining multisensory information with internal models, that is, with neural processes which mimic a physical event.Intuitively, sensing gravity effects should be a trivial problem for a complex nervous system such as our own. On the one hand, direction and magnitude of gravity are quasi-constant on Earth. Thus, gravitational acceleration varies by <1% by changing latitude or altitude, while the vertical deflection is <0.05°. On the other hand, our nervous system is computationally high-powered, being endowed with ≈10Sensing and coping with gravity is crucial for space perception, control of upright posture, and generation of movements. Indeed, gravity provides a unique reference axis to which we can anchor body orientation and monitor orientation changes. Gravity effects on limb and body movements are two-sided, insofar as gravity acts both as a perturbing force that must be counteracted to avoid falling down and as a facilitating force which allows walking and running via the ground contact forces.The vestibular receptors lie inside the labyrinth of the temporal bone. Somewhat similar sensors evolved first in invertebrates and then in vertebrates about 500 Myrs ago . The vesg cos α, where α is the angle of tilt of the head relative to the gravity direction, whereas the component of gravitational acceleration projected on the utricle macula is g sin α. Gravity accelerates the body downwards and is opposed by the ground contact forces. These contact forces are transmitted to all body segments and to the head, where they are monitored by the otolith receptors. These receptors respond to a tilt of the head relative to gravity, but in general they cannot provide a unique measurement of gravity effects. As any accelerometer, also the sacculus and utricle respond to net gravitoinertial accelerations, and they cannot distinguish between the gravitational and the inertial component. For instance, otolith afferents cannot distinguish whether we are accelerating backward (a) resulting from the vector difference between the gravity vector (g) and the linear acceleration vector (f):The widely distributed polarities of response of the otolith receptors in the maculae allow monitoring acceleration vectors in any arbitrary direction . These rbackward  or tiltibackward . This isThis intrinsic ambiguity can give rise to perceptual illusions which become extremely dangerous under some specific conditions. For instance, during takeoff, an airplane pilot may sense an erroneously high value of upward pitch, because the resultant of the vector sum of gravity and backward inertial acceleration is misperceived as the actual orientation relative to the vertical. Under conditions of low visibility and without the aid of instruments, the pilot may then attempt to correct the aircraft attitude by pitching downward, with the risk of impacting the ground. Spatial disorientations originating from sensory ambiguities of this kind are often involved in severe aviation accidents .Under usual conditions, however, we have no difficulty in sensing the orientation of the head relative to the vertical, even with the eyes closed and in the presence of appreciable accelerations, provided the latter have short duration (as those of a car or train). This is because the ambiguity can be solved by the brain using a variety of “tricks.” First, the brain filters the otolith signals, so that the low-frequency (longer lasting) signals are automatically interpreted as a change in the tilt angle of the head relative to gravity . Conversω denotes the angular velocity, and × denotes vector cross-product. An internal three-dimensional estimate of the gravity vector in head coordinates can then be obtained by integrating  occurs in the so-called Vestibular-only neurons of the vestibular nuclei, in the rostral portion of cerebellar fastigium and nodulus [Neural correlates of the operations described above have been discovered in the monkey by Angelaki and colleagues, who found that the neural computation of translation , and visual signals. Vision, in particular, provides both static and dynamic  signals about the orientation of the body relative to the vertical. Finally, also the so-called efference copy of motor signals  and internal estimates of the body axis orientation  contribuhttp://en.wikipedia.org/wiki/File:Bomarzo_parco_mostri_casa_pendente.jpg).Under normal light conditions of daily life, there are several visual cues which point to the direction of gravity . Thus, tExcept when some cue is so strong as to drive space perception by itself , neural estimates of gravity direction normally are computed by the central nervous system as a weighted average of multicue information, including vestibular, visual, neck, and truncal signals, plus a prior distribution about head and body orientation based on experience , 22–24. So far, we considered the problem of monitoring the direction of gravity. A different problem concerns monitoring its magnitude. How do we estimate the gravitational acceleration of an object in a visual scene? This situation occurs quite frequently, as when we experience the vision of objects in free-fall, projectile, or pendulum motion. In addition to object motion, also self-motion may involve visual stimuli (optic flow) accelerated by gravity, as when we fall or jump from a height. When confronted with gravity effects, the visual system faces a unique challenge. In contrast with body graviceptors , the visual system does not deal with physical gravity directly, but only with the acceleration of the retinal image. Whereas gravitational acceleration is constant at a given location, the corresponding retinal acceleration varies inversely with the viewing distance (distance between the observer and the scene). Therefore, the visual estimate of gravity effects on a target motion requires accurate estimates of both image acceleration and viewing distance. Both types of estimates are potentially problematic. Indeed, while the visual system is very accurate in velocity estimates, it is rather poor in acceleration estimates. In fact, the visual discrimination of acceleration is about 5 times worse than that of velocity . Also, vAn internal model of gravity effects represents a critical component of the visual estimates in addition to raw sensory signals. Indeed, gravity represents a special case of visual acceleration to which we are exposed since birth. Therefore, it is very likely that it has been internalized in the brain. In fact, it has been shown that gravity effects on a visual object are detected early in life . BetweenStrikingly, however, the motor system has an implicit knowledge of physics which is much better than that available to the cognitive system . Daily lThis tuning persists at the beginning of orbital flight, despite the sensory and cognitive evidence of weightlessness, and despite the motor responses being inappropriate to the new conditions . These rGravity effects are taken into account not only by the motor system but also perceptually, as when people judge the duration of motion of a falling target , 33 or tJust as in the case of the estimates of the direction of gravity, also those of visual gravitational acceleration generally depend on a combination of multiple cues, and such combination may obey Bayes' rules. The internal model provides the prior, while various sensory cues provide the likelihood of the estimate with a reliability that depends on the context. In one study, observers were asked to judge the duration of motion of a target accelerating in one of four different directions, downwards, upwards, leftwards, and rightwards, relative to a visual scene . DownwarThe interaction of the visual signals with vestibular signals about subject orientation relative to physical gravity was shown in a study performed during a parabolic flight campaign . During The hypothesis that the effects of gravity on a target motion are taken into account by combining multisensory information, including visual and vestibular cues, is supported by human neuroimaging studies. In a series of fMRI studies , 38–40, As reviewed earlier, electrophysiological studies in the monkey showed that a population of Purkinje cells in the caudal cerebellar vermis encodes head tilt, thus reflecting an estimate of gravity direction based on vestibular information . InteresIn sum, the neuroimaging studies reviewed above indicate that the effects of gravity on visual motion are encoded in a highly distributed cortical-subcortical network. Several regions of this network colocalize with the regions independently activated by vestibular caloric stimuli . These rWe argued that an apparently simple problem such as that of monitoring gravity effects on our body and on the external environment is in fact computationally very demanding, even for a high-powered brain such as that of primates. Measurements derived from individual sensory organs are often ambiguous  and noisy . However, the combination of multisensory signals  and the reliance on internal models of physics yield estimates which are very accurate under normal conditions, but which can fail badly under anomalous conditions (such as the early phases of space flight). Central processing of multisensory information and internal models occurs in a widely distributed network of cortical and subcortical regions. The extensive integration of sensory and motor information in this network makes gravity-related information available to many vital functions of the organism.


In this review, we compare the use of coercion in mental health care in Germany and in the Netherlands. Legal frameworks and published data on involuntary commitment, involuntary medication, seclusion, and restraint are highlighted as well as the role of guidelines, training, and attitudes held by psychiatrists and the public. Legal procedures regulating involuntary admission and commitment are rather similar, and so is the percentage of involuntary admissions and the rate per 100,000 inhabitants. However, opposing trends can be observed in the use of coercive interventions during treatment, which in both countries are considered as a last resort after all other alternative approaches have failed. In the Netherlands, for a long time seclusion has been considered as preferred intervention while the use of medication by force was widely disapproved as being unnecessarily invasive. However, after increasing evidence showed that number and duration of seclusions as well as the number of aggressive incidents per admission were considerably higher than in other European countries, attitudes changed within recent years. A national program with spending of 15 million € was launched to reduce the use of seclusion, while the use of medication was facilitated. A legislation is scheduled, which will allow also outpatient coercive treatment. In Germany, the latter was never legalized. While coercive treatment in Germany was rather common for involuntarily committed patients and mechanical restraint was preferred to seclusion in most hospital as a containment measure, the decisions of the Constitutional Court in 2011 had a high impact on legislation, attitudes, and clinical practice. Though since 2013 coercive medication is approvable again under strict conditions, it is now widely perceived as very invasive and last resort. There is evidence that this change of attitudes lead to a considerable increase of the use of seclusion and restraint for some patients. Mental disorders are by definition mental and behavioral disorders. Severe deviations of behavior such as violent, suicidal, and many other features of bizarre and inappropriate behavior belong to typical symptoms of mental disorders. Up to nowadays, besides of psychotherapeutic and pharmacological interventions, the use of coercion is sometimes considered as inevitable in managing dangerous and severely disturbing behavior. The issue of coercion with its many facets is the oldest problem of psychiatric institutions. The history of psychiatry is essentially characterized by attempts to abolish coercion and by failing of such attempts, up to episodes of excessive violence against mentally ill people such as during the Nazi regime in Germany . Not accThus maybe the most fundamental ethical conflict in clinical psychiatry exists between the ethical principles of respect for the patient’s autonomy and dignity and the duty to avoid harm for the patient and others. The undesirable result of this conflict sometimes is the use of coercion, which can occur in many different aspects of psychiatric treatment – coercive admission to psychiatric hospitals, safety measures within psychiatric institutions, coercive treatment inside and outside psychiatric hospitals, referral to forensic psychiatric units, and more. All of these measures are increasingly under regulation of laws, court decisions, guidelines, and ethical considerations, and have repeatedly been a subject of concern in the public and in the media in many developed countries. Moreover, within recent years, digital data processing from electronic charts has provided the possibility to discuss the issue of coercion in psychiatry not only based on qualitative arguments but also based on data covering the practice of mental health care.Germany and the Netherlands are neighboring countries with a comparable social structure, comparable social standards, and roughly similar politics, both being confronted with similar challenges to find appropriate, human, and safe solutions for the use of coercion in mental health care. The challenge is to balance requirements and expectations of patients, relatives, hospital staff, the justice systems, policy makers, and society as a whole. In this article, we will elucidate the current practice in both countries, the differences and how they emerged and interactions with learning from each other’s practice.According to the complexity of the issue, this is a review based essentially on personal knowledge of the authors who had a kind of central role in collecting and interpreting data and phrasing clinical recommendations in the respective country. The literature review covers the relevant publications of the last decade. It is amended by knowledge of relevant court decisions, policies, clinical guidelines, legislation changes, initiatives, and current, still unpublished developments. We selected 10 topics related to the use of coercion, which taken together to cover the relevant aspects sufficiently.Coercive interventions in psychiatry are regulated in the law of guardianship (Betreuungsrecht), as a federal law valid everywhere in the country, and in the public laws  with slightly different regulations in the 16 German federal states (Bundesländer)  . It had Currently, the Law for special admissions in psychiatric hospitals Bijzondere Opnemingen Psychiatrische Ziekenhuizen (BOPZ) primarily regulates admission and allows coercive interventions to some extent under strict conditions. The law contains two different sections describing the procedures of involuntary admission. The first relates to short-term involuntary admission because of immediate danger for the patient himself or others and has to be initiated by the mayor, accompanied by a written certificate of a physician. The other procedure is mandated by a judge and concerns long-term admissions aiming at treatment of patients who suffer from a severe psychiatric disorder leading to danger for others or self, including severe self-neglect or social breakdown. After involuntary admission, community treatment orders can be used.This law regulates explicitly, which measures are possible in case of emergency. Seclusion, mechanical restraint, and enforced medication may be applied for no more than 7 days. Actions taken are communicated to the Dutch health inspectorate. If coercive measures are required for more than 7 days, a treatment plan has to be established and has to be approved by a psychiatrist not involved in treatment. The patient can take legal action also against the independent psychiatrist’s second opinion. In practice, procedures associated with coercive treatment can be complex and time consuming and may delay remission if a patient is reluctant to accept treatment. This law is effective since 1994.Psychiatrists have to document, which measures were taken and are obliged to use the least restrictive method. According to a governmental order of 2012, documenting all coercive measures at an accuracy of 15 min is mandatory, allowing for a nation-wide registration of coercive measures and careful monitoring at ward, hospital, and national level . In 2008Involuntary outpatient treatment has never been legalized in Germany. Only in 2003, the Federal Council (Bundesrat) passed a draught legislation, which provided an amendment to the guardianship law, allowing delivery of outpatients to treatment by force. However, after some intense political debates and strong objections by patients’ organizations, the Federal Parliament (Bundestag) rejected the draught law in 2004. Community treatment orders are possible only for former forensic patients in specialized outpatient services for these patients.Under the current Dutch law involuntary outpatient treatment, i.e., administering drugs by direct coercion, is not legal. However, it is possible to mandate community treatment orders. If the patient does not comply with the conditions of the outpatient treatment order, involuntary admission can be immediately put into effect. Besides of taking prescribed drugs, the patient can be obliged to visit outpatient services at regular intervals, and keeping to appointments. Violation of these obligations can lead to an immediate search warrant by the local authorities followed by an involuntary admission. In the near future, Dutch law will allow involuntary outpatient treatment irrespective of admission under two separate laws for patients with a psychiatric illness and patients with a mental handicap or a severe old age impairment.Hospital admission under coercion is possible under different pathways: by a court decision, by decision of the police in some German federal states and, more informally, but not unfrequently, by psychological pressure of doctors and relatives. Thus no reliable data on the frequency is available. Some earlier publications probably merged involuntary admission with involuntary commitment . InvolunThe number of patients detained in forensic psychiatry in Germany increased about 2.5-fold from about 4,000 in 1993 to about 10,000 in 2009 , similarIn a study comparing involuntary placements of mentally ill people across EU member states, the number of civilly committed patients was determined as 163,000 in the year of 2000, yielding a rate of 175 per 100,000 population and a quota of 17.7% of all psychiatric admissions. The rate was one of the highest in a range between Portugal  and Finland , and even so the quota, ranging from 3.2%  to 30% (Sweden)  is displAgain, there are considerable and not convincingly explained differences between the 16 German federal states , rates aAs stated above, in the Netherlands, hospital admission is regulated in a special law regulating involuntary admissions in psychiatric hospitals (Law BOPZ). As in Germany, admissions to forensic settings can be mandated after a criminal offense, by the “law regulating principles of care for people under governmental mandate” (beginselenwet verpleging ter beschikking gestelden). Table As mentioned above, in 2011 the Constitutional Court (Bundesverfassungsgericht) decided that the current laws are unconstitutional. Data how frequently involuntary medication really happened until then is not available, amongst others due to the lack of clear definitions. From then on, involuntary medication was only possible in cases of acute emergency until the novel law formulation was adopted by the parliament (Bundestag) in the beginning of 2013. Thus currently involuntary medication is possible after a distinct court decision and an expert opinion by a doctor not involved into treatment. Data on how frequent such kind of involuntary medication and also medication in emergencies happens is not yet available. It is known from anecdotal evidence that sometimes procedures are very long and cumbersome resulting in periods of weeks or even months with patients being committed without receiving treatment. The latter is a point of concern for psychiatrists with respect to ethical considerations and ward atmosphere . InvolunAccording to Dutch law, a psychiatrist has to apply the least invasive approach in dealing with aggression or other behavior, which is dangerous for the patient himself or others. The patient’s mental capacity and ability to balance decisions determine the extent to which psychiatrists are allowed to impose treatment against a patient’s will. In the Netherlands, involuntary medication was traditionally viewed as a more invasive approach than the use of seclusion, so that the frequency of its use was only a fourth of the use of seclusion after implementation of the law for special admissions , 19. WitThere is some data available on the use of freedom-restrictive coercive measures in psychiatric hospitals, but only very little data indicating whether the measure used is seclusion or mechanical restraint. Anecdotal evidence indicates that seclusion is considered as the measure of choice in child- and adolescent psychiatry and in forensic psychiatry, while in adult general psychiatry many hospitals prefer to use mechanical restraint and a considerable number does not provide seclusion rooms. A survey of the use of coercive interventions in psychiatric hospitals in Germany in 2012 revealed that 51% of the responding hospitals used seclusion, 53% with continuous observation, and 16% without continuous observation. However, these figures have to be interpreted with caution since the response rate of this survey was only 20% . Data onTraditionally, and especially after a change in the Dutch mental health act, seclusion was the coercive measure of first choice in the Netherlands , 25. BetAfter 2007, an increasing number of hospitals have registered their data in a daily database on the use of coercive measures; this database is now available on a national level. The database was designed similarly to the database developed by the German working group for prevention of violence and coercion in psychiatry . In the Mechanical restraint has been considered as the measure of choice in the management of violent behavior in general adult psychiatry until within recent years the idea of the necessity to provide a broader range of possible interventions gained importance. The first publication reporting data on the use of such measures in a hospital stems from 1991 . BeginniFurther comprehensive data have not been published since then. Smaller data sets and unpublished results from the participating hospitals indicate that the percentage of admissions exposed to coercive measures and the mean duration of a coercive measure have slightly decreased since then .A survey of the use of coercive interventions in psychiatric hospitals in Germany in 2012  revealedWhilst seclusion is the measure of first choice, mechanical restraint is seldom used in adult psychiatric care. It is primarily used in old age psychiatry for people with dementia . Table 5So-called net-beds or cage-beds, which still are in use in Austria and some other European countries  have beeIn 2007, a group of German psychiatrists and nurses visited a hospital in the UK to study the practice of physical restraint without mechanical devices. Since then, a working group of nurses developed a new manual-based technique called four-step-program. The technique comprises holding techniques without pain-inducing elements accompanied by continuous verbal de-escalation and offers to the patient to cooperate . This ap“Time out” (order to the patient to stay in his/her own room for a defined time) is mostly used in child and adolescence psychiatry, in adult psychiatry in 13% of the hospitals .In the care for people with dementia, net-beds are considered as a better alternative for mechanical restraint. However, the use of “Domotica” , which cOne in one support is considered as a preferable alternative to coercive measures. Also, time out and room programs are viewed as alternatives. Documentation of these measures proved to be less reliable than of seclusion or restraint, primarily because nurses consider these measures as “care as usual” rather than as containment or coercive measures .About 20 years ago, de-escalation training for psychiatric hospitals was essentially unknown in Germany. This has continuously been changing since then. After about the year of 2000, de-escalation trainings have been introduced from the Netherlands and the U.S. and became increasingly popular and widespread. Today, private and hospital-based organizations as well offer different kinds of de-escalation techniques and trainings for different patient populations. The training of such techniques for all professionals with patient contact is strongly encouraged by the current German guidelines . In the Awareness concerning dangerousness of psychiatric patients at closed wards arised from halfway the 90s . SeveralAn evaluation of initiatives within the nation-wide program showed that 92% of Dutch mental health care participated, while all of the participating hospitals provided some way of aggression containment training. From 2011 onward aggression training is obligatory and participation is subject to audits of the Dutch health inspectorate. At least once in 2 years most mental health professionals participate in some kind of training. However, participation of nurses in the program as well as in these trainings is by far higher than of doctors, psychologists, or psychiatristsThe first guideline on the use of coercive measures, an internal guideline framed by doctors and nurses of our (T.S.) psychiatric hospital, was published in 1998 . A natioThe current clinical guideline was compiled in 2005, which is before the nation-wide effort to reduce seclusion. A new guideline is currently under way. More recently, in line with the English Psychiatric Intensive Care Units (PICU’s) a number of hospitals are developing intensive care as a specialization of Mental health care. Development of intensive care units not only aims at new building environments , but alsThe awareness of the ethical and legal problems in the use of any kind of coercive interventions has considerably been increasing during the past years, due to the changes of legislation induced by the constitutional court, continuing criticism by patients’ organizations, criticism by the German Institute for Human Rights, and others and due to public debates on justification of long lasting detention in forensic psychiatry in a special case. This increased awareness is reflected in recent publications in German journals, by an increased importance of the issue in education and training and by changes in legislation. The willingness to reduce the use of coercion and to replace the use of mechanical restraint by softer techniques such as de-escalation and holding is widely present, but to some extent decelerated by concerns of future budget restrictions by the introduction of a new reimbursement system for psychiatric hospitals.The wide use of electronic charts has considerably improved the possibilities to record all kinds of coercive measures in detail and to perform hospital comparisons. First German federal states will introduce a legal obligation to register coercive measures and to collect them at a central institution in 2014.Further changes in legislation are also expected, which refers particularly to forensic psychiatry. A reform of the admission criteria, which are intended to be phrased more restrictively, is intended. Currently no details are known, however.In Dutch mental health care, three changes are simultaneously under way. First, the Government together with health insurance offices has been initiating a policy to reduce the number of psychiatric hospital beds by 30% within the next 5 years. This policy was endorsed in 2011, became effective in 2012 and has lead to closure of more than 10% of psychiatric hospital beds over the last 2 years . This poThe second change encompasses the closure of a large number of forensic beds. This closure is not only due to Governmental policy, but also an effect of advice given by an increasing number of lawyers of mentally ill offenders to refuse collaboration with psychiatric observation. Mostly, this observation is not in the interest of the offender as it usually leads to longer time in detainment.The third change is a pending change in the Law on involuntary admission. In 2015, or at the latest 2016 the current law is to be replaced by two laws regulating involuntary admission as well as involuntary treatment. The first new law will regulate involuntary treatment of psychiatric patients, inside as well as outside of the psychiatric hospital. Under this law, involuntary treatment will be possible under a number of strict conditions. These are related to being a danger for self or a danger for others. The second new law will regulate the involuntary care for patients with a mental disability or a cognitive disorder who are admitted to other than psychiatric services. Both laws aim at treatment rather than at admission. We expect that these laws will have a substantial impact on the distribution of the current figures on coercive measures. While currently seclusion is the measure of first choice and the most used, we expect that this will change when the new law will allow involuntary treatment to a far larger extent than the current law does.We tried to give a comprehensive overview on the role of coercion in mental health care in Germany and the Netherlands, in terms of clinical practice, policies, ethical views, and the expected future. Mental health care in these neighboring countries features many similarities and interesting differences as well. Both countries have a comparable per capita income and spend comparable percentages of their gross domestic product for health care and mental health care. In both countries, ethical questions around topics of mental health have been repetitively issues of ongoing public debate. However, the historical background is different. In Germany, psychiatry is still (or at least its exponents feel) burdened by the grim heritage of Nazi psychiatry, when psychiatrists and representatives of the states abused the so far well-doing health care system to record, sterilize, and later kill 10,000 of patients. Against this background, for example the German attitude to euthanasia is very different to the Netherlands, where a relatively liberal practice has been legalized in recent decades. In Germany, instead, the code of medical ethics explicitly forbids physicians even any assistance in suicide, even if it may not be unlawful. Similarly, whatever psychiatrists and judges do against a patient’s will, in Germany always is under latent suspicion of Nazi psychiatry. Nonetheless, the legal framework for involuntary admission and detention of mentally ill people is rather similar in Germany and the Netherlands. Also the rate of involuntary admissions per 100,000 inhabitants is somewhat lower in the Netherlands, but not to a striking extent, and the percentage (quota) of involuntary admissions to psychiatric hospitals is nearly identical. However, the rise of the quota of involuntary admissions within the past 10 years, which has been found in the Netherlands could not be confirmed for Germany. The reasons are unknown.In some aspects, the practice of the countries has fertilized each other. De-escalation and aggression-management trainings have been introduced in Germany by commercial trainers from the Netherlands about 15 years ago. By now such trainings are recommended by guidelines and implemented in routine practice in most psychiatric hospitals . On the Most striking, however, is the diverging development of attitudes toward the use of different coercive interventions. For a long time, the use of coercive medication was viewed as most restrictive intervention in the Netherlands, being an intrusion into the body. Accordingly, legal requirements were high and, in practice, remained confined to emergency situation, since psychiatrists themselves held the same attitude. However, becoming aware that reported aggressive incidents in psychiatric hospitals as well as number and duration of seclusions were higher than in any other European country , the assGermany, however, seems to be on a way just in the direction where the Netherlands came from. Until 2011, the use of involuntary medication was widely accepted, possible in involuntarily committed patients and viewed as therapy, not as a mode of restraint . Only for patients committed by Guardianship law a separate decision by a judge was required. Since the decisions of the Constitutional Court in 2011, there has been a considerable change in opinions held about coercive medication, but just in the other direction than in the Netherlands. Though laws have been revised since then and coercive medication is possible again under the strict requirements defined by the Constitutional Court, psychiatrists have recognized that it has been possible in most cases to convince patients to accept treatment without coercion and they rarely apply at courts for the respective intricated procedures. Attitudes of physicians, patients’ representatives, and the general public toward the use of coercive medication seem to have become more critical. The change of attitude is best characterized by the statement by the Ethics Committee at the Federal Chamber of Physicians published in 2013 , which eImportantly, evidence does not seem to play a role in most of discussions on the issue. Studies showed that patients do not necessarily prefer one coercive practice above the other; in several studies it was found that in case of a need for a coercive measure almost half of patients prefer medication, and the other half prefer seclusion . IdeallyOne other large difference in coercive practices is the use of outpatient commitment and involuntary treatment in the Netherlands as opposed to Germany. Even the new Dutch law that will be in practice the coming years, heavily invests in outpatient involuntary treatment, thereby hoping to reduce involuntary admissions. Scientific evidence, however, points in another direction, since all three randomized clinical trials studying outpatient commitment found that outpatient commitment did not lead to a reduction of the number of (in)voluntary admissions –59.Further differences between the countries strike with respect to the culture of setting standards and evaluations. In the Netherlands with the Dutch health inspectorate there is a governmental authority having the power to enforce changes in practice and the power to phrase and control obligatory standards such as for intensive care units. The awareness of the need to evaluate actions taken and to base political decisions on available evidence is not really widespread but is at least increasing. In Germany, in contrast, the federal government is not responsible for mental health care, which is under regulation of 16 different states instead. Hospitals are led by different public, private, and confessional providers, and the German Society of Psychiatry and Psychotherapy (DGPPN) basically is a club of psychiatrists with no political authority. Therefore, there is no control whether guidelines are followed, quality standards are based mostly on agreement and evaluation of measures has been scarce.For the future, we hope that both countries will benefit from the observation of the developments in the respective other country and include evidence from scientific studies into legislation and political decision making, realizing a reasonable, evidence-based practice committed to therapeutic goals, and human dignity in a modern civil society.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


This literature review evaluates the current state of knowledge about the impact of process redesign on the quality of healthcare.Pubmed, CINAHL, Web of Science and Business Premier Source were searched for relevant studies published in the last ten years [2004–2014]. To be included, studies had to be original research, published in English with a before-and-after study design, and be focused on changes in healthcare processes and quality of care. Studies that met the inclusion criteria were independently assessed for excellence in reporting by three reviewers using the SQUIRE checklist. Data was extracted using a framework developed for this review.Reporting adequacy varied across the studies. Process redesign interventions were diverse, and none of the studies described their effects on all dimensions of quality defined by the Institute of Medicine.The results of this systematic literature review suggests that process redesign interventions have positive effects on certain aspects of quality. However, the full impact cannot be determined on the basis of the literature. A wide range of outcome measures were used, and research methods were limited. This review demonstrates the need for further investigation of the impact of redesign interventions on the quality of healthcare. It called upon providers to ensure more efficient, safe, timely, effective, patient-centered and equitable care [Growing expenditure on healthcare and ongoing efforts to improve services give impetus to change in processes and systems . As lifeble care , 4.Although some initiatives were undertaken before 2001, the publication of the IoM report served as a catalyst . NumerouThis study seeks to establish, through a review of the literature, what is known about the influence of redesigning healthcare processes on the quality of care delivered in the last ten years. Its specific aims are to report (a) the content of the interventions (their objectives and implementation methods); (b) the characteristics of the redesign investigations (study design and setting); and (c) the outcomes on quality of care . The objective of this literature review is to summarize the current state of knowledge on redesigning healthcare processes and present an overview of improvement efforts in the field.The review applies several key concepts. The first is ‘process redesign’, defined as any methodology that focuses on creating new processes or changing existing ones in major ways . That deAn extensive search in Pubmed, CINAHL, Business Source Premier and Web of Science, using predefined search terms and free-text words;A search of the reference lists in the included full-text articles.The search strategy was guided by the PRISMA statement . It was From March 2014 through April 2014, the databases PubMed, CINAHL, Web of Science and Business Premier Source (EBSCO-host) were searched by one reviewer (JvL). In PubMed, MeSH terms were used; CINAHL Heading terms were used for CINAHL; and Thesaurus terms were used for Business Premier Source. For Web of Science no predefined keywords were available. Additionally, free-text words were used for all databases. An overview of the search terms is given in The database search was limited to articles published in English between January 2004 and April 2014. Articles were included if they presented original research on redesign of healthcare processes, quality of care, and if they assessed the same outcome measures before and after an intervention. , prior to inclusion in light of the Standards for Quality Improvement Reporting Excellence (SQUIRE). That checklist provides guidelines for reporting of studies assessing the effectiveness of interventions to improve quality and safety of care. Its 19 items comprise 38 components . Any disAfter compliance with the reporting guidelines had been assessed, data were extracted independently by three reviewers  from the results and discussion/conclusion sections. For that purpose, a form was developed. The form contained variables such as publication year, study objectives, characteristics of the redesign and outcome measures. Any disagreements were resolved through consensus. Meta-analysis could not be performed because the studies used different outcome measures and research designs.Figure Table Table Fourteen studies were performed in the USA , 25–29, In summary, half of the redesign interventions were characterized as ‘lean thinking’ and took place in a hospital setting. Length of follow-up and sample size diverged widely, and most studies used an uncontrolled before-and-after design to evaluate the effectiveness of the intervention.Table Changes in effectiveness were demonstrated in 12 studies , 27, 29.Two studies , 15 founNone of the studies measured equity of care. Eight mentioned other outcomes unrelated to the six quality dimensions, such as changes in provider satisfaction , 22, staThe need to redesign healthcare processes in order to address deficits in quality of care and create more sustainable care processes is acknowledged worldwide , 3, 5. TApplying the SQUIRE guidelines demonstrated that overall the reporting was weak. Given the study designs, the results are subject to bias, as changes in the research settings might be responsible for the effects , 31. In To the best of our knowledge, this is the first systematic review of the effect of process redesign on quality of care, using broad definitions for both study setting and types of redesign. Elkhuizen et al.  performeSpecific redesign interventions have been reviewed recently. In one, Mazzocato et al.  reviewedThe impact of quality-improvement collaboratives was reviewed by Schouten et al. . AlthougThe findings of the present review are therefore in line with those of earlier studies on this topic in the sense that a broad perspective on redesign interventions and settings generates similar results.Even though a systematic approach guided this review, the findings might be subject to some bias, which should be kept in mind when interpreting them.First, publication bias might be present: most of the studies report on positive findings, and there is a general tendency in scientific literature to over-represent positive results . As prevSecond, limiting the scope by only including studies that used before-and-after measurement might have led to some selection bias. Nonetheless, limiting the search strategy did ensure a solid basis for comparison of the effects of the redesign interventions.Third, since the terminology used to describe the interventions varies greatly, we could have missed some relevant studies. We circumvented this problem by searching multiple databases with database-specific headings like MeSH terms and amplifying the strategy by searching with free-text words.Fourth, the SQUIRE guidelines might not be the only instrument for assessing excellence in reporting. Although they were specifically developed to assess reporting excellence for this type of studies, the checklist does not provide a value judgment on the methodology (or strength of evidence) of the studies . NonetheFinally, using the IoM dimensions of quality of care might have made it difficult to compare findings across studies. Since the IoM does not specify which outcome measures belong to the six dimensions, there is room for interpretation. Even though this might have influenced the presentation of findings in this review, using the IoM dimensions facilitated classification of the outcomes, thereby revealing gaps in the research literature.Scientific evidence supporting process redesign in healthcare is limited and inconsistent. Outcome measures for the effect of redesign interventions vary across studies to the extent that it is impossible to draw conclusions about the impact on overall quality of care, or even on some of its dimensions. The findings of this systematic review suggest that the evaluation of process redesign interventions should be improved to reveal their full effect. It should meet the basic standards for reporting (SQUIRE guidelines) and apply more robust research designs. The influence of process redesign on patient-centered care, equity of care and timeliness warrants further research, applying outcome measures that capture the full scope of quality of care. Current research tends to ignore the long-term effects of process redesigns. Robust evaluations of their implementation should also identify the mechanisms through which effects were realized. This would help researchers and policymakers determine the value of specific interventions and offer an overview of improvement efforts that is less fragmented.


Several components that interact with each other to evolve a complex, and, in some cases, unexpected behavior, represents one of the main and fascinating features of the mammalian immune system. Agent-based modeling and cellular automata belong to a class of discrete mathematical approaches in which entities (agents) sense local information and undertake actions over time according to predefined rules. The strength of this approach is characterized by the appearance of a global behavior that emerges from interactions among agents. This behavior is unpredictable, as it does not follow linear rules. There are a lot of works that investigates the immune system with agent-based modeling and cellular automata. They have shown the ability to see clearly and intuitively into the nature of immunological processes. NetLogo is a multiagent programming language and modeling environment for simulating complex phenomena. It is designed for both research and education and is used across a wide range of disciplines and education levels. In this paper, we summarize NetLogo applications to immunology and, particularly, how this framework can help in the development and formulation of hypotheses that might drive further experimental investigations of disease mechanisms. Complex biological scenarios have been recently investigated with the synergic union between computational modeling and high-throughput experimental data. This approach has helped the generation of novel insights and hypotheses for further research and development, with a considerable saving in terms of time and costs. Moreover, it allowed experiments and/or measurements that cannot be easily achievable in a laboratory environment .Once developed and validated, models can be adapted in different ways  to enable examination of different qualities. These in silico (or dry-laboratory) experiments are of course complementary to traditional wet-laboratory experimental approaches .During the last decades many mathematical and computational models have been developed to model and describe the immune system processes and features. Nevertheless it is possible to group most models in two large classes according to the modeling approach used: Top-down and bottom-up approaches (see ).The Top-down approach works by estimating the mean behavior at a macroscopic level, thus modeling populations and not single entities. By using such an approach it is possible to model and represent a large number of entities. The oldest and most famous top-down approach has been represented by the use of ordinary and partial differential equations- based (ODE and PDE) models. Usually ODE models ignore the topology of the problem, whereas PDE can also be used when the space distribution is of importance for the problem. Both techniques neglect individual interactions. Models based on these approaches rely on a strong mathematical theory that allows in some cases analytical study and asymptotic analysis. However complex problems may entitle intractable models, and approximations of the biological scenario become a prerogative. Examples of models based on these approaches are presented in –8. This agents) and interactions are described and followed individually, and the general behavior of the system arises from the sum of the local behaviors of the involved entities. In this way it is possible to describe local immunological processes with greater accuracy, avoiding rough approximations that are typical of top-down approaches. Furthermore spatial distribution and stochastic behaviors generally are already inside, since they normally represent two intrinsic features of the modeling techniques that are based on a bottom-up approach. Conversely, since entities are followed individually, such modeling techniques require a bigger computational effort and there are no strong mathematical instruments that can permit any analytical study. Cellular automata and (multi-) agent-based methods are the most used bottom-up approaches, also in immunology [The bottom-up approach works at a microscopic level. Entities  or Fortran. Soon after that the strength of these modeling techniques became clear to the scientific community; many agent-based languages and frameworks that enabled creating agent-based applications were developed  computer platforms. It is also possible to perform better statistical analysis of results thanks to a plug-in that allows communication between NetLogo and R , a very In this review we will focus on the use of NetLogo to model the immune system processes and features.NetLogo framework has been used extensively to further our understanding of systems in several different disciplines, including biology, ecology, economics, and sociology. Here we will show several applications of NetLogo to model, at different extent, immune system dynamics.Toll-like receptors (TLRs) represent a class of proteins playing an important function in the innate immune system. They are receptors usually expressed in macrophages and dendritic cells that recognize structurally conserved molecules derived from microbes. They are fundamental in activating the innate immune system response. In , the autThe model was able to accurately reproduce the dynamics of TLR-4 signaling in response to LPS stimulation. In particular, it was capable of showing that there was a dose dependent proinflammatory response effect and also the establishment of tolerance.Inflammation is part of the first immune response, typically innate immune response to harmful stimuli, such as pathogens, damaged cells, or irritants. There are two main types of inflammation: acute or chronic. The former is the initial response of the body to dangerous stimuli and is sustained by the increased movement of plasma and leukocytes  from the blood into the injured tissues. The former is represented by a protracted inflammation, characterized by both destruction and healing of the tissue involved in the inflammatory process.Brown et al.  developeAnother example of inflammation modeling is given in . Here thA particular form of inflammation is characterized from the acute inflammatory response that arises initially in response to several biological stressors, including infection, burns, trauma, and invasive surgery. Under normal circumstances this kind of inflammation is strictly supervised by the immune systems and is regulated and self-limited. However when anti-inflammatory processes fail, one can observe an amplified inflammatory state that is depicted by severe, uncontrolled systemic inflammation and multiple organ dysfunction. In , Dong etHuman papillomavirus (HPV) is a DNA virus from the papillomavirus family that is capable of infecting humans. The main targets of HPV are the keratinocytes of the skin or mucous membranes. Some types of infections can trigger benign papillomas, while others can lead to cancers of the cervix, vulva, vagina, penis, oropharynx, and anus . NetLogoIn the adaptive immune response to a virus of an intracellular bacterium, the presentation of the antigen on the surface of the infected cell is of extreme importance. One way to perform this communication strategy is represented by the displaying of viral antigen on major histocompatibility complex of class I of the infected cell. Recently, another mode of communication has been revealed, namely, the transport of antigen from one cell to another through gap junctions . Gap junDeveloping and using mathematical and simulation strategies cover also an important role in the analysis of the dynamics of infectious diseases in populations. Recently, such models integrate population structure and viewed differences between individuals in traits that impact transmission . In thisUnderstanding the role of leukocyte trafficking through the microcirculation and into tissues is of fundamental importance in vascular-associated pathologies like atherosclerosis, stroke, chronic wounds, and peripheral vascular diseases. In particular, methodologies that explore leukocyte adhesion and its dynamics are central. A computational framework that combines agent-based modeling (ABM) with a network flow analysis to study monocyte homing is presented in . Here thMultiple sclerosis (MS) is an inflammatory disease that affects the brain and spinal cord. MS is considered a CD4+ Th1-mediated autoimmune disease . A NetLo Aspergillus fumigatus that leads to mortality rates of 60–90% [Several diseases like, for example, human immunodeficiency virus (HIV) or during some kind of medical interventions leave the immune system debilitated and not more able to fight properly against pathogens. Some opportunistic agents could invade the host with a damaged immune system and could lead to dangerous situations, and, in some cases, to the death of the patient. One class of these opportunist pathogens is represented by human pathogenic fungi like the ubiquitous fungusf 60–90% . It is o behavior space.Tokarski et al.  settled The immune system is able to protect the host from tumor onset, and immune deficiencies are accompanied by an increased risk of cancer. The immune surveillance of tumors is not 100% effective. Tumors arise in hosts with a severe and stable immune deficiency. The study of tumor immunology has led to the development of approaches to further stimulate antitumor immunity. Immunological strategies for the cure of established tumor masses (immunotherapy) have given poor results suggesting that successful antitumor strategies should be addressed to adequately stimulate immune system before tumor onset (immunoprevention), to protect the organism from specific cancers, and to prevent tumor which is more effective than cure in the tumor immunology field .In  the authIn the last decades many mathematical and computational models have been developed to model and describe the immune system processes and features. Immune system is a complex biological system and has been recently investigated with the synergic union between computational modeling and high-throughput experimental data. There are several modeling techniques, each of them having both pros and cons. Among these, NetLogo may represent a mature choice for a number of reasons, spanning from its flexibility and its suitability for unskilled researchers and developers.For multiscale or natural scale simulations the use of a high performance computing infrastructure, including machines and parallel code, is imperative. An evolution on this direction for such kind of tools would be important.In this paper, we critically reviewed a large collection of works dealing with immune system modeling that successfully used NetLogo framework.


It was used a form that encompassed twocategories of descriptive statements about quality in the professional exercise ofnurses. This study had ethical committee approval.  the nurses' population was mainly women  with an average age of 35,5years. There was more practices of the hospital's nurses related to theidentification of potential problems of the patient (p=0.001) and supervision ofthe activities that put in place the nursing interventions and the activities thatthey delegate (p=0.003).  the nurses perform health promotion and complications' prevention activities,however not in a systematic fashion and professional practices differ by context.This study is relevant as it may promote the critical consciousness of the nursesabout the need of stressing quality practices. Health promotion and complications' prevention are two descriptive statements of thequality standards for the professional exercise of nurses in Portugal. Nursing carequality standards were established in 2001 by the Portugal Order of Nurses, aiming toimprove the services performed by these practitioners, and gaining visibility to theprofessional group with regard to the role that hey have in society as a wholeThe World Health Organization (WHO) defined health promotion in 1986 as "the processthat trains individuals to get grasp of and improve their own healthNurses may help to foster this process. For that end they need to place the patient inthe center stage of care and be able to perform a holistic analysis of the person,family groups and community in a way that allows identifying their peculiarities in therealm of health promotion. The patient-centered care demands for the comprehensivenessof the health promotion activities within the nurses' clinical practice, thus being arequisite for their professional practice.Implementing interventions in the realm of health promotion, directed towards empoweringof the patient and developing coping strategies, may help to manage the weaknesses thata chronic disease carries in itself. These interventions are even more remarkable in thesituation when there are low availability of psychosocial resources, such as those ofsocial isolation and loneliness, low self-esteem, feeling unsafe, exhaustion, depressionand low socioeconomic levelThe health promotion interventions may be of the individual, community, organizationalor governmental types. The individual-level interventions are directed to knowledge,attitudes and/or behaviors. The organizational, community or environmental interventionsare focused on policies, programs, facilities or resources; and the governmental levelones act on the legislation, regulation and execution of the health policiesIn spite of this, the health promotion concept is oftentimes mistaken with thecomplications' prevention, being the latter related to the potential problems of thepatient and to the risks that are intrinsic or extrinsic to the individual, problemsthat frequently demand the nurses' interventions for their control.In this perspective and considering that the Portuguese nurses have the duty toimplement in their clinical activities the interventions as proposed by the qualitystandards that were developed by the Portugal Order of Nurses, it was proposed todevelop this pioneering study with the aim to know and compare the nurses' practices intwo organizational contexts, primary health care and hospital. For this end it was useda guiding question: to know "if there are significant differences between the nurses'practices in their work in a hospital or in primary care units, in the realms of healthpromotion and complications' prevention" th2013 and 68/13 of February 14th 2014, observing the ethical principlesinherent to research as defined by Law 21/2014 of Portugal of April 16th.Exploratory, descriptive and crosscutting study using a quantitative approach, approvedby the Ethics in Health Committees and by the Administrative Boards of the institutionswhere the study was developed, according to the verdicts 159/13 of July 25**) of the center region ofPortugal. Based in the previous partnership for in-service educational activities thatthe researchers had in the past with those institutions where the study was developed,the convenience non-probabilistic sampling method was adopted. The inclusion criteriawere linked to the availability and interest in answering to the survey form, decisionthat was preceded by information about the objectives and aims of the study, and theagreement in freely participating of the research. The Free and Informed Consent Formwas handed out at the same moment with the survey form and with an envelope to returnthe survey form after completion. Previously to the data collection, members of theresearch team personally contacted each one of the research subjects. The return of thesurvey form was done in an envelope that was sealed by the respective chief ofnursing.The sample was made up with 474 nurses exercising in the care area: 235 nursespertaining to a central hospital in the North of Portugal and 239 nurses working aspractitioners in a Group of Health Centers ; 3 - sometimes ; 4 - always.The analysis of data for describing the demographic and professional profile was donethrough descriptive statistics through absolute and relative frequency distribution, andfor continuous variables the central trend and dispersion measures were used. Thecomparison between groups was done through inferential statistic using Student's t-testin the continuous variables and Pearson Chi-squared test (χ2) for the categoricalvariables for a significance level of p < 0.05.From the 474 nurses participating in the study, 49,6% (235) were from the hospital and50,4% (239) from the primary health care: 87,3% were female and 12,7% male; ages rangedbetween 24 and 60 years old; time in the profession and in the present post rangedbetween 1 and 38 years; 68,1% had only degrees in nursing and 31,9% had also post-graduate courses. The participants coming from the hospital had an age average of35,5±8,2 y.o., average of practicing the profession of 12,8±8,1 years and average ofperforming as professionals in the present site of 8,1±7,1 years. The participants fromthe primary health care setting had an age average of 35,5±9,1 y.o., average ofpracticing the profession of 8,4±6,5 years and average of performing as professionals inthe present site of 2,1±0,9 years. The groups show differences regarding the socio-demographic variables, and thosedifferences are statistically significant.The answers of the interviewees are statistically significant for all questions.The practices of nurses regarding the quality standard health promotion, analyzed byhealth institution are presented in The nurses' practices regarding the quality standard complications' prevention, analyzedby health organizations are shown in When comparing the nurses' practices in both health institutions, we can observestatistically significant differences at the standard of quality for health promotion inthe statement "Nurses use the opportunity of hospitalization to promote healthylifestyles" (p<0.001) and of the quality standard for complications' prevention inthe statements "Nurses identify the potential problems of the patients" (p=0.001),"Nurses refer problematic cases to other professionals according to social mandates"(p=0.039), "Nurses supervise the activities that put in place nursing interventions andthose that they delegate" (p=0.003).The largest share of nurses that were part of this study are women in the sample as awhole and also in the population of each institution. This is also pointed out as anational and international fact, as the prevalence of females in the Nursing professionis still true nowadays and for a long timeStatistic differences were found in nurses in both contexts, hospital and primary care,related to socio-demographic profile and also to the practices related to healthpromotion and complications' prevention.The prevalence of male nurses is larger in the hospital and the female nurses are moreprevalent in the primary health care.The population in this study is young, mainly under 40 years in both institutions.However in the older age groups, nurses in primary care are double in proportion thanthose in the hospital.In primary health care, most nurses have less than 10 years of lifelong practice ofnursing, they all have less than 10 years of practice in the present site and themajority has post-graduate diplomas. This situation may be a result of there-organization of primary health care that happened in the last decade in Portugal,when the ACeS, Group of Health Units and the Family Health Units were installed, openingemployment opportunities in primary care both for recently graduated and post-graduatednurses.With regard to the category of the quality standard for health promotion, in the wholesample there was found that majority of nurses identify the population's healthsituations and the resources of the patient, family and community, and use theopportunity of the hospitalization to promote healthy lifestyles and to provideinformation that will foster the cognitive learning and new capabilities for thepatient. Not withstanding this fact, they do not perform these practices in a systematicfashion, once that is observed that the prevalence of the category "sometimes" is largerthan the category "always". In this quality standard, there was also a significant difference between the practicesof nurses in the two contexts, in relation to the promotion of healthy lifestyles thatis a more permanent practice in practitioners acting in primary care in this study. Thisis also seen in other contexts. A study in Australia reveals that even having evidencethat nurses are efficient making interventions for health promotion, it is still neededto enlarge their competencies and expand their interventions to other contexts beyondprimary care, as they have a considerable potential in this fieldIn the same fashion, in the category of the quality standard for complications'prevention, the most cited answer is "sometimes", excepted the statement "Nurses showresponsibility for their decisions, for their acts and for those that they delegate".Nurses in a non-systematic way: identify the potential problems of the patients;prescribe and implement interventions geared towards the complications' prevention,assess the interventions that will help to avoid problems or minimize undesirableeffects, show stringent scientific and technical stance in implementing nursinginterventions, refer problematic cases to other professionals according to socialmandates, and supervise the activities of direct or indirect care.In the statements regarding the quality standard for complications' prevention, it isimplicit the nursing process for practice systemization, and the findings confirm someweakness in its use.The nursing process seen as a systematic and dynamic way of delivering care, centered inthe patient, is geared towards a result, with evidence of being cost-beneficial and haveby foundations the fact that planning and implementation of the nursing interventionsshould not be dissociated from the values, interests and desires of individuals,families and communitiesWhen comparing the participants' practices in both contexts it was found that nurses inprimary care develop strategies to promote healthy lifestyles and send problematicsituations to be seen by other professionals, according to social mandates, in a moresystematic fashion than the hospital's nurses. On the other hand, hospital's nursesidentify potential problems of the patient and supervise direct and indirect activitiesof care in a more careful way than the primary care nurses. These results show that nurses in primary care are more comfortable using thedevelopment and community extension models in their practices, based in the socialframework of health, than the hospital's nurses. This confirms the findings of otherstudies that reveal that health promotion activities are more strongly performed byprimary health care nursesThe physical aspects of illness have guided the clinical practices in the hospitalcontext and in this milieu, nurses not only are not associating health promotion totheir practices, but they also consider it a second level priorityThe request to use the principles of health promotion in all organizations, includinghospitalsSupply of preventative health services may rise health levels and prevent illnessesOn the other hand, the programs for health promotion may foster self-protectivebehaviors, responsibility for own health, community participation and adoption ofhealthy lifestylesConsidering that health promotion is associated with the universal principles ofNursing, nurses should have knowledge, competency and skills to articulate its actionsin their clinical practice, being this practice in the hospital or primary carecontexts.Under this perspective, it is needed to re-structure professional practices, implyingpreviously a change in the mindset that substitutes the bio-medical paradigm approach bythe paradigm that generates health, a process that needs individual adaptation andprofessional competency development to foster knowledge, skills, attitudes andconsciousness in the patients as pre-requisites for efficient self-care.The results of this study allowed the understanding of how the Portuguese nursesarticulate in their clinical practices the interventions regarding to quality standards,health promotion and complications' prevention. Not withstanding this finding, thisprocess is not performed in a systematic manner and professional practices divergeaccording with the context. Nurses need to involve themselves deeper with the practices that put in operation thequality standards, not just because they need to conform to professional norms linked totheir performance quality, but also because they may fulfill higher purposes associatedto raising the visibility of the role of nurses in society. We need to remark, as a study limitation, the fact that we examined just two differentinstitutional contexts and two categories of standards for quality of nursing. For awider vision of the Portuguese practitioners ownership of the quality standards ofnursing care as stated by the Portugal Order of Nurses, it is suggested to developlarger studies, at a national level and approaching all the categories of the qualitystandards that are inherent to nurses' professional practice.


Social media use is highly prevalent among children, youth, and their caregivers, and its use in healthcare is being explored. The objective of this study was to conduct a systematic review to determine: 1) for what purposes social media is being used in child health and its effectiveness; and 2) the attributes of social media tools that may explain how they are or are not effective.We searched Medline, CENTRAL, ERIC, PubMed, CINAHL, Academic Search Complete, Alt Health Watch, Health Source, Communication and Mass Media Complete, Web of Knowledge, and Proquest Dissertation and Theses Database from 2000–2013. We included primary research that evaluated the use of a social media tool, and targeted children, youth, or their families or caregivers. Quality assessment was conducted on all included analytic studies using tools specific to different quantitative designs.We identified 25 studies relevant to child health. The majority targeted adolescents (64%), evaluated social media for health promotion (52%), and used discussion forums (68%). Most often, social media was included as a component of a complex intervention (64%). Due to heterogeneity in conditions, tools, and outcomes, results were not pooled across studies. Attributes of social media perceived to be effective included its use as a distraction in younger children, and its ability to facilitate communication between peers among adolescents. While most authors presented positive conclusions about the social media tool being studied (80%), there is little high quality evidence of improved outcomes to support this claim.This comprehensive review demonstrates that social media is being used for a variety of conditions and purposes in child health. The findings provide a foundation from which clinicians and researchers can build in the future by identifying tools that have been developed, describing how they have been used, and isolating components that have been effective. The popularity of social media has changed the way healthcare providers and consumers access and use information, providing new avenues for interaction and care. This advancement of technology has created an environment in which individuals have the opportunity to participate and collaborate in the sharing of information, and may be particularly relevant for children and youth. In a 2013 report on adolescents’ use of social media and mobile technology, researchers from the Pew Internet and American Life Project found that 95% of teens surveyed used the Internet, a figure that has remained constant in the United States since 2006 . Two. Two8]. One NRCT  and two Using the Risk of Bias tool  for the Two of the included cross-sectional studies evaluated health outcomes following exposure to a social media intervention ,29. One While the social media tools and the conditions and outcomes they aim to address vary widely, we used descriptive, qualitative, and mixed methods studies to explore whether there were overlapping characteristics of social media generally that may help to explain their effectiveness or lack thereof.Three cross-sectional studies were used to evaluate users’ experiences with social media interventions. Yager et al.  investigAll seven of the qualitative and mixed methods studies that met our inclusion criteria evaluated social media tools that were intended to provide support to their users. Two studied a virtual world and five studied discussion forums.The two evaluations of Zora, a virtual world designed to help young users explore identity issues, highlighted different aspects of what made the tool successful. In children and adolescents with end-stage renal failure undergoing dialysis, Zora provided an opportunity for distraction from their illness, and a means by which to escape their reality . While hMirroring the findings related to the virtual world, the studies evaluating discussion forums found a dichotomy in that some groups preferred to use the social media tools as a distraction from their illness ,22, whilThe use of new technology such as social media in child health is rapidly expanding and evolving. This systematic review provides a comprehensive review of the research that has been conducted in order to serve as a resource to guide future clinical and research efforts in this area.The majority of studies included in our review investigated the use of a discussion forum and assessed social media as one component of a complex intervention. Discussion forums were often intended to provide support, and were particularly prevalent in studies of chronic conditions. While there were reported benefits in this context, especially from the qualitative investigations, none of the studies that used a discussion forum to effect change in a health outcome reported significant results. Given the focus on health promotion in this group of studies, and the familiarity that children and youth have with current social media platforms, outreach strategies may be more effective if efforts are made up-front to identify the tools that the target audience is already using and tailor the intervention accordingly, rather than expect the group to find and adopt new technologies that have been developed to suit a more limited, condition-specific purpose.The use of complex interventions limits the ability to tease out any effects specific to the social media component; however, the inclusion of qualitative research helped to provide context to some of the attributes that were perceived to be effective. In general, users were most drawn to the ability of social media to facilitate the development of a support network. This did not apply to all populations, though, and tended to be more relevant to older children, and parents or caregivers. In the study populations including younger children, the reported advantage of the social media intervention tended to lie within its ability to serve as a distraction from their illness.The use of social media varied according to the type of condition studied. Tools applied to acute conditions targeted the parents, and were intended to be educational resources and promoted information sharing. As described above, provision of support, either to the patient or to the caregiver, was the primary goal in chronic conditions. Health promotion was the category that most directly targeted children and youth, and demonstrated the greatest variety in tools used and outcomes measured, perhaps indicating potential for future development.The authors’ conclusions tended to be positive with respect to the effectiveness and promise of social media as an intervention or promotional tool for child health. However, this was rarely supported by the statistical significance of the results. While this is a new technology with plenty of advocates and hypothesized benefits, there is no clear evidence that it is effective in improving health outcomes in children and youth. The included studies were of poor to moderate quality and many did not use rigorous study designs. Moving forward, an emphasis on well-conducted experimental designs and qualitative research, rather than on descriptive studies, would help to illuminate whether social media demonstrates effectiveness, and what characteristics contribute to that potential impact. This could include an increased focus on head-to-head comparisons of the effectiveness of specific social media tools, qualitative evaluations of their perceived strengths and limitations, and the use of changes in health outcomes as end-points.We conducted a comprehensive systematic review of the literature following well-endorsed methods ,39. Our This systematic review demonstrates that social media is being used extensively in child health for a variety of purposes. The most common uses for social media were for health promotion with a focus on healthy diet and exercise, sexual health, smoking cessation, and parenting issues. Adolescents were the most common target audience, discussion forums were the most commonly used tools, and the tools were largely community-based. Nearly all studies concluded that the social media tool evaluated showed evidence of utility; however, results of the primary outcomes from the majority of comparative studies showed no significant effect. This synthesis offers an important resource for those who are developing and evaluating interventions involving social media.NRCT: Non-randomized controlled trial; PICU: Pediatric intensive care unit; RCT: Randomized controlled trial.The authors declare that they have no competing interests.MPH, SDS, and LH designed the study. MPH coordinated the project and is the guarantor. AM conducted the literature search and contributed to drafting the manuscript. MPH, JS, GW, and AM screened articles and performed data extraction and quality assessment. MPH and LH interpreted the data. MPH drafted and all authors critically reviewed the manuscript. All authors read and approved the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/14/138/prepubSample Search Strategy (Medline).Click here for file


To analyze characteristics of clinical practice guidelines (CPGs) for the management of rheumatoid arthritis (RA) developed in Latin American (LA) countries and to describe the knowledge, use, and barriers for their implementation perceived among LA rheumatologists, a comprehensive literature search including Medline, PubMed, Cochrane Library, LILACS and Scielo was performed. The Appraisal of Guidelines for Research and Evaluation (AGREE) instrument was applied for evaluation. A survey was sent to PANLAR members containing questions related to knowledge about guidelines, application of the recommendations, and difficulties in implementing CPGs. Eight guidelines were identified. Most guidelines were evidence based (62 %), but in only 37 % a systematic literature search was done. None of the guidelines included patients’ views and preferences, and only few of them stated an updating procedure. Funding body independence and disclosure of conflicts of interest were rarely reported. The survey was answered by 214 rheumatologists from all Latin American countries. Most rheumatologist reported knowledge and use of clinical guidelines, mainly international ones. In general, rheumatologist felt that guidelines apply to only a minority of patients seen in daily clinical practice. Limited access expensive drugs, suggested by the guidelines, was the most frequent barrier to guidelines implementation that was reported. A good number of guidelines on the treatment of rheumatoid arthritis have been developed in Latin America. Most of them are lacking some of the components recognized for high-quality clinical guidelines development. In spite that most rheumatologist know and apply guidelines, access to drugs is still a very important barrier to their implementation in Latin America. The movement to develop and disseminate clinical practice guidelines (CPGs) has been well established for more than two decades . This moAs the years passed the procedures and requirements for development of clinical guidelines have been more and more standardized, guideline clearing houses created, and robust guideline appraisal instruments developed –6.Guidelines are not self-implementing. Developing guidelines and making them available to health-care professionals does not ensure their use . Two of In 2014, the European League Against Rheumatism (EULAR) updated the standardized operating procedures for the elaboration, evaluation, dissemination, and implementation of recommendations endorsed by the EULAR standing committees for musculoskeletal disorders, either in general  or specific  , 8. EULASeveral guidelines or recommendations have been developed in Latin America for the management of rheumatoid arthritis. The aim of this study is to describe and analyze the characteristics and differences of these guidelines, and to describe a survey performed among Latin American rheumatologists, related to the knowledge and use of clinical guidelines for the management of rheumatoid arthritis, and the implementation of clinical guidelines in their own setting.A comprehensive literature search was performed including the following databases: Medline, PubMed, Cochrane Library, LILACS, and Scielo. The words rheumatoid arthritis, and recommendation or guide or guidelines and Latin America, or each one of the Latin American countries was used for the search. All Latin American rheumatology societies or associations were contacted, and their official journals were searched by hand looking for rheumatoid arthritis guidelines or recommendations. Only guidelines developed by scientific societies have been included; recommendations or guidelines developed by governments or regulatory agencies were not considered. When a guideline had several updates, only the last one was included.Guidelines were analyzed using the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument  and summOn the other hand, a survey with five specific questions related to the use of treatment guidelines in clinical practice was sent to all PANLAR members. The main topics addressed were knowledge about guidelines worldwide, application of the recommendations, extrapolation to whole rheumatoid arthritis (RA) patient population, and difficulties in implementing clinical guidelines in different countries.Nine National and one Latin American guidelines Table  were ideAll guidelines recommended traditional disease modifying antirheumatic drugs (DMARDs) monotherapy or DMARDs combination as first line therapy Table . All guiTwo hundred and fourteen rheumatologists, from different Latin American (LA) countries, answered the survey. Most of the rheumatologists reported knowledge about at least one guideline on the treatment of RA (94.59 %). Among them, 82.45 % declared that they apply the recommendations in their daily clinical practice. Several guidelines from different countries and scientific societies were mentioned as used for treating patients with RA. Guidelines from the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) were reported as the more frequently used. However, recommendations of other scientific societies were cited, such as from Argentina, Brazil, Bolivia, Chile, Colombia, Costa Rica, Mexico, and Spain. Some countries have government guidelines that are used by rheumatologists like Brazil, Chile, and Peru. More than a half of physicians answering the survey referred that guidelines are not suitable for a high proportion of their patients, and are not suitable and practical for the management of individual patient. According to their view, this was due at least in part, to the presence of comorbidities in their population, not contemplated in the guidelines.An interesting point about barriers to implementation of guidelines in clinical settings was addressed. Most of the physicians (63.9 %) think that patients have limited access to drugs. Several reasons were mentioned to explain that, including poorly organized health-care systems, government economic issues, low socioeconomic status, and low education level. Another explanation suggested is that there might be a lack of knowledge about the guidelines by physicians treating patients with RA. A low percentage of responders had difficulties using the guidelines because some of them are outdated. Less than 5 % of colleagues do not agree with the treatment recommendations in the guidelines.In 1992, the Institute of Medicine report defined guidelines as “systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances.” It is a generalized view that in spite of the existence of internationally accepted guidelines, local guidelines have an important role in the management of diseases at regional level. Several Latin American rheumatology societies and associations members of PANLAR have developed their own guidelines or recommendations for the management of rheumatoid arthritis. Rheumatoid arthritis is a frequent disease in Latin America, and the appearance of new effective high-cost therapies urged medical associations to develop guidelines to standardize the management of this disease, before it was done by governments or payers, which are not directly dealing with patients themselves. As most of the guidelines have been evidence based, they look very much alike.There are however some issues nowadays considered an indispensable part of high-quality developed clinical practice guidelines, which most of the Latin American guidelines have not included: patients’ views and preferences, procedures for updating the guidelines, and disclosure of conflicts of interest of guideline development members. These issues should be considered in future guidelines to be developed. The survey, although answered by a low number of rheumatologists, produced some interesting results that are very much in line with the previous thoughts on the issue. Most of rheumatologists are aware of the existence of international and local guidelines and they use them in clinical practice. In spite that most of them agree with the guidelines and only a very few minority disagrees, most of them think that the recommendations do not apply to a large number of their patients. That most probably happens because guidelines are evidence based, and the best evidence comes from randomized clinical trials that in fact do exclude many of the usual patients seen in daily clinical practice. The Latin American social economic situation was also pointed out, where in many regions and countries most patients do not have access to effective, high-cost treatments. Inequities among different countries and among different health-care systems even in the same country are the norm in Latin America, and medical associations have an important role to help to narrow the gap.Guidelines are also important for health authorities and payers, to unify the way patients are treated. In spite that, as shown here, many rheumatology societies have developed their own guidelines, health regulatory authorities do not always accept them, and there is an increased tendency from governments in Latin America to develop their own recommendations. Examples are the Peruvian and Colombian governments , 18. It In summary, there is an important work that has been done in Latin America in order to improve the knowledge and management of rheumatoid arthritis according to evidence. There is still however much more to do if we want that the guidelines are fully implemented and patients have access to the treatments they deserve.