http://www.biomedcentral.com/bmcmed/ The latest research articles published by BMC Medicine 2013-05-22T00:00:00Z Background: Falls are one of the most frequently occurring adverse events that impact upon the recovery of older hospital inpatients. Falls can threaten both immediate and longer-term health and independence. There is need to identify cost-effective means for preventing falls in hospitals. Hospital-based falls prevention interventions tested in randomized trials have not yet been subjected to economic evaluation. Methods: Incremental cost-effectiveness analysis was undertaken from the health service provider perspective, over the period of hospitalization (time horizon) using the Australian Dollar (A$) at 2008 values. Analyses were based on data from a randomized trial among n = 1,206 acute and rehabilitation inpatients. Decision tree modeling with three-way sensitivity analyses were conducted using burden of disease estimates developed from trial data and previous research. The intervention was a multimedia patient education program provided with trained health professional follow-up shown to reduce falls among cognitively intact hospital patients. Results: The short-term cost to a health service of one cognitively intact patient being a faller could be as high as A$14,591 (2008). The education program cost A$526 (2008) to prevent one cognitively intact patient becoming a faller and A$294 (2008) to prevent one fall based on primary trial data. These estimates were unstable due to high variability in the hospital costs accrued by individual patients involved in the trial. There was a 52% probability the complete program was both more effective and less costly (from the health service perspective) than providing usual care alone. Decision tree modeling sensitivity analyses identified that when provided in real life contexts, the program would be both more effective in preventing falls among cognitively intact inpatients and cost saving where the proportion of these patients who would otherwise fall under usual care conditions is at least 4.0%. Conclusions: This economic evaluation was designed to assist health care providers decide in what circumstances this intervention should be provided. If the proportion of cognitively intact patients falling on a ward under usual care conditions is 4% or greater, then provision of the complete program in addition to usual care will likely both prevent falls and reduce costs for a health service.Trial registrationAustralia and New Zealand Clinical Trials Register: ACTRN12608000015347.https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=82500. http://www.biomedcentral.com/1741-7015/11/135 Terry Haines Anne-Marie Hill Keith Hill Sandra Brauer Tammy Hoffmann Christopher Etherton-Beer Steven McPhail BMC Medicine 2013, null:135 2013-05-22T00:00:00Z doi:10.1186/1741-7015-11-135 Cost-effective prevention of hospital falls <p>Economic analysis of a clinical trial shows that a patient education program to prevent falls in hospitalized elderly people is effective and cost-saving, provided 4% of these patients would otherwise fall under usual care.</p> /content/figures/1741-7015-11-135-toc.gif BMC Medicine 1741-7015 ${item.volume} 135 2013-05-22T00:00:00Z PDF Background: Acute graft-versus-host disease (aGVHD) poses a major limitation for broader therapeutic application of allogeneic hematopoietic cell transplantation (allo-HCT). Early diagnosis of aGVHD remains difficult and is based on clinical symptoms and histopathological evaluation of tissue biopsies. Thus, current aGVHD diagnosis is limited to patients with established disease manifestation. Therefore, for improved disease prevention it is important to develop predictive assays to identify patients at risk of developing aGVHD. Here we address whether insights into the timing of the aGVHD initiation and effector phases could allow for the detection of migrating alloreactive T cells before clinical aGVHD onset to permit for efficient therapeutic intervention. Methods: Murine major histocompatibility complex (MHC) mismatched and minor histocompatibility antigen (miHAg) mismatched allo-HCT models were employed to assess the spatiotemporal distribution of donor T cells with flow cytometry and in vivo bioluminescence imaging (BLI). Daily flow cytometry analysis of peripheral blood mononuclear cells allowed us to identify migrating alloreactive T cells based on homing receptor expression profiles. Results: We identified a time period of 2 weeks of massive alloreactive donor T cell migration in the blood after miHAg mismatch allo-HCT before clinical aGVHD symptoms appeared. Alloreactive T cells upregulated alpha4beta7 integrin and P-selectin ligand during this migration phase. Consequently, targeted preemptive treatment with rapamycin, starting at the earliest detection time of alloreactive donor T cells in the peripheral blood, prevented lethal aGVHD. Conclusions: Based on this data we propose a critical time frame prior to the onset of aGVHD symptoms to identify alloreactive T cells in the peripheral blood for timely and effective therapeutic intervention. http://www.biomedcentral.com/1741-7015/11/134 Carina Bäuerlein Simone Riedel Jeanette Baker Christian Brede Ana-Laura Garrote Martin Chopra Miriam Ritz Georg Beilhack Stephan Schulz Robert Zeiser Paul Schlegel Hermann Einsele Robert Negrin Andreas Beilhack BMC Medicine 2013, null:134 2013-05-21T00:00:00Z doi:10.1186/1741-7015-11-134 T cells permit early diagnosis of GVHD <p>Alloreactive T cells are present in the blood 2 weeks before the onset of acute graft-versus-host disease (GVHD) symptoms in a mouse model, suggesting these cells could be measured to allow early diagnosis and timely therapeutic intervention.</p> /content/figures/1741-7015-11-134-toc.gif BMC Medicine 1741-7015 ${item.volume} 134 2013-05-21T00:00:00Z PDF The revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM) provides a useful opportunity to revisit debates about the nature of psychiatric classification. An important debate concerns the involvement of mental health consumers in revisions of the classification. One perspective argues that psychiatric classification is a scientific process undertaken by scientific experts and that including consumers in the revision process is merely pandering to political correctness. A contrasting perspective is that psychiatric classification is a process driven by a range of different values and that the involvement of patients and patient advocates would enhance this process. Here we draw on our experiences with input from the public during the deliberations of the Obsessive Compulsive-Spectrum Disorders subworkgroup of DSM-5, to help make the argument that psychiatric classification does require reasoned debate on a range of different facts and values, and that it is appropriate for scientist experts to review their nosological recommendations in the light of rigorous consideration of patient experience and feedback. http://www.biomedcentral.com/1741-7015/11/133 Dan Stein Katharine Phillips BMC Medicine 2013, null:133 2013-05-17T00:00:00Z doi:10.1186/1741-7015-11-133 OCD diagnosis revised in DSM-5 <p>Dan Stein and Katharine Phillips comment on the patient experience that has helped define the psychiatric classification of obsessive-compulsive spectrum disorders (OCD) in DSM-5, and&nbsp;describe the importance of taking patient opinion into account.</p> /content/figures/1741-7015-11-133-toc.gif BMC Medicine 1741-7015 ${item.volume} 133 2013-05-17T00:00:00Z XML The central theme of personalized medicine is the premise that an individual's unique physiologic characteristics play a significant role in both disease vulnerability and in response to specific therapies. The major goals of personalized medicine are therefore to predict an individual's susceptibility to developing an illness, achieve accurate diagnosis, and optimize the most efficient and favorable response to treatment. The goal of achieving personalized medicine in psychiatry is a laudable one, because its attainment should be associated with a marked reduction in morbidity and mortality. In this review, we summarize an illustrative selection of studies that are laying the foundation towards personalizing medicine in major depressive disorder, bipolar disorder, and schizophrenia. In addition, we present emerging applications that are likely to advance personalized medicine in psychiatry, with an emphasis on novel biomarkers and neuroimaging. http://www.biomedcentral.com/1741-7015/11/132 Uzoezi Ozomaro Claes Wahlestedt Charles Nemeroff BMC Medicine 2013, null:132 2013-05-16T00:00:00Z doi:10.1186/1741-7015-11-132 Personalized medicine in psychiatry <p>Charles Nemeroff and colleagues review the genetics, epigenetics, biomarkers, treatment response and environmental factors of mood disorders and schizophrenia, and describe the impact of neuroimaging on personalized medicine in psychiatry.</p> /content/figures/1741-7015-11-132-toc.gif BMC Medicine 1741-7015 ${item.volume} 132 2013-05-16T00:00:00Z PDF Background: Depression is firmly established as an independent predictor of mortality and cardiac morbidity in patients with coronary heart disease (CHD). However, it has been difficult to determine whether it is a causal risk factor, and whether treatment of depression can improve cardiac outcomes. In addition, research on biobehavioral mechanisms has not yet produced a definitive causal model of the relationship between depression and cardiac outcomes.DiscussionKey challenges in this line of research concern the measurement of depression, the definition and relevance of certain subtypes of depression, the temporal relationship between depression and CHD, underlying biobehavioral mechanisms, and depression treatment efficacy.SummaryThis article examines some of the methodological challenges that will have to be overcome in order to determine whether depression should be regarded as a key target of secondary prevention in CHD. http://www.biomedcentral.com/1741-7015/11/131 Kenneth Freedland Robert Carney BMC Medicine 2013, null:131 2013-05-15T00:00:00Z doi:10.1186/1741-7015-11-131 Depression: a risk factor for heart disease? <p>Kenneth Freedland and Robert Carney argue that depression predicts coronary heart disease (CHD) but better methods are required to ascertain whether depression is a causal risk factor for CHD, which could help determine treatment strategies for CVD prevention.</p> /content/figures/1741-7015-11-131-toc.gif BMC Medicine 1741-7015 ${item.volume} 131 2013-05-15T00:00:00Z XML Background: After decades of investigations, explanations for the prospective association between depression and coronary heart disease (CHD) are still incomplete.DiscussionDepression is often suggested to be causally related to CHD. Based on the available literature, we would rather argue that depression can best be regarded as a variable risk marker, that is, a variable that fluctuates together with mechanisms leading to poor cardiovascular fitness. Despite numerous efforts, no evidence is found that manipulation of depression alters cardiovascular outcomes - a key premise for determining causality. To explain the concept of a variable risk marker, we discuss several studies on the heterogeneity of depression suggesting that depression is particularly harmful for the course of cardiovascular disease when it appears to be a physiological consequence of the cardiovascular disease itself.SummaryWe conclude that instead of depression being a causal risk factor for CHD, the association between depression and CHD is likely confounded, at least by the cardiac disease itself. http://www.biomedcentral.com/1741-7015/11/130 Anna Meijer Marij Zuidersma Peter de Jonge BMC Medicine 2013, null:130 2013-05-15T00:00:00Z doi:10.1186/1741-7015-11-130 Depression is non-causal in CHD <p>Peter de Jonge and colleagues argue that, although there is a link between coronary heart disease (CHD) and depression, this association is confounded by heterogeneity, such that depression is a non-causal risk factor CHD.</p> /content/figures/1741-7015-11-130-toc.gif BMC Medicine 1741-7015 ${item.volume} 130 2013-05-15T00:00:00Z XML Depression is the most common psychiatric disorder worldwide. The burden of disease for depression goes beyond functioning and quality of life and extends to somatic health. Depression has been shown to subsequently increase the risk of, for example, cardiovascular, stroke, diabetes and obesity morbidity. These somatic consequences could partly be due to metabolic, immuno-inflammatory, autonomic and hypothalamic-pituitary-adrenal (HPA)-axis dysregulations which have been suggested to be more often present among depressed patients. Evidence linking depression to metabolic syndrome abnormalities indicates that depression is especially associated with its obesity-related components (for example, abdominal obesity and dyslipidemia). In addition, systemic inflammation and hyperactivity of the HPA-axis have been consistently observed among depressed patients. Slightly less consistent observations are for autonomic dysregulation among depressed patients. The heterogeneity of the depression concept seems to play a differentiating role: metabolic syndrome and inflammation up-regulations appear more specific to the atypical depression subtype, whereas hypercortisolemia appears more specific for melancholic depression. This review finishes with potential treatment implications for the downward spiral in which different depressive symptom profiles and biological dysregulations may impact on each other and interact with somatic health decline. http://www.biomedcentral.com/1741-7015/11/129 Brenda Penninx Yuri Milaneschi Femke Lamers Nicole Vogelzangs BMC Medicine 2013, null:129 2013-05-15T00:00:00Z doi:10.1186/1741-7015-11-129 Biological dysregulation in depression <p>Consequences of depression include somatic diseases, such as obesity and cardiovascular disease; Brenda Penninx and colleagues review the biological pathways and their dysregulation between depressive symptoms and somatic health, and describe the therapeutic implications.</p> /content/figures/1741-7015-11-129-toc.gif BMC Medicine 1741-7015 ${item.volume} 129 2013-05-15T00:00:00Z XML The furore preceding the release of the new edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) is in contrast to the incremental changes to several diagnostic categories, which are derived from new research since its predecessor’s birth in 1990. While many of these changes are indeed controversial, they do reflect the intrinsic ambiguity of the extant literature. Additionally, this may be a mirror of the frustration of the field’s limited progress, especially given the false hopes at the dawn of the “decade of the brain”. In the absence of a coherent pathophysiology, the DSM remains no more than a set of consensus based operationalized adjectives, albeit with some degree of reliability. It does not cleave nature at its joints, nor does it aim to, but neither does alternate systems. The largest problem with the DSM system is how it’s used; sometimes too loosely by clinicians, and too rigidly by regulators, insurers, lawyers and at times researchers, who afford it reference and deference disproportionate to its overt acknowledged limitations. http://www.biomedcentral.com/1741-7015/11/128 Michael Berk BMC Medicine 2013, null:128 2013-05-14T00:00:00Z doi:10.1186/1741-7015-11-128 Debating the DSM-5 criteria <p>In an editorial to launch our article collection on Current Controversies in Psychiatry, Michael Berk discusses the debate on diagnostic categories in mental health based on the new edition of diagnostic criteria; the DSM-5.</p> /content/figures/1741-7015-11-128-toc.gif BMC Medicine 1741-7015 ${item.volume} 128 2013-05-14T00:00:00Z XML Background: The fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) opted to retain existing diagnostic boundaries between bipolar I disorder, schizoaffective disorder, and schizophrenia. The debate preceding this decision focused on understanding the biologic basis of these major mental illnesses. Evidence from genetics, neuroscience, and pharmacotherapeutics informed the DSM-5 development process. The following discussion will emphasize some of the key factors at the forefront of the debate.DiscussionFamily studies suggest a clear genetic link between bipolar I disorder, schizoaffective disorder, and schizophrenia. However, large-scale genome-wide association studies have not been successful in identifying susceptibility genes that make substantial etiological contributions. Boundaries between psychotic disorders are not further clarified by looking at brain morphology. The fact that symptoms of bipolar I disorder, but not schizophrenia, are often responsive to medications such as lithium and other anticonvulsants must be interpreted within a larger framework of biological research.SummaryFor DSM-5, existing nosological boundaries between bipolar I disorder and schizophrenia were retained and schizoaffective disorder preserved as an independent diagnosis since the biological data are not yet compelling enough to justify a move to a more neurodevelopmentally continuous model of psychosis. http://www.biomedcentral.com/1741-7015/11/127 V Cosgrove Trisha Suppes BMC Medicine 2013, null:127 2013-05-14T00:00:00Z doi:10.1186/1741-7015-11-127 DSM-5 retains psychosis diagnosis <p>Victoria Cosgrove and Trisha Suppes agree that boundaries between the diagnosis of bipolar disorder I, schizophrenia and schizoaffective disorder are preserved in the DSM-5 criteria, as there is not yet enough data to justify a continuous model of psychosis.</p> /content/figures/1741-7015-11-127-toc.gif BMC Medicine 1741-7015 ${item.volume} 127 2013-05-14T00:00:00Z XML Background: After 30 years of consensus-derived diagnostic categories in mental health, it is time to head in new directions. Those categories placed great emphasis on enhanced reliability and the capacity to identify them via standardized checklists. Although this enhanced epidemiology and health services planning, it failed to link broad diagnostic groupings to underlying pathophysiology or specific treatment response.DiscussionIt is time to adopt new goals that prioritize the validation of clinical entities and foster alternative strategies to support those goals. The value of new dimensions (notably clinical staging), that are both clinically relevant and directly related to emerging developmental and neurobiological research, is proposed. A strong emphasis on ‘reverse translation’ (that is, working back from the clinic to the laboratory) underpins these novel approaches. However, it relies on using diagnostic groupings that already have strong evidence of links to specific risk factors or patterns of treatment response.SummaryThe strategies described abandon the historical divides between clinical neurology, psychiatry and psychology and adopt the promotion of pathways to illness models. http://www.biomedcentral.com/1741-7015/11/125 Ian Hickie Jan Scott Daniel Hermens Elizabeth Scott Sharon Naismith Adam Guastella Nick Glozier Patrick McGorry BMC Medicine 2013, null:125 2013-05-14T00:00:00Z doi:10.1186/1741-7015-11-125 Psychiatric diagnosis: time for change? <p>There is much debate on DSM-5 diagnosis in mental health, and Ian Hickie and colleagues argue for the development of new approaches that identify pathways underlying the illnesses rather than using broad categories to describe psychiatric disorders.</p> /content/figures/1741-7015-11-125-toc.gif BMC Medicine 1741-7015 ${item.volume} 125 2013-05-14T00:00:00Z XML