Translating Research into Agile Development (TRIAD): Development of Electronic Health Record Tools for Primary Care Settings.

OBJECTIVES: This article describes a method for developing electronic health record (EHR) tools for use in primary care settings. METHODS: The "Translating Research into Agile Development" (TRIAD) method relies on the close collaboration of researchers, end users, and development teams. This five-step method for designing a tailored EHR tool includes (1) assessment, observation, and documentation; (2) structured engagement for collaboration and iterative data collection; (3) data distillation; (4) developmental feedback from clinical team members on high-priority EHR needs and input on design prototypes and EHR functionality; and (5) agile scrum sprint cycles for prototype development. RESULTS: The TRIAD method was used to modify an existing EHR for behavioral health clinicians (BHCs) embedded with primary care teams, called the BH e-Suite. The structured engagement processes stimulated discussions on how best to automate BHC screening tools and provide goal tracking functionality over time. Data distillation procedures rendered technical documents, with information on workflow steps, tasks, and associated challenges. In the developmental feedback phase, BHCs gave input on screening assessments, scoring needs, and other functionality to inform prototype feature development. Six 2-week sprint cycles were conducted to address three domains of prototype development: assessment and documentation needs, information retrieval, and monitoring and tracking. The BH e-Suite tool resulted with eight new EHR features to accommodate BHCs' needs. CONCLUSION: The TRIAD method can be used to develop EHR functionality to address the evolving needs of health professionals in primary care and other settings. The BH e-Suite was developed through TRIAD and was found to be acceptable, easy to use, and improved care delivery during pilot testing. The BH e-Suite was later adopted by OCHIN Inc., which provided the tool to its 640 community health centers. This suggests that the TRIAD method is a promising research and development approach.

Health care clinicians' engagement in organizational redesign of care processes: The importance of work and organizational conditions.

The Swedish health care system is reorienting towards horizontal organization for care processes. A main challenge is to engage health care clinicians in the process. The aim of this study was to assess engagement (i.e. attitudes and beliefs, the cognitive state and clinical engagement behaviour) among health care clinicians, and to investigate how engagement was related to work resources and demands during organizational redesign. A cohort study was conducted, using a questionnaire distributed to clinicians at five hospitals working with care process improvement approaches, two of them having implemented Lean production. The results show that kinds of engagement are interlinked and contribute to clinical engagement behaviour in quality of care and patient safety. Increased work resources have importance for engagements in organizational improvements, especially in top-down implementations. An extended work engagement model during organizational improvements in health care was supported. The model contributes to knowledge about how and when clinicians are mobilized to engage in organizational changes.

A human factors engineering paradigm for patient safety: designing to support the performance of the healthcare professional.

The goal of improving patient safety has led to a number of paradigms for directing improvement efforts. The main paradigms to date have focused on reducing injuries, reducing errors, or improving evidence based practice. In this paper a human factors engineering paradigm is proposed that focuses on designing systems to improve the performance of healthcare professionals and to reduce hazards. Both goals are necessary, but neither is sufficient to improve safety. We suggest that the road to patient and employee safety runs through the healthcare professional who delivers care. To that end, several arguments are provided to show that designing healthcare delivery systems to support healthcare professional performance and hazard reduction should yield significant patient safety benefits. The concepts of human performance and hazard reduction are explained.

Tumor necrosis factor-alpha: a continuum of liability between insulin-dependent diabetes mellitus, non-insulin-dependent diabetes mellitus and carcinoma (review).

In this review, tumor necrosis factor-alpha (TNF-alpha) is identified as the uniting principle linking the pathogenesis of insulin-dependent diabetes mellitus (IDDM), non-insulin dependent diabetes mellitus (NIDDM) and carcinoma. Elevated TNF-alpha initially increases, and then inhibits, the activity of a number of key enzymes involved in energy metabolism and major histocompatibility (MHC) class I molecule expression. These enzymes include: protein-tyrosine kinase (PTKase) and protein-tyrosine phosphatase (PTPase--enzymes involved in energy metabolism, cell proliferation and stimulation of the MHC class I molecule pathway. Of primary importance is the inhibiting effect of TNF-alpha on PTKase, since this induces insulin resistance in NIDDM and carcinoma, and PTPase, which inhibits MHC class I molecule expression. Studies have shown that IDDM is associated with an increase in PTPase activity which leads to overexpression of MHC class I molecules and a concomitant destruction of pancreatic beta cells. Conversely, carcinoma is associated with an inhibition of PTPase activity, which reduces the expression of MHC class I antigen expression on the cell surface thereby allowing malignant cells to escape immune surveillance. It will be argued that there is continuum of liability between these three conditions, initiated by the effect of TNF-alpha on these key enzymes.

The p53 paradox in the pathogenesis of tumor progression.

Recent evidence suggests that the p53 molecule appears in two different forms: the mutant p53 that stimulates tumor progression, and wild type p53 that inhibits tumor progression. In addition, it has been established that tumor necrosis factor-alpha (TNF-alpha) can activate the expression of wild type p53 in concert with the nuclear transcription factor, NF-kappa B. Both TNF-alpha and NF-kappa B are also involved in the stimulation of the pathway that leads to the expression of major histocompatibility complex (MHC) class I molecules and, hence, antigen presentation to the T cells. In this paper we shall advance the hypothesis that: (i) TNF-alpha indirectly controls immune surveillance; and (ii) TNF-alpha controls DNA repair and tumor suppression through the regulation of wild type p53. Thus, it is hypothesized that elevated TNF-alpha is primarily responsible for promoting tumor progression.

The role of brain insulin in the neurophysiology of serious mental disorders: review.

The purpose of this review is to indicate the role insulin plays in normal brain neurophysiology, together with the role insulin may play in the regulation of regional cerebral blood flow (rCBF). The relationship between sustained elevation of the inflammatory cytokines and brain insulin dysregulation, with respect to the serious mental disorders, is also discussed. It has been observed that, as the inflammatory cytokines increase, they exert a synergistic influence on insulin and somatostatin, by initially increasing and then decreasing insulin secretion. In the brain, increased levels of insulin result in increased glucose utilization and over-stimulation of the autonomic nervous system (ANS), while the inhibition of insulin secretion results in decreased glucose utilization and dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis. It will further be argued that these alterations in brain insulin influence rCBF in the serious mental disorders such as schizophrenia and the affective disorders. It is hypothesized that insulin regulates rCBF either directly, or indirectly via GLUT4 in the hypothalamus now considered the glucose-sensing, insulin-sensing mechanism of the brain and the body. Thus, we shall propose that insulin plays an important role in normal neurophysiology and that sustained elevation of the inflammatory cytokines dysregulates insulin secretion, rCBF, ANS and the HPA-axis in serious mental disorders.

Tumor necrosis factor-alpha: is there a continuum of liability between stress, anxiety states and anorexia nervosa?

Since the time of Freud, psychiatry has embraced the proposition that physiological and/or psychological stress precipitates various psychiatric disorders. To this effect, we propose that a continuum of liability obtains between stress, anxiety states and anorexia nervosa--a continuum which is grounded on a cytokine profile common to each of these conditions. For example, the biological response to stress, anxiety states and anorexia nervosa includes the elevation of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), and downregulation of interferon-gamma (IFN-gamma). Sustained elevation of IL-1 beta and TNF-alpha dysregulates both somatostatin and insulin secretion, the latter of which influences regional cerebral blood flow (rCBF) and brain energy metabolism. In addition, IL-1 beta and TNF-alpha influence the expression of certain crucial neuropeptides, which are known to be associated with anxiety states and anorexia nervosa. These neuropeptides include: beta-endorphin, cholecystokinin (CCK), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). beta-endorphin effects glucose metabolism in the limbic system, CCK increases the release of beta-endorphin from the anterior pituitary, NPY is a powerful anxiolytic that regulates beta-endorphin and insulin, while VIP indirectly regulates the expression of TNF-alpha through the inhibition of interleukin-4 (IL-4).

An immunological model connecting the pathogenesis of stress, depression and carcinoma.

Recently there has been considerable conjecture in the literature concerning a possible relationship between stress, depression and bereavement, and carcinoma. We shall propose a causal model in which the relationship between stress, depression and carcinoma is clarified. This relationship is grounded on dysregulation of the inflammatory cytokines in stress and depression. Stress is associated with increased expression of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), and reduced expression of IL-2, interferon-gamma (IFN-gamma), major histocompatability complex (MHC) class II molecules and natural killer cell activity (NKA). Depression is associated with elevated IFN-gamma and IL-1 beta, downregulated IL-2, and reduced NKA. Most organ-related carcinomas are associated with elevated TNF-alpha, which inhibits the activity of protein tyrosine phosphatase (PTPase), the enzyme that initiates activation of the MHC class I pathway. Sustained elevation of TNF-alpha inhibits the activity of PTPase which results in diminished expression of the MHC class I antigen on the cell surface and thus, malignant cells escape immune surveillance. Therefore, stress and depression can foster tumor progression by means of inhibiting the expression of MHC class I and II molecules and through the reduction of NKA.

The role of tumor necrosis factor-alpha in the pathogenesis of anorexia and bulimia nervosa, cancer cachexia and obesity.

In this paper a new immunological model of anorexia and bulimia nervosa will be presented in which the inflammatory cytokines are conceived as the fundamental regulators of body metabolism. This conception differs from the conventional view in which the inflammatory cytokines are perceived primarily as peptide molecules utilized by the immune system to control infection, inflammation and tissue or neuronal damage. Given that the inflammatory cytokines are also fundamental regulators of body metabolism, when they become dysregulated they create physiological chaos which results in the development of a number of autoimmune, metabolic and psychiatric disorders. In this proposed immunological model of anorexia and bulimia nervosa, elevated tumor necrosis factor-alpha features as the primary cause of these conditions. Pathophysiological parallels are drawn between anorexia nervosa and cancer cachexia in terms of the causal role the cytokines, neuropeptides and neurotransmitters play in the manifestation of shared symptoms. These shared symptoms include elevated tumour necrosis factor-alpha, down-regulated interleukin-2 and interleukin-4 and depletion of lean body mass. Furthermore, the following neuropeptides are dysregulated in both anorexia nervosa and cancer cachexia: vasoactive intestinal peptide, cholecystokinin, corticotropin-releasing factor, neuropeptide Y, peptide YY and beta-endorphin. In addition, in anorexia and bulimia nervosa, secretion of the neurotransmitter serotonin is inhibited while norepinephrine is enhanced. It will be argued that the causal interplay between the cytokines, neuropeptides and neurotransmitters initiates a cascade of biochemical events which may result in either anorexia or bulimia nervosa, or cancer cachexia. The extent to which these inflammatory cytokines, neuropeptides and neurotransmitters are causally efficacious in the pathogenesis of other autoimmune disorders, such as diabetes mellitus and rheumatoid arthritis, will also be addressed.

Interleukin-1 beta: a common cause of Alzheimer's disease and diabetes mellitus.

Alzheimer disease is characterized by the presence of beta-amyloid protein deposits, neurofibrillary tangles and cholinergic dysfunction throughout the hippocampal region. In addition, the hippocampus, hypothalamus and olfactory bulb--the three areas where the insulin receptors are most dense--are also subject to neurodegeneration. The exact cause of the beta-amyloid deposits and NFTs is unknown. However, it is our intention to explicate the various pathogenic pathways through which Alzheimer disease arises. Fundamentally, the structural and metabolic damage found in Alzheimer disease is due to sustained elevation of interleukin-1 beta, a feature which is also found in insulin-dependent diabetes mellitus. Similarly, the beta-AP deposits found in the Alzheimer brain share the same molecular structure as the amylin deposits found in the pancreatic beta-cells in non-insulin-dependent diabetes mellitus (NIDDM), and are equally neurotoxic. These, and other pathophysiological parallels, afford some insight into the probably cause of Alzheimer disease and, as such, forms the basis of the causal hypothesis advanced in this paper.

Immunological influences in attention-deficit disorder and schizophrenia; is there a link between these two conditions?

This paper aims to explore the influence of the immune system on the pathobiochemistry of movement disorders (Tourette syndrome, obsessive compulsive disorders and attention-deficit disorder, with and without hyperactivity) and schizophrenia. In children, a temporal relationship has been observed between contraction of a group A beta-hemolytic streptococcal infection and subsequent presentation with one of the movement disorders. Pathology investigations reveal that elevated antineuronal antibodies are associated with movement disorders. Similarly, elevations in interleukin-1 beta and interleukin-6 have been reported in schizophrenia. It is now known that the immune system can be activated by conditions other than a viral or bacterial infection, such as: neurological insult, neurotoxicity--endogenous and environmental, neurotransmitter and cholesterol dysregulation. These latter avenues of immune system activation will be explored with respect to schizophrenia.

The estrogen connection: the etiological relationship between diabetes, cancer, rheumatoid arthritis and psychiatric disorders.

For some considerable time, there has been a growing awareness that defective essential fatty acid metabolism plays a causal role in the pathogenesis of both schizophrenia and non-insulin-dependent diabetes mellitus (NIDDM) but the influence of defective essential fatty acid metabolism in the pathogenesis of rheumatoid arthritis and cancer is less well appreciated. An EFA deficiency, or defective EFA metabolism, negatively influences prostaglandin synthesis and glucose regulation and transport. Moreover, defective EFA metabolism negatively influences estrogen availability which contributes to the observed gender bias some of these illnesses manifest. While fluctuations of estrogen are known to contribute to the pathogenesis of these conditions, so also do fluctuations of IGF-II and there is some suggestion that IGF-II and insulin may well be inversely regulated. In addition, insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis, and schizophrenia are thought to be autoimmune disorders, while cancer is associated with immune system failure. Consequently, this paper aims to examine the pathophysiological similarities and differences between mental illness, diabetes, rheumatoid arthritis and cancer in respect of which the causal relationship that obtains between essential fatty acids, estrogen, IGF-II, glucose regulation and autoimmunity will be addressed.

Schizophrenia, suicide and the serotonin story.

In this paper, the relationship between schizophrenia, suicide and serotonin will be examined. Throughout, it will be argued that the fundamental problem does not lie with the neurotransmitter per se, but rather with uncontrolled fluctuations of brain glycaemic levels acting in conjunction with insulin resistance. It will be shown that the area of dopaminergic and serotonergic activity in the brain is intimately tied to the relative distribution of the central glucose transporters and, hence, to glucose metabolism and insulin activity. It will be argued that mania and positive schizophrenia represent a continuum of liability associated with hyperglycaemia, hyperdopaminergia, and hyperserotonergia. In contrast, depression and negative schizophrenia represent another continuum of liability involving hypoglycaemia, hypodopaminergia, and hyposerotonergia. This serves as a useful distinction in drawing together a large number of seemingly unrelated, diverse facts concerning both schizophrenia and suicide and, in particular, the possible relationship that obtains between cholesterol-lowering drugs, low serotonin and suicide. Essentially, this paper reaffirms a previously stated contention that mental illness, in its many guises, is a general manifestation of a diabetic brain state which has been termed 'cerebral diabetes'.

Schizophrenia, smoking, and smog.

The article outlines the relationships that obtain among schizophrenia, smoking, and smog. An overview of known scientific facts concerning the pathogenesis of schizophrenia is first provided. The relationship this has with nicotine addiction is discussed next, and finally the notion is introduced that heterocyclic amines found in cigarette smoke and petroleum fumes serve as a potent environmental neurotoxin that seriously compromises mental health in biologically susceptible individuals. It is argued that such biologic susceptibility takes the form of cerebral diabetes, which accounts for the serious impairment of glucose metabolism as demonstrated by positron emission tomography. Central to this argument is the view that diabetes can be peripheral, without affecting the central nervous system, or central, without affecting the peripheral system.

Schizophrenia is a diabetic brain state: an elucidation of impaired neurometabolism.

In this paper a detailed argument will be advanced in support of the notion that schizophrenia is fundamentally a diabetic brain state, henceforth referred to as 'cerebral diabetes'. Many extraneous features of cerebral diabetes have been observed, including positron emission tomography (PET) scans which reflect abnormal distribution patterns and diminished supplies of glucose in the brain. Equally, empirical research has demonstrated that plasma levels of essential fatty acids and prostaglandins are abnormally low, and low levels of glycoproteins in the urine of cerebral diabetics have also been observed. In addition, cerebral diabetics manifest a wide range of disturbing physical symptoms, such as, impaired sexual function, temperature control, low blood pressure, disrupted sleep patterns, excessive thirst, poor memory, insensitivity to pain, and chronic unhappiness, all of which can be attributed to disrupted neuroendocrine function. Thus, in order to persuasively assert the redefinition of schizophrenia as 'cerebral diabetes', we shall first explicate glucose regulation and transport in the brain and then outline how this interacts with essential fatty acids and prostaglandins, neurotransmission, and the neuroendocrine system. In so doing, we shall provide a metabolic explanation for all the prominent symptoms currently known to be associated with cerebral diabetes and indicate some future therapeutic interventions.

Schizophrenia: an extended etiological explanation.

Schizophrenia has become an elusive medical conundrum since it was first described at the turn of the 19th century. Over time, a variety of causal hypotheses have been advanced to explain the spectrum of schizophreniform disorders. This etiological explanation outlines the relationship that obtains between smoking, schizophrenia, and impaired glycometabolism which also includes disruption to the dopaminergic and serotinergic pathways. A possible genetic explanation for this disruption will be identified which links mental illness to a locus of genes contained on the short arm of chromosome 11. These genes are all essential to normal glucose transport which positron emission tomography (PET) scans show is seriously abnormal in schizophrenia. Thus, a redefinition of schizophrenia as 'cerebral diabetes' will be proposed since this term implies a diabetic brain state consistent with PET scans of schizophrenic patients.