Recurrent Episodes of Acute Pancreatitis Present to the ED with More Severe Disease by CT than First-Time Acute Pancreatitis

Study Objective: Approximately 30% of patients with one episode of acute pancreatitis experience a recurrent episode. The objective of this study is to compare the severity of the first-time episode versus recurrent episodes of acute pancreatitis based on CT scan. Methods: This study was conducted as part of a retrospective chart review at a single academic urban emergency department from 2012-2016. Criteria for inclusion included clinical symptoms of pancreatitis, age greater than or equal to 18 years, ED diagnosis of acute pancreatitis, and, an abdominal CT scan within 24 hours of triage. Exclusion criteria were traumatic cause of acute pancreatitis and pregnancy. Charts were reviewed by a trained abstractor using structured data collection sheets which included data elements such as a history of acute pancreatitis and the results of an abdominal CT scan. Data abstraction was confirmed for interrater reliability. CT Scans were graded using the Modified CT Severity Index (MCTSI) which grades acute pancreatitis by the presence of inflammation, fluid accumulation, necrosis or extra-pancreatic findings. Results: 283 patients were included in the study. Of these, 110 patients resented with recurrent acute pancreatitis and 173 patients presented with first-time acute pancreatitis. We calculated the mean MCTSI score in both groups and found a significantly higher rate of severity in recurrent acute pancreatitis versus first episode (2.09 vs. 1.43, p\u3c0.05.) Conclusion: Patients with recurrent acute pancreatitis are more likely to present with a more severe episode of acute pancreatitis than patients presenting with first-time acute pancreatitis

Study protocol of cost-effectiveness and cost-utility of a biopsychosocial multidisciplinary intervention in the evolution of non-specific sub-acute low back pain in the working population: cluster randomised trial.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain (LBP), with high incidence and prevalence rate, is one of the most common reasons to consult the health system and is responsible for a significant amount of sick leave, leading to high health and social costs. The objective of the study is to assess the cost-effectiveness and cost-utility analysis of a multidisciplinary biopsychosocial educational group intervention (MBEGI) of non-specific sub-acute LBP in comparison with the usual care in the working population recruited in primary healthcare centres. Methods/design: The study design is a cost-effectiveness and cost-utility analysis of a MBEGI in comparison with the usual care of non-specific sub-acute LBP.Measures on effectiveness and costs of both interventions will be obtained from a cluster randomised controlled clinical trial carried out in 38 Catalan primary health care centres, enrolling 932 patients between 18 and 65 years old with a diagnosis of non-specific sub-acute LBP. Effectiveness measures are: pharmaceutical treatments, work sick leave (% and duration in days), Roland Morris disability, McGill pain intensity, Fear Avoidance Beliefs (FAB) and Golberg Questionnaires. Utility measures will be calculated from the SF-12. The analysis will be performed from a social perspective. The temporal horizon is at 3 months (change to chronic LBP) and 12 months (evaluate the outcomes at long term. Assessment of outcomes will be blinded and will follow the intention-to-treat principle. Discussion: We hope to demonstrate the cost-effectiveness and cost-utility of MBEGI, see an improvement in the patients' quality of life, achieve a reduction in the duration of episodes and the chronicity of non-specific low back pain, and be able to report a decrease in the social costs. If the intervention is cost-effectiveness and cost-utility, it could be applied to Primary Health Care Centres. Trial registration: ISRCTN: ISRCTN5871969

The aetiology of social deficits within mental health disorders:The role of the immune system and endogenous opioids

The American National Institute for Mental Health (NIMH) has put out a set of research goals that include a long-term plan to identify more reliable endogenous explanations for a wide variety of mental health disorders (Insel, 2013). In response to this, we have identified a major symptom that underlies multiple mental health disorders – social bonding dysfunction. We suggest that endogenous opioid abnormalities can lead to altered social bonding, which is a symptom of various mental health disorders, including depression, schizophrenia and ASD. This article first outlines how endogenous opioids play a role in social bonding. Then we show their association with the body’s inflammation immune function, and review recent literature linking inflammation to mental health ‘immunophenotypes’. We finish by explaining how these immunophenotypes may be caused by alterations in the endogenous opioid system. This is the first overview of the role of inflammation across multiple disorders where we provide a biochemical explanation for why immunophenotypes might exist across diagnoses. We propose a novel mechanism of how the immune system may be causing ‘sickness-type’ behaviours (fatigue, appetite change, social withdrawal and inhibited motivation) in those who have these immunophenotypes. We hope that this novel aetiology can be used as a basis for future research in mental health

Change of dopamine receptor mRNA expression in lymphocyte of schizophrenic patients

BACKGROUND: Though the dysfunction of central dopaminergic system has been proposed, the etiology or pathogenesis of schizophrenia is still uncertain partly due to limited accessibility to dopamine receptor. The purpose of this study was to define whether or not the easily accessible dopamine receptors of peripheral lymphocytes can be the peripheral markers of schizophrenia. RESULTS: 44 drug-medicated schizophrenics for more than 3 years, 28 drug-free schizophrenics for more than 3 months, 15 drug-naïve schizophrenic patients, and 31 healthy persons were enrolled. Sequential reverse transcription and quantitative polymerase chain reaction of the mRNA were used to investigate the expression of D3 and D5 dopamine receptors in peripheral lymphocytes. The gene expression of dopamine receptors was compared in each group. After taking antipsychotics in drug-free and drug-naïve patients, the dopamine receptors of peripheral lymphocytes were sequentially studied 2nd week and 8th week after medication. In drug-free schizophrenics, D3 dopamine receptor mRNA expression of peripheral lymphocytes significantly increased compared to that of controls and drug-medicated schizophrenics, and D5 dopamine receptor mRNA expression increased compared to that of drug-medicated schizophrenics. After taking antipsychotics, mRNA of dopamine receptors peaked at 2(nd) week, after which it decreases but the level was above baseline one at 8(th) week. Drug-free and drug-naïve patients were divided into two groups according to dopamine receptor expression before medications, and the group of patients with increased dopamine receptor expression had more severe psychiatric symptoms. CONCLUSIONS: These results reveal that the molecular biologically-determined dopamine receptors of peripheral lymphocytes are reactive, and that increased expression of dopamine receptor in peripheral lymphocyte has possible clinical significance for subgrouping of schizophrenis

Monoaminergic and histaminergic strategies and treatments in brain diseases

The monoaminergic systems are the target of several drugs for the treatment of mood, motor and cognitive disorders as well as neurological conditions. In most cases, advances have occurred through serendipity, except for Parkinson's disease where the pathophysiology led almost immediately to the introduction of dopamine restoring agents. Extensive neuropharmacological studies first showed that the primary target of antipsychotics, antidepressants, and anxiolytic drugs were specific components of the monoaminergic systems. Later, some dramatic side effects associated with older medicines were shown to disappear with new chemical compounds targeting the origin of the therapeutic benefit more specifically. The increased knowledge regarding the function and interaction of the monoaminergic systems in the brain resulting from in vivo neurochemical and neurophysiological studies indicated new monoaminergic targets that could achieve the efficacy of the older medicines with fewer side-effects. Yet, this accumulated knowledge regarding monoamines did not produce valuable strategies for diseases where no monoaminergic drug has been shown to be effective. Here, we emphasize the new therapeutic and monoaminergic-based strategies for the treatment of psychiatric diseases. We will consider three main groups of diseases, based on the evidence of monoamines involvement (schizophrenia, depression, obesity), the identification of monoamines in the diseases processes (Parkinson's disease, addiction) and the prospect of the involvement of monoaminergic mechanisms (epilepsy, Alzheimer's disease, stroke). In most cases, the clinically available monoaminergic drugs induce widespread modifications of amine tone or excitability through neurobiological networks and exemplify the overlap between therapeutic approaches to psychiatric and neurological conditions. More recent developments that have resulted in improved drug specificity and responses will be discussed in this review.peer-reviewe

Promise and Pitfalls of Animal Models of Schizophrenia

Animal models are indispensible tools for advancing understanding of the cause of any given disease and developing new treatments. Developing animal models for schizophrenia presents formidable challenges owing to the distinctively human nature of the symptoms that define it and the thus-far-obscured underlying biological mechanisms. Nevertheless, progress has been and continues to be made in this important field of endeavor. This article discusses the challenges facing investigators who seek to develop and use animal models for translational research in schizophrenia and the responses that have emerged to those challenges, as well as the likely pathways that will lead to future progress

Simulation suggests that rapid activation of social distancing can arrest epidemic development due to a novel strain of influenza

<p>Abstract</p> <p>Background</p> <p>Social distancing interventions such as school closure and prohibition of public gatherings are present in pandemic influenza preparedness plans. Predicting the effectiveness of intervention strategies in a pandemic is difficult. In the absence of other evidence, computer simulation can be used to help policy makers plan for a potential future influenza pandemic. We conducted simulations of a small community to determine the magnitude and timing of activation that would be necessary for social distancing interventions to arrest a future pandemic.</p> <p>Methods</p> <p>We used a detailed, individual-based model of a real community with a population of approximately 30,000. We simulated the effect of four social distancing interventions: school closure, increased isolation of symptomatic individuals in their household, workplace nonattendance, and reduction of contact in the wider community. We simulated each of the intervention measures in isolation and in several combinations; and examined the effect of delays in the activation of interventions on the final and daily attack rates.</p> <p>Results</p> <p>For an epidemic with an R₀value of 1.5, a combination of all four social distancing measures could reduce the final attack rate from 33% to below 10% if introduced within 6 weeks from the introduction of the first case. In contrast, for an R₀of 2.5 these measures must be introduced within 2 weeks of the first case to achieve a similar reduction; delays of 2, 3 and 4 weeks resulted in final attack rates of 7%, 21% and 45% respectively. For an R₀of 3.5 the combination of all four measures could reduce the final attack rate from 73% to 16%, but only if introduced without delay; delays of 1, 2 or 3 weeks resulted in final attack rates of 19%, 35% or 63% respectively. For the higher R₀values no single measure has a significant impact on attack rates.</p> <p>Conclusion</p> <p>Our results suggest a critical role of social distancing in the potential control of a future pandemic and indicate that such interventions are capable of arresting influenza epidemic development, but only if they are used in combination, activated without delay and maintained for a relatively long period.</p

Nicotinic α7 and α4β2 agonists enhance the formation and retrieval of recognition memory: potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders

YesCholinergic dysfunction has been shown to be central to the pathophysiology of Alzheimer’s disease and has also been postulated to contribute to cognitive dysfunction observed in various psychiatric disorders, including schizophrenia. Deficits are found across a number of cognitive domains and in spite of several attempts to develop new therapies, these remain an unmet clinical need. In the current study we investigated the efficacy of donepezil, risperidone and selective nicotinic α7 and α4β2 receptor agonists to reverse a delay-induced deficit in recognition memory. Adult female Hooded Lister rats received drug treatments and were tested in the novel object recognition (NOR) task following a 6 h inter-trial interval (ITI). In all treatment groups, there was no preference for the left or right identical objects in the acquisition trial. Risperidone failed to enhance recognition memory in this paradigm whereas donepezil was effective such that rats discriminated between the novel and familiar object in the retention trial following a 6 h ITI. Although a narrow dose range of PNU-282987 and RJR- 2403 was tested, only one dose of each increased recognition memory, the highest dose of PNU-282987 (10 mg/kg) and the lowest dose of RJR-2403 (0.1 mg/kg), indicative of enhanced cognitive performance. Interestingly, these compounds were also efficacious when administered either before the acquisition or the retention trial of the task, suggesting an important role for nicotinic receptor subtypes in the formation and retrieval of recognition memory.This work was conducted at the University of Bradford and was funded by b-neuro. However all our recent studies mentioned in the discussion section have been conducted at the University of Manchester (UoM), and funded by b-neuro, Autifony, Innovate UK (formerly TSB) and Uo