tbuckley/cabot-search huggingface dataset:
PTU-289 Embedding pharmaceutical care into the multidisciplinary team
Authors: A St. Clair Jones, MA Smith
Journal: Gut (2015)

<h3>Introduction</h3> Pharmacists traditionally do not get involved in the long-term management of patients with chronic disease. This service development aimed to integrate pharmacy-lead IBD medication optimisation into the IBD Multi Disciplinary Team (MDT). We report our experience of extending our specialist pharmacist’s remit. <h3>Method</h3> A weekly pharmacist outpatient clinic was established, to initiate immunomodulating drugs and undertake biochemical monitoring. The pharmacist optimised therapy according to blood levels, adverse drug reactions (ADRs) and concordance. Strategic and operational management of the biologics infusion clinic was transferred to the pharmacist. A new blood and therapeutic drug monitoring (TDM) service for immunomodulators and biologics was introduced to optimise therapy decisions. The rapid access (helpline) service was reviewed to see whether the pharmacist could add value. The pharmacist facilitated MDT-approved pathways to initiate and review immunomodulators. A workload and prescription audit was conducted over four months with financial impact assessment. Patient and anonymous colleague feedback was sought. <h3>Results</h3> In the four months analysed, 14 pharmacist clinics were held, serving 138 patients. 382 patients had blood monitoring, ensuring clinical governance. The biologics infusion clinic expanded to include a cross-speciality services. 65 patients had their immunosupressant therapy adjusted in the TDM service. The pharmacist is gatekeeper for testing and is responsible for optimising therapies (as a non-medical prescriber). The advice sought from the rapid access service was primarily nurse-orientated and the service remains nurse-lead, with pharmacist deputising to maximise resources. In 4 months 142 of 1032 queries were answered by the pharmacist. The MDT reviewed 42 patients on biologics according to the new pathways. The TDM service resulted in a minimum of £60,000 savings for the health economy. 6 of 6 peer-assessors returned overwhelmingly positive reviews of the service and patient feedback was fa. <h3>Conclusion</h3> Involving the pharmacist in all aspects of the long-term care of patients with IBD enhanced patient safety and standardised treatment and monitoring protocols, whilst individualising therapy. The focus of the MDT shifted to early medicines optimisation, realising considerable cost savings. Interprofessional relationships profited from working closely together / deputising for each other. Embedding pharmaceutical skills into the multidisciplinary team influenced therapeutic decision making, ensuring that services incorporated good medicine management and medicine optimisation principles at conception to guarantee high-quality, compassionate care and strong governance. <h3>Disclosure of interest</h3> None Declared.
The Importance of Differences in Morphology in Inbred Strains&lt;xref ref-type="fn" rid="fn1"&gt;1&lt;/xref&gt;
Authors: Thelma B. Dunn
Journal: JNCI Journal of the National Cancer Institute (1954)

The Importance of Differences in Morphology in Inbred Strains Get access Thelma B. Dunn Thelma B. Dunn Laboratory of Pathology, National Cancer Institute,2Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 3, December 1954, Pages 573–591, https://doi.org/10.1093/jnci/15.3.573 Published: 01 December 1954
Expansion of Medical Institutions into Urban Residential Areas
Authors: Howard Waitzkin
Journal: New England Journal of Medicine (1970)

Medical institutions in many American cities at present are expanding into urban residential areas. Harvard Medical School, for example, has attempted to destroy low-income housing to permit construction of a new hospital complex, but no convincing reason has been offered for Harvard's decision to build where housing would be destroyed rather than on other available land. Although Harvard's rental policies have fragmented the community, a tenants' association has formed to resist destruction of housing. The Harvard Corporation's publicized intention to build relocation housing represented a political response to pressure from students and faculty; it showed little consideration of the concrete needs of present tenants. The Medical School's administration has tried to neutralize opposition by establishing a powerless committee unable to halt Harvard's impingement on the community. At Harvard and elsewhere, it is questionable whether the medical elite alone is competent to make decisions resulting in the destruction of urban housing.
Definition of a Novel Feed-Forward Mechanism for Glycolysis-HIF1α Signaling in Hypoxic Tumors Highlights Aldolase A as a Therapeutic Target
Authors: Geoffrey Grandjean, Petrus R. de Jong, Brian P. James, Mei Yee Koh, Robert Lemos, John Kingston, Alexander Aleshin, Laurie A. Bankston, Claudia P. Miller, Eun Jeong Cho, Ramakrishna Edupuganti, Ashwini Devkota, Gabriel Stancu, Robert C. Liddington, Kevin N. Dalby, Garth Powis
Journal: Cancer Research (2016)

Abstract The hypoxia-inducible transcription factor HIF1α drives expression of many glycolytic enzymes. Here, we show that hypoxic glycolysis, in turn, increases HIF1α transcriptional activity and stimulates tumor growth, revealing a novel feed-forward mechanism of glycolysis-HIF1α signaling. Negative regulation of HIF1α by AMPK1 is bypassed in hypoxic cells, due to ATP elevation by increased glycolysis, thereby preventing phosphorylation and inactivation of the HIF1α transcriptional coactivator p300. Notably, of the HIF1α-activated glycolytic enzymes we evaluated by gene silencing, aldolase A (ALDOA) blockade produced the most robust decrease in glycolysis, HIF-1 activity, and cancer cell proliferation. Furthermore, either RNAi-mediated silencing of ALDOA or systemic treatment with a specific small-molecule inhibitor of aldolase A was sufficient to increase overall survival in a xenograft model of metastatic breast cancer. In establishing a novel glycolysis–HIF-1α feed-forward mechanism in hypoxic tumor cells, our results also provide a preclinical rationale to develop aldolase A inhibitors as a generalized strategy to treat intractable hypoxic cancer cells found widely in most solid tumors. Cancer Res; 76(14); 4259–69. ©2016 AACR.
PWE-411 Sepsis in surgical patients – are we good enough?
Authors: PB Sarmah, N Green, H Youssef
Journal: Gut (2015)

<h3>Introduction</h3> Sepsis is a leading cause of morbidity and mortality in the UK, with diagnosis and treatment being highlighted nationally by the UK Sepsis Trust. Our aim was to assess if sepsis is appropriately recognised and managed in acute surgical admissions using the systemic inflammatory response syndrome (SIRS) criteria and Sepsis 6 as per Trust and national guidelines. <h3>Method</h3> A prospective audit was conducted, focusing on the initial assessment by a surgical doctor for all acute surgical admissions over 14 days. Notes were reviewed for documented evidence of SIRS criteria, infection and Sepsis 6 bundle. Our standards were taken from the UK Sepsis Trust guidelines. A re-audit following departmental education for all grades of doctors was performed after 3 months. <h3>Results</h3> 102 patients were included in the audit. No patient was fully assessed for SIRS criteria, correlating with a missed diagnosis in 7 patients who presented with sepsis. The most frequently neglected SIRS criteria were mental state and glucose (not assessed in 83/102 and 98/102 respectively). None of the patients identified as septic during data collection had the full Sepsis 6 bundle implemented, although all were given antibiotics and intravenous (IV) fluids. None were given supplementary oxygen. Re-audit identified 78 patients for inclusion. Diagnosis of sepsis improved to 22% (total of 18 septic patients), again with mental state and glucose being overlooked frequently. However, implementation of the Sepsis 6 bundle was more varied, with fewer patients receiving antibiotics (11/18) and IV fluids (13/18) but an increase in the percentage receiving supplementary oxygen (5%). 100% of patients with infection were diagnosed as such in both the audit and re-audit. <h3>Conclusion</h3> The audit identified poor diagnosis but consistent delivery of antibiotics and IV fluids, which challenged initial assumptions of good diagnosis with poor management. The re-audit highlighted improvements in diagnosis suggesting that re-education with respects to SIRS criteria had worked to a degree. However, the poorer levels of implementation of the Sepsis 6 were unexpected. On reflection, this may have been due to rotation of junior doctors out of the department, as the new cohort were not given formal re-education. We must endeavour to identify interventions that lead to a sustainable rise in standards despite personnel changes, and ensure these interventions to improve patient safety are introduced early to new cohorts of doctors. <h3>Disclosure of interest</h3> None Declared.
A Bicentennial address: Benjamin Rush and those who came after him
Authors: F J Braceland
Journal: American Journal of Psychiatry (1976)

In this Bicentennial year, the author takes a look at the early days of Amercan psychiatry, focusing on some of the great men who helped to form the discipline. These men have much to teach us in a time when the field is divided within and faces a crisis of public confidence without. We can learn much from men like Benjamin Rush, who although they were actively involved in the social movements of their day, remained always the physician. Dr. Braceland suggests that it is time for psychiatry to move back into the mainstream of medicine, retaining, of course, mastery of psychotherpeutic techniques and knowledge of psychodynamics. This move can best be accomplished by employing the principle of complementarity, the art of encompassing different approaches to problems and utilizing the essentials of each to arrive at workable solutions.
Nivolumab and Pembrolizumab for Non–Small Cell Lung Cancer
Authors: Daniel Morgensztern, Roy S. Herbst
Journal: Clinical Cancer Research (2016)

Abstract The outcomes for patients with previously treated advanced stage non–small lung cancer (NSCLC) are very poor, with a modest benefit from chemotherapy over best supportive care. Immunotherapy offers a novel approach for the treatment of these patients, with two anti-programmed death 1 (PD-1) checkpoint inhibitors, nivolumab and pembrolizumab, recently approved by the FDA based on large randomized clinical trials showing increased overall survival compared with standard second-line docetaxel. Although only a subset of patients benefit from these drugs, the treatment is usually well tolerated and the responses are often durable, with an unprecedented number of survivors 3 years after starting the therapy. The next steps should be the identification of reliable predictors for benefit from immunotherapy with checkpoint inhibitors and the pursuit of well-designed combination therapies. In this article, we review the rationale for the use of checkpoint inhibitors in NSCLC, the data from phase I and randomized clinical trials, and future directions. Clin Cancer Res; 22(15); 3713–7. ©2016 AACR.
Hormonal Modulation of Pheromone Detection Enhances Male Courtship Success
Authors: Hui-Hao Lin, De-Shou Cao, Sachin Sethi, Zheng Zeng, Jacqueline S.R. Chin, Tuhin Subhra Chakraborty, Andrew K. Shepherd, Christine A. Nguyen, Joanne Y. Yew, Chih-Ying Su, Jing W. Wang
Journal: Neuron (2016)
The activation-synthesis hypothesis of dreams: a theoretical note
Authors: A L Labruzza
Journal: American Journal of Psychiatry (1978)

The author examines Hobson and McCarley's activation-synthesis hypothesis of dreams from the point of view of theory construction and the logic of science. After reviewing pertinent literature, he concludes that modern sciences has not yet established a well-defined mind-body isomorphism. Therefore, conclusions about the psychological meaning and motive of dreams cannot validly be drawn from neurobiological data.
Plasma concentrations of melatonin in panic disorder
Authors: I M McIntyre, F K Judd, G D Burrows, S M Armstrong, T R Norman
Journal: American Journal of Psychiatry (1990)

Nocturnal plasma melatonin concentrations were measured in seven patients with panic disorder and eight healthy control subjects. The five patients who had never received psychotropic medication had significantly greater melatonin concentrations from 4:00 a.m. to 7:00 a.m. than the control subjects. In addition it is possible that a phase delay occurred in these unmedicated patients. The findings are discussed in terms of previous studies showing increased melatonin in manic patients and the effect of intense stress on melatonin synthesis. The two patients who had been medication free for only 1 week showed a decreased melatonin rhythm, which is consistent with previous findings in medicated patients.
SP0077 ICF Related Patient Reported Outcome Measures, Proms, in RMDS- What is Useful in The Clinical Situation
Authors: R.H. Moe
Journal: Annals of the Rheumatic Diseases (2015)

According to the International Classification of Functioning, Disability and Health (ICF), the concept “function” is an umbrella term for Body Functions, Body Structures, Activities and Participation. The WHO encouraged all member countries to use the ICF in clinical care and research fourteen years ago, but did not describe how to do this. There are several patient reported outcome measures (PROM) available assessing aspects of outcomes in use within the field of Rheumatic and Musculoskeletal Diseases (RMD). They are commonly used for monitoring function or evaluating effects of interventions. Several of these most common PROMS have been linked to the ICF and disease specific Core Sets; these will be reviewed focusing on which aspects of function the PROMs usually cover. Aspects considered important in the clinic that may not be directly linkable to the ICF, and aspects that needs more attention in the future development of PROMs will also be addressed. <h3>Disclosure of Interest</h3> None declared
Epistaxis
Authors: Rodney J. Schlosser
Journal: New England Journal of Medicine (2009)

A 61-year-old man presents to the emergency room with left-sided epistaxis that has continued for 1 hour. He estimates having lost approximately 1/2 cup of blood and reports no history of nasal obstruction, epistaxis, trauma, bleeding diathesis, or easy bruising. He has a history of hypertension. Medications include atenolol and baby aspirin. How should this patient be evaluated and treated?
Regressive alterations of the self concept
Authors: M J Horowitz, N Zilberg
Journal: American Journal of Psychiatry (1983)

When clinicians formulate a case for treatment by dynamic psychotherapy they include an assessment of ego functions, including the capacity for self symbolization. Terminology for this purpose has been diffusely defined. This paper reviews concepts for describing self symbolization and emphasizes ways of describing the multiplicity of symbols present within any individual. Some regressive transference phenomena during treatment are briefly discussed to illustrate use of the suggested terminology in case formulation.
Migraine and vascular disease
Authors: Rebecca C Burch, Melissa L Rayhill
Journal: BMJ (2016)

The medical implications of migraine are not limited to the brain

In the linked paper (doi:10.1136/bmj.i2610), Kurth and colleagues examine the link between migraine and cardiovascular events by using data from the Nurses’ Health Study II. The study followed a large cohort of female nurses for more than 20 years, 17 531 of whom reported a physician’s diagnosis of migraine at baseline. When compared with participants without migraine, those with migraine had an elevated risk of myocardial infarction, angina, or coronary revascularization and of cardiovascular mortality. Their relative risk for the combined outcome of all those events or stroke was roughly 50% higher than that for women without migraine, an effect that was not modified by age.1

Not all of these findings are new. The elevated risk of stroke in people with migraine is well established, for example. This increased risk of stroke is driven by and probably limited to the roughly 30% of people with migraine who experience aura—a focal neurologic event that usually precedes the headache. Migraine is associated with a roughly …
Psychosocial interventions?
Authors: Dave W H Baillie
Journal: BMJ (2007)

Brazil's market is unregulatedFarrell warns of the health implications of the unwelcome partnership between the alcohol industry and the health sector. 1 Brazil has one million selling points for alcohol in a population of 180 million.These points can sell alcohol at any time of day, to anybody, including minors.We have a very aggressive advertising strategy on television that reaches millions of children.In recent research on a random sample of drivers, 30% of them had alcohol in their blood.Brazil is by any account an unregulated market for alcohol, and the alcohol industry is trying to keep it that way.This lack of regulation contributes to the 10% increase in consumption each year.If that were not enough, the alcohol industry has approached health professionals to advocate a harm reduction approach as the best policy for tackling this problem in Brazil.
AB0264 STAT4 RS7574865 Gene Polymorphism is not Associated with Severe Disease Phenotype and Response to Tumor Necrosis Factor-α Inhibitor Treatment in Patients with Rheumatoid Arthritis
Authors: G. Ozen, B. Saglam, A. Odabasi, O. Ozluk, S.P. Yentur, G. Saruhan-Direskeneli, N. Inanc, H. Direskeneli
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> To investigate the association between single nucleotide polymorphism (SNP) of rs7574865 in signal transducer and activator of transcription 4 (<i>STAT4)</i> gene and RA susceptibility among the Turkish population and to determine the effects of this genetic variant on disease characteristics and response to tumor-necrosis factor-α inhibitor (TNFi) treatment. <h3>Methods</h3> rs7574865 SNP of <i>STAT4</i> was genotyped in a total of 389 Turkish RA patients fulfilling the 1987 ACR classification criteria (F/M: 324/65, mean age: 52.8±12.6 years, 66.8% RF positive) and 573 healthy controls (F/M: 248/275, mean age: 30.1±9.9 years). Retrospectively, along with disease characteristics, EULAR response to biologic DMARDs, especially TNFi, DAS28 scores of each visit during the entire follow-up of RA patients (complete disease activity data were obtained from 318 patients) were recorded. <h3>Results</h3> The genotype distribution showed that RA cohort (GG: 297 [76.3%], GT: 79 [20.4%], TT: 13 [3.3%] patients) had significantly higher rate of TT genotype compared to HC (GG:431 [82.4%], GT:84 [16.1%], TT: 8 [1.5%] individuals) (<i>P</i>=0.04). Presence of T minor allele (GT or TT genotype) was also significantly higher in RA patients (23.7% vs 17.6%, OR=1.44; CI:95% 1.042-1.99, <i>P</i>=0.03). However, T allele carrier rates of seronegative (16.9%) and seropositive (25.6%) (either RF or Anti-CCP) patients were similar (<i>P</i>=0.14). Biologic treatment requirements, extra-articular involvement and joint surgery rates were similar in RA patients with and without T allele (Table 1). During 6.0±4.0 years follow-up period, in a median of 10 (min-max: 2-42) visits, the ratio of visits in moderate-high disease activity and remission-low disease activity and sustained remission rate (remission in 3 consecutive visits) were not different in patients with and without T allele (Figure 1). Of the 161 patients treated with biologic DMARDs, 141 received TNFi (infliximab 51, adalimumab 47, etanercept 43 patients) and the EULAR response to TNFi at 6th month were also similar in T allele carrier and non-carrier patients (59.3% vs 71.9%, <i>P</i>=0.19). Seropositivity for either RF or anti-CCP (82.4% vs 80.5%), disease durations (13.9 vs 14.3 years) and baseline DAS28 scores (5.34 vs 5.31) were also comparable in TNFi responders and nonresponders. <h3>Conclusions</h3> The data revealed that T allele of <i>STAT4</i> rs7574865 was associated with an increased risk of RA in Turkish population. However presence of T allele does not seem to have an effect on disease phenotype and TNFi response. <h3>Disclosure of Interest</h3> None declared
The opiate receptor and morphine-like peptides in the brain
Authors: S H Snyder
Journal: American Journal of Psychiatry (1978)

Opiate receptors--neuronal membrane proteins that have been identified by the direct binding to membranes of radioactive opiates--have been shown to mediate the pharmacological effects of opiate drugs. Examination of brain extracts for substances that mimic effects of opiates on the opiate receptor permitted identification of the enkephalins, two peptides, each containing five amino acids, which are the normal substrates for the opiate receptor. Enkephalins are contained in specific neurons localized to areas of the brain enriched in opiate receptors. Enkephalin-containing neurons and opiate receptors are concentrated in portions of the brain that mediate pain perception, emotional behavior, and other functions altered by opiates. beta-Endorphin, an opiate-like peptide containing 31 amino acids, is localized to the pituitary gland from which it can be released into the circulation to act presumably at peripheral target organs. In the brain beta-endorphin is concentrated in the hypothalamus.