tbuckley/cabot-search huggingface dataset:
The Modern Doctor's Dilemma: Rationing and Ethics in Healthcare
Authors: John Butler
Journal: Journal of the Royal Society of Medicine (1999)

From one point of view, to talk about rationing and ethics is
to engage in subversion, for in the eyes of the UK
government there is no such thing as rationing in
healthcare. The Prime Minister has committed his
government to providing healthcare of a nationally attested
standard wherever and whenever it is needed, and ministers
have held unswervingly to the line that rationing is neither
necessary nor practised in the National Health Service1.
They insist that the NHS is still committed to providing
and is still providing-a comprehensive range of services
from the cradle to the grave. Rationing from this very
particular standpoint would mean the total removal of
certain services from the menu of availability through the
NHS, and this, ministers claim, is simply not happening.
Aging-Related Early Changes in Markers of Ventricular and Matrix Remodeling After Reperfused ST-Segment Elevation Myocardial Infarction in the Canine Model
Authors: Bodh I. Jugdutt, Anwar Jelani, Ariv Palaniyappan, Halliday Idikio, Richard E. Uweira, Vijay Menon, Catherine E. Jugdutt
Journal: Circulation (2010)

Background— Elderly patients with reperfused ST-segment-elevation myocardial infarction are at increased risk for left ventricular remodeling. Extracellular matrix damage has been implicated in early remodeling. We hypothesized that aging results in enhanced early reperfusion injury and left ventricular remodeling after reperfused ST-segment-elevation myocardial infarction and that early therapy initiated at the time of reperfusion with an angiotensin II type 1 receptor blocker such as candesartan attenuates age-related increases in reperfusion injury and remodeling. Methods and Results— We randomized 3 groups of dogs (age, 1 to 2, 2.1 to 5, and 5.1 to 10 years) with reperfused ST-segment-elevation myocardial infarction (90 minutes of ischemia, 2 hours of reperfusion) to therapy with placebo or candesartan (1 mg/kg CV-11974) over 30 minutes from the onset of reperfusion. Reperfusion in placebo groups was associated with aging-related changes in the ischemic zones in markers of damage (increased ischemic injury, infarct size [as percent risk], cardiomyocyte apoptosis, blood flow impairment, no reflow), structural remodeling (increased left ventricular dilation and dysfunction), extracellular matrix remodeling (increased expression of secretory leucocyte protease inhibitor, secreted protein acidic and rich in cysteine, osteopontin, a disintegrin and metalloproteinase-10 and -17, and matrix metalloproteinase-9 and -2), and inflammation (increased inducible nitric oxide synthase, proinflammatory cytokines interleukin-6 and tumor necrosis factor-α, and transforming growth factor-β 1 ; decreased antiinflammatory cytokine interleukin-10). Compared with placebo, candesartan attenuated these age-dependent changes. Conclusion— Aging results in age-dependent early increases in markers of damage and adverse structural and matrix remodeling after ST-segment-elevation myocardial infarction reperfused after 90 minutes of ischemia, and early therapy initiated at the time of reperfusion with the angiotensin II type 1 receptor blocker candesartan attenuates these changes. This strategy needs clinical confirmation.
A randomized placebo-controlled study of tamoxifen after adjuvant chemotherapy in premenopausal women with early breast cancer (National Cancer Institute of Canada—Clinical Trials Group Trial, MA.12)
Authors: V.H.C. Bramwell, K.I. Pritchard, D. Tu, K. Tonkin, H. Vachhrajani, T.A. Vandenberg, J. Robert, A. Arnold, S.E. O'Reilly, B. Graham, L. Shepherd
Journal: Annals of Oncology (2009)
Management of chronic pain in older adults
Authors: M. C. Reid, C. Eccleston, K. Pillemer
Journal: BMJ (2015)

Chronic pain is one of the most common conditions encountered by healthcare professionals, particularly among older (≥65 years) patients. 12][3] Its negative effects extend beyond the patient, to disrupt both family and social relationships.Chronic pain poses a significant economic burden on society. 1 Prevalence rates for pain are expected to increase as populations continue to age-by 2035 an estimated one quarter of the population in the European Union will be 65 or older-thereby increasing the public health impact of pain.Healthcare providers, irrespective of specialty, should develop competencies to assess and manage chronic pain in their older patients.In this review we summarize recent evidence on the assessment and management of pain in older patients.Evidence is taken from systematic reviews, meta-analyses, individual trials, and clinical guidelines.
Increased Cyclooxygenase-2 Expression in Juvenile Polyposis Syndrome
Authors: W. Arnout van Hattem, Lodewijk A.A. Brosens, Susan Y. Marks, Anya N.A. Milne, Susanne van Eeden, Christine A. Iacobuzio–Donahue, Ari Ristimäki, Francis M. Giardiello, G. Johan A. Offerhaus
Journal: Clinical Gastroenterology and Hepatology (2008)
Increased Levels of Lipid-Bound Sialic Acid in Thymic Lymphocytes and Plasma From Leukemic AKR/J Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Ernest E. Lengle
Journal: JNCI Journal of the National Cancer Institute (1979)

Lipid-bound sialic acid levels for thymic lymphocytes and plasma were elevated twofold in leukemic AKR/J mice as compared to the levels observed in young, nonleukemic mice. In contrast, lipid-bound phosphorus levels were similar for thymic lymphocytes from both groups of mice.
Total ischemia in dog hearts, in vitro. 1. Comparison of high energy phosphate production, utilization, and depletion, and of adenine nucleotide catabolism in total ischemia in vitro vs. severe ischemia in vivo.
Authors: R B Jennings, K A Reimer, M L Hill, S E Mayer
Journal: Circulation Research (1981)

This study was done to compare rates of high energy phosphate (HEP) utilization and depletion, as well as the production and distribution of catabolic products of adenine nucleo tides in dog heart during total ischemia in vitro and severe ischemia in vivo.Both HEP production from anaerobic glycolysis and HEP utilization occurred much more quickly during the fir»t 15 mmtuet of severe ischemia in vivo than in total ischemia in vitro.HEP utilization exceeded production in both types of ischemia and tissue HEP decreased progressively.Much of the creatine phosphate (CP) was lost within the first 1-3 minutes; adenosine triphosphate (ATP) depletion occurred more slowly than CP and more slowly in vitro than in vivo.ATP was reduced from control contents of 5-6 /imol/g to 1.0 jirool/g by 75 minutes of total ischemia in vitro, but reached a similar level within only 30 minutes of severe ischemia in vivo.HEP utilization and production during ischemia were estimated from the rate of accumulation of myocardial lactate and essentially ceased when the ATP reached 0.4 jimol/g wet weight.At this time, more than 80% of the HEP that had been utilized in ischemia in vivo or in total ischemia in vitro had been derived from anaerobic glycolysis.ATP depletion was paralleled by dephosphorylation of adenine nucleottdeg.The lost nucleotides were recovered stoichiometrically as adenosine, inosine, hypoxantbine, and xanthine in both models of ischemia, a finding which demonstrates that the low collateral flow of severe ischemia allows little washout of nucleosides, bases, or lactate to the systemic circulation.These results Indicate that total ischemia in vitro can be used as a model of severe ischemia in vivo in that the pathways of energy production and depletion and of adenine nucleotide degradation generally are similar.Moreover, the larger quantities of uniformly ischemic tissue and the slower time course of changes make total ischemia well suited to the study of relationships between the metabolic, ftmctional, and structural consequences of ischemic injury, drc
The behavior of alpha2-plasmin inhibitor in fibrinolytic states.
Authors: N Aoki, M Moroi, M Matsuda, K Tachiya
Journal: Journal of Clinical Investigation (1977)

Human plasma alpha2-plasmin inhibitor in fibrinolytic states was studied using immunochemical methods and radioiodinated plasminogen. The concentration and activity of plasma alpha2-plasmin inhibitor decreased when urokinase was added to plasma in vitro or infused intravenously in man. The decrease was associated with the appearance of plasmin-alpha2-plasmin inhibitor complex which subsequently disappeared from the circulation in a short time. A decrease of other major inhibitors, such as alpha2-macroglobulin and alpha1-antitrypsin, was not observed when the amount of urokinase added or infused was relatively small, and conversion of plasminogen to plasmin was not extensive. The formation of plasmin-alpha2-macroglobulin complex was observed only when plasma plasminogen was activated with a larger amount of urokinase, and after most of the alpha2-plasmin inhibitor was consumed by forming complexes with plasmin. The formation of plasmin-alpha1-antitrypsin complex was not observed even in the highly activated plasma unless exogenous plasmin was added to the plasma. alpha2-Plasmin inhibitor was the only inhibitor of which the concentration in plasma was significantly decreased in patients with disseminated intravascular coagulation and fibrinolysis among the major plasmin inhibitors in plasma. The most reactive inhibitor for regulating plasma fibrinolysis very likely is alpha2-plasmin inhibitor.
A critical assessment of Mus musculus gene function prediction using integrated genomic evidence
Authors: Lourdes Peña-Castillo, Murat Tasan, Chad L Myers, Hyunju Lee, Trupti Joshi, Chao Zhang, Yuanfang Guan, Michele Leone, Andrea Pagnani, Wan Kim, Chase Krumpelman, Weidong Tian, Guillaume Obozinski, Yanjun Qi, Sara Mostafavi, Guan Lin, Gabriel F Berriz, Francis D Gibbons, Gert Lanckriet, Jian Qiu, Charles Grant, Zafer Barutcuoglu, David P Hill, David Warde-Farley, Chris Grouios, Debajyoti Ray, Judith A Blake, Minghua Deng, Michael I Jordan, William S Noble, Quaid Morris, Judith Klein-Seetharaman, Ziv Bar-Joseph, Ting Chen, Fengzhu Sun, Olga G Troyanskaya, Edward M Marcotte, Dong Xu, Timothy R Hughes, Frederick P Roth
Journal: Genome biology (2008)

Several years after sequencing the human genome and the mouse genome, much remains to be discovered about the functions of most human and mouse genes. Computational prediction of gene function promises to help focus limited experimental resources on the most likely hypotheses. Several algorithms using diverse genomic data have been applied to this task in model organisms; however, the performance of such approaches in mammals has not yet been evaluated. In this study, a standardized collection of mouse functional genomic data was assembled; nine bioinformatics teams used this data set to independently train classifiers and generate predictions of function, as defined by Gene Ontology (GO) terms, for 21,603 mouse genes; and the best performing submissions were combined in a single set of predictions. We identified strengths and weaknesses of current functional genomic data sets and compared the performance of function prediction algorithms. This analysis inferred functions for 76% of mouse genes, including 5,000 currently uncharacterized genes. At a recall rate of 20%, a unified set of predictions averaged 41% precision, with 26% of GO terms achieving a precision better than 90%. We performed a systematic evaluation of diverse, independently developed computational approaches for predicting gene function from heterogeneous data sources in mammals. The results show that currently available data for mammals allows predictions with both breadth and accuracy. Importantly, many highly novel predictions emerge for the 38% of mouse genes that remain uncharacterized.
Usage and Effect of Health Information Exchange
Authors: Robert S. Rudin, Aneesa Motala, Caroline L. Goldzweig, Paul G. Shekelle
Journal: Annals of Internal Medicine (2014)

Background: Health information exchange (HIE) is increasing in the United States, and it is incentivized by government policies. Purpose: To systematically review and evaluate evidence of the use and effect of HIE on clinical care. Data Sources: Selected databases from 1 January 2003 to 31 May 2014. Study Selection: English-language hypothesis-testing or quantitative studies of several types of data exchange among unaffiliated organizations for use in clinical care that addressed health outcomes, efficiency, utilization, costs, satisfaction, HIE usage, sustainability, and attitudes or barriers. Data Extraction: Data extraction was done in duplicate. Data Synthesis: Low-quality evidence from 12 hypothesis-testing studies supports an effect of HIE use on reduced use or costs in the emergency department. Direct evidence that HIEs were used by providers was reported in 21 studies involving 13 distinct HIE organizations, 6 of which were located in New York, and generally showed usage in less than 10% of patient encounters. Findings from 17 studies of sustainability suggest that approximately one quarter of existing HIE organizations consider themselves financially stable. Findings from 38 studies about attitudes and barriers showed that providers, patients, and other stakeholders consider HIE to be valuable, but barriers include technical and workflow issues, costs, and privacy concerns. Limitation: Publication bias, possible selective reporting of outcomes, and a dearth of reporting on context and implementation processes. Conclusion: Health information exchange use probably reduces emergency department usage and costs in some cases. Effects on other outcomes are unknown. All stakeholders claim to value HIE, but many barriers to acceptance and sustainability exist. A small portion of operational HIEs have been evaluated, and more research is needed to identify and understand success factors. Primary Funding Source: U.S. Department of Veterans Affairs. (PROSPERO registration number: CRD42014007469)
Eight more people in UK sue Grunenthal and Diageo over thalidomide
Authors: C. Dyer
Journal: BMJ (2014)

A group of people who claim that they were damaged by the drug thalidomide before their birth have launched a compensation claim at the High Court in London, more than 50 years after they were born.

Eight claimants have filed a negligence action against the drug’s German manufacturer, Grunenthal, and against Diageo, which took over the drug company’s UK distributor, Distillers. The solicitor for the …
International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion
Authors: Andrew J Molyneux, Richard SC Kerr, Ly-Mee Yu, Mike Clarke, Mary Sneade, Julia A Yarnold, Peter Sandercock
Journal: The Lancet (2005)
Spontaneous Abnormal Involuntary Movements in First-Episode Schizophrenia and Schizophreniform Disorder: Baseline Rate in a Group of Patients From an Irish Catchment Area
Authors: Maurice Gervin, Stephen Browne, Abbie Lane, Mary Clarke, John L. Waddington, Conall Larkin, Eadbhard O’Callaghan
Journal: American Journal of Psychiatry (1998)

Objective: This study investigated the rate of spontaneous abnormal involuntary movements in a group of patients presenting with a first episode of schizophrenia or schizophreniform psychosis. Method: Seventy-nine patients with a first episode of schizophrenia or schizophreniform psychosis who presented to a catchment area psychiatric service over a 3-year period, and who were neuroleptic-naive or had been medicated for less than 1 month, were examined for the presence of involuntary movements with use of the Abnormal Involuntary Movement Scale.Results: Six patients (7.6%) had spontaneous dyskinesia as defined by the criteria of Schooler and Kane, and nine other patients had mild orofacial involuntary movements. The patients with spontaneous dyskinesia had completed significantly fewer years of education than the patients without dyskinesia. Spontaneous involuntary movements were unrelated to age at presentation for treatment. Conclusions: Spontaneous abnormal involuntary movements were evident among a proportion of patients with first-episode schizophrenia or schizophreniform psychosis at baseline presentation and were associated with reduced educational attainment. This finding supports previous suggestions that abnormal involuntary movements in schizophrenia may be related to the pathophysiology of the illness and therefore cannot be attributed entirely to the adverse effects of neuroleptic medication. Am J Psychiatry 1998; 155: 1202-1206
In silico analysis of HLA associations with drug-induced liver injury: use of a HLA-genotyped DNA archive from healthy volunteers
Authors: Ana Alfirevic, Faviel Gonzalez-Galarza, Catherine Bell, Klara Martinsson, Vivien Platt, Giovanna Bretland, Jane Evely, Maike Lichtenfels, Karin Cederbrant, Neil French, Dean Naisbitt, B Kevin Park, Andrew R Jones, Munir Pirmohamed
Journal: Genome Medicine (2012)

Drug-induced liver injury (DILI) is one of the most common adverse reactions leading to product withdrawal post-marketing. Recently, genome-wide association studies have identified a number of human leukocyte antigen (HLA) alleles associated with DILI; however, the cellular and chemical mechanisms are not fully understood.To study these mechanisms, we established an HLA-typed cell archive from 400 healthy volunteers. In addition, we utilized HLA genotype data from more than four million individuals from publicly accessible repositories such as the Allele Frequency Net Database, Major Histocompatibility Complex Database and Immune Epitope Database to study the HLA alleles associated with DILI. We utilized novel in silico strategies to examine HLA haplotype relationships among the alleles associated with DILI by using bioinformatics tools such as NetMHCpan, PyPop, GraphViz, PHYLIP and TreeView.We demonstrated that many of the alleles that have been associated with liver injury induced by structurally diverse drugs (flucloxacillin, co-amoxiclav, ximelagatran, lapatinib, lumiracoxib) reside on common HLA haplotypes, which were present in populations of diverse ethnicity.Our bioinformatic analysis indicates that there may be a connection between the different HLA alleles associated with DILI caused by therapeutically and structurally different drugs, possibly through peptide binding of one of the HLA alleles that defines the causal haplotype. Further functional work, together with next-generation sequencing techniques, will be needed to define the causal alleles associated with DILI.
Respiratory monitoring: revisiting classical physiological principles with new tools
Authors: M.I. Polkey
Journal: European Respiratory Journal (2004)

<h3>BACKGROUND:</h3> Adherence to guidelines for endotracheal tube (ETT) insertion depth may not be sufficient to prevent malposition or harm to the patient. To obtain an estimate of ETT malpositioning, we evaluated initial postintubation chest radiographs and hypothesized that many ETTs in multiple intubation settings would be malpositioned despite adherence to Pediatric Advanced Life Support and Neonatal Resuscitation Program guidelines. <h3>METHODS:</h3> In a random subset (randomization table) of 2,000 initial chest radiographs obtained from January 1, 2009, to May 5, 2012, we recorded height, weight, age, sex, ETT inner diameter, and cm marking at the lip from the electronic health record. Chest radiographs of poor quality and with spinal or skeletal deformities were excluded. We defined adherence to Pediatric Advanced Life Support or Neonatal Resuscitation Program guidelines as the difference between predicted and actual ETT markings at the lip as ± 0.25, ± 0.50, or ± 1.0 cm for ETTs of 2.5–4, 4.5–6.0, or &gt;6.5 mm inner diameter, respectively. We defined the proper position as the ETT tip being below the thoracic inlet (superior border of the clavicular heads) and ≥1 cm above the carina. Descriptive statistics reported demographics, guideline adherence, and malposition incidence. The chi-square test was used to assess relationships among intubation setting, malposition, and depth guideline adherence (<i>P</i> &lt; .05, significant). <h3>RESULTS:</h3> We reviewed 507 records, 477 of which met inclusion criteria and had sufficient data for analysis. Fifty-six percent of the subjects were male, with median (interquartile range) age 15.2 (3.4–59.4) months, and 330 ETTs (69%) were malpositioned: 39 above the thoracic inlet, and 291 &lt; 1 cm above the carina. Of 79 ETTS (17%) that adhered to depth guidelines, 56 (74%) were malpositioned. Three-hundred seventy-three ETTs (83%) did not meet guidelines. Two-hundred sixty-four (68%) were malpositioned. The intubation setting did not influence malposition or guideline adherence (<i>P</i> = .54). <h3>CONCLUSIONS:</h3> In infants and children, a high proportion of ETTs were malpositioned on the first postintubation chest radiograph, with little influence of guideline adherence.
Epidemiological and clinical outcome comparison of indirect (‘strain’) versus direct (‘contusion’) anterior and posterior thigh muscle injuries in male elite football players: UEFA Elite League study of 2287 thigh injuries (2001–2013)
Authors: Peter Ueblacker, Hans-Wilhelm Müller-Wohlfahrt, Jan Ekstrand
Journal: British Journal of Sports Medicine (2015)

Data regarding direct athletic muscle injuries (caused by a direct blunt or sharp external force) compared to indirect ones (without the influence of a direct external trauma) are missing in the current literature--this distinction has clinical implications.To compare incidence, duration of absence and characteristics of indirect and direct anterior (quadriceps) and posterior thigh (hamstring) muscle injuries.30 football teams and 1981 players were followed prospectively from 2001 until 2013. The team medical staff recorded individual player exposure and time-loss injuries. Muscle injuries were defined as indirect or direct according to their injury mechanism.In total, 2287 thigh muscle injuries were found, representing 25% of all injuries. Two thousand and three were valid for further analysis, of which 88% were indirect and 12% direct. The incidence was eight times higher for indirect injuries (1.48/1000 h) compared to direct muscle injuries (0.19/1000 h) (p<0.01). Indirect muscle injuries caused 19% of total absence, and direct injuries 1%. The mean lay-off time for indirect injuries amounted to 18.5 days and differed significantly from direct injuries which accounted for 7 days (p<0.001). 60% of indirect injuries and 76% of direct injuries occurred in match situations. Foul play was involved in 7% of all thigh muscle injuries, as well as in 2% of indirect injuries and 42% of direct injuries.Muscle anterior and posterior thigh injuries in elite football are more frequent than have been previously described. Direct injuries causing time loss are less frequent than indirect ones, and players can usually return to full activity in under half the average time for an indirect injury. Foul play is involved in 7.5% of all thigh muscle injuries.