tbuckley/cabot-search huggingface dataset:
Choice and place of death: individual preferences, uncertainty, and the availability of care
Authors: D. Munday, J. Dale, S. Murray
Journal: Journal of the Royal Society of Medicine (2007)

Never before have people been faced with such levels of choice as now enjoyed by those living in affluent societies. Increases in technological possibilities and relatively high levels of disposable income have enabled large numbers of citizens to exercise choice in a wide variety of areas, from contraception to managing their infertility, from deciding where to educate children to which career to follow, which TV/DVD/computer to buy, where to holiday, etc.

However, when it comes to deciding about death, choice is a more contentious notion. As the comedian Woody Allen once said ‘I am not afraid of death, I just don't want to be there when it happens.’ While individuals can influence their health and illness through lifestyle choices, most have relatively little choice with respect to the time, manner and place of their death.1 With recent moves to legalize euthanasia and physician-assisted suicide in some countries, choice regarding place and time of death has been extended. However, even where such choice is available, it tends to be utilized by relatively few people. Less than four percent of deaths in the Netherlands are reported to be by euthanasia.2

Although most people say that they would prefer to die at home, there has been a persistent fall in the proportion of people doing so. This trend has continued, with only 22% of cancer deaths in the UK in 2003 occurring there.3 The reasons for this are undoubtedly complex, involving many aspects of health-care practice and provision as well as social changes.4 The trend in falling home death rate has continued despite the rise in community palliative care services in the UK over the last 20 years.

In line with the all-pervading choice agenda, health care professionals are increasingly expected to ascertain a patient's choice about preferred place of death, record it and aim to deliver it. Little is known about how health-care professionals elicit patients' preferences and the extent to which eliciting such views enables them to facilitate their realization. In this paper we present an overview of the UK policy context and the published literature on preferred place of death, and examine key issues which arise for health-care professionals in exploring preferred place of death with patients. The purpose is to inform debate about the role health-care professionals play in helping patients make this most important of choices, and in enabling their preferences regarding preferred place of death to be respected.
Development Gone Awry
Authors: Peter J. Gruber, Jonathan A. Epstein
Journal: Circulation Research (2004)

Significant advances in the understanding of the molecular and genetic basis of congenital heart disease have emerged from gene inactivation studies in mice and from human genetic investigations. However, the ability to utilize information gleaned from animal models to inform clinical care of patients depends on an accurate anatomic analysis and presentation in terms that are meaningful to the clinical pediatric cardiologist. Likewise, the enormous depth and breadth of accumulated clinical experience can inform the developmental biologist and can highlight the importance and interrelationships of particular phenotypes. The explosion of potentially informative genetic tools demands that basic scientists and clinicians concerned with congenital cardiac disease enhance the ongoing bidirectional dialogue. In some cases, categories of congenital disease familiar to clinicians are not recognized by developmental biologists, and mechanisms accepted by the biologist seem inconsistent with clinical experience. In this review, we summarize some of the more clinically significant forms of congenital heart disease, and we highlight relevant genetic and developmental pathways.
Immunohistochemical characterization of the 'intimal proliferation' phenomenon in Sneddon's syndrome and essential thrombocythaemia
Authors: E. TAMM, W. JUNGKUNZ, M. WOLTER, W.CH. MARSCH
Journal: British Journal of Dermatology (1994)

Journal Article Immunohistochemical characterization of the 'intimal proliferation' phenomenon in Sneddon's syndrome and essential thrombocythaemia Get access E. TAMM, E. TAMM Department of Anatomy, Friedrich‐Alexander‐Universitäat Erlangen‐Nürnberg, Erlangen, Germany Privatdozent Dr Ernst Tamm. Anatomisches Institut II. Universität Erlangen‐Nürnberg. Universitätsstr. 19, D‐91054 Erlangen, Germany. Search for other works by this author on: Oxford Academic Google Scholar W. JUNGKUNZ, W. JUNGKUNZ Department of Dermatology, Johann Wolfgang Goethe Universität Frankfurt am Main, Germay Search for other works by this author on: Oxford Academic Google Scholar M. WOLTER, M. WOLTER Department of Dermatology, Johann Wolfgang Goethe Universität Frankfurt am Main, Germay Search for other works by this author on: Oxford Academic Google Scholar W.CH. MARSCH W.CH. MARSCH Department of Dermatology, Martin Luther Universität, Halle Wittenberg, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 131, Issue 6, 1 December 1994, Pages 814–821, https://doi.org/10.1111/j.1365-2133.1994.tb08583.x Published: 01 December 1994 Article history Accepted: 24 March 1994 Published: 01 December 1994
New Insulin Glargine 300 Units/mL Versus Glargine 100 Units/mL in People With Type 2 Diabetes Using Basal and Mealtime Insulin: Glucose Control and Hypoglycemia in a 6-Month Randomized Controlled Trial (EDITION 1)
Authors: Matthew C. Riddle, Geremia B. Bolli, Monika Ziemen, Isabel Muehlen-Bartmer, Florence Bizet, Philip D. Home
Journal: Diabetes Care (2014)

OBJECTIVE To compare the efficacy and safety of new insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in people with type 2 diabetes on basal insulin (≥42 units/day) plus mealtime insulin. RESEARCH DESIGN AND METHODS EDITION 1 (NCT01499082) was a 6-month, multinational, open-label, parallel-group study. Adults with glycated hemoglobin A1c (HbA1c) 7.0–10.0% (53–86 mmol/mol) were randomized to Gla-300 or Gla-100 once daily with dose titration seeking fasting plasma glucose 4.4–5.6 mmol/L. Primary end point was HbA1c change from baseline; main secondary end point was percentage of participants with one or more confirmed (≤3.9 mmol/L) or severe nocturnal hypoglycemia from week 9 to month 6. RESULTS Participants (n = 807) had mean age 60 years, diabetes duration 16 years, BMI 36.6 kg/m2, and HbA1c 8.15% (65.6 mmol/mol). HbA1c reduction was equivalent between regimens; least squares mean difference –0.00% (95% CI –0.11 to 0.11) (–0.00 mmol/mol [–1.2 to 1.2]). Fewer participants reported one or more confirmed (≤3.9 mmol/L) or severe nocturnal hypoglycemic events between week 9 and month 6 with Gla-300 (36 vs. 46% with Gla-100; relative risk 0.79 [95% CI 0.67–0.93]; P &amp;lt; 0.005); nocturnal hypoglycemia incidence and event rates were also lower with Gla-300 in the first 8 weeks of treatment. No between-treatment differences in tolerability or safety were identified. CONCLUSIONS Gla-300 controls HbA1c as well as Gla-100 for people with type 2 diabetes treated with basal and mealtime insulin but with consistently less risk of nocturnal hypoglycemia.
Acupuncture for Cancer-Related Fatigue in Patients With Breast Cancer: A Pragmatic Randomized Controlled Trial
Authors: Alexander Molassiotis, Joy Bardy, Jennifer Finnegan-John, Peter Mackereth, David W. Ryder, Jacqueline Filshie, Emma Ream, Alison Richardson
Journal: Journal of Clinical Oncology (2012)

We aimed to assess the effectiveness of acupuncture for cancer-related fatigue (CRF) in patients with breast cancer.We conducted a pragmatic, randomized controlled trial comparing acupuncture with enhanced usual care. Three hundred two outpatients with breast cancer participated. We randomly assigned 75 patients to usual care and 227 patients to acupuncture plus usual care (random assignment of 1:3 respectively) with minimization controlling for baseline general fatigue and maintenance treatment. Treatment was delivered by acupuncturists once a week for 6 weeks through needling three pairs of acupoints. The usual care group received a booklet with information about fatigue and its management. Primary outcome was general fatigue at 6 weeks, measured with the Multidimensional Fatigue Inventory (MFI). Other measurements included the Hospital Anxiety and Depression Scale, Functional Assessment of Cancer Therapy-General quality-of-life scale, and expectation of acupuncture effect. Analyses were by intention to treat.Two hundred forty-six of 302 patients randomly assigned provided complete data at 6 weeks. The difference in the mean General Fatigue score, between those who received the intervention and those who did not, was -3.11 (95% CI, -3.97 to -2.25; P < .001). The intervention also improved all other fatigue aspects measured by MFI, including Physical Fatigue and Mental Fatigue (acupuncture effect, -2.36 and -1.94, respectively; both at P < .001), anxiety and depression (acupuncture effect, -1.83 and -2.13, respectively; both at P < .001), and quality of life (Physical Well-Being effect, 3.30; Functional Well-Being effect, 3.57; both at P < .001; Emotional Well-Being effect, 1.93; P = .001; and Social Functioning Well-Being effect, 1.05; P < .05).Acupuncture is an effective intervention for managing the symptom of CRF and improving patients' quality of life.
Multifunctional T-cell Analyses to Study Response and Progression in Adoptive Cell Transfer Immunotherapy
Authors: Chao Ma, Ann F. Cheung, Thinle Chodon, Richard C. Koya, Zhongqi Wu, Charles Ng, Earl Avramis, Alistair J. Cochran, Owen N. Witte, David Baltimore, Bartosz Chmielowski, James S. Economou, Begonya Comin-Anduix, Antoni Ribas, James R. Heath
Journal: Cancer Discovery (2013)

Adoptive cell transfer (ACT) of genetically engineered T cells expressing cancer-specific T-cell receptors (TCR) is a promising cancer treatment. Here, we investigate the in vivo functional activity and dynamics of the transferred cells by analyzing samples from 3 representative patients with melanoma enrolled in a clinical trial of ACT with TCR transgenic T cells targeted against the melanosomal antigen MART-1. The analyses included evaluating 19 secreted proteins from individual cells from phenotypically defined T-cell subpopulations, as well as the enumeration of T cells with TCR antigen specificity for 36 melanoma antigens. These analyses revealed the coordinated functional dynamics of the adoptively transferred, as well as endogenous, T cells, and the importance of highly functional T cells in dominating the antitumor immune response. This study highlights the need to develop approaches to maintaining antitumor T-cell functionality with the aim of increasing the long-term efficacy of TCR-engineered ACT immunotherapy.A longitudinal functional study of adoptively transferred TCR–engineered lymphocytes yielded revealing snapshots for understanding the changes of antitumor responses over time in ACT immunotherapy of patients with advanced melanoma.
Prostaglandins modulate the responsiveness of the gastric microcirculation of sodium nitroprusside in cirrhotic rats
Authors: J Geraldo, P Ferraz, J L Wallace
Journal: Hepatology (1996)

Cirrhotic rats have an increased susceptibility to ethanol-induced gastric injury, related to an inability to mount a defensive gastric hyperemic response to luminal irritants, and associated with an impaired reactivity of the gastric microcirculation to nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)-dependent vasodilators. Whether this hyporesponsiveness is in some way related to depressed prostaglandin synthesis by the stomach of cirrhotic rats is not clear. The aims of this study were to evaluate the role of NO and prostaglandins in the regulation of the gastric microcirculation under resting conditions and in response to administration of sodium nitroprusside, as well as to investigate the mechanisms of the hyporesponsiveness of the gastric microcirculation to nitrovasodilators. Cirrhosis was induced in rats by bile duct ligation, and controls had sham-operation. N G -nitro-l-arginine-methyl-ester (l- NAME) and indomethacin administration produced a greater reduction in gastric blood flow in cirrhotic rats than controls. Indomethacin pretreatment almost completely abolished the responsiveness to sodium nitroprusside (NaNP) in cirrhotic rats, while not affecting controls. Long-term administration of misoprostol to cirrhotic rats restored to normal the responsiveness to NaNP, whereas long-term administration of aspirin to healthy rats resulted in a hyporesponsiveness of the gastric microcirculation to NaNP similar to that seen in cirrhotic rats. We conclude that there are interactions between NO and prostaglandins in regulating gastric blood flow in both healthy and cirrhotic rats. The hyporesponsiveness of the gastric microcirculation of cirrhotic rats to a nitrovasodilator may occur as a consequence of prolonged depression of gastric prostaglandin synthesis.
SURFACE TENSION OF SERUM OF THE SENSITIZED GUINEA PIG
Authors: Susan Griffith Ramsdell
Journal: The Journal of Experimental Medicine (1928)

The change in surface tension behavior in the serum of sensitized guinea pigs is, as du Noüy has concluded for immunized rabbit serum, not referable to an antibody content, since we know that the capacity for transfer of sensitization remains in the serum indefinitely, while the increased time-drop phenomenon is a transitory manifestation. That this phenomenon cannot be invoked by a new antigen capable of calling out its specific antibody would seem to make this response one due to some basic stable alteration of a tissue active in the general process of sensitization: That this alteration is not one called out by such a simple toxic injury as a uranium nitrate nephritis is contributory evidence that the primary toxicity of the horse serum is not the specific factor involved.
Alpha 1-antitrypsin alleles in patients with pulmonary emphysema, detected by DNA amplification (PCR) and oligonucleotide probes
Authors: K Bruun-Petersen, G Bruun-Petersen, R Dahl, B Larsen, S Kølvraa, J Koch, L Bolund, N Gregersen
Journal: European Respiratory Journal (1992)

Alpha 1-antitrypsin (AAT) deficiency is a serious predisposing factor for the development of pulmonary emphysema. Twelve representative Danish families were studied. AAT typing was performed as a comparative study between the traditional protein typing by isoelectrical focusing and the deoxyribonucleic acid (DNA) technique of enzymatic amplification and subsequent typing with radioactively labelled oligonucleotide probes. On the basis of clinical and radiological signs of pulmonary emphysema, 25 patients were selected. AAT typing was performed by use of the two techniques in combination, in search for new point-mutations among the patients. Results obtained with the two techniques were discordant in one patient, suggesting an unknown variant. The unexpectedly high PiZ frequency of 0.22 found in the study group is discussed.
ARDS outcomes: a marker of critical care quality in the UK?
Authors: M. P. Wise, N. Hart, P. J. Frost
Journal: Thorax (2010)

<h3>Introduction</h3> Little quantitative data are available on the global impact of diet on chronic diseases, including cardiovascular diseases, type 2 diabetes and cancer. <h3>Methods</h3> We used a comparative risk assessment framework to develop systematic and comparable methods to establish for selected dietary risk factors the effect sizes of probable or convincing causal diet-disease relationships; the alternative minimum risk exposure distribution; and the exposure distribution. These inputs, together with disease-specific mortality rates, allow computation of the numbers of events attributable to each dietary factor globally and in 21 world regions. <h3>Results</h3> Using WHO evidence criteria for convincing / probable causal effects, we identified potential causal diet-disease relationships. Effect sizes and ranges of uncertainty were derived from published or de-novo systematic reviews and meta-analyses of trials or high-quality observational studies. Alternative minimum-risk distributions were identified based on amounts corresponding to lowest disease rates in existing populations. Optimal and alternative definitions for each diet exposure were established based on the data used to quantify the harmful or protective effects. We developed methods for identifying and obtaining comparable data from nationally representative diet surveys throughout the world (see separately submitted Abstract). Multi-level hierarchical models will be developed and will be presented to handle the diversity of diet metrics, units of measure, energy-adjustment techniques, and to impute missing data. <h3>Conclusions</h3> These new methods will allow, for the first time, comparable and quantitative assessment of the global impact of specific dietary factors on chronic disease mortality. Such global assessment is not only possible, but imperative for priority setting and policy making.
Abnormally high thromboxane biosynthesis in homozygous homocystinuria. Evidence for platelet involvement and probucol-sensitive mechanism.
Authors: G Di Minno, G Davì, M Margaglione, F Cirillo, E Grandone, G Ciabattoni, I Catalano, P Strisciuglio, G Andria, C Patrono
Journal: Journal of Clinical Investigation (1993)

Homocystinuria due to homozygous cystathionine beta-synthase deficiency is an inborn error of metabolism characterized by a high incidence of thrombosis and premature atherosclerosis. We evaluated TXA2 biosynthesis in vivo and several in vitro tests of platelet function in 11 homocystinuric patients and 12 healthy controls. In vitro, patients' platelet aggregation was within control values as were TXB2 formation, fibrinogen binding, and ATP secretion in response to thrombin. In contrast, the urinary excretion of 11-dehydro-TXB2, a major enzymatic derivative of TXA2, was > 2 SD of controls in all patients (1,724 +/- 828 pg/mg creatinine, mean +/- SD, in patients vs. 345 +/- 136 in controls, P < 0.001). The administration to four patients of low-dose aspirin (50 mg/d for 1 wk) reduced metabolite excretion by > 80%. The recovery of 11-dehydro-TXB2 excretion over the 10 d that followed aspirin cessation occurred with a pattern consistent with the entry into the circulation of platelets with intact cyclooxygenase activity. Prolonged partial reduction in the abnormally high excretion of both 11-dehydro-TXB2 and 2,3-dinor-TXB2, was also observed in seven patients who ingested 500 mg daily for 3 wk of the antioxidant drug probucol. These results provide evidence for enhanced thromboxane biosynthesis in homocystinuria and for its partial dependence on probucol-sensitive mechanisms. Furthermore, the elevated TXA2 formation in homocystinuria is likely to reflect, at least in part, in vivo platelet activation.
Assessment of Plasma C-Reactive Protein as a Biomarker of Posttraumatic Stress Disorder Risk
Authors: Satish A. Eraly, Caroline M. Nievergelt, Adam X. Maihofer, Donald A. Barkauskas, Nilima Biswas, Agorastos Agorastos, Daniel T. O’Connor, Dewleen G. Baker
Journal: JAMA Psychiatry (2014)

<h3>Importance</h3> Posttraumatic stress disorder (PTSD) has been associated in cross-sectional studies with peripheral inflammation. It is not known whether this observed association is the result of PTSD predisposing to inflammation (as sometimes postulated) or to inflammation predisposing to PTSD. <h3>Objective</h3> To determine whether plasma concentration of the inflammatory marker C-reactive protein (CRP) helps predict PTSD symptoms. <h3>Design, Setting, and Participants</h3> The Marine Resiliency Study, a prospective study of approximately 2600 war zone–deployed Marines, evaluated PTSD symptoms and various physiological and psychological parameters before deployment and at approximately 3 and 6 months following a 7-month deployment. Participants were recruited from 4 all-male infantry battalions imminently deploying to a war zone. Participation was requested of 2978 individuals; 2610 people (87.6%) consented and 2555 (85.8%) were included in the present analysis. Postdeployment data on combat-related trauma were included for 2208 participants (86.4% of the 2555 included) and on PTSD symptoms at 3 and 6 months after deployment for 1861 (72.8%) and 1617 (63.3%) participants, respectively. <h3>Main Outcomes and Measures</h3> Severity of PTSD symptoms 3 months after deployment assessed by the Clinician-Administered PTSD Scale (CAPS). <h3>Results</h3> We determined the effects of baseline plasma CRP concentration on postdeployment CAPS using zero-inflated negative binomial regression (ZINBR), a procedure designed for distributions, such as CAPS in this study, that have an excess of zeroes in addition to being positively skewed. Adjusting for the baseline CAPS score, trauma exposure, and other relevant covariates, we found baseline plasma CRP concentration to be a highly significant overall predictor of postdeployment CAPS scores (<i>P</i> = .002): each 10-fold increment in CRP concentration was associated with an odds ratio of nonzero outcome (presence vs absence of any PTSD symptoms) of 1.51 (95% CI, 1.15-1.97;<i>P</i> = .003) and a fold increase in outcome with a nonzero value (extent of symptoms when present) of 1.06 (95% CI, 0.99-1.14;<i>P</i> = .09). <h3>Conclusions and Relevance</h3> A marker of peripheral inflammation, plasma CRP may be prospectively associated with PTSD symptom emergence, suggesting that inflammation may predispose to PTSD.
Electrical and mechanical restitution of the human heart at different rates of stimulation.
Authors: M R Franz, J Schaefer, M Schöttler, W A Seed, M I Noble
Journal: Circulation Research (1983)

Action potential duration and contractility are reduced following premature excitations, and gradually increase as the stimulus interval is lengthened. To examine these phenomena of electrical and mechanical restitution in the human heart, we simultaneously measured action potential duration and the maximum rate of left ventricular pressure in five patients undergoing electrophysiological study. Test beats were introduced at varying intervals after the last of a series of steady state intervals. By plotting action potential duration and maximum rate of left ventricular pressure as a function of the test interval, we formed electrical and mechanical restitution curves. When the rate of steady state pacing was increased, there was a decrease in action potential duration and an increase in the maximum rate of left ventricular pressure for all test intervals; i.e., a change in pacing rate affected action potential duration and maximum rate of left ventricular pressure of test responses in a reciprocal fashion. In addition, a higher steady state pacing rate allowed action potentials and contractile responses to be elicited at shorter test intervals, thereby displacing the electrical and mechanical restitution curves to the left. The magnitude of the leftward shift of both curves corresponded closely to the shortening of the steady state action potential duration induced by the increase in pacing rate. These findings confirm for the human heart that both electrical and mechanical restitution occur after membrane repolarization, i.e., as a function of the electrical diastolic interval preceding a beat, and not the stimulus interval.
Fpies Epidemiology in Australia: Results from a 2-Year Prospective Population Study
Authors: Sam S. Mehr, Dianne Campbell, Preeti Joshi, Joanne Smart, Jane E. Peake, Peter Kenneth Smith, Michael Gold, Brynn Wainstein, Katrina Jane Allen, Mimi L.K. Tang, Richard K.S. Loh, Alyson Margaret Kakakios, Melanie Wong, Yvonne Zurynski, Katie Frith
Journal: Journal of Allergy and Clinical Immunology (2015)