tbuckley/cabot-search huggingface dataset:
Effectiveness of a partnership based self-management program for individuals with mild to moderate COPD and their families
Authors: Helga Jonsdottir, Alda Gunnarsdottir, Bryndis Halldorsdottir, Gunnar Gudmundsson, Ingibjorg Stefansdottir, Jon Steinar Jonsson, Olof Amundadottir, Rosa Jonsdottir, Thorbjorg Soley Ingadottir
Journal: European Respiratory Journal (2013)

Background Self-management educational programs are crucial to manage COPD in people with advanced disease, but have achieved less attention for people with beginning disease.

Aims Following hypothesis was tested: Individuals with mild to moderate COPD who participate in family partnership-based self-management program versus those who receive usual care will demonstrate a significant difference in health related quality of life, illness intrusiveness, anxiety and depression, self-reported physical activity, smoking status and self-reported exacerbations at 12 months.

Methods With an RCT participants were recruited in healthcare centres and lung physicians’ offices. Intervention consisting of 3-4 conversations, smoking cessation and a group meeting was provided for 6 months with 6 months follow-up. Control group received usual care.

Results Of 291 individuals 72 rejected invitation, 100 were excluded or unreachable, with 119 randomized into groups. 24% didn‘t know of the disease. More than half smoked, mean age was 59 years, women were 54 and men 46. There was no difference between experimental and control groups on St. Georges Respiratory Questionnaire, Hospital Anxiety and Depression Scale, self-reported physical activity, smoking status and self-reported exacerbations. Experimental group was significantly less influenced by disease on Illness Intrusiveness Rating Scale. Satisfaction with participation was 87-98% and 65-80% in experimental and control groups.

Conclusions Limited effectiveness is contributed to considerable gains of participation in control group, as well as timing, length and relatively low intensity of the program.
Abstract 14209: Prospective Validation of a Standardized, Previously Validated, 3D-Quantitative Analysis of CTA-Derived Geometrical and Plaque Compositional Parameters, Using Intravascular Ultrasound with Radiofrequency Backscatter Analysis ("VH") in Non-Obstructive and Obstructive Lesions
Authors: Sarah Rinehart, Gustavo Vazquez, Zhen Qian, Anna Kalynych, Laura Murrieta, Dimitri Karmpaliotis, Parag Joshi, Abhinav Sharma, Charles Brown, Szilard Voros
Journal: Circulation (2011)

Background: Quantitative plaque analysis with CTA has been validated against intravascular ultrasound with radiofrequency backscatter analysis (“VH”) in non-obstructive lesions, but little data is available in obstructive stenoses. Methods: Prospectively, 68 patients (Age 60±7; 60% male) underwent CTA and VH. Quantitative CTA (Vital Images; Vitrea 4.0) and VH analysis (Volcano) were conducted in anatomically co-registered segments. Mean percent diameter stenosis was 56±19 by quantitative coronary angiography; 19 of 68 cases (27.9%) were obstructive. Minimal lumen diameter (MLD) and minimal lumen area (MLA) were measured on both modalities. Calcified, low-density, high-density, and total non-calcified plaque volumes and percentages (CAP [%], LDNCP, HDNCP, NCP [%]) were determined on CTA. NCP on CTA was defined as LDNCP + HDNCP. LDNCP: -100 to 30 Hounsfield Units (HU); HDNCP: 30 to 150 HU; CAP ≥150 HU. VH compositions, including necrotic core, fibro-fatty, fibrous, and dense calcium, (NC, FF, FI, CAP) were ...
Activation of the Calcium Receptor by a Calcimimetic Compound Halts the Progression of Secondary Hyperparathyroidism in Uremic Rats
Authors: JI CHIN, SCOTT C. MILLER, MICHIHITO WADA, NOBUO NAGANO, EDWARD F. NEMETH, JOHN FOX
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The secondary hyperparathyroidism that develops in rats with chronic renal insufficiency (CRI) can be totally prevented by activation of the parathyroid Ca 2+ receptor with a calcimimetic compound, when treatment is initiated before parathyroid cell hyperplasia and increased circulating parathyroid hormone levels develop. In clinical practice, however, secondary hyperparathyroidism is usually manifest by the time CRI is diagnosed. This study examined the effects of daily oral gavage or continuous subcutaneous infusion for 8 wk of the calcimimetic NPS R-568 on the progression of established mild or moderate-to-severe secondary hyperparathyroidism in rats with CRI induced by 5/6 nephrectomy. Both oral and infused NPS R-568 completely prevented further hyperplasia but did not reduce total parathyroid cell number below that present at the initiation of treatment. This prevention of cellular proliferation occurred despite increases in plasma phosphate and decreases in Ca 2+ and 1,25-dihydroxyvitamin D levels, and supports the view that the Ca 2+ receptor is the dominant regulator of parathyroid cell hyperplasia in addition to parathyroid hormone secretion. The clinical implications of these findings suggest that controlling Ca 2+ receptor activity with calcimimetic compounds could be sufficient to manage secondary hyperparathyroidism in CRI.
Association Between Novelty Seeking and the Type 4 Dopamine Receptor Gene in a Large Finnish Cohort Sample
Authors: Jesper Ekelund, Dirk Lichtermann, Marjo-Ritta Järvelin, Leena Peltonen
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: An association between the type 4 dopamine receptor (DRD4) gene and the behavioral trait of novelty seeking has been reported, but several studies have failed to replicate this finding. In the present study, the authors tested for this association in a representative sample from the Finnish population. METHOD: The authors administered the Temperament and Character Inventory to 4,773 individuals from the 1966 birth cohort of northern Finland. They then genotyped 190 subjects with extreme scores for a 48 base-pair repeat polymorphism in the DRD4 gene. RESULTS: There was a significant difference in allele frequencies between the two groups. The 2- and 5-repeat alleles were significantly more common in the group of high scorers than in the group of low scorers. CONCLUSIONS: These results confirm the original findings of an association between the DRD4 gene and novelty seeking, while showing that novelty seeking is probably not influenced by the polymorphism itself but, rather, a different DNA variant in the DRD4 gene or another gene in linkage disequilibrium with it.
Nonclinical influences, beyond diagnosis and severity, on clinical decision making in dermatology: understanding the gap between guidelines and practice
Authors: F.M. Hajjaj, M.S. Salek, M.K.A. Basra, A.Y. Finlay
Journal: British Journal of Dermatology (2010)

Clinical decision making in dermatology is a complex process and might be influenced by a wide range of nonclinical factors.The aim of this study was to explore the role of nonclinical influences, beyond diagnosis and severity, on clinical decision making in dermatology.Semi-structured qualitative interviews were conducted with 46 clinicians working in departments of dermatology of nine different hospitals in Wales. Interviews were audio-recorded and later transcribed and their contents analysed.Nonclinical factors influencing patient management decisions in dermatology that were identified related to patients, clinicians and practice characteristics. Patient-related factors included place of residence, socioeconomic circumstances, education and intelligence, ethnicity, age, treatment adherence, expectations from treatment, quality of life, concerns and worries, difficult patients, and family members or friends. Clinician-related factors included time constraints in clinic, clinicians' personal circumstances, relationship with colleagues, and relationship with pharmaceutical companies. Practice-related factors included working in private practice, cost of treatment to the National Health Service (NHS), prescribing bureaucracy, and availability of treatment service in the work place. There was a difference between the consultants' views and those of the other clinicians over the impact of pharmaceutical companies on clinicians' prescribing and the awareness of treatment costs to the NHS. Most of the factors identified could potentially influence the clinicians' decision-making process subconsciously. Some clinicians highlighted that these factors are untaught in the medical curriculum, and are usually ignored in clinical guidelines, and therefore represent a challenge to the practice of evidence-based medicine.This study has described one aspect of the reality of medical decision making beyond the conventional evidence-based guidelines approach. Proper understanding of nonclinical influences on decision making is of paramount importance for the best patient-centred treatment outcomes.
Frequency, severity and risk factors of drug-induced liver injury during treatment of new tuberculosis patients
Authors: Diana Ivanova, Serge Borisov, Alexander Ryzhov
Journal: European Respiratory Journal (2012)

Background  Drug-induced liver injury (DILI) is one of the most serious problems complicating anti-tuberculosis (anti-TB) treatment. The aim of the study was to assess the incidence, severity of and risk factors for DILI among new TB patients.  Methods  200 HIV-uninfected new pulmonary TB patients admitted to Research and Clinical Center for TB control 2009 to 2011 were monitored for clinical and laboratory signs of DILI during the intensive phase of treatment. The median age was 28.0 (IQR 22-44) yrs, 93 were female, 108 were smear-positive, 172 received only first-line anti-TB drugs. The relationship between independent covariates (demographic and clinical data of patients) with frequency of DILI was analysed using multivariate logistic regression.  Results  The frequency of DILI (serum alanine aminotransferase (ALT) > 3 x the upper limit of normal [ULN]) was 32.5% (65/200 patients). Severe hepatotoxicity (ALT > 10 x ULN) occurred in 10.5% (21/200). 42 patients (21%) experienced hepatic adaptation (asymptomatic, transient elevation of ALT   Conclusion  Drug-induced liver injury is frequent complication of anti-TB treatment among new TB cases associated with female sex and a history of drug/food allergy, but not with alcohol abuse and concomitant diseases.
Proteinase activated receptor-1 (F2R) polymorphisms and susceptibility to exacerbations in COPD
Authors: Manuela Plate, Jennifer K. Quint, Jadwiga A. Wedzicha, Rachel C. Chambers, John R. Hurst
Journal: European Respiratory Journal (2012)

Introduction: COPD is a condition of global importance, characterized by accelerated lung function decline and an abnormal inflammatory response. Exacerbations (i.e. episodes of acute deterioration of respiratory health) account for much of the morbidity and mortality in COPD. The reasons why some patients are more susceptible to exacerbations is poorly understood, but familial clustering suggests that there may be a genetic basis. Proteinase activated receptor-1 (PAR 1 ) activation leads to the generation of several inflammatory mediators involved in COPD and our unpublished data have shown that functional polymorphisms of PAR 1  are protective in sarcoidosis.  Aims & objectives: The aim of this study was to investigate whether PAR 1  polymorphisms are associated with COPD exacerbation frequency (ExF).  Methods: Two PAR 1  SNPs (rs2227744 and rs32934) and a 13bp in/del (rs11267092) were genotyped in 136 infrequent and 67 frequent exacerbators.  Results: The genotypic distributions of all polymorphisms were in Hardy-Weinberg equilibrium. The rs2227744 SNP showed a statistically significant association with ExF. Frequency of the minor allele was 0.47 in infrequent and 0.37 in frequent exacerbators (OR 1.5, 95%CI 1.0-2.4, p=0.04). Considering exacerbations as a continuous variable, the presence of the minor allele was associated with a significantly lower exacerbation rate (3.03 vs 1.98 exacerbations/year, MWU p=0.04).  Conclusions: Taken together with our previous studies showing that the presence of the minor allele at SNP rs2227744 increases PAR 1  expression, these data suggest that this SNP may confer a degree of protection against exacerbations in COPD by increasing PAR 1  expression.  Funded by the BLF.
GSK3 inhibition induces glioma cell death through c-MYC, NF-κB and glucose regulation and represents a new therapeutic target in glioma
Authors: Svetlana Kotliarova, Sandra Pastorino, Lara Kovell, Yuri Kotliarov, Rolanda Bailey, Wei Zhang, Hua Song, Dragan Maric, Jeongwu Lee, Jean Claude Zenklusen, Howard Fine
Journal: Clinical Cancer Research (2008)

B52   Glycogen synthase kinase-3 (GSK3), a serine/threonine kinase, is involved in diverse cellular processes ranging from nutrient and energy homeostasis to proliferation and apoptosis. Its role in glioblastoma (GBM) has yet to be elucidated. Hereby, we identify GSK3 as a regulator of GBM cell survival using microarray analysis, small molecule and genetic inhibitors of GSK3 activity.  We demonstrate that multiple small molecular inhibitors of GSK3 activity and genetic down-regulation of GSK3α/β significantly inhibit glioma cell survival and clonogenicity. The potency of the cytotoxic effects is directly correlated with decreased enzyme activity-activating phosphorylation of GSK3α/β Y276/Y216 and with increased enzyme activity-inhibitory phosphorylation of GSK3α S21. Inhibition of GSK3 activity results in c-MYC-activation leading to the induction of Bax, Bim, DR4/DR5 and TRAIL expression and subsequent cytotoxicity. Additionally, down-regulation of GSK3 activity results in alteration of intracellular glucose metabolism resulting in dissociation of hexokinase (HK) II from the outer mitochondrial membrane with subsequent mitochondrial destabilization. Finally, inhibition of GSK3 activity causes a dramatic decrease in intracellular nuclear factor-kappa B (NF-kB) activity.  Inhibition of GSK3 activity results in c-MYC dependent glioma cell death through multiple mechanisms, all of which converge on the apoptotic pathways. GSK3 may therefore be an important therapeutic target for gliomas. Future studies will further define the optimal combinations of GSK3 inhibitors and cytotoxic agents for use in gliomas and other cancers.
Conflict of interest: forward not backward
Authors: F. Godlee
Journal: BMJ (2015)

The Catholic Church in England and Wales has brought the medieval manuscript Ars Moriendi – The Art of Dying – into the digital age, with a website -www.artofdyingwell.org – aimed at helping terminally ill people and their loved ones deal with death. Like the original 15th century work, The Art of Dying Well is intended to bring spiritual comfort and to offer practical guidance to people in the final stage of life. The modern – day version offers videos, animations and interviews with terminally ill people and their carers. <h3>Who is it for?</h3> • People who are dying • People with a friend or relative who is dying/has died • People who care for the dying in a professional context • People who are surviving death, or battling a life – threatening disease <h3>The national conversation around death</h3> As well as developing the Art of Dying Well website and engaging in the digital conversation around death, the Art of Dying Well initiative is taking part in the national conversation around death and helping to raise ‘literacy levels’ on the topic of dying well and appreciation of spiritual care in the process. To date, the Art of Dying Well has and continues to receive significant coverage in the Guardian, Times, LBC radio, BBC News, BBC Five Live, BBC Radio 2, Vatican Radio, and the Catholic press. <h3>What People Say</h3> ‘It speaks powerfully into this awkward, immature silence around death. And I believe it has the potential to alleviate much suffering. I’ve seen it used with clinicians, families and patients. And I have seen it be a powerful help.’ Jim McManus, Director of Public Health, Hertfordshire County Council.
Abstract 2379: Use of Hospice and Acute Care in Heart Failure vs. Cancer at End-of-Life
Authors: Soko Setoguchi, Robert J Glynn, Carol N Flavell, Raisa Levin, Lynne W Stevenson
Journal: Circulation (2008)

Advances in heart failure (HF) have prolonged survival but more patients (pts) die from HF than from any type of cancer. Quality of care improvement for HF has focused largely on initiation of life-saving treatments. Pts dying of HF were less likely to be supported by hospice and more likely to die in hospitals than pts with terminal cancer. Two end-of-life cohorts (HF and cancer) were identified using Medicare data. The HF cohort consisted of pts with 2 HF hospitalizations before cardiac death. The cancer cohort had registry-defined solid-organ cancer and death attributed to cancer. We assessed hospice use, ER visit, and acute hospitalization during 30 days prior to death and deaths in hospitals. Time trend and predictors of hospice use were also assessed. Among 7,930 HF pts with median age 82, 78% female and 5% black, 20% were referred to hospice compared to 51% in 7,565 cancer patients. The mean duration of hospice prior to death was longer with heart failure (68 for HF and 15 days for cancer). A modest rise in hospice use over time was parallel in the two groups. Acute care prior to death was higher for HF than cancer pts. (59 vs. 40% for ER visit and 62 vs. 45% for hospitalizations). More HF pts died in acute care hospitals than cancer pts (37 vs. 21%). Younger age, male gender, black race and dialysis therapy were associated with lower use of hospice in multivariate analyses. Although hospice use is increasing slowly over time, the contribution of hospice remains lower in HF, and more HF deaths occur in acute care settings. Further studies are needed to assess indications for hospice and acute care services in HF patients at the end of life.
Abstract 653: Flow-Dependent Accumulation of Inflammatory Cells in the Upstream Shoulder of Atherosclerotic Plaques
Authors: Atilla Yilmaz, Bettina Lipfert, Iwona Cicha, Katja Schubert, Dorette Raaz, Thomas Anger, Michael Klein, Raithel Dieter, Werner G. Daniel, Christoph D. Garlichs
Journal: Circulation (2006)
Inflammatory rheumatic disorders
Authors: B Pal
Journal: Annals of the Rheumatic Diseases (2004)

I was interested to read the paper by Guillemin et al , where the authors used a detailed questionnaire for a telephone survey of patients to assess rheumatic problems.1 I have used a similar but somewhat more extensive questionnaire, which was initially designed for doctors such as general practitioners to complete and return through my cyberclinic project.2

In this study we evaluated the feasibility of a rheumatology consultation and advisory service using internet and email. We devised and posted a detailed rheumatology pro forma on our website (www.cyberrheum.org; accessed 26 February 2004) for general practitioners to complete and return on the internet. Two trainee doctors interviewed and completed the pro forma for 207 new patients. Based on this information from the questionnaire alone we were then able to provide provisional diagnoses and management plans, which we compared with those drawn up after a face to face …
Politics surrounding last winter's flu crisis
Authors: N. Edwards
Journal: BMJ (2000)

Politics surrounding last winter's flu crisis NHS's fundamental problems must be solvedEditor-The NHS Confederation and the BMA have argued that the recent problems in dealing with emergency demand conceal more fundamental problems: the NHS has too little capacity run at too high a rate of use. 1 Running hospitals at the current rates of occupancy is not efficient.Bagust et al show that hospital occupancy of more than 85% will guarantee periodic bed crises and the cancellation of hospital admissions. 2 NHS occupancy information excludes patients who stay less than one day and therefore underestimates the true picture.In critical care a growing body of evidence suggests that there is insufficient spare capacity in the system.Many NHS staff have a ridiculous workload.They are required to cope with the chaotic results of high levels of admissions and occupancy and, in particular, the problem of patients on outlying wards.There is no time for staff to muster new resources, and nurses have had the parts of their work that allowed recuperation devolved to other staff.There is growing evi-dence that these problems affect outcomes and lead to staff seeking employment elsewhere, further exacerbating the pressure on those staff who remain.These problems have arisen because for 20 years the NHS has sought to do more work for less money.The measures of efficiency used by the government have in general paid little attention to the quality of the result, although there has been more of a move in this direction recently. 3The tight finances of the NHS have meant that improvements in efficiency can lead to a dilution of quality services, overstretching staff, being slow to adopt new medicines and technology, and failing to invest in major change that could improve the quality of what we do.Unfortunately, the latest planning guidance issued by the NHS Executive requires a further 3% increase in efficiency, which could make the problems worse. 4he absence of good baseline data means that it is difficult to prove that this will cause problems, and there is a danger of appearing to complain without evidence.We need to look at the way we measure performance and relate this more closely to broader measures than simple efficiency.
Increased LTB4 metabolites and PGD2 in BAL fluid after methacholine challenge in asthmatic subjects
Authors: D Nowak, F Grimminger, R Jorres, M Oldigs, KF Rabe, W Seeger, H Magnussen
Journal: European Respiratory Journal (1993)

The bronchoconstrictor potency of inhaled methacholine is widely used to assess airway responsiveness. However, evidence has accumulated that methacholine inhalation challenge may lead to an inflammatory response in the lower respiratory tract. We therefore compared cellular, leukotriene and prostanoid profiles in bronchoalveolar lavages (BAL) obtained five hours after methacholine challenge to control lavages without prior challenge. Eight subjects with asymptomatic to mild bronchial asthma and nine nonatopic healthy controls were enrolled in the study. Without prior challenge, the percentage of BAL eosinophils was higher in the asthmatic subjects ((mean +/- SD), 1.1 +/- 0.9%) than in the control subjects (0.1 +/- 0.1%. Leukotriene B4 (LTB4), and its omega-oxidation products (20-OH-LTB4 and 20-COOH-LTB4) were the only leukotrienes detectable in the baseline BAL fluids in five of the eight asthmatic patients. After methacholine challenge, no change in BAL cell profile occurred, but in the asthmatic patients, the total amounts of LTB4 and its omega-oxidation products rose from 0.52 +/- 0.50 ng.ml-1 (pre-challenge) to 1.55 +/- 1.32 ng.ml-1 (post-challenge), and prostaglandin D2 (PGD2) rose from 49.1 +/- 15.7 (pre-challenge) to 94.4 +/- 25.4 pg.ml-1 (post-challenge), with no change in 6-keto-PGF1 alpha, thromboxane B2 (TXB2), and prostaglandins F2 alpha and E2 (PGF2 alpha and PGE2). In the healthy controls, no consistent change in BAL cell profile and mediators occurred after methacholine provocation. We conclude that inhaled methacholine stimulates LTB4 and PGD2 release in asthmatics, but not in healthy controls, without affecting the number of inflammatory cells in BAL fluid.