tbuckley/cabot-search huggingface dataset:
Fortnightly Review: Methadone maintenance treatment in opiate dependence: a review
Authors: M Farrell, J Ward, R Mattick, W Hall, G V Stimson, D des Jarlais, M Gossop, J Strang
Journal: BMJ (1994)

This paper examines the changes and advances in research and clinical practice and examines the role of treatment structure and programme characteristics in the delivery of methadone maintenance. Methadone prescribing has become much more available over the past decade, both in countries with a history of its use, such as the United Kingdom and Australia, and in countries around the world which previously had not endorsed substitute prescribing.1 There is a need to examine closely the framework in which this treatment is delivered to ensure that the modes of delivery most effective from both cost and benefit perspectives are utilised. This review focuses entirely on methadone maintenance because this is the most extensively evaluated and most used treatment, with about a quarter of a million drug misusers receiving methadone treatment globally. A small number of experimental diamorphine and buprenorphine substitute programmes are being evaluated in several countries.

Most studies have come from the United States and focus on the long term use of methadone in a specific setting; in contrast, methadone treatment in the United Kingdom has received virtually no formal evaluation to date bar one study.2 There is concern that a considerable amount of the methadone prescribing could be having little impact on illicit drug use or risk taking behaviour,3 a recent study of drug users in police custody echoes this.4 The Advisory Council on the Misuse of Drugs has recommended a shift to a more structured approach for delivery of oral methadone maintenance.

The organisation and regulation of methadone maintenance treatment varies widely, with explicit guidelines for programme operation in the United States and Australia and a virtual absence of structure and regulation in Britain. It is likely that policy analysts and treatment providers in countries with high levels of regulation and structured programmes …
Alterations in gene expression of RAGE and its sheddases in blood of COPD patients do not relate to decreased plasma (e)sRAGE levels
Authors: Poornima Gopal, Erica Rutten, Frits Franssen, Emiel Wouters, Niki Reynaert
Journal: European Respiratory Journal (2014)

Plasma sRAGE levels are decreased in COPD, correlating with airflow limitation and emphysema. sRAGE originates from alternative splicing (esRAGE) and cleavage by ADAM10 and MMP9, and acts as a decoy receptor limiting pro-inflammatory signalling. The current study evaluated gene expression of RAGE and its sheddases in circulating cells and their relation with plasma (e)sRAGE levels in COPD.

The study included 160 COPD patients, 79 smoking and 41 never smoking age-matched control subjects. Full lung function was assessed and gene expression of total, membrane and esRAGE and sheddases was determined in circulating white blood cells by QPCR. Plasma levels of sRAGE and esRAGE were measured by ELISA.

Total RAGE gene expression was decreased in COPD, whereas membrane and esRAGE expression was unaffected. Expression of the sheddase ADAM10 was decreased while MMP9 expression increased. Decreased plasma levels of sRAGE and esRAGE were found in COPD patients compared to smoking and never-smoking controls, and total plasma sRAGE, but not esRAGE correlated with lung function (FEV1 β=0.314, p‹0.001), DLCO (β=0.197, p=0.016), and emphysema severity (β=-0.273, p=0.001). No significant associations of gene expression of RAGE or its sheddases to plasma (e)sRAGE levels were observed.

This study confirms the potential of plasma sRAGE as a biomarker of lung function and emphysema in COPD. Despite observed alterations in expression of RAGE and its sheddases in white blood cells in COPD, decreased sRAGE levels in the circulation are likely not attributable to these changes. Pulmonary RAGE expression and shedding should therefore be examined in parallel with plasma sRAGE.
Insulin Resistance, Subclinical Left Ventricular Remodeling, and the Obesity Paradox
Authors: Ravi V. Shah, Siddique A. Abbasi, Bobak Heydari, Carsten Rickers, David R. Jacobs, Lu Wang, Raymond Y. Kwong, David A. Bluemke, Joao A.C. Lima, Michael Jerosch-Herold
Journal: Journal of the American College of Cardiology (2013)
Cardiac Munchausen's syndrome
Authors: E J Dickinson, T R Evans
Journal: Journal of the Royal Society of Medicine (1987)

Ten years' experience of cardiac Munchausen's syndrome in the Cardiac Care Unit of an Inner London teaching hospital is reported. Thirty-six admissions in this category were identified and analysed, and 4 typical cases are described. The common presenting complaints, recurring features and the relationship with other forms of Munchausen's syndrome are discussed, as are posible strategies available to deal with this clinical entity.
Tackling the NHS’s unprecedented deficit and securing reform
Authors: Kieran Walshe, Judith Smith
Journal: BMJ (2015)

The new government’s response has so far largely missed the point

The Conservative Party finds itself unexpectedly in government without a coalition partner and able to pursue its own health policies at last.1 It has called for seven day working in hospitals and primary care; sought improvements in rates of early diagnosis of cancer; and endorsed the vision in the NHS Five Year Forward View 2 of radically different models of care, such as integrated accountable care organisations and a stronger role for preventive care.

But many of these initiatives require an increase in health spending. In a review of the government’s first 100 days,3 the King’s Fund outlined the miscellany of government initiatives so far—financial control, devolution, quality and safety, primary care, mental health, public health, and social care. But Chris Ham, its chief executive, said that the immediate concern should be dealing with the looming financial crisis.4

The financial position is indeed dire. The Chartered Institute of Public Finance and Accountancy predicts a £2.1bn (€2.9bn; $3.2bn) overall deficit for the NHS this year,5 two and a half times last year’s record £820m deficit. Most NHS trusts and foundation trusts, including those that have been financially secure in the past, are …
Involvement of the BK channels/G proteins processes in the synergistic effects between anticholinergic agents and beta2-adrenoceptor agonists in airway smooth muscle
Authors: Hiroaki Kume, Shu Imbe, Takashi Iwanaga, Osamu Nishiyama, Hiroyuki Sano, Yuji Tohda
Journal: European Respiratory Journal (2013)

Rationale:  Long-acting muscarinic antagonists (LAMAs) and long-acting beta 2 -adrenoceotor agonists (LABAs) are widely used therapy for COPD. This study was designed to determine whether synergistic effects are observed between LAMAs and LABAs in airway smooth muscle. Moreover, signal transduction pathways were examined in this phenomenon.   Methods:  For record of isometric tension, the strips of tracheal smooth muscle of guinea pigs were placed in the organ bath and were perfused with the physiological solution at constant flow rate of 3 ml/min.   Results:  1 nM indacaterol, a LABA, and 10 nM glycopyrronium bromide (GB), a LAMA, caused 8.9% (n=21) and 24.9% (n=12) inhibition of 1 μM methacholine-induced contraction, respectively. However, when 10 nM GB was applied in the presence of 1 nM indacaterol, the inhibitory effects of GB/indacaterol combination were markedly augmented to 49.1% inhibition (n=10,  P  2+ -activated K +  (BK) channels, this greater effect in indacaterol/GB combination was markedly attenuated. When the tissues were treated with 1 μg/ml pertussis toxin, which inhibits G i , or 2 μg/ml cholera toxin, which activates G s , for 6h, the effects of GB was significantly enhanced.   Conclusions:  The combination of indacaterol with GB causes synergistic action against muscarinic contraction in airway smooth muscle. This phenomenon is mediated by attenuation in the G i /BK channel inhibitory linkage and augmentation in the G s /BK channel stimulatory linkage. Therefore, LAMA/LABA combination may be a useful therapy for COPD.
Stage IV diffuse large-cell lymphoma: a long-term analysis.
Authors: S Jagannath, W S Velasquez, S L Tucker, J T Manning, P McLaughlin, L M Fuller
Journal: Journal of Clinical Oncology (1985)

A long-term analysis of the clinical outcome of previously untreated adult patients who presented with stage IV diffuse large-cell lymphoma at diagnosis was performed to identify possible prognostic factors. Sixty-one patients were seen between 1974 and 1981; all were treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin followed by cyclophosphamide, vincristine, prednisone, and bleomycin for a total of one year. Overall five-year survival was 48.5%, with a median follow-up of 53 months. Of the 56 patients evaluable for remission status, 41 achieved a complete remission, and 27 are alive and disease free. Clinical factors of prognostic importance for survival included age, constitutional symptoms, lactate dehydrogenase (LDH) level, presence of mediastinal disease, large-cell infiltration of bone marrow, and number of extranodal sites of disease. The proportional hazards model then identified age, number of extranodal sites, and, to a lesser extent, serum LDH level as independent risk factors for survival. Four distinct patient risk groups were identified using these three factors. Younger patients with only one extranodal site of disease and normal LDH levels responded well on this therapy, with 100% alive at five years. In contrast, survival was less than 30% at five years for patients in the lowest risk group. There were 11 relapses; LDH level, constitutional symptoms, and mediastinal disease predicted for relapse. Knowledge of these risk factors permits individualization of treatment planning and allows more meaningful comparisons with the results of treatment studies using other intensive regimens.
No quick fixes
Authors: Elizabeth Loder
Journal: BMJ (2015)

Three recent research papers in The BMJ have looked at common problems for which there are no easy solutions: falls among elderly people, pelvic organ prolapse, and lapses in handwashing among healthcare workers. The good news is that some progress has been made on each of these fronts. The bad news is that progress is slow, and there are no quick fixes. 

A two year programme of balance training reduced the number of injurious falls in older women, but the relative improvement came at the cost of some severe adverse events, which paradoxically included three falls that occurred before or after the exercise sessions, found Fabienne El-Khoury and colleagues (doi:10.1136/bmj.h3830).

The standard treatment for uterine prolapse is hysterectomy with suspension of the …
Cyberknife radiosurgery for liver metastases and primary liver tumors.
Authors: R. M. Lanciano, J. Johnstun, J. Lamond, J. Yang, J. D. Sprandio
Journal: Journal of Clinical Oncology (2010)

e14037 Background: Radiosurgery is an emerging radiation technique recently reported for liver metastases and primary liver tumors with encouraging local control rates and the ability to spare normal liver tissue radiation toxicity. Phase I/II trials have been published for radiosurgery to the liver however the trials are small with only 20–70 patients in each trial and various dose schedules reported. We report our experience with Cyberknife radiosurgery for this population of patients. Methods: From 8/2007 to 9/2009, 49 patients with 62 liver tumors were treated with Cyberknife. Thirty patients with 40 tumors were treated with curative doses (defined as BED > 79 Gy10 or 66 Gy in 2 Gy per fraction) and further analyzed. Median follow up for the group is 9 months (range 1–23). 83% of patients were treated for metastatic disease to liver from GI or primary liver cancer. Patients were heavily pretreated prior to radiosurgery (83% chemotherapy, 37% liver directed therapy). The goal of treatment was local control of the liver tumor while preserving adequate liver reserve defined as at least 700 cc receiving ≤ 15 Gy. Results: Median tumor volume was 61 cc. Patients who received previous liver directed therapy had a smaller median liver volume of 1,346 cc vs. 1,638 cc and subsequently had less liver receiving ≤ 15 Gy (1,041 cc vs. 1,215 cc) despite similar tumor volumes (26.9 cc vs. 24.2 cc). Crude local control rate was 90% evaluated by CT/PET in most cases. A dose response was demonstrated with local failure of 3/19 tumors (16%) seen with dose of ≤ 84 Gy10 vs. 0/21 (0%) for > 84 Gy10. Patients with local control had higher liver volume to tumor volume ratio (median 22.7 vs. 8.1) suggesting higher doses were possible because of larger uninvolved liver size and/or smaller tumors. The predominant pattern of failure was distant (63%) both within liver and abdominal/lung metastases. No significant adverse events were noted. Only one patient died secondary to metastatic disease. Conclusions: Cyberknife radiosurgery is an effective modality to treat metastatic disease to liver and primary liver tumors with good local control rates and low morbidity. Future study is necessary with Cyberknife radiosurgery as first-line treatment in combination with chemotherapy for liver metastases. No significant financial relationships to disclose.
First dose response to tiotropium in COPD: Impact on dyspnea, lung hyperinflation and distal airways
Authors: Jean Pastre, Stephanie Fry, Clement Fournier, Arnaud Scherpereel, Francois Denis, Thierry Perez
Journal: European Respiratory Journal (2013)

In COPD, response to bronchodilators is not limited to FEV1, distal airways may also be a target of bronchodilators. Our aim was to evaluate the impact of tiotropium 18 µg on lung volumes and airway resistance (plethysmography and forced oscillation).  Patients and methods  Response to tiotropium after the first dose (at 90 minutes) and 6 weeks later was assessed in 10 patients (mean FEV1: 48±11% pred, aged 61±6 years) by spirometry, plethysmography (including specific conductance (sGaw)), forced oscillation resistance (Rrs) and reactance (Xrs). Rrs and Xrs at 6 Hz preferentially evaluate distal airways. Change in dyspnea was assessed by a visual analog scale (VAS).  Results  At baseline forced oscillation and lung hyperinflation were related (Rrs6/RV: r=0.63, p=.0001; Xrs6/RV: r=0.72, p  These responses increased or were maintained at six weeks of treatment.  Conclusion  Despite clear limitations (small sample, no comparator), these results suggest that lung volumes and low frequency oscillation parameters (particularly Xrs) are useful to assess the response to long acting bronchodilators, and show significant changes in distal airways at the first dose. FIV1 is also highly related to dyspnea improvement.  This study is an Investigator Initiated Study (IIS).
Changes in Extracellular Matrix and Tissue Viscoelasticity in Bleomycin–induced Lung Fibrosis
Authors: TAKAE EBIHARA, NARAYANAN VENKATESAN, RYOICHI TANAKA, MARA S. LUDWIG
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Bleomycin-induced lung fibrosis results in changes in tissue mechanical properties due to alterations in the extracellular matrix (ECM). How oscillatory mechanics and changes in the matrix evolve over time has not been addressed. Sprague–Dawley rats were instilled with bleomycin sulfate (BM) (1.5 U) intratracheally; control animals (C) received saline. At 7, 14, and 28 d after BM, parenchymal strips (7 × 2 × 2 mm) were obtained and strips suspended in a Krebs-filled organ bath. One end of the strip was attached to a force (F) transducer and the other to a lever arm that effected sinusoidal length (L) oscillations. Strips were oscillated at varying amplitudes (1, 3, and 10% of resting L) and frequencies (f = 0.3, 1, 3, and 10 Hz) at an operating stress of 2 kPa. Resistance (R) and elastance (E) were estimated by fitting changes in F and L to the equation of motion. Hysteresivity ( η ) was calculated as η = (R/E) 2 π f. Strips were then fixed for morphological study of collagen, elastic fibers, and the small proteoglycans (PGs), biglycan and fibromodulin (FM). R and E were significantly greater and η significantly less in BM versus C strips (p < 0.001). The increase in R and E peaked at 14 d after BM; the decrement in η was maximal at Day 7. Biglycan was increased in BM lung strips at all time points, FM and elastic fibers were increased at 14 and 28 d, and collagen was increased at 28 d only. Hence, changes in mechanics were maximal before collagen content had increased. In addition, we demonstrated a significant correlation between biglycan and all mechanical parameters. These data suggest that changes in PGs may be critical in determining changes in lung tissue viscoelastic behavior in this fibrosis model
The Role of Autologous and Allogeneic Hematopoietic Stem Cell Transplantation for Hodgkin Lymphoma
Authors: Leona Holmberg, David G. Maloney
Journal: Journal of the National Comprehensive Cancer Network (2011)

Patients with Hodgkin lymphoma are usually cured by primary therapy using chemotherapy alone or combined modality therapy with external beam radiation. Patients who do not experience a complete remission or those who experience relapse may by salvaged by high-dose therapy and autologous hematopoietic stem cell transplantation (ASCT). Success of this approach is largely dependent on the tumor being sensitive to salvage chemotherapy before transplant. More studies are showing the predictive value of functional imaging in this setting. Allogeneic hematopoietic stem cell transplantation has greater risk of nonrelapse mortality and is generally reserved for patients who experience relapse post-ASCT, but may provide long-term survival for some patients through graft-versus-tumor immune effects.
Abstract 2617: Inhibition of Secretory Phospholipase A2 Activity Attenuates Acute Cardiogenic Pulmonary Congestion Induced by Isoproterenol Infusion in Mice with Post-Myocardial Infarction
Authors: Ken-ichi Kawabata, Tsuyoshi Kobayashi, Yousuke Watanabe, Kazuhiro Watanabe, Toshiaki Yano, Ryota Sato, Yukio Saito, Kazuto Nakamura, Kiyotaka Kugiyama
Journal: Circulation (2008)

Several types of secretory phospholipase A2 (sPLA2) are expressed in airway epithelial cells and alveolar inflammatory cells, yielding various eicosanoids that might cause pulmonary edema. This stu...
Death Certificate Study of Leukemia Among Farmers From Wisconsin
Authors: Aaron Blair, Deborah W. White
Journal: JNCI Journal of the National Cancer Institute (1981)

The risk of leukemia among farmers and dairy farmers in particular was studied with the use of mortality records from Wisconsin, 1968-76. A comparison of occupation as noted on the death certificate for 1,499 cases and a like number of matched controls revealed a slight [odds ratio (OR) = 1.10], but statistically nonsignificant, excess risk of leukemia among farmers. The risk was highest among those born after 1897 (OR approximately 1.50) or dying before age 71 years (OR approximately 1.35) among dairy farmers (whether noted on death certificates or identified by county agricultural agents of the Cooperative Extension Programs of the University of Wisconsin) and all farmers alike. The under-representation of farmers among controls with smoking-related causes of death, however, may partially account for these findings. Stratification by county of residence showed significantly elevated risks among farmers from counties with heavy dairy production (OR = 1.40) and fertilizer use (OR = 1.42).
Paradoxical Outcome after use of Hyaluronate Barrier to Prevent Intra-Abdominal Adhesions
Authors: J P Trickett, R M Rainsbury, R Green
Journal: Journal of the Royal Society of Medicine (2001)

Intra-abdominal adhesions are the commonest cause of small-bowel obstruction and secondary female infertility. At operation, strategies to prevent adhesions include the use of absorbable barriers. Seprafilm (Genzyme BV, Naarden, Netherlands) is a sterile translucent membrane comprising sodium hyaluronate and carboxymethylcellulose; it temporarily separates potentially adherent surfaces, turning to a gel within 24 h and being cleared from the abdominal cavity in 7 days. Sepracoat (Genzyme BV) is a solution of hyaluronidase in phosphate buffered saline, reabsorbed from the body cavity and excreted in 5 days. In animal models and patients, these agents have reduced adhesion formation by about 44% without any apparent excess of adverse events1,2,3.
A cohort study for improvement of asthma attack by noninvasive positive pressure ventilation (NPPV)
Authors: Tomoya Katsuta, Toshimitsu Suwaki, Takayuki Kamao, Shuzi Okahara
Journal: European Respiratory Journal (2012)

Objective: A few study of efficacy of NPPV therapy in asthmatic patients have been reported. We studied efficacy and incidence rate of NPPV therapy.  Method: This prospective cohort study was performed in two hospitals in Okayama prefecture, Japan. All of the patients admitted because of asthma attack between January 2005 and June 2010.Patients had to fulfill the following criteria before hospitalization. 1. The patients9 peak flow is less than 200L/min or 30% of his or her best peak flow 2. Borg scale is nine or ten. Hospitalization patients had to fulfill the following criteria for NPPV therapy. 1. Patients received PaCO 2  >45mmHg and pH   Figure 1  shows profile of pH in the patients receiving NPPV.   Figure 2  shows profile of Borg scale in the patients receiving NPPV.  Conclusion; The proportion of patients need NPPV therapy is 15%. In asthmatic patients NPPV therapy appears highly effective in correcting gas exchange abnormalities and severe dyspnea.
Determining of predicting factors affecting disposition of patients with acute asthma referred to emergency ward
Authors: Ali Taghizadieh
Journal: European Respiratory Journal (2011)

Introduction:  Acute asthma is associated with morbidity and mortality in patient referred to emergency department (ED). Our study was focused on simple objective measures in ED to predicting factors affecting disposition of patients with acute asthma referred to emergency ward.   Methods and materials:  Data were collected prospectively at one center over 12-month period on 103 adult patients. Asthma step severity categorization and management was determined by GINA guidelines. Presenting ED vital signs, OSAT values, pulmonary function testing (spirometry, flow-volume loop, PImax, PEmax) and disposition were recorded for each study subject.   Results:  In this study 103 patients were studied. In our patients 56 cases (%54.4) admitted and 47 (45.6) cases were discharged. There is no significant difference between admission rates and these variables: Age, Weight, Height, BMI (Body Mass Index), History of previous hospitalization, Living place (urban/rural), peripheral edema and some spirometric parameters; but significant difference were seen between admission rates and these variables: Functional stage of dyspnea, Pulsus Paradoxus, Intercostal retraction, Respiratory Rate (RR), Heart Rate, Arterial saturation of oxygen, Arteial pH. Variables that predict admission rates in our patients are as follows: Sex, RR and SaO2in first visit, PEmax in second measurement.   Discussion:  Finding those variables that predict admission in asthmatic patients is very important and cost effective. We recommend further studies in this field, especially in measurement of new pulmonary function variables such as PImax and PEmax.   Key words:  Asthma, emergency, PEmax