tbuckley/cabot-search huggingface dataset:
National guidance and allocation of resources
Authors: G C W Howard
Journal: BMJ (2002)

Editor—I think that Cookson et al in their criticisms of the Scottish Intercollegiate Guidelines Network (SIGN) show a lack of understanding of the role of this organisation and the methods it uses to develop its guidelines.1 Evidence based guidelines will not resolve all healthcare issues, just as randomised controlled trials are not appropriate to resolve all therapeutic controversies. There are, however, areas of healthcare delivery where there are variations in practice and outcome, and where there is also evidence to support one practice over another.

This is where SIGN concentrates its resources to produce guidelines. SIGN does not differentiate in its methodology between costly and non-costly treatments, and, contrary to the authors' supposition, the adherence to such guidelines will reduce variations in treatments of all costs and therefore the possibility of decision making behind the scenes. In addition to this, SIGN guidelines are not only in the public domain, but the public have a key part in their development, and this involvement is an important driver for change.

Cookson et al are also concerned that resource allocation might be distorted. The opposite is the case. Adherence to evidence based guidelines will lead to a more efficient use of resources and concentrate this on areas where there is a clear benefit from a therapeutic intervention. It should also be made clear that SIGN guidelines are not just about advising on treatment but offer guidance to assist with the management of patients at all stages of their disease, and where there is robust economic information, this is incorporated into the guideline.
Pulmonary lymphangioleiomyomatosis in postmenopausal women: report of two cases and review of the literature
Authors: S Baldi, M Papotti, ML Valente, M Rapellino, E Scappaticci, B Corrin
Journal: European Respiratory Journal (1994)

Pulmonary lymphangioleiomyomatosis, a disease largely confined to women in their reproductive years, is reported in two postmenopausal patients. Nine similar cases in the literature are reviewed. In older women, the disease appears to be similar to that described in younger women, with the possible exception that the clinical course may be longer and more benign after the menopause. It would appear that hormonal factors play a role in the development of the disease both before and after the menopause, and that hormonal treatment may be beneficial in the older women.
Endobronchial valves for bilateral endoscopic lung volume reduction
Authors: Philipp M. Lepper, Franziska Trudzinski, Dominik Ballek, Christian Lensch, Frank Langer, Katharina Rentz, Heinrike Wilkens, Martin Hetzel, Robert Bals
Journal: European Respiratory Journal (2014)

Background: Endoscopic lung volumen reduction (eLVR) with endobronchial valves (EBV) is an established therapy option for patients with severe emphysema. Patients are mostly treated unilaterally, rarely EBV is performed bilaterally.   Methods:  We retrospectively evaluated all patients treated in our department with EBV bilaterlally regarding lung function and six-minute walking test (6-MWT). All patients underwent V/Q-Scan and were evaluated for collateral ventilation using Chartis measurement to determine the target lobe.   Results:  Up to now, we treated 8 patients with valves only (aged 59.3 ± 6.8 years), bilaterally (3/8 female). Patients recieving hybrid procedures (combination of valves and coils) were not included. Mean [± SD] FEV 1  prior to the first EBV implantation was 22.6 ± 9.8 % pred. with a residual volume (RV) of 308.3 ± 53.2 % pred. The 6-MWT was 246 ± 88 m. Mean FEV 1  prior to the 2nd EBV implantation was betrug 26.1 ± 8.3 % pred. (+15%) at a RV of 276.1 ± 41.8 % pred. (-10%). 6-MWT was 338.5 ± 75 m (+43%). After bilateral treatment, mean FEV 1  was 28.4 ± 8.1 % pred. (+23%); RV was 252.4 ± 48 % pred.; -18%). Die 6-MWT was relatively constant at 327 ± 126 m (+42% from baseline). The pneumothorax rate was 32 % (5/16 procedures); all pneumothoraces were treatable by chest tube only. After the first treatment, one patient developed pneumonia of the non-treated side.   Discussion:  At a low rate of complications patients benefitted from uni- and later bilateral eLVR with EBV. Bilateral eLVR with EBV could further improve the results of the first treatment. Bilateral eLVR with EBV is feasible and safe.
The efficacy of cyclosporine A in patients with clinicoradiologically diagnosed idiopathic nonspecific interstitial pneumonia
Authors: Takashi Niwa, Hiromasa Tachibana, Machiko Arita, Tadashi Ishida, Takuya Takaiwa, Kenjiro Furuta, Maki Tanaka, Fumiaki Tokioka, Toru Hashimoto
Journal: European Respiratory Journal (2014)

BACKGROUND: Cyclosporine A (CsA) is used widely for collagen vascular disease (CVD) related nonspecific interstitial pneumonia (NSIP) cases. But it is unclear whether CsA is effective for cases of clinicoradiologically diagnosed idiopathic NSIP (iNSIP).  OBJECTIVE: To assess the efficacy of CsA in cases of clinicoradiologically diagnosed iNSIP.  METHOD: We reviewed the records of 65 NSIP patients who received CsA treatment from 1999 to 2013. Cases of acute onset and without pre-treatment lung function data were excluded. Included patients were classified into 2 groups according to etiology, CVD and lung dominant connective tissue disease (ldCTD) as group A (n=37), and iNSIP as group B (n=28). Overall time to progression (TTP), and the pre- and post-treatment values of % predicted vital capacity (%VC), % diffusing capacity of the lung for carbon monoxide (%DLCO) and serum markers (KL-6, SP-D, LDH) were analyzed retrospectively.  RESULTS: The median age of patients in this study was 66.5 yrs (range: 64.0-68.9), and 63% were women. No patients had completed CsA therapy resulting from improvement. There was no significant difference between group A and B in median TTP (840 days vs 936 days: Log-rank p=0.854) and the proportion of patients in which %VC and %DLCO improved [45.9% vs 57.1% (p=0.45) and 29.7% vs 28.5% (p=0.99)]. There was a significant relation between SP-D, LDH and TTP (Cox regression. SP-D: HR1.004 p=0.043, LDH : HR1.005 p=0.013).  CONCLUSION: The efficacy of CsA in cases of clinicoradiologically diagnosed iNSIP was similar to that in cases of CVD and ldCTD. This study also suggests that SP-D and LDH might be indicators of treatment efficacy.
The relationship between delayed anti-TB treatment and hospital mortality in critically ill patients
Authors: Chen-Yu Wang, Chih-Hung Wang, Jing-Yun Hu, Bor-Jen Lee
Journal: European Respiratory Journal (2014)

Background: In patients coexist with pulmonary TB requiring intensive care, the mortality rate approached 50%, Previous studies reported that the survival of patients with TB can be significantly improved if anti-TB therapy is started within 14 days of hospitalization. This retrospective study aimed to investigate the impact of delayed anti-TB treatment on the survival of patients coexisted with pulmonary TB requiring intensive care.   Materials and methods: This study reviewed medical records of critically ill patients with pulmonary tuberculosis under anti-tuberculosis treatment, admitted to ICU from January 2008 to December 2011. The inclusion criteria were age >18 years, culture confirmed pulmonary TB/previous TB history under anti-TB therapy, admitted to ICU during any time point during hospitalization. The identified patients were divided into three groups: patients who received anti-TB therapy before ICU admission (Group A); patients who started anti-TB therapy within two weeks after ICU admission (Group B); and patients with initiation of anti-TB therapy two weeks after ICU admission(Group C).   Results: We enrolled 127 patients. The group A/B/C patients was 42 (33%)/53(42%)/32(25%) respectively. The overall hospital mortality rate was 32%. In subgroup analysis, patients with initiation of anti-TB therapy two weeks after ICU admission (95% CI 2.069-0.858, OR:2.41) was a poor prognosis factor for hospital mortality for patients who ventilated more than 2 weeks.   Conclusion: The critically ill patients coexisted pulmonary tuberculosis who use ventilator longer than 2 weeks and delayed anti-TB therapy two weeks after ICU admission would associate with higher hospital mortality.
Benign and Malignant Thyroid Neoplasms After Childhood Irradiation for Tinea Capitis&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: E Ron, B Modan
Journal: JNCI Journal of the National Cancer Institute (1980)

The incidence of all thyroid surgery was studied among 10,842 persons whose thyroid glands had been exposed in childhood to an average dose of 9 rads of X-radiation during treatment for tinea capitis and among 2 matched control groups. A statistically significant increased risk for both benign and malignant neoplasms was found in the exposed group. The excess risk was 8.3 cases/year/rad/million population. There were no differences in other surgical conditions between the irradiated and nonirradiated groups. Persons irradiated under age 6 years had the highest excess risk for developing carcinomas. The incidence of thyroid neoplasms was approximately threefold higher in women than in men among the irradiated persons and among the controls, but the relative risk for the irradiated group of women was greater than the addition of the relative risks of the other groups. Low-dose radiation is instrumental in the development of both benign and malignant thyroid neoplasms.
Comparative cytotoxicity of dexamethasone and prednisolone in childhood acute lymphoblastic leukemia.
Authors: C Ito, W E Evans, L McNinch, E Coustan-Smith, H Mahmoud, C H Pui, D Campana
Journal: Journal of Clinical Oncology (1996)

PURPOSE The relative cytotoxicity of prednisolone and dexamethasone in acute lymphoblastic leukemia (ALL) is controversial. We therefore compared the direct antileukemic activities of these compounds in stroma-supported cultures of leukemic lymphoblasts. MATERIALS AND METHODS Bone marrow samples from children with B-lineage ALL were cultured on allogeneic bone marrow-derived stromal layers and exposed to various concentrations of glucocorticoids. After 4 days of culture, the number of viable leukemic cells was counted by flow cytometry and compared with that in parallel cultures without drugs. RESULTS In 28 B-lineage ALL samples tested, the concentration producing 50% cytotoxicity (LC50) of prednisolone ranged from 2.0 to 7,978 nmol/L (median, 43.5 nmol/L), and that of dexamethasone from 0.6 to 327 nmol/L (median, 7.5 nmol/L). Despite the wide variability of responses among samples, there was an excellent correlation between LC50 values obtained with the two drugs (linear r = .99, P &lt; .0001; Spearman rank-order r = .77, P &lt; .0001). The median ratio of dexamethasone to prednisolone LC50 and LC90 values was 1:5.5 (range, 1:1.0 to 1:24.4 for LC50; 1:1.1 to 1:25.5 for LC90). Studies with ALL cell lines demonstrated that both drugs were cytotoxic through induction of apoptosis. Stromal layers did not absorb or inactivate measurable amounts of corticosteroids, which indicates that the assay system did not bias results toward increased drug resistance. CONCLUSION In a bone marrow-derived microenvironment, dexamethasone is five to six times more cytotoxic (on a molar basis) than prednisolone, in agreement with the antiinflammatory activities of these drugs. This finding may serve to guide the selection of dexamethasone dosage in the treatment of ALL.
Structural lung disease in adult survivors of bronchopulmonary dysplasia
Authors: Steven Caskey, Scott Gillespie, Jim Clarke, Henry Halliday, Mike Shields, Lorcan McGarvey
Journal: European Respiratory Journal (2013)

Objective:  To determine the nature and extent of structural lung abnormalities on high resolution computed tomography (HRCT) of the chest in a cohort of adult survivors of bronchopulmonary dysplasia (BPD) compared with adults born preterm who did not develop BPD.   Methods:  20 adult BPD (14 male, mean (SD) age at study 24.4 (3.5) years, mean gestational age 27.8 (2.2) weeks, mean birthweight 901 (260) g) and 19 preterm non BPD subjects (14 male, mean (SD) age at study 25.88 (3.7), mean gestational age 30.6 (2.1) weeks, mean birthweight 1248 (188) g) underwent HRCT scanning of the chest. A validated scoring tool was used to assess HRCT 1  scans, independently by two thoracic radiologists, blinded to the subject’s group.   Results:  The BPD group had more severe scores [mean (SD) 7.11 (4.7); range: 2 -20)] than the non BPD group [Mean (SD) 2.11 (2.11); range: 0-6)], (p=0.001). This was significant when corrected for birthweight and gestational age. Abnormal HRCT findings were seen in all BPD adults and two-thirds of preterm non BPD. Among BPD adults, the most common findings were subpleural opacities (20/21), air-trapping (16/21), bullae (4/21), sub-segmental atelactasis (4/21) and mosaic perfusion (4/21). In the preterm non BPD group, the common abnormalities were subpleural opacities (9/19) and air-trapping (6/19). Subpleural opacities were significantly more likely in BPD (p=0.008).   Conclusion:  Significantly more structural lung abnormalities are present in adult survivors of BPD compared to those born preterm without BPD.   References:    1.  Aukland SM, et al. Neonatal BPD predicts abnormal pulmonary HRCT in long term survivors of EP birth. Thorax 2009;64:405-10.
Family support in general practice
Authors: Clare Goodhart, Layzell Sarah, Alice Cook, Jonathan Graffy
Journal: Journal of the Royal Society of Medicine (1999)

At a time when social services are overburdened in Britain, family support in general practice offers one way to fill the gap. In the WellFamily Project, a ‘family support coordinator’ worked within a general practice in Hackney, London. In the first eighteen months she saw 113 clients. Evaluation was by semistructured interviews with a sample of these clients and with professional workers. Comments from those interviewed indicate that the family support was valued. The general practice base was convenient and non-stigmatizing. By adopting a proactive approach, the project was able to work with clients who had previously ‘slipped through the net’. Some of the professionals interviewed would have liked to provide the same help, but were unable to do so because of time and other constraints. Family support provided through general practice was well received by vulnerable families. Although there was overlap with the remit of health visitors and social workers, the protected time and the independence of the coordinator enabled clients to obtain the help they wanted. The replicability of this strategy now needs to be assessed.
Cough reflex sensitivity during acute viral upper respiratory tract infection (common cold)
Authors: Peter Dicpinigaitis, Amit Tibb, David Hull, Angela Qu
Journal: European Respiratory Journal (2011)

One previous study has demonstrated that cough reflex sensitivity to inhaled capsaicin is transiently enhanced during acute viral respiratory tract infection (URI) by comparing single cough reflex sensitivity measurements at baseline and during URI (O9Connell F, et al. Respir Med 1996;90:279-286). To our knowledge, no one has performed multiple measurements of cough reflex sensitivity during acute URI to evaluate presence or absence of stability during the acute viral illness. To date, we have evaluated 37 otherwise healthy adult nonsmokers with acute URI. Subjects underwent capsaicin cough challenge testing, as previously described in the ERS guidelines (Morice et al. Eur Respir J 2007;29:1256-1276), on 2 consecutive days within the first 8 days of their illness, and again after 4-8 weeks (post-recovery). Briefly, subjects inhaled single, vital-capacity breaths of nebulized capsaicin, administered in incremental doubling concentrations, until the concentration inducing 5 or more coughs (C5) was attained. All 37 subjects had serial C5 measurements within 1 doubling concentration during the acute illness. Post-recovery mean log C5 was significantly higher than during illness (0.84±0.08 [SEM] vs. 0.50±0.08; p=0.000004). Our results demonstrate that cough reflex sensitivity remains stable in the acute phase of URI, and confirm previous findings of a transient increase of cough reflex sensitivity during URI compared to healthy baseline levels. The demonstration of stability of cough reflex sensitivity during the early stages of URI is relevant to potential investigators planning to evaluate the effect of a pharmacological intervention on cough reflex sensitivity during URI.
Effect of Progesterone and Diethylstilbestrol on Hepatic Carcinogenesis and Cirrhosis in A × C Rats Fed &lt;italic&gt;N&lt;/italic&gt;-2-Fluorenyldiacetamide&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Melvin D. Reuber, Harlan I. Firminger
Journal: JNCI Journal of the National Cancer Institute (1962)

Inbred A × C strain male and female rats were fed 0.025 percent N-2-fluorenyldiacetamide in the diet. Progesterone or diethylstilbestrol was administered to both intact and castrated animals to evaluate their role in carcinogenesis and cirrhosis of the liver. In intact male animals given carcinogen, cirrhosis was usually present. Areas of hyperplasia developed in the parenchyma and grew to become nodules which later developed into carcinomas. In male rats receiving diethylstilbestrol, cirrhosis was prevented and the incidence of tumors was markedly reduced. These results resembled those in castrated males. In female rats, with or without diethylstilbestrol, cirrhosis was absent and the parenchymal lesions failed to progress beyond areas or nodules of hyperplasia. In all groups receiving diethylstilbestrol the hyperplastic lesions were much larger and the cells in the areas of hyperplasia in female rats were often atypical. The two male rats receiving diethylstilbestrol and the castrated males that developed tumors had fewer and smaller tumors per liver than the male rats. All the tumors in the diethylstilbestrol-treated and castrated animals were well-differentiated carcinomas. By contrast, progesterone increased the incidence of hepatocellular carcinoma in intact male, castrated male, and castrated female rats but did not affect the incidence in intact females. Also the tumors tended to be less differentiated carcinomas. The incidence of cirrhosis was also increased by progesterone in castrated animals of both sexes.
Serum interleukin-6 levels correlate with prognosis in diffuse large-cell lymphoma.
Authors: J F Seymour, M Talpaz, F Cabanillas, M Wetzler, R Kurzrock
Journal: Journal of Clinical Oncology (1995)

Interleukin-6 (IL-6) is a potent immunomodulatory cytokine that may have pathogenetic and prognostic significance in a number of disorders. The objective of this study was to examine the correlation between serum IL-6 levels and phenotypic characteristics, as well as outcome of patients with diffuse large-cell lymphoma (DLCL).Using an enzyme-linked immunosorbent assay (ELISA; lower limit of sensitivity, 0.35 pg/mL), we measured IL-6 levels in frozen sera from 33 healthy controls and 58 untreated patients with DLCL who were enrolled onto a single combination chemotherapy protocol. Serum IL-6 levels were correlated with clinical and laboratory features at diagnosis and with failure-free and overall survival.Serum IL-6 levels in the lymphoma patients (median, 4.37 pg/mL; range, < 0.35 to 110 pg/mL) were significantly higher than in the control group (median, < 0.35 pg/mL; range, < 0.35 to 1.87 pg/mL) (P < .0001). Serum IL-6 levels were higher in patients with B symptoms (P = .012), an elevated beta 2-microglobulin level (> or = 3.0 mg/L) (P = .017), and a poor performance status (P = .02). Direct linear correlations with the erythrocyte sedimentation rate (ESR), platelet count, and total WBC count, and an inverse linear correlation with the serum albumin level, were observed (all P < .02). Patients with elevated serum IL-6 levels had inferior failure-free (P = .042) and overall survival (P = .05) compared with those with normal serum IL-6 levels.In patients with DLCL, elevated serum levels of IL-6 at diagnosis are frequent, strongly associated with many adverse disease features, and predictive of a poor failure-free and overall survival.
Analysis of an algorithm incorporating limited and whole-leg assessment of the deep venous system in symptomatic outpatients with suspected deep-vein thrombosis (PALLADIO): a prospective, multicentre, cohort study
Authors: Walter Ageno, Giuseppe Camporese, Nicoletta Riva, Matteo Iotti, Eugenio Bucherini, Marc Righini, Pieter W Kamphuisen, Peter Verhamme, James D Douketis, Chiara Tonello, Paolo Prandoni
Journal: The Lancet Haematology (2015)
Studies on the Relationship of the B700 and B50 Murine Melanoma Antigens
Authors: Vincent J. Hearing, John J. Marchalonis, Douglas M. Gersten
Journal: JNCI Journal of the National Cancer Institute (1986)

The B50 and B700 proteins of B16 murine melanoma were studied; they were determined to be distinct, unrelated molecules. This was determined by V8 peptide mapping, N-terminal amino acid sequencing, absence of cross-reactivity with specific polyclonal antibodies, and monoclonal antibodies recognizing different epitopes.
Tipping the Balance of Benefits and Harms to Favor Screening Mammography Starting at Age 40 Years
Authors: Nicolien T. van Ravesteyn, Diana L. Miglioretti, Natasha K. Stout, Sandra J. Lee, Clyde B. Schechter, Diana S.M. Buist, Hui Huang, Eveline A.M. Heijnsdijk, Amy Trentham-Dietz, Oguzhan Alagoz, Aimee M. Near, Karla Kerlikowske, Heidi D. Nelson, Jeanne S. Mandelblatt, Harry J. de Koning
Journal: Annals of Internal Medicine (2012)

Background: Timing of initiation of screening for breast cancer is controversial in the United States. Objective: To determine the threshold relative risk (RR) at which the harm–benefit ratio of screening women aged 40 to 49 years equals that of biennial screening for women aged 50 to 74 years. Design: Comparative modeling study. Data Sources: Surveillance, Epidemiology, and End Results program, Breast Cancer Surveillance Consortium, and medical literature. Target Population: A contemporary cohort of women eligible for routine screening. Time Horizon: Lifetime. Perspective: Societal. Intervention: Mammography screening starting at age 40 versus 50 years with different screening methods (film, digital) and screening intervals (annual, biennial). Outcome Measures: Benefits: life-years gained, breast cancer deaths averted; harms: false-positive mammography findings; harm–benefit ratios: false-positive findings/life-years gained, false-positive findings/deaths averted. Results of Base-Case Analysis: Screening average-risk women aged 50 to 74 years biennially yields the same false-positive findings/life-years gained as biennial screening with digital mammography starting at age 40 years for women with a 2-fold increased risk above average (median threshold RR, 1.9 [range across models, 1.5 to 4.4]). The threshold RRs are higher for annual screening with digital mammography (median, 4.3 [range, 3.3 to 10]) and when false-positive findings/deaths averted is used as an outcome measure instead of false-positive findings/life-years gained. The harm–benefit ratio for film mammography is more favorable than for digital mammography because film has a lower false-positive rate. Results of Sensitivity Analysis: The threshold RRs changed slightly when a more comprehensive measure of harm was used and were relatively insensitive to lower adherence assumptions. Limitation: Risk was assumed to influence onset of disease without influencing screening performance. Conclusion: Women aged 40 to 49 years with a 2-fold increased risk have similar harm–benefit ratios for biennial screening mammography as average-risk women aged 50 to 74 years. Threshold RRs required for favorable harm–benefit ratios vary by screening method, interval, and outcome measure. Primary Funding Source: National Cancer Institute.