tbuckley/cabot-search huggingface dataset:
Differences between the recommended and real dose in a smoking cessation practice
Authors: Ana Gómez-Bastero, Virginia Almadana, Concepción Romero, Estefania Luque, Andrés Vega, Soledad Montserrat, Teodoro Montemayor
Journal: European Respiratory Journal (2012)

Aims:To analyze the dose and time decided by the patient regarding what is recommended and its influence on the tobacco cessation rate. Methods: We included patients who attended our practice during the last 6 months.We analyzed several variables:recommended dose(varenicline(V):0.5/1mgrs,2 months;bupropion(B):150 mgrs/day,2 months),real dose and duration of the treatment,tobacco cessation rates and causes of early abandonment of medication. Results: n=312 patients:V(56%) and B(44%).By comparing both groups,we couldn9t find differences regarding cessation rate after 3 (V:64.4%/B:67.2%) or 6 months (V:64.2%/B: 67.2%).We realized the patients followed the recommended dose (V:82.3%/B:94.2%,p=0.001).Cessation rates are shown in figure 1.  Regarding the duration of treatment:V:6.6±1.6/B:7.9±0.7,p  Conclusions: Using 2 month treatments and half the recommended dose of B,cessation rates are good >64%.Below 5 week treatments are clearly insufficient with B as well as V.Causes of early abandonment of medication were mainly due to economic and psychological reasons.
Lebrikizumab Treatment in Adults with Asthma
Authors: Jonathan Corren, Robert F. Lemanske, Nicola A. Hanania, Phillip E. Korenblat, Merdad V. Parsey, Joseph R. Arron, Jeffrey M. Harris, Heleen Scheerens, Lawren C. Wu, Zheng Su, Sofia Mosesova, Mark D. Eisner, Sean P. Bohen, John G. Matthews
Journal: New England Journal of Medicine (2011)

Many patients with asthma have uncontrolled disease despite treatment with inhaled glucocorticoids. One potential cause of the variability in response to treatment is heterogeneity in the role of interleukin-13 expression in the clinical asthma phenotype. We hypothesized that anti–interleukin-13 therapy would benefit patients with asthma who had a pretreatment profile consistent with interleukin-13 activity.
Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study
Authors: Cloé Charpentier, Julia Salleron, Guillaume Savoye, Mathurin Fumery, Véronique Merle, Jean-Eric Laberenne, Francis Vasseur, Jean-Louis Dupas, Antoine Cortot, Luc Dauchet, Laurent Peyrin-Biroulet, Eric Lerebours, Jean-Frédéric Colombel, Corinne Gower-Rousseau
Journal: Gut (2013)

<h3></h3> Data on the natural history of elderly-onset inflammatory bowel disease (IBD) are scarce. <h3>Methods</h3> In a French population-based cohort we identified 841 IBD patients &gt;60 years of age at diagnosis from 1988 to 2006, including 367 Crohn9s disease (CD) and 472 ulcerative colitis (UC). <h3>Results</h3> Median age at diagnosis was similar for CD (70 years (IQR: 65–76)) and UC (69 years (64–74)). Median follow-up was 6 years (2–11) for both diseases. At diagnosis, in CD, pure colonic disease (65%) and inflammatory behaviour (78%) were the most frequent phenotype. At maximal follow-up digestive extension and complicated behaviour occurred in 8% and 9%, respectively. In UC, 29% of patients had proctitis, 45% left-sided and 26% extensive colitis without extension during follow-up in 84%. In CD cumulative probabilities of receiving corticosteroids (CSs), immunosuppressants (ISs) and anti tumor necrosis factor therapy were respectively 47%, 27% and 9% at 10 years. In UC cumulative probabilities of receiving CS and IS were 40% and 15%, respectively at 10 years. Cumulative probabilities of surgery at 1 year and 10 years were 18% and 32%, respectively in CD and 4% and 8%, respectively in UC. In CD complicated behaviour at diagnosis (HR: 2.6; 95% CI 1.5 to 4.6) was associated with an increased risk for surgery while CS was associated with a decreased risk (HR: 0.5; 0.3 to 0.8). In UC CS was associated with an increased risk (HR: 2.2; 1.1 to 4.6) for colectomy. <h3>Conclusions</h3> Clinical course is mild in elderly-onset IBD patients. This information would need to be taken into account by physicians when therapeutic strategies are established.
Acral Metastases From Laryngeal Carcinoma
Authors: Jay Nayak, Yun Zhong, Missak Haigentz
Journal: Journal of Clinical Oncology (2010)

Case Report A 69-year-old man presented with painful swelling of several finger tips over a period of 2 months that interfered with activities of daily life and had not responded to topical or oral antibiotics prescribed by his primary care physician. The patient was diagnosed with locoregionally advanced laryngeal squamous cell carcinoma 18 months before this presentation, which was initially treatedwithtotallaryngectomyandpostoperativeconcurrentchemoradiotherapy but had recurred with lung metastases. On examination,thepatienthadhard,erythematous,andtenderswellingof several finger pulps in both hands (Fig 1A, arrows), most pronounced in the third finger of both hands. There was no fluctuationorwarmth.A3-cmerythematousmasswasalsopresentinthe left thigh (Fig 1B). Cytologic examination from a fine-needle aspiration of an involved digit confirmed metastatic squamous cell carcinoma (Fig 2A, diff quick stain; Fig 2B, papanicolaou stain). The patient expired as a result of myocardial infarction before initiation of palliative chemotherapy.
Genetic Susceptibility and the Setting of Occupational Health Standards
Authors: Paul Schulte, John Howard
Journal: Annual Review of Public Health (2011)

As more is learned about genetic susceptibility to occupational and environmental hazards, there will be increasing pressure to use genetic susceptibility information in setting occupational health standards. Historically, this has not been done, but a growing body of research assesses inherited genetic factors as modifiers of the effects of hazardous exposures. Additionally, acquired genetic and epigenetic characteristics could also be used in standard setting. However, for both inherited and acquired genetic characteristics, many scientific, ethical, legal, and social issues could arise. Investigators need to examine the potential role and implications of using genetic information in standard setting. In this review, we focus primarily on inherited genetic factors and their role in occupational health standard setting.
Axillary Ultrasound After Neoadjuvant Chemotherapy and Its Impact on Sentinel Lymph Node Surgery: Results From the American College of Surgeons Oncology Group Z1071 Trial (Alliance)
Authors: Judy C. Boughey, Karla V. Ballman, Kelly K. Hunt, Linda M. McCall, Elizabeth A. Mittendorf, Gretchen M. Ahrendt, Lee G. Wilke, Huong T. Le-Petross
Journal: Journal of Clinical Oncology (2015)

The American College of Surgeons Oncology Group Z1071 trial reported a 12.6% false-negative rate (FNR) for sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in cN1 disease. Patients were not selected for surgery based on response, but a secondary end point was to determine whether axillary ultrasound (AUS) after NAC after fine-needle aspiration cytology can identify abnormal nodes and guide patient selection for SLN surgery.Patients with T0-4, N1-2, M0 breast cancer underwent AUS after neoadjuvant chemotherapy. AUS images were centrally reviewed and classified as normal or suspicious lymph nodes. AUS findings were tested for association with pathologic nodal status and SLN FNR. The impact of AUS results to select patients for SLN surgery to reduce the FNR was assessed.Postchemotherapy AUS images were reviewed for 611 patients. One hundred thirty (71.8%) of 181 AUS-suspicious patients were node positive at surgery compared with 243 (56.5%) of 430 AUS-normal patients (P < .001). Patients with AUS-suspicious nodes had a greater number of positive nodes and greater metastasis size (P < .001). The SLN FNR was not different based on AUS results; however, using a strategy where only patients with normal AUS undergo SLN surgery would potentially reduce the FNR in Z1071 patients with ≥ two SLNs removed from 12.6% to 9.8% when preoperative AUS results are considered as part of SLN surgery.AUS is recommended after chemotherapy to guide axillary surgery. An FNR of 9.8% with the combination of AUS and SLN surgery would be acceptable for the adoption of SLN surgery for women with node-positive breast cancer treated with neoadjuvant chemotherapy.
Why tomorrow's doctors need primary care today
Authors: David J Pearson, Robert K McKinley
Journal: Journal of the Royal Society of Medicine (2010)

Generations of medical students have received the majority of their clinical education in hospitals. This fosters an impression that healthcare happens in hospitals which rescue patients from primary care and surrender them back when their care is complete. In reality, the majority of healthcare has always been delivered in primary care and the community. For most people this continuing care from general medical practitioners and their colleagues is only rarely interrupted by hospital contacts. The current emphasis on providing care close to patients' homes recognizes this reality and is driving huge change in healthcare and the medical profession. Medical education must change quickly to respond to these challenges.

As we look again at the education of tomorrow's doctors we ask whether the profession, its executive bodies and those who hold the purse-strings have the will to challenge current mindsets and shift funding to allow primary care to achieve its potential in integrated medical curricula in equal partnership with secondary care.
Complaints about advertising of medicines are encouraged
Authors: H. Simmonds
Journal: BMJ (2002)

EDITOR—Carvel has given his personal view about advertising by pharmaceutical companies and the code of practice for the pharmaceutical industry of the Association of the British Pharmaceutical Industry.1 The code is administered by the Prescription Medicines Code of Practice Authority, at arm's length from the association itself. The code is available from the authority, the association's website (www.abpi.org.uk/), its medicines compendium, and the eMC website (www.emc.vhn.net/).

The Prescription Medicines Code of Practice Authority supports Carvel's view …
Tirapazamine Administered as a Neoadjuvant to Radiotherapy Reduces Metastatic Dissemination
Authors: Sarah Jane Lunt, Brian A. Telfer, Richard J. Fitzmaurice, Ian J. Stratford, Kaye J. Williams
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The level of hypoxia in primary tumors has been linked both clinically and experimentally to the incidence of metastases. This study was designed to address the effect of selectively targeting hypoxic cells in primary tumors on subsequent presentation of metastasis. Experimental Design: The murine KHT model was used as a reproducible temporal and spatial onset of metastases is revealed following treatment of primary (∼400 mm3) s.c. tumors with a 25 Gy radiation dose. The bioreductive drugs tirapazamine and RB6145 were administered in multiple doses before radiotherapy. Results: Fractionated treatment with both tirapazamine and RB6145 significantly reduced the hypoxic fraction of the primary tumor, as assessed by pimonidazole binding, and had no effect on the overall growth rate of the primary tumor. Excision assays showed an increased level of cell kill in tirapazamine-treated versus RB6145-treated tumors consistent with tirapazamine targeting hypoxic cells at a broader range of oxygen tensions than RB6145. Tirapazamine treatment significantly reduced the presentation of metastases following radiotherapy (P = 0.003 versus saline controls) whereas RB6145 had no effect. Local control rates increased from 20% to 32% and 50% when radiation was combined with RB6145 and tirapazamine, respectively. Conclusions: These data provide direct evidence that selective targeting of hypoxic cells in primary tumors is a viable approach in the control of metastatic disease. The enhanced efficacy of tirapazamine versus RB6145 suggests that the radioresistant cells at intermediate oxygen tensions, conducive to targeting with tirapazamine but not with the more stringent bioreductive RB6145, predominate in terms of linking primary tumor hypoxia and metastases.
Primary prevention of asthma and atopy during childhood by allergen avoidance in infancy: a randomised controlled study
Authors: S H Arshad
Journal: Thorax (2003)

<b>Background:</b> Recent increases in the prevalence of asthma and atopy emphasise the need for devising effective methods for primary prevention in children at high risk of atopy. <b>Method:</b> A birth cohort of genetically at risk infants was recruited in 1990 to a randomised controlled study. Allergen avoidance measures were instituted from birth in the prophylactic group (n=58). Infants were either breast fed with mother on a low allergen diet or given an extensively hydrolysed formula. Exposure to house dust mite was reduced by the use of an acaricide and mattress covers. The control group (n=62) followed standard advice as normally given by the health visitors. At age 8, all 120 children completed a questionnaire and 110 (92%) had all assessments (skin prick test, spirometry, and bronchial challenges). <b>Results:</b> In the prophylactic group eight children (13.8%) had current wheeze compared with 17 (27.4%) in the control group (p=0.08). Respective figures were eight (13.8%) and 20 (32.3%) for nocturnal cough (p=0.02) and 11 of 55 (20.0%) and 29 of 62 (46.8%) for atopy (p=0.003). After adjusting for confounding variables, the prophylactic group was found to be at a significantly reduced risk for current wheeze (odds ratio (OR) 0.26 (95% confidence interval (CI) 0.07 to 0.96)), nocturnal cough (OR 0.22 (95% CI 0.06 to 0.83)), asthma as defined by wheeze and bronchial hyperresponsiveness (OR 0.11 (95% CI 0.01 to 1.02)), and atopy (OR 0.21 (95% CI 0.07 to 0.62)). <b>Conclusion:</b> Strict allergen avoidance in infancy in high risk children reduces the development of allergic sensitisation to house dust mite. Our results suggest that this may prevent some cases of childhood asthma.
Evidence in support of the validity of the TNF brake hypothesis
Authors: Walter P Maksymowych
Journal: Annals of the Rheumatic Diseases (2013)

Metabolic processes studied by PET are quantified traditionally using compartmental models, which relate the time course of the tracer concentration in tissue to that in arterial blood. For liver studies, the use of arterial input may, however, cause systematic errors to the estimated kinetic parameters, because of ignorance of the dual blood supply from the hepatic artery and the portal vein to the liver. <b>Methods:</b> Six pigs underwent PET after [<sup>15</sup>O]carbon monoxide inhalation, 3-<i>O</i>-[<sup>11</sup>C]methylglucose (MG) injection, and [<sup>18</sup>F]FDG injection. For the glucose scans, PET data were acquired for 90 min. Hepatic arterial and portal venous blood samples and flows were measured during the scan. The dual-input function was calculated as the flow-weighted input. <b>Results:</b> For both MG and FDG, the compartmental analysis using arterial input led to systematic underestimation of the rate constants for rapid blood–tissue exchange. Furthermore, the arterial input led to absurdly low estimates for the extracellular volume compared with the independently measured hepatic blood volume of 0.25 ± 0.01 mL/mL (milliliter blood per milliliter liver tissue). In contrast, the use of a dual-input function provided parameter estimates that were in agreement with liver physiology. Using the dual-input function, the clearances into the liver cells (K<sub>1</sub> = 1.11 ± 0.11 mL/min/mL for MG; K<sub>1</sub> = 1.07 ± 0.19 mL/min/mL for FDG) were comparable with the liver blood flow (F = 1.02 ± 0.05 mL/min/mL). As required physiologically, the extracellular volumes estimated using the dual-input function were larger than the hepatic blood volume. The linear Gjedde–Patlak analysis produced parameter estimates that were unaffected by the choice of input function, because this analysis was confined to time scales for which the arterial-input and dual-input functions were very similar. <b>Conclusion:</b> Compartmental analysis of MG and FDG kinetics using dynamic PET data requires measurements of dual-input activity concentrations. Using the dual-input function, physiologically reasonable parameter estimates of K<sub>1</sub>, k<sub>2</sub>, and V<sub>p</sub> were obtained, whereas the use of conventional arterial sampling underestimated these parameters compared with independent measurements of hepatic flow and hepatic blood volume. In contrast, the linear Gjedde–Patlak analysis, being less informative but more robust, gave similar parameter estimates (K, V) with both input functions.
Circulating Endothelial Progenitors and Tumor Resistance to Vascular-Targeting Therapies
Authors: Michele De Palma, Silvia Nucera
Journal: Cancer Discovery (2012)

Abstract Acute mobilization of circulating endothelial progenitors has been implicated in tumor resistance to vascular-disrupting agents. In the current issue of Cancer Discovery, Taylor and colleagues provide novel insight into the kinetics of endothelial progenitor mobilization by vascular-disrupting agents in both mouse tumor models and cancer patients. Cancer Discov; 2(5); 395–7. ©2012 AACR. Commentary on Taylor et al., p. 434.
Contemporary Percutaneous Treatment of Unprotected Left Main Coronary Stenoses
Authors: Stephen G. Ellis, Hideo Tamai, Masakiyo Nobuyoshi, Kunihiko Kosuga, Antonio Colombo, David R. Holmes, Carlos Macaya, Cindy L. Grines, Patrick L. Whitlow, Harvey J. White, Jeffrey Moses, Paul S. Teirstein, Patrick W. Serruys, John A. Bittl, Michael R. Mooney, Thomas M. Shimshak, Peter C. Block, Raimund Erbel
Journal: Circulation (1997)

Background Coronary artery bypass surgery (CABG) has been considered the therapy of choice for patients with unprotected left main (ULMT) coronary stenoses. Selected single-center reports suggest that the results of percutaneous intervention may now approach those of CABG. Methods and Results To assess the results of percutaneous ULMT treatment from a wide variety of experienced interventional centers, we requested data on consecutive patients treated after January 1, 1994, from 25 centers. One hundred seven patients were identified who were treated either electively (n=91) or for acute myocardial infarction (n=16). Of patients treated electively, 25% were considered inoperable, and 27% were considered high risk for bypass surgery. Primary treatment included stents (50%), directional atherectomy (24%), and balloon angioplasty (20%). Follow-up was 98.8% complete at 15±8 months. Results varied considerably, depending on presentation and treatment. For patients with acute myocardial infarction, technical success was achieved in 75%, and survival to hospital discharge was 31%. For elective patients, technical success was achieved in 98.9%, and in-hospital survival was strongly correlated with left ventricular ejection fraction ( P =.003). Longer-term event (death, infarction, or bypass surgery) -free survival was correlated with ejection fraction ( P &lt;.001) and was inversely related to presentation with progressive or rest angina ( P &lt;.001). Surgical candidates with ejection fractions ≥40% had an in-hospital survival of 98% and a 9-month event-free survival of 86±5%, whereas patients with ejection fractions &lt;40% had 67% and 22±12% in-hospital and 9-month event-free survivals, respectively. Nine hospital survivors (10.6%) experienced cardiac death within 6 months of hospital discharge. Conclusions While results for selected patients appear promising, until early post–hospital discharge cardiac death can be better understood and minimized, percutaneous revascularization of ULMT stenosis should not be considered an alternative to bypass surgery for most patients. When percutaneous revascularization of ULMT is required, directional atherectomy and stenting appear to be the preferred techniques, and follow-up angiography 6 to 8 weeks after treatment is probably advisable.
Vascular biology and bone formation: hints from HIF
Authors: Dwight A. Towler
Journal: Journal of Clinical Investigation (2007)

In this issue of the JCI, Wang, Clemens, and colleagues demonstrate that hypoxia-inducible factor alpha (HIF alpha) signaling in bone-building osteoblasts is central to the coupling of angiogenesis and long bone development in mice (see the related article beginning on page 1616). They show that bone formation controlled by osteoblast HIF alpha signaling is not cell autonomous but is coupled to skeletal angiogenesis dependent upon VEGF signaling. Thus, strategies that promote HIF alpha signaling in osteoblasts may augment bone formation and accelerate fracture repair.
Phosphodiesterase 5 inhibition blocks pressure overload-induced cardiac hypertrophy independent of the calcineurin pathway
Authors: S. Hsu, T. Nagayama, N. Koitabashi, M. Zhang, L. Zhou, D. Bedja, K. L. Gabrielson, J. D. Molkentin, D. A. Kass, E. Takimoto
Journal: Cardiovascular Research (2008)

Cyclic GMP (cGMP)-specific phosphodiesterase 5 (PDE5) inhibition by sildenafil (SIL) activates myocardial cGMP-dependent protein kinase G (PKG) and blunts cardiac hypertrophy. To date, the only documented target of PKG in myocardium is the serine–threonine phosphatase calcineurin (Cn), which is central to pathological cardiac hypertrophy. We tested whether Cn suppression is necessary in order to observe anti-hypertrophic effects of SIL. Mice lacking the Cn-Aβ subunit (CnAβ−/−) and wild-type (WT) controls were subjected to transverse aorta constriction (TAC) with or without SIL (200 mg/kg/day, p.o.) for 3 weeks. TAC-induced elevation of Cn expression and activity in WT was absent in CnAβ−/− hearts, and the latter accordingly developed less cardiac hypertrophy (50 vs. 100% increase in heart weight/tibia length, P < 0.03) and chamber dilation. SIL remained effective in CnAβ−/− mice, increasing PKG activity similarly as in WT, suppressing hypertrophy and fetal gene expression, and enhancing heart function without altering afterload. TAC-stimulated calcium–calmodulin kinase II, Akt, and glycogen synthase kinase 3β in both groups (the first rising more in CnAβ−/− hearts), and SIL also suppressed these similarly. Activation of extracellular signal-regulated kinase observed in WT-TAC but not CnAβ−/− hearts was also suppressed by SIL. PDE5A inhibition and its accompanying PKG activation blunt hypertrophy and improve heart function even without Cn activation. This occurs by its modulation of several alternative pathways which may result from concomitant distal targeting, or activity against a common proximal node.