tbuckley/cabot-search huggingface dataset:
Investigation for asthma-related healthcare utilization and prescription of pregnant women with asthma in Korea
Authors: Sujeong Kim, Yunjin Park, Jinhee Kim, Hyouk-Soo Kwon, Tae-Bum Kim
Journal: European Respiratory Journal (2013)

Background: National Health Insurance(NHI) claims data is an ideal source to study real-world effectiveness and utilization patterns of asthma.However, there have been few studies about pregnant asthmatis using NHI claims database. Objective: To evaluate asthma-related healthcare use and prescriptions in pregnant asthmatics in Korea.To investigate the association between asthma exacerbations during pregnancy and adverse perinatal outcomes. Method: Of the NHI claim records from January, 2006 to December, 2010, pregnant women who had ICD-10 codes related to delivery during 2008 were enrolled. Asthma-related healthcare use and prescription of pregnant asthmatics compared with non-pregnant asthmatics.And perinatal outcomes of patients who had acute asthma exacerbation during pregnancy against patients who had no acute exacerbation were measured. Result: About 19.3% of the pregnant subjects were hospitalized and 18.8% were treated in ED at least once due to exacerbation during pregnancy.Pregnant asthmatics underwent asthma-related hospitalization, ED and outpatient visits more frequently than non-pregnant asthmatics.The 45.7%experienced acute attacks of asthma at least once during pregnancy.There was no significant difference in the incidence of preterm labor, placenta previa, preeclampsia, gestational dibetes mellitus, caesarean section, and spontaneous abortion between subjects who had acute exacerbation and others. Conclusion: Pregnant asthmatic subjects had more acute asthma exacerbations and related healthcare needs than non-pregnant women asthmatics.Adverse perinatal outcomes between women who had acute asthma attack and women had no attack during pregnanct were not differed.
Combination chemotherapy with carboplatin, etoposide, and vincristine as first-line treatment in small-cell lung cancer.
Authors: U Gatzemeier, D K Hossfeld, R Neuhauss, M Reck, W Achterrath, L Lenaz
Journal: Journal of Clinical Oncology (1992)

PURPOSE The antineoplastic activity of carboplatin and etoposide may be improved by the addition of vincristine (CEV) because of its low myelosuppressive potential and its activity in small-cell lung cancer (SCLC). A phase II study with CEV was carried out. PATIENTS AND METHODS One hundred twenty-one untreated patients with SCLC (63 with limited disease [LD], 58 with extensive disease [ED]) were treated with a combination of 300 mg/m2 intravenous (IV) on day 1, etoposide 140 mg/m2 IV daily on days 1 to 3, and vincristine 1.4 mg/m2 IV on days 1, 8, and 15 every 4 weeks. RESULTS A 90% rate overall response rate including 56% complete responses (CRs) was achieved in LD and an 83% overall response rate including 35% CRs was observed in ED. Median survival time was 13 months in limited disease and 9.5 months in extensive disease. The 24 and 36 months survival rates were 29% in LD and 9% in ED. Myelosuppression was the main form of toxicity. CONCLUSION The combination of CEV is a new active and well-tolerated regimen in the treatment of SCLC. Prospective randomized studies of CEV with conventional chemotherapy are warranted.
Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: population based cohort study and sibling design
Authors: K. Furu, H. Kieler, B. Haglund, A. Engeland, R. Selmer, O. Stephansson, U. A. Valdimarsdottir, H. Zoega, M. Artama, M. Gissler, H. Malm, M. Norgaard
Journal: BMJ (2015)

<b>Objective</b> To assess whether use of specific selective serotonin reuptake inhibitors (SSRIs) or venlafaxine in early pregnancy is associated with an increased risk of birth defects, with emphasis on cardiovascular birth defects even when accounting for lifestyle or other familial confounding. <b>Design</b> Multicountry population based cohort study, including sibling controlled design. <b>Setting</b> Nordic population (Denmark, Finland, Iceland, Norway, and Sweden) identified from nationwide health registers at different periods in 1996-2010. <b>Population</b> The full study cohort included women giving birth to 2.3 million live singletons. The sibling cohort included 2288 singleton live births. The sibling controlled analyses included sibling pairs who were discordant for exposure to SSRIs or venlafaxine and birth defects. <b>Main outcome measure</b> Prevalence of birth defects, including subtypes of cardiac defects. Odds ratio of birth defects from logistic and conditional logistic regression. <b>Results</b> Among 36 772 infants exposed to any SSRI in early pregnancy, 3.7% (n=1357) had a birth defect compared with 3.1% of 2 266 875 unexposed infants, yielding a covariate adjusted odds ratio of 1.13 (95% confidence interval 1.06 to 1.20). In the sibling controlled analysis the adjusted odds ratio decreased to 1.06 (0.91 to 1.24). The odds ratios for any cardiac birth defect with use of any SSRI or venlafaxine were 1.15 (95% confidence interval 1.05 to 1.26) in the covariate adjusted analysis and 0.92 (0.72 to 1.17) in the sibling controlled analysis. For atrial and ventricular septal defects the covariate adjusted odds ratio was 1.17 (1.05 to 1.31). Exposure to any SSRI or venlafaxine increased the prevalence of right ventricular outflow tract obstruction defects, with a covariate adjusted odds ratio of 1.48 (1.15 to 1.89). In the sibling controlled analysis the adjusted odds ratio decreased to 0.56 (0.21 to 1.49) for any exposure to SSRIs or venlafaxine and right ventricular outflow tract obstruction defects. <b>Conclusions</b> In this large Nordic study no substantial increase was found in prevalence of overall cardiac birth defects among infants exposed to SSRIs or venlafaxine in utero. Although the prevalence of septal defects and right ventricular outflow tract defects was higher in exposed infants, the lack of an association in the sibling controlled analyses points against a teratogenic effect of these drugs.
Effect of Diet High in Beef Fat on the Composition of Fecal Bile Acids During Intestinal Carcinogenesis in the Rat2
Authors: Norman D. Nigro, Robert L. Campbell, Dharm V. Singh, Yuh Nan Lin
Journal: JNCI Journal of the National Cancer Institute (1976)

Two groups of 20 male Sprague-Dawley rats each were given sc 8 mg azoxymethane/kg body weight and fed a normal diet or one high in beef fat. Control groups were not given azoxymethane. Fat-control animals did not excrete more total bile acids than did the normal-control group but did excrete more deoxycholic acid as the result of increased cholic acid degradation. Azoxymethane itself caused an increase in fecal bile acid concentratation but tended to reduce the level of cholic acid degradation. Fatty acid content in the feces increased in the animals on the fat diet but was not affected by azoxymethane. A fat-diet-dependent increase was apparent in total fecal neutral steroids and a carcinogen-dependent increase in cholesterol degradation. Dietary fat and bile steroids altered by gut microflora were important interrelated factors in the intestinal carcinogenic process of this animal model.
First-Line Treatment of Advanced Epidermal Growth Factor Receptor (Egfr) Mutation Positive (M+) Non-Squamous Non-Small Cell (Nsclc) Lung Cancer – a Cochrane Collaboration Meta-Analysis
Authors: J.A. Green, K. Dwan, V. Bates, A. Boland, P. Jain, J. Greenhalgh
Journal: Annals of Oncology (2014)
Abstract 2949: Improvement in Ventilatory Efficiency and Dyspnea on Exertion Are Related to Reduced Pulmonary Pressure in Heart Failure Patients Undergoing Chronic Phosphodiesterase-5 Inhibition
Authors: Marco Guazzi, Jonathan Myers, Mary Ann Peberdy, Daniel Bensimhon, Paul Chase, Sherry Pinkstaff, Ross Arena
Journal: Circulation (2008)

Chronic phosphodiesterase-5 inhibition with Sildenafil has been shown to improve peak oxygen consumption (VO2), ventilatory efficiency (VE/VCO2 slope) and pulmonary artery pressure (PAP) in patient...
Localized resectable neuroblastoma: results of the second study of the Italian Cooperative Group for Neuroblastoma.
Authors: B De Bernardi, M Conte, A Mancini, A Donfrancesco, P Alvisi, P Tomà, F Casale, L Cordero di Montezemolo, P E Cornelli, M Carli
Journal: Journal of Clinical Oncology (1995)

PURPOSE To optimize treatment for children with localized resectable neuroblastoma in 21 Italian institutions using a common protocol based on previous experience. PATIENTS AND METHODS Between January 1985 and December 1992, 152 children aged 0 to 15 years with nondisseminated neuroblastoma were entered onto this study following complete resection of tumor without tumor rupture (TR) (stage 1), or resection with minimal tumor residue, and/or tumor infiltration of regional lymph nodes (LN+), and/or TR (stage 2). Of 144 assessable children, 69 were classified as having stage 1 disease and 75 as stage 2. Of stage 2 children, 49 had low-risk (LR) characteristics (age, 0 to 11 months or 1 to 15 years but negative lymph nodes and no TR). Stage 1 and stage 2 LR children did not receive adjuvant therapy. The remaining 26 stage 2 children had high-risk (HR) characteristics (age, 1 to 15 years with LN+ and/or TR) and received adjuvant chemotherapy for 6 months. RESULTS Of 144 children, three died of therapy-related complications and 19 relapsed, of whom six died of disease. The estimated 5-year overall survival (OS) rate was 93% and the event-free survival (EFS) rate was 83%. Of 69 stage 1 children, one died postoperatively and five relapsed (one local and four disseminated, two of whom died), for 94% OS and 90% EFS rates. Of 49 stage 2 LR children, six relapsed (four local and two disseminated); relapses occurred in five of 20 infants with LN+, in one of four infants with TR, and in none of the remaining 25 children. One child died of disease and one of toxicity, for 96% OS and 85% EFS rates. Of 26 stage 2 HR children, eight relapsed (three of 20 with LN+, three of four with TR, and two of two with LN+ and TR), of whom three died of disease and one of toxicity, for 87% OS and 61% EFS rates. CONCLUSION Our data confirm the overall good prognosis of children with localized resectable neuroblastoma. LN+ and TR predisposed to relapse at all ages, but infants tended to have a less aggressive course after relapse. Stage 1 and 2 LR children had 94% and 96% OS rates, respectively, which justifies a policy of no adjuvant chemotherapy. Eight of 26 children with stage 2 HR relapsed despite 6 months of chemotherapy; for these children, more intensive chemotherapy may be required.
Preliminary studies of a novel oral fluoropyrimidine carbamate: capecitabine.
Authors: D R Budman, N J Meropol, B Reigner, P J Creaven, S M Lichtman, E Berghorn, J Behr, R J Gordon, B Osterwalder, T Griffin
Journal: Journal of Clinical Oncology (1998)

PURPOSE To evaluate the toxicology and pharmacology of an orally active fluoropyrimidine given as a continuous daily dose divided into two portions for 6 weeks, and to determine the maximal-tolerated daily dose (MTD) and the suggested phase II daily dose. PATIENTS AND METHODS Solid-tumor patients with a Karnofsky performance status greater than 70 who had normal organ function and resolution of the effects of prior therapy, and who gave informed written consent, were enrolled. Oral capecitabine, as a divided morning and evening dose, was administered to cohorts of a minimum of 3 patients starting at 110 mg/m2 and escalating by means of a modified Fibonacci scheme to 1,657 mg/m2/d. Pharmacologic samples were obtained on days 1 and 15. Toxicity evaluations were performed approximately every 3 days for the first 43 days. Antitumor effect was evaluated at day 42 of therapy. RESULTS Thirty-three patients entered the study. Few side effects occurred at or below 1,331 mg/m2/d. The MTD was 1,657 mg/m2/d with limiting toxicities of palmar-plantar erythrodysesthesia, nausea, vomiting, vertigo, abdominal pain, diarrhea, and thrombocytopenia. All toxicities were reversible. A mixed response was seen in one breast cancer patient. Pharmacologic studies showed rapid and extensive metabolism of the parent drug into cytotoxic metabolites with a maximum plasma concentration (Cmax) 1 hour after ingestion. Linear increases in the area under the concentration-time curve (AUC) and Cmax were seen with linear increases in administered dose. CONCLUSION The suggested phase II dose on a continuous 42-day dosing schedule is 1,331 mg/m2/d. Linear pharmacologic parameters of the parent compound and metabolites are demonstrated.
Randomized trial of etoposide and cisplatin versus etoposide and carboplatin in patients with good-risk germ cell tumors: a multiinstitutional study.
Authors: D F Bajorin, M F Sarosdy, D G Pfister, M Mazumdar, R J Motzer, H I Scher, N L Geller, W R Fair, H Herr, P Sogani
Journal: Journal of Clinical Oncology (1993)

PURPOSE This multicenter, randomized phase III clinical trial evaluated the efficacy of etoposide plus carboplatin (EC) versus etoposide plus cisplatin (EP) in good-risk germ cell tumor (GCT) patients. PATIENTS AND METHODS Between October 1986 and December 1990, 270 patients with good-risk GCTs were randomized to receive four cycles of either EP or EC. The etoposide dose in all patients was 100 mg/m2 on days 1 through 5. EP patients received cisplatin at 20 mg/m2 on days 1 through 5 and therapy was recycled at 21-day intervals. For EC patients, the carboplatin dose was 500 mg/m2 on day 1 of each cycle and the EC recycling interval was 28 days. RESULTS Two hundred sixty-five patients were assessable: 131 patients treated with EC and 134 treated with EP. One hundred fifteen of 131 assessable patients (88%) treated with EC achieved a complete response (CR) versus 121 of 134 patients (90%) treated with EP (P = .32). Sixteen patients (12%) treated with EC relapsed from CR versus four patients (3%) treated with EP. Therefore, 32 patients (24%) who received carboplatin experienced an event (incomplete response [IR] or relapse) compared with 17 of 134 patients (13%) who received cisplatin (P = .02). At a median follow-up of 22.4 months, event-free and relapse-free survival were inferior for patients treated with EC (P = .02 and P = .005, respectively). No difference in overall survival was evident (P = .52). CONCLUSION Two-drug therapy with EC using this dose and schedule was inferior to therapy with EP. Cisplatin remains as the standard platinum analog in the treatment of patients with good-risk GCTs. Carboplatin should be restricted to investigational trials in GCT.
Severe asthma in old patients is characterized by signs of immunosuppression and by lymphocyte resistance to glucocorticoids
Authors: Alexander Pukhalsky, Galina Shmarina, Tamara Vylegzhanina, Tamara Chervinskaya, Olga Kozyreva, Vladimir Alioshkin
Journal: European Respiratory Journal (2012)

The aim of this study was to investigate the adaptation system in asthmatic patients. Twenty one patients were enrolled into the study. In 15 patients the clinical course was evaluated as severe and 6 patients demonstrated the middle asthma (mean age, 60.3±2.5 and 30.8±3.0 years, respectively). Individual susceptibility of peripheral blood lymphocytes (PBL) to glucocorticoids (GCs) was evaluated by Δh value calculation: an integrative parameter, including the level of mitogen-induced lymphocyte proliferation and inhibition degree of the cell proliferation by dexamethasone. In healthy subjects the mean Δh level was −0.24±0.30 (negative values of Δh correspond to high cell sensitivity to GCs). Results of the study are presented in the Table.

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The results show that severe asthma is associated with low PBL sensitivity to GCs, HPA axis exhaustion (low ACTH level) and the signs of immunosuppression (high TGFβ1 level and low PBL proliferative response).
Global genetic analyses reveal strong inter-ethnic variability in the loss of activity of the organic cation transporter OCT1
Authors: Tina Seitz, Robert Stalmann, Nawar Dalila, Jiayin Chen, Sherin Pojar, Joao N. Dos Santos Pereira, Ralph Krätzner, Jürgen Brockmöller, Mladen V. Tzvetkov
Journal: Genome Medicine (2015)
Heterozygous<i>RTEL1</i>mutations are associated with familial pulmonary fibrosis
Authors: Caroline Kannengiesser, Raphael Borie, Christelle Ménard, Marion Réocreux, Patrick Nitschké, Steven Gazal, Hervé Mal, Camille Taillé, Jacques Cadranel, Hilario Nunes, Dominique Valeyre, Jean François Cordier, Isabelle Callebaut, Catherine Boileau, Vincent Cottin, Bernard Grandchamp, Patrick Revy, Bruno Crestani
Journal: European Respiratory Journal (2015)

Pulmonary fibrosis is a fatal disease with progressive loss of respiratory function. Defective telomere maintenance leading to telomere shortening is a cause of pulmonary fibrosis, as mutations in the telomerase component genes TERT (reverse transcriptase) and TERC (RNA component) are found in 15% of familial pulmonary fibrosis (FPF) cases. However, so far, about 85% of FPF remain genetically uncharacterised. Here, in order to identify new genetic causes of FPF, we performed whole-exome sequencing, with a candidate-gene approach, of 47 affected subjects from 35 families with FPF without TERT and TERC mutations. We identified heterozygous mutations in regulator of telomere elongation helicase 1 ( RTEL1 ) in four families. RTEL1 is a DNA helicase with roles in DNA replication, genome stability, DNA repair and telomere maintenance. The heterozygous RTEL1 mutations segregated as an autosomal dominant trait in FPF, and were predicted by structural analyses to severely affect the function and/or stability of RTEL1. In agreement with this, RTEL1 -mutated patients exhibited short telomeres in comparison with age-matched controls. Our results provide evidence that heterozygous RTEL1 mutations are responsible for FPF and, thereby, extend the clinical spectrum of RTEL1 deficiency. Thus, RTEL1 enlarges the number of telomere-associated genes implicated in FPF.
Clara cells serve as the progenitors to regenerate alveolar epithelium in response to severe lung injury
Authors: Dahai Zheng, Gino Limmon, Lu Yin, Nicola Leung, Hanry Yu, Vincent Chow, Jianzhu Chen
Journal: European Respiratory Journal (2012)

Bleomycin treatment or influenza virus infection can induce severe damage in distal lung with the loss of large amounts of alveolar type II (AT2) and type I (AT1) cells. During the repair process, new AT2s and AT1s have to be produced to regenerate the damaged alveoli. A recent study showed that the newly generated AT2s were not derived from pre-existing AT2s after bleomycin treatment, indicating the existence of other progenitor cells for alveolar regeneration [1]. We have used a genetic lineage tracing system to follow Clara cells in mice. We show that large numbers of the newly generated AT2s and AT1s are derived from Clara cells after alveoli damage by bleomycin treatment or influenza virus infection. The intermediates between Clara cells and AT2s are SPC-expressing bronchiolar cells (or SBECs). SBECs are only observed in damaged area and initially positive for Clara cell marker Clara Cell Secretory Protein (CCSP) and gradually become CCSP negative. Anatomical analysis shows that SBECs at the tips of bronchioles appear to dilate to regenerate alveolar epithelium in a process similar to that seen during the development of embryonic alveolar epithelium. These findings show that Clara cells are the progenitors to regenerate alveolar epithelium in response to severe lung damage.  [1] Chapman, H. A. et al. Integrin alpha6beta4 identifies an adult distal lung epithelial population with regenerative potential in mice. J Clin Invest 121, 2855-2862 (2011).
Associations of BMI, fat mass and lean mass with childhood asthma: Mendelian randomization study
Authors: Raquel Granell, John Henderson, David Evans, George Smith, Andy Ness, Sarah Lewis, Tom Palmer, Jonathan Sterne
Journal: European Respiratory Journal (2013)

Studies have reported associations between body mass index (BMI) and asthma in childhood, but it is difficult to exclude confounding and reverse causality as explanations. Genomewide association studies have identified 32 independent loci associated with BMI ( Speliotes EK et al. 2010 ).  We used Mendelian randomization to investigate the causal effect of BMI, fat mass and lean mass on childhood asthma.  A weighted allele score was derived from 32 imputed SNPs. We multiplied the imputation weight of the risk allele by a SNP-specific weight as estimated in the reported meta-analysis by Speliotes et al., then averaged across SNPs. We estimated associations of the weighted allele score with BMI, fat mass, lean mass and asthma at age 7-7.5. The generalized method of moments was used to estimate causal (instrumental variable) risk ratios for the effect of BMI, fat and lean mass on asthma ( Palmer TM et al. 2011 ).  4835 children had complete data on 32 BMI-associated SNPs, asthma and BMI at 7-7.5 years. The weighted allele score was strongly associated with BMI (regression coefficient 2.22, 95% CI 1.76-2.67, p=2.3×10 -21 ), fat mass (2.88, 2.35-3.42, p=2.0×10 -25 ), lean mass (1.22, 0.80-1.64, p=1.6×10 -8 ) and childhood asthma (risk ratio [RR] 2.56, 1.38-4.76, p=0.003). The estimated causal RR for the effect of BMI on asthma was 1.55 (1.16-2.07), p=0.003. This effect appeared stronger in girls (1.77, 1.13-2.77, p=0.01) than boys (1.40, 0.96-2.04, p=0.08). The estimated causal RRs for the effect of fat mass and lean mass on asthma were 1.41 (1.11-1.79), p=0.01 and 2.25 (1.23-4.11), p=0.01 respectively.  Higher BMI, fat mass and lean mass in mid childhood cause increases in the risk of childhood asthma.
Can serum (CRP) levels estimate the outome of talc pleurodesis in malignant pleural effusions
Authors: Khaled Hassaan, Mohamed Fathy
Journal: European Respiratory Journal (2012)

Objective : to evaluate whether serum C-reactive protein (CRP) could help to predict the success rate and/or side effects of pleurodesis.  Methods:  In a prospective study, 25 consecutive patients with recurrent and biopsy-proven malignant effusions were included. Five grams of talc mixed in 150 ml of normal saline were administered via tube thoracostomy. Serial determinations of CRP were made in serum at the beginning of pleurodesis (baseline), and 24 h and 72 h after the procedure. Successful therapy was defined as a complete absence or minor re-accumulation of pleural effusion one month after pleurodesis.  Results:  Pleurodesis was successful in 22 of 25 patients (88%). The patients had significantly higher serum CRP levels at 24 h and 72 h than at baseline (p  th  h and 72 nd  h were 4.5 ± 3.5 mg / dL, 25.3 ± 5.6 mg / dL and 75.5 ± 15.6 mg / dL, respectively. Mean serum CRP levels were significantly higher in patients with successful pleurodesis compared with unsuccessful patients (baseline: 4.5 ± 3.5 mg / dL & 4.4 ± 2.5 mg / dL; at 24h: 25.3 ± 5.6 mg / dL & 6. 5 ± 3.5 mg / dL; at 72h: 75.5± 15.6 mg / dL & 8.7 ± 4.6 mg / dL, respectively) (p  nd  h (75.5 mg / dL & 72.7 mg / dL), but this was not statistically significant (p=0.143).  Conclusion:  The inflammatory response in the pleural cavity due to talc pleurodesis is reflected in the systemic circulation, and high serum CRP after chemical pleurodesis, is a good predictor of the success in pleurodesis.