tbuckley/cabot-search huggingface dataset:
Public Health Campaign Focuses on Teen Sexual Health
Authors: Julie A. Jacob
Journal: JAMA (2016)

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Negative Regulation by Interleukin-3 (IL-3) of Mouse Early B-Cell Progenitors and Stem Cells in Culture: Transduction of the Negative Signals by βc and βIL-3 Proteins of IL-3 Receptor and Absence of Negative Regulation by Granulocyte-Macrophage Colony-Stimulating Factor
Authors: Takuya Matsunaga, Fumiya Hirayama, Yuji Yonemura, Richard Murray, Makio Ogawa
Journal: Blood (1998)
Cetuximab in combination with docetaxel in patients (pts) with metastatic castration resistant (mCRPC) and docetaxel-refractory prostate cancer: A multicenter phase II trial (SAKK 08/07).
Authors: R. Cathomas, C. Rothermundt, R. von Moos, D. C. Betticher, R. C. Winterhalder, C. Droege, D. Siciliano, D. R. Berthold, M. Pless, S. Gillessen
Journal: Journal of Clinical Oncology (2010)

4666 Background: No standard treatment options exist for pts with mCRPC who progressed during or shortly after docetaxel (doc) therapy. The epidermal growth factor receptor (EGFR) is overexpressed in >90% of mCRPC. We tested the efficacy and safety of the combination of cetuximab (cet), a monoclonal antibody against EGFR, and doc in pts with mCRPC who are doc-refractory. Methods: This phase II trial included pts with mCRPC progressing during or < 90 days after at least 12 weeks of doc. Treatment (ttr) consisted of the same doc regimen as prior to progression (35mg/m2 d1,8,15 q4w or 75mg/m2 q3w) in combination with cet (400mg/m2 d1, then 250mg/m2 weekly). Primary endpoint was progression free survival (PFS) rate at 12 weeks defined as no evidence of PSA progression or progression of metastases. Secondary endpoints included toxicity, PFS at 24 weeks, PSA response, response of measureable disease and overall survival. 35 pts were needed in a Simon's two stage optimal design with a power of 90% and a significance level of 5% in order to test PFS rate at 12 weeks of ≤10% vs ≥30%. Results: 38 pts were enrolled at 15 centers between 7/08 and 9/09. 35 pts were evaluable having received at least one dose of trial ttr. 26 pts (74%) received the q3w schedule and 9 (26%) the weekly schedule. Median age was 68 (45-82) years, performance status was 0 in 26%, 1 in 60% and 2 in 24%; initial Gleason score was ≥8 in 55%. PSA decline >30% and >50% was seen in 31% and 17%, respectively. Main ttr related grade 3/4 toxicity included skin changes (6/35;17%), leucopenia (4/35;11%), hypersensitivity to cet (3/37;8%) and fatigue (2/35;6%). Conclusions: This is the first trial to test cet in combination with doc in pts with mCRPC. Toxicity of the combination was not greater than anticipated. PSA responses are encouraging. Mature results on the primary and secondary endpoints will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Bristol-Myers Squibb, Essex Pharma, Novartis, Roche, sanofi-aventis Amgen, sanofi-aventis
A Randomized, Double-blind, Placebo-Controlled Study of Latrepirdine in Patients With Mild to Moderate Huntington Disease
Journal: JAMA Neurology (2012)

BACKGROUND Latrepirdine is an orally administered experimental small molecule that was initially developed as an antihistamine and subsequently was shown to stabilize mitochondrial membranes and function, which might be impaired in Huntington disease. OBJECTIVE To determine the effect of latrepirdine on cognition and global function in patients with mild to moderate Huntington disease. DESIGN Randomized, double-blind, placebo-controlled study. SETTING Sixty-four research centers in Australia, Europe, and North America. PATIENTS Four hundred three patients with mild to moderate Huntington disease and baseline cognitive impairment (Mini-Mental State Examination score, 10-26). INTERVENTION Latrepirdine (20 mg) vs matching placebo administered orally 3 times daily for 26 weeks. MAIN OUTCOME MEASURES The co-primary outcome measures were cognition as measured by the change in Mini-Mental State Examination score from baseline to week 26 and global function at week 26 as measured by the Clinician Interview-Based Impression of Change, plus carer interview, which ranges from 1 (marked improvement) to 7 (marked worsening). Secondary efficacy outcome measures included behavior, daily function, motor function, and safety. RESULTS The mean change in Mini-Mental State Examination score among participants randomized to latrepirdine (1.5-point improvement) did not differ significantly from that among participants randomized to placebo (1.3-point improvement) (P=.39). Similarly, the distribution of the Clinician Interview-Based Impression of Change, plus carer interview did not differ significantly among those randomized to latrepirdine compared with placebo (P=.84). No significant treatment effects were detected on the secondary efficacy outcome measures. The incidence of adverse events was similar between those randomized to latrepirdine (68.5%) and placebo (68.0%). CONCLUSION In patients with mild to moderate Huntington disease and cognitive impairment, treatment with latrepirdine for 6 months was safe and well tolerated but did not improve cognition or global function relative to placebo. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00920946.
Cetuximab plus irinotecan for metastatic colorectal cancer (mCRC): Safety analysis of 800 patients in a randomized phase III trial (EPIC)
Authors: Y. Abubakr, C. Eng, L. Wong, V. Pautret, W. Scheithauer, J. Maurel, H. Kroening, M. Lutz, A. Zubel, A. Sobrero
Journal: Journal of Clinical Oncology (2006)

3556 Background: EPIC is a randomized phase III study comparing cetuximab plus irinotecan to irinotecan in second-line metastatic, EGFR-expressing mCRC patients (pts) (target N=1,300 pts). Following an independent Data Safety Monitoring Board (DSMB) review of 400 pts., the pooled safety data was presented at ASCO 2005 (#3580). The DSMB has recently reviewed safety data on the first 800 patients. Methods: Patients with EGFR-expressing mCRC who had failed first-line oxaliplatin in combination with a fluoropyrimidine and an ECOG performance status ≤ 2 were randomized to either Arm A (cetuximab 400 mg/m 2 followed by 250 mg/ m 2 weekly and irinotecan 350 mg/ m 2 q 3 weeks) or to Arm B (irinotecan 350 mg/ m 2 q 3 weeks). A pooled safety analysis is presented. Results: Eight hundred patients were randomized from May 2003 to March 2005 in Europe, Australia, Asia, and the US: 309 women and 491 men, with a median age of 61 years (range 21–90) and ECOG performance status (PS) of: 0= 53%, 1= 42%, 2= 5%. Seventeen pts received no study therapy and are excluded from the analysis. A total of 3,629 chemotherapy cycles were administered to the 783 pts with a median of 4 cycles per pt (range 1–23). Four (0.5%) subjects experienced severe infusion reactions: 2 grade 3 and 2 grade 4, none were fatal. In this pooled analysis, 59 deaths occurred within 30 days of last study therapy: 45 disease-related, 5 study drug related, 6 due to other causes, and 3 with unknown etiology. A summary table of adverse events (AE’s) is included. Conclusions: The DSMB raised no concerns after reviewing the safety data from 800 pts. In this pooled analysis characteristic toxicities of cetuximab and irinotecan do not appear to be increased, incidences and severities are similar to the earlier safety report based on the initial 400 patients. The study is currently nearing completion of accrual. [Table: see text] [Table: see text]
Involvement of prostaglandin E receptor subtype EP4 in head and neck squamous cell carcinoma (HNSCC)
Authors: Mariana S. De Lorenzo, Erik G. Cohen, Baoheng Du, Mindy Chang, Agnieszka Lantowski, Jay O. Boyle, Babette B. Weksler, Kotha Subbaramaiah, Andrew J. Dannenberg
Journal: Cancer Research (2005)

5890   Increased levels of PGE 2  have been detected in a variety of malignancies including HNSCC. Several lines of evidence, beyond the finding of elevated levels of PGE 2  in tumors, suggest that PGE 2  plays a role in tumor growth. For example, PGE 2  can stimulate cell proliferation, cell motility and angiogenesis while inhibiting apoptosis and immune surveillance. Treatment with anti-PGE 2  monoclonal antibody has been reported to suppress the growth of transplantable HNSCC in experimental animals. PGE 2  elicits cellular responses via interaction with four cell surface receptors, EP 1-4 . In this study, we first investigated the expression of EP 1-4  in human HNSCC and then attempted to identify which EP receptor was responsible for mediating the growth of experimental HNSCC. Real-time PCR indicated that each of the four EP receptors was commonly expressed in human HNSCC and in 1483 cell xenografts, a transplantable model of HNSCC. Treatment with ONO-8713, an EP 1  receptor antagonist (RA), did not suppress the growth of 1483 cell xenografts. In contrast, ONO-AE3-208, an EP 4  receptor antagonist (EP 4 RA), caused dose-dependent inhibition of xenograft growth. At a dose of 500 ppm, ONO-AE3-208 caused more than a 50% reduction in tumor growth. Because EP 4  receptor signaling is mediated by the cAMP/protein kinase A (PKA) pathway, levels of cAMP and PKA activity were measured. Treatment with the EP 4 RA caused a reduction in both amounts of cAMP and PKA activity in 1483 xenografts. Immunohistochemistry was performed to elucidate the mechanism underlying the anti-tumor activity of the EP 4 RA. Treatment with ONO-AE3-208 led to more than a 50% reduction in cell proliferation (Ki-67) and microvessel density (CD-34). These findings provided the rationale for complementary  in vitro  studies to further characterize the growth inhibitory effects of ONO-AE3-208. Neither treatment with exogenous PGE 2  nor the EP 4 RA altered the growth of 1483 cells in culture. Human endothelial cells were employed to begin to define the anti-angiogenic properties of the EP 4 RA. Treatment with 0-100 nM ONO-AE3-208 caused dose-dependent suppression of endothelial capillary tube formation. Taken together, these results suggest that the EP 4  receptor plays a significant role in mediating the growth promoting effects of PGE 2  in experimental HNSCC. Decreased tumor cell proliferation in xenografts may be a consequence of the anti-angiogenic effects of the EP 4 RA. Therapies that target PGE 2  synthesis or EP receptor antagonists may be useful in the treatment of malignancies including HNSCC.
Alopecia in a Boy With Nephrotic Syndrome
Authors: Moeko Hotta, Mitsuhito Ota
Journal: JAMA (2016)

A 5-year-old boy presented with erythematous alopecia, crusting, and pustules on the right frontal scalp, without local warmth. He receives prednisone and cyclosporine for nephrotic syndrome; has cervical adenopathy; and owns a cat. Laboratory findings were unremarkable. What would you do next?
Risk of mortality in patients with cancer experiencing febrile neutropenia
Authors: R. Barron, S. L. Michels, M. W. Reynolds, K. Tomic, J. Yu, G. Lyman
Journal: Journal of Clinical Oncology (2009)

9561 Background: Febrile neutropenia (FN) is a serious and potentially life-threatening condition that may develop in patients with cancer treated with chemotherapy. The risk of mortality from FN is not well characterized in clinical practice. Methods: Patients with cancer receiving chemotherapy in clinical practice were identified from the HealthCore Integrated Research Database, a geographically diverse spectrum of fully adjudicated longitudinal claims data from 13 health plans with over 20 million US lives. Patient enrollment data, full medical care, prescription drug use and mortality (confirmed using the National Death Index) were examined for each eligible patient. Patients experiencing FN were compared to propensity score-matched patients not experiencing FN within tumor types of Non-Hodgkin lymphoma (NHL), breast, lung, colorectal and ovarian cancer. Study endpoints included overall mortality (anytime during follow-up) and early mortality (during a chemotherapy course). Logistic regression was used to calculate odds ratios (OR), adjusted for demographics, comorbidities, and other covariates. Results: Matched FN and control groups each contained 5,176 patients. Crude incidence rates of overall and early mortality were significantly higher for patients in FN group compared to controls for all tumor types [7.9/1000 person-months (PM) (95% confidence interval [CI] = 7.3, 8.5) vs. 5.6/1000 PM (CI = 5.1, 6.1), P &lt; 0.0001; and 3.4/1000 PM (CI = 3.1, 3.9) vs. 2.4/1000 PM (CI = 2.1, 2.8), P = 0.0001, respectively]. Within tumor strata, lung cancer had the highest mortality rates and breast cancer had the lowest; NHL had the largest magnitude of difference between FN and controls (overall mortality: 7.2/1000 PM [CI = 5.3, 9.7] and 3.3/1000 PM [CI = 2.1, 5.1], P = 0.0035; early mortality: 3.0/1000 PM [CI = 1.8, 4.8] and 1.5/1000 PM [CI = 0.8, 3.0], P = 0.1103). Logistic regression demonstrated a significant increase in risk of overall and early mortality in patients with FN compared to controls (OR = 1.77 [1.53, 2.05] and OR = 1.73 [1.41, 2.11]) respectively. Conclusions: The crude and adjusted risk of mortality in patients experiencing FN is almost two-fold higher than comparably matched patients without FN. Prevention of FN is of high importance and should be carefully considered in clinical practice. [Table: see text]
Exhaled nitric oxide (FeNO), asthmatic symptoms and respiratory infections among junior high school students in Penang, Malaysia, in relation to fungal DNA in settled dust in schools
Authors: Guihong Cai, Jamal Hisham Hashim, Gunilla Wieslander, Zailina Hashim, Dan Norbäck
Journal: European Respiratory Journal (2013)

Background:  We studied associations between fungal DNA in schools and FeNO (by NIOX-MINO) and respiratory symptoms among students in Malaysia.   Methods:  Totally 8 junior high schools were randomly selected in Penang, 4 classes in each school and 20 students in each class, 368 (58%) participated. Vacuuming of dust from floors and desks/chairs on ALK-filters were done in all classrooms. Fungal DNA was analysed by quantitative PCR. Multiple logistic and linear regression was used, adjusting for gender, race, smoking and atopy.   Results:  Median level of FeNO was 17ppb (IQR 10-39). Totally 14% had wheeze, 38% daytime and 11% night time attacks of breathlessness last 12 months, 11% doctors’ diagnosed asthma and 37% any respiratory infection last 3 months. GM levels for total fungal DNA was 7.31*10 4  cell equivalents (CE)/g dust, 3.34*10 4  CE/g dust for  Aspergillus/Penicillium  DNA, 15 CE/g dust for  Aspergillus versicolor  DNA, and 7 CE/g dust for  Streptomyces  DNA. Low levels of  Stachybotrys  DNA (5 CE/g dust) was detected in one classroom only. FeNO was higher at higher levels of total fungal DNA (P=0.06),  Aspergillus/Penicillium  DNA (p=0.05) and  Aspergillus versicolor  DNA (p=0.02). Wheeze was more common at higher levels of  Aspergillus versicolor  DNA (p=0.003). Respiratory infections were more common at higher levels of  Aspergillus/Penicillium  DNA (p=0.05) and  Aspergillus versicolor  DNA (p=0.004).   Conclusion:  The level of FeNO was relatively high and fungal exposure in schools in Malaysia, especially to  Aspergillus versicolor,  can be associated with eosinophilic airway inflammation, wheeze and airway infections.
Jamaica advises women to avoid pregnancy as Zika virus approaches
Authors: Owen Dyer
Journal: BMJ (2016)

Zika, the mosquito-borne virus that has caused a public health crisis in Brazil after being linked to a sharp increase in birth defects, has spread rapidly across the Caribbean this month, prompting Jamaican health authorities to issue an unprecedented warning days before its expected arrival.

“The Ministry of Health is advising women to delay becoming pregnant for the next six to 12 months,” wrote Horace Dalley, health minister, in a public statement. He urged those who were already pregnant to take extra precautions to avoid being bitten.

Confirmation of the first infection in Haiti on 15 January had driven the Jamaican government to act, Dalley said later. The past week has also seen the virus confirmed in Barbados, Ecuador, Guadeloupe, Guyana, and Saint Martin.1

“The Zika virus …
Final results of a phase II PETHEMA trial of alternating bortezomib and dexamethasone as induction regimen prior autologous stem cell transplantation (ASCT) in younger patients with multiple myeloma (MM): Efficacy and clinical implications of tumor response
Authors: L. Rosiñol, A. Oriol, M. Mateos, A. Sureda, J. Díaz-Mediavilla, C. Herrero, X. Liu, H. Van de Velde, J. San Miguel, J. Bladé
Journal: Journal of Clinical Oncology (2007)

8024 Background: Dexamethasone-based combinations are the standard induction regimens for younger patients with MM prior ASCT. This is the first study in which bortezomib and dexamethasone were administered on an alternating basis. Aims: efficacy and kinetics of response. Methods: patients with newly diagnosed MM under the age of 66 years were treated with bortezomib at 1.3 mg/m 2 on days 1, 4, 8 and 11 (cycles 1, 3, 5) and dexamethasone 40 mg p.o. on days 1–4, 9–12 and 17–20 (cycles 2, 4 and 6), followed by ASCT with melphalan-200. Responses were evaluated by the EBMT criteria but a VGPR was included. Random effects models were utilized to analyze the tumor response kinetics to bortezomib and dexamethasone with the absolute value of M-protein overtime and decrease by cycle. Because the nonlinearity in the change of M-protein overtime, a piecewise linear model was employed. Results: between August, 2005 and March, 2006, 40 patients (median age 57) were enrolled. The response rate was 82% with 12% CR plus 10% VGPR. The response was quick with 82% M-protein reduction achieved with the first 2 cycles. There was no further decrease of the mean M-protein in cycles 5 and 6. The M-protein decrease was not different with dexamethasone and with bortezomib (p=0.48). Chromosome 13 deletion as well as t(4;14) and t(14;16) did not had a negative impact on response. Toxicity was very low: ten (25%) patients had mild peripheral neuropathy (grade 1:9 cases, grade 2:1 case) and 11 grade 1 thrombocytopenia. Grade 3 toxicity was observed in 7 patients (neutropenia 6, skin/liver 1 case). No patient developed grade 4 toxicity. In all patients stem cells could be adequately collected (median of CD34+ 5 ×10 6 /Kg). The overall response rate after ASCT was 90% with 40% CR plus 20% VGPR. Conclusions: Bortezomib alternating with dexamethasone is highly effective as up-front therapy in patients with MM, and is associated with a very low toxicity. The results of the tumor response kinetics analysis support a short program of alternating bortezomib and dexamethasone (i.e., maximum of 4 cycles) as an effective and safe therapy for younger myeloma patients prior ASCT. [Table: see text]
Sleep disordered breathing detected by a new automated ECG analysis in subjects with insomnia
Authors: Thomas Penzel, Carmen Garcia, Martin Glos, Christoph Schoebel, Martina Sebert, Ingo Fietze
Journal: European Respiratory Journal (2011)

Patients with severe complaints of insomnia are sometimes investigated in a sleep laboratory in order to test for other causes of their complaints such as sleep disordered breathing or other sleep disorders.  We investigated 64 patients with primary insomnia with cardiorespiratory polysomnography. Sleep stages, arousal and respiratory events were scored according to AASM criteria. ECG was analyzed by a special software (Hypnocore) which can provide a sleep evaluation and a respiratory event score by a new automated analysis. All patients were analyzed in two steps. The second analysis was performed on 54 patients after removing those with bad signal quality, arrhythmias and a total sleep time below 3 hours.  The analysis of respiratory events based on ECG in the group of 64 subjects resulted in 52 subjects (48 true negative, 4 false negative) with an RDI0 5/h. Agreement was 0.91. For the second analysis agreement remained the same. Sleep stages in the second analysis were scored surprisingly good: 48.9% (ECG) vs. 48.7% (PSG) for light sleep, 15.7% (ECG) vs. 15.8% (PSG) for slow wave sleep, 14.0% (ECG) vs. 23.4% (PSG) for wake, and 19.9% (ECG) vs. 12.2% (PSG) for REM sleep.  Not many respiratory events occur in insomnia patients. These events are detected with a sufficient accuracy using the new ECG based algorithms. Sleep stage analysis based on ECG did show a good ability to distinguish light sleep, slow wave sleep, and wake/REM sleep. To distinguish wake and REM sleep by ECG alone has a lower accuracy due to high sympathetic activity in both states.