tbuckley/cabot-search huggingface dataset:
The role of neurosis in phylogenetic adaptation, with particular reference to early man
Authors: L Sloman
Journal: American Journal of Psychiatry (1976)

The author hypothesizes that neurosis results from maladaptation and leads to further maladaptation, thus creating a vicious cycle that can be viewed as having played a significant role in human evolution. Individuals who were less successful in the struggle for survival during prehistory would have been more likely to become neurotic, a maladaptation that would magnify existing genetically transmitted differences in their viability and affect both the choice of a mate and the viability of their offspring. This process would have accelerated human evolution by favoring the most viable. The author relates this theory to his concepts of assortative mating and to other theories of the role of neurosis.An hypothesis that neurosis emanates from maladaptation and tends toward further maladaptation, and that individual maladaptation could have played an adaptive role for the human species is presented. Those individuals in prehistory who could not struggle as well for survival as others would have been more likely to develop neuroses, thereby intensifying already existing genetically transmitted differences and affecting the choice of a mate and the viability of offspring. Such a dynamic would hasten human evolution by favoring the most viable individuals. The hypothesis is discussed in relation to the concept of assortative mating and other theories of the role of neurosis.
Abstract P212: Blood pressure lowering and clinical outcomes in patients with acute ischemic stroke: China Antihypertensive Trial in Acute Ischemic Stroke (CATIS)
Authors: Jiang He, Yonghong Zhang, Tan Xu, Qi Zhao, Chung-Shiuan Chen, Weijun Tong, Katherine Mills, Jing Chen
Journal: Circulation (2014)

Introduction: Observational studies have reported that a decrease in blood pressure (BP) within the first several days after stroke onset was associated with poorer, better, or no difference in adverse clinical outcomes among patients with acute ischemic stroke. Hypothesis: We investigated the association of immediate BP lowering in acute ischemic stroke patients with major clinical outcomes at 14 days or hospital discharge and at a 3 month follow-up visit. Methods: CATIS is a randomized clinical trial conducted in 4,071 Chinese patients with ischemic stroke within 48 hours of onset and elevated systolic BP (SBP). Patients were randomly assigned to receive antihypertensive treatment or control. The primary outcome was a combination of death and major disability (a modified Rankin score ≥3) at 14 days or hospital discharge or at the 3 month follow-up visit. Multiple logistic regression analysis was used to adjust for baseline age, gender, SBP, NIHSS score, time of stroke onset, history of antihypertensive treatment, and intervention assignment. Results: Compared to patients with a &gt;0-10% reduction in systolic BP within the first 24 hours after admission, the multivariable-adjusted odds ratios (95% confidence interval [CI]) for patients with ≤0%, 11-20%, and ≥21% reduction in SBP were 1.40 (1.08, 1.82), 1.00 (0.81, 1.23), and 0.98 (0.73, 1.30) at 14 days or hospital discharge; and 1.31 (1.00, 1.71), 0.82 (0.66, 1.02), and 0.78 (0.58, 1.05) at 3 months follow-up. Compared to patients with a BP 130-139/85-89 mmHg at 7 days after admission, the multivariable-adjusted odds ratios (95% CI) for patents with BP &lt;130/85, 140-159/90-99, and ≥160/100 mmHg were 1.07 (0.82, 1.38), 1.09 (0.89, 1.34), and 1.58 (1.18, 2.11) at 14 days or hospital discharge, and 0.89 (0.67, 1.17), 1.10 (0.89, 1.36), and 1.50 (1.11, 2.03) at 3 months follow-up, respectively. Conclusions: These data indicate that a lack of BP reduction in the first 24 hours of hospitalization and higher BP levels at 7 days after admission predict increased risk of death and major disability at 14 days or hospital discharge and at 3 months follow-up.
Evaluation of supportive care needs: Comparison between patients and physicians’ perception
Authors: S. Vignot, M. Delgado, M. Levy-Soussan, L. Taillade, M. Rocher, S. Lopez, J. Lassauniere, J. Spano, D. Khayat
Journal: Journal of Clinical Oncology (2009)

e20649 Background: In order to optimize supportive care for cancer patients, we proposed them to fill a short questionnaire evaluating their potential complaints and we evaluated the concordance of their answers with the perception of their referent physician. Methods: Patients seen in consultation in an oncology unit were proposed to answer anonymously to 7 questions designed to identify potential social, psychological, nutritional problems or uncontrolled pain. Their physician answered to a similar questionnaire. Physicians were blinded to patients’ answers. Results: 155 patients accepted to complete the questionnaire. Median age was 60 yrs [21–85], 45% of patients were in metastatic setting. 70% of patients reported at least one problem, especially in the field of potential social problems (35%) or sleep disorders (25%). Concordance between patients and physicians was high for psychological support need (81%) or nutritional problems (87%) but was lower for social problems (62%) or uncontrolled pain (69%). Physicians tended to underestimate patients’ problems and missed social issues for 30% of patients or sleep disorders for 18% of patients. On the contrary and surprisingly, physicians overestimate patients’ complaints about uncontrolled pain (underestimation in 9% of cases but overestimation in 20% of cases for the item). Conclusions: Discordance between physicians and patients’ perception of supportive care needs emphasizes the importance of extending the use of screening tolls in daily practice. No significant financial relationships to disclose.
Abstract 10957: Combined Assessment of High-Sensitive Troponin I and N-Terminal Pro-B-Type Natriuretic Peptide Levels Improves the Prediction of Cardiovascular Event in Outpatients With Hypertension
Authors: Shigeru Matsui, Junichi Ishii, Hiroshi Takahashi, Ryuunosuke Okuyama, Hideki Kawai, Takashi Muramatsu, Akira Yamada, Sadako Motoyama, Hiroyuki Naruse, Mutsuharu Hayashi, Hideo Izawa, Yukio Ozaki
Journal: Circulation (2015)

Background: Hypertension is one of the most prevalent risk factors in the development of cardiovascular diseases and events. We prospectively investigated the predictive value of a combination of high-sensitive troponin I (hsTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for cardiovascular event in outpatients with hypertension. Methods: Baseline serum levels of hsTnI and NT-proBNP were measured in 701 outpatients (mean age: 68.3 years; male 71%) with hypertension, of whom 30% had a history of cardiovascular disease; 45%, diabetes; and 56%, chronic kidney disease (estimated GFR &lt;60 mL/min/1.73 m 2 ). Left ventricular ejection fraction (LVEF) and E/e’ ratio were estimated using echocardiography with tissue Doppler imaging. Cardiovascular event was defined as cardiovascular death or admission for acute coronary syndrome, decompensated heart failure, or stroke. Results: hsTnI levels significantly correlated with NT-proBNP levels (r = 0.29; p &lt; 0.0001). During a mean follow-up period of 959 days, there were 111 (16%) cardiovascular events, including 16 cardiovascular death cases. Multivariate Cox regression analysis, including 6 clinical, biochemical, and echocardiographic variables, identified increased hsTnI (relative risk: 1.92 per 10-fold increment; p = 0.001) and NT-proBNP levels (relative risk: 2.28 per 10-fold increment; p = 0.0001) as independent predictors of cardiovascular events. Combined hsTnI and NT-proBNP tertiles was significantly associated with cardiovascular event rates (Figure). Furthermore, adding both hsTnI and NT-proBNP levels to a baseline model improved the C-index (0.769 vs. 0.736; p = 0.005), net reclassification improvement (0.387; p &lt; 0.0001), and integrated discrimination improvement (0.044; p = 0.001) greater than a baseline model. Conclusions: The combined assessment of hsTnI and NT-proBNP levels may improve the prediction of cardiovascular event in outpatients with hypertension.
In Vitro Hypersensitivity to Oxygen of Fanconi Anemia (FA) Cells Is Linked to Ex Vivo Evidence for Oxidative Stress in FA Homozygotes and Heterozygotes
Authors: Giovanni Pagano, Ludmila G. Korkina, Paolo Degan, Domenico Del Principe, Barbara Lindau-Shepard, Adriana Zatterale, Claudio Franceschi
Journal: Blood (1997)
Comment on Haroon et al. Risk of Dementia in Seniors With Newly Diagnosed Diabetes: A Population-Based Study. Diabetes Care 2015;38:1868–1875
Authors: Tomoyuki Kawada
Journal: Diabetes Care (2016)

Haroon et al. (1) conducted a cohort study targeting seniors aged 69–78 years with and without diabetes to elucidate the predictors of dementia. They reported that the risk of dementia in patients with diabetes was 16% higher than that in patients without diabetes. I have some queries on their study.

First, hypertension was a protective factor for the incidence of dementia. Although the significance disappeared after adjusting some information on medication, other …
Preclinical <i>in vivo</i> characterization of INCB028060, a novel, potent and highly selective c-Met inhibitor
Authors: H. K. Koblish, X. Liu, L. Hall, J. Boer, C. He, S. Yeleswaram, R. C. Newton, K. Vaddi, W. Yao, P. A. Scherle, J. S. Fridman
Journal: Journal of Clinical Oncology (2008)

14561 Background: c-Met is a receptor tyrosine kinase that exclusively binds Hepatocyte Growth Factor (HGF). Enhanced activity of c-Met, through autocrine stimulation, receptor overexpression or activating mutations, has been correlated with poor prognosis in a variety of human cancers. We sought to identify potent and highly selective c-Met inhibitors that might have therapeutic utility. Methods: INCB028060 exhibits desirable pharmacological and pharmaceutical qualities in a variety of assays. This compound has pM activity in c-Met enzymatic assays, yet remains greater than 10,000-fold selective over a broad sampling of the kinome. The remarkable enzymatic potency translates to nM activity in proliferation, cell migration and soft agar assays. Based on in vitro ADMET properties, potency and selectivity, INCB028060 was selected for characterization in vivo in Met/HGF-driven human and mouse xenograft tumor models. Drug plasma levels were ascertained and correlated with measures of pharmacodynamic activity and tumor growth inhibition. Results: INCB028060 has a favorable pharmacokinetic profile, characterized by low clearance and moderate volume of distribution. Oral doses of INCB028060 of less than 1 mg/kg are sufficient to significantly inhibit tumor c-Met phosphorylation. Tumor growth is inhibited in multiple models with ED50s of <10 mg/kg correlating with decreases in phosphorylated Met and increases in apoptosis. All dose regimens of INCB028060 were well tolerated in these studies. Conclusions: INCB028060 is a potent and highly selective c-Met inhibitor capable of suppressing tumor growth in mice at doses that are extremely well tolerated. This activity combined with a favorable pharmacokinetic profile suggests that compounds such as INCB028060 may have therapeutic utility and should be considered for clinical development. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Incyte Corporation Incyte Corporation
THE LANGUAGE OF HEALTH CARE: Open peer review: a route to democracy
Authors: S. Pharaon
Journal: Journal of the Royal Society of Medicine (2006)

When I contacted your Journal, I discovered that you practice the ‘open peer review system’ and felt happy on reading it. The reason is very simple: it represents a form of ‘democratic practice’ in medicine. Anybody submitting an article can discuss with the peer-reviewer any differences of opinion, without causing any bitter after-sentiments. This will result in convincing views as to what is more appropriate. To illustrate, I wish to narrate a memory about my work in British hospitals. When I worked at St Mary's Hospital, Manchester, I dared to ask my boss, Dr Robert Newton, about his surgical techniques. To my surprise, he was kind, understanding and encouraging! He asked me where I had worked before coming to the British Isles: ‘With Professor Hermann Knaus in Vienna, where we were taught the hard habit of never asking the Chef any question, but only to reply when he asked. In his department, we had to walk in a military-like line, after the Chef.’ The late Bob Newton smiled and assured me that I could safely ask him any question I wanted, and argue as much as I liked.

The open peer review that you practice is a wonderful application of democracy. Why don't other peer-reviewed journals follow this method? Apparently, it is because open peer review can be time-consuming and might cause some headaches...

In life, one should attempt to go by the narrow gate. I do hope all other medical journals would follow suit and adopt this system. Thus will democracy and freedom prevail all over the world.
Identification of the most frequent causes of screening failures (SF) in oncology clinical trials (OCT).
Authors: R. A. Sala, A. Romera, M. C. Micheri, M. I. Diaz, L. E. Fein
Journal: Journal of Clinical Oncology (2010)

e16544 Background: Site recruitment prediction is one of the most important variables in order to reach accrual commitments in OCT. Information about the incidence of the most frequent causes of SF may help sites to accurately predict recruitment and may lead to proper design of recruitment strategies. Methods: Retrospective analysis of the recruitment and clinical records of all the patients that sign informed consent to participate in an OCT at COR from 2005 to 2009 to identify the causes of SF. Results: Total of patients screened: 488. Average age: 60 years (range 36 to 89). 52% women. Total of SF: 146 (29,9%). 117 (80%) patients for not fulfilling an inclusion criteria (IC), see Table. 29 patients (19.8%) for fulfilling an exclusion criteria (presence of metastases 9.59%, cardiovascular disease 4.11%, other concomitant diseases 2.74%, synchronic or history of other malignancies 2.05% and lab abnormalities 1.37%. Discussion: 30% of candidate patients were SF mostly due to inclusion criteria. 57% of these SF (84 patients) were impossible to determine clinically when informed consent was signed and therefore impossible to avoid. 15.7% (22 patients) had an evolutive condition (ECOG progression, acute infections during screening) as a cause of SF that were also unpredictable at the time of informed consent. Biomarker status (HER2, MAGE, Kras, etc.) was the single most important cause of SF. Conclusions: Our results did not identify a predominant modifiable reason to improve recruitment avoiding SF. For future feasibility analyses our estimation of 30% SF will be considered standard but, as targeted therapy development needs specific biomarkers, determination of known or new biomarkers will increase SF due to this cause. Inclusion criteria Total % Receptor or biomarkers 30 20.55 Clinical stage 27 18.49 Laboratory abnormalities 22 15.07 ECOG 18 12.33 RECIST (imaging stage) 10 6.85 Previous treatment 9 6.16 Advanced age 1 0.68 117 80.14 No significant financial relationships to disclose.
Economic evaluation of a randomized clinical trial comparing vinorelbine, vinorelbine plus cisplatin, and vindesine plus cisplatin for non-small-cell lung cancer.
Authors: T J Smith, B E Hillner, D M Neighbors, P A McSorley, T Le Chevalier
Journal: Journal of Clinical Oncology (1995)

PURPOSE To estimate the comparative cost-effectiveness of three regimens for metastatic non-small-cell lung cancer (NSCLC). METHODS Results from a randomized clinical trial of 612 European patients with NSCLC, and cost data from an academic cancer center, the Medical College of Virginia, were analyzed. In this post-hoc economic analysis, we compared vinorelbine alone, vinorelbine plus cisplatin, and a common regimen of vindesine plus cisplatin. RESULTS Vinorelbine plus cisplatin resulted in the longest mean survival time of the three regimens, 49.6 weeks, followed by vindesine plus cisplatin, 44.3 weeks, and vinorelbine, 41.6 weeks. Compared with vinorelbine alone, vinorelbine plus cisplatin added 56 days at a cost of $2,700, resulting in a cost-effectiveness ratio of $17,700 per year of life gained. Similarly, vindesine plus cisplatin added 19 days at a cost of $1,150, or $22,100 per year of life gained. Compared with vindesine plus cisplatin, vinorelbine plus cisplatin added 37 days at a cost of $1,570, or $15,500 per year of life gained. CONCLUSION The most effective regimen of vinorelbine plus cisplatin added substantial benefit compared with vinorelbine alone or another common treatment, vindesine plus cisplatin, at a cost-effectiveness within accepted limits for medical interventions. Vindesine plus cisplatin also added benefit at an acceptable cost per year of life gained. If vinorelbine is preferred because of its toxicity profile, the additional effectiveness of cisplatin added substantial benefit at an acceptable cost. Compared with other common medical interventions, chemotherapy for NSCLC has acceptable efficacy and cost-effectiveness and should not be arbitrarily denied based on clinical or economic grounds.
Does BCR-ABL transcript type predict cytogenetic response to imatinib mesylate in chronic phase, chronic myeloid leukemia patients?
Authors: P. Sharma, L. Kumar, S. Mohanty, S. Bose, V. Kochupillai
Journal: Journal of Clinical Oncology (2007)

7043 Background: We prospectively studied BCR-ABL transcript type (b2a2, b3a2, e1a2 and e19a2 in 100 CML-CP patients treated with Imatinib mesylate therapy and studied their correlation with the cytogenetics responses. Methods: Between Aug, 2004 and Sep, 2006, 100 CML –CP patients (median age was 32 years, range, 11 to 62 years, M: F: 2.5: 1) were treated prospectively with imatinib mesylate 400 mg daily on outpatients. 70 patients were pre-treated with interferon Alfa. The mean duration of Gleevec treatment was 24 months (range 3 to 38 months). Patients were monitored closely for clinical, hematological, cytogenetic &amp; molecular response as per standard guidelines. Bone marrow was studied at 3, 6, 9 then 4–6 months interval for cytogenetic response (CGR) and also for the presence of BCR-ABL transcript types by multiplex and nested RT-PCR technique. Results: 96% of patients achieved complete hematological remission (CHR); median time being 21 days, ranging from 7 to 110 days. 60% of patients achieved Major CGR (complete 32, partial CGR-28); median time 8 months, ranging from 6 to 22 months. Previously untreated patients had higher major (70% vs 55.7%) and complete (46.6% vs 25.7%) CGR compared to patients previously treated with interferon alfa. Analysis for BCR-ABL transcript type revealed - b2a2 in 38%, b3a2 -54% and both in 8% of patients. 28 of 38(74%) patients with b2a2 type acieved Major CGR compared to 24 of 54 (44%) patients with b3a2 transcript, p&lt;0.002. Of remaining 40 patients with minor or no CGR, 10(25%) had b2a2 compared to 30 (75 %) b3a2 type, p&lt;.002. However, there was no significant correlation between transcript type and pre-treatment characteristics e.g. spleen size (in cm), Hb (G/dl), WBC &amp; platelets counts. Conclusions: Present study suggests that site of breakpoint in major breakpoint cluster region might be predictive of cytogenetic responses to Imatinib Mesylate in CML patients. No significant financial relationships to disclose.
A phase I dose-escalation and pharmacokinetic (PK) study of sunitinib (SU) plus docetaxel (D) in patients (pts) with advanced solid tumors (STs)
Authors: F. Robert, A. Sandler, J. H. Schiller, J. Ilagan, W. VerMeulen, K. Harper, G. Liu, L. Tye, R. Chao, A. Traynor
Journal: Journal of Clinical Oncology (2007)

3543 Background: SU is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET and FLT3, approved multinationally for the treatment of advanced RCC and imatinib-resistant or -intolerant GIST. In mouse xenograft models of breast cancer, SU enhanced the antitumor activity of D. This study was designed to assess the safety/maximum tolerated doses (MTDs), PK profile and preliminary efficacy of SU+D in pts with advanced STs. Methods: This is a phase I, dose-finding study in pts with advanced STs. The primary objective is to determine the MTD and safety of SU and D administered in combination. Successive cohorts of pts with advanced STs were to receive oral SU at 25, 37.5 or 50 mg daily for 4 wks of a 6-wk cycle (4/2 schedule) or for 2 wks of a 3-wk cycle (2/1 schedule) in combination with IV D at 60 or 75 mg/m 2 every 21 days (q21d). The MTD was defined as the highest dose at which 0 of 3 or 1 of 6 pts encountered dose-limiting toxicities (DLTs) during cycle 1. Antitumor activity was assessed by CT or MRI scan. Results: 37 pts (most common primary tumor types: mRCC [n=10], NSCLC [n=13]) have been enrolled as of Nov. 2006: 10 pts on the 4/2 schedule and 27 pts on the 2/1 schedule (see table ). The most commonly observed DLT was neutropenia (with or without fever; maximum grade 4), which occurred in 5 pts and was manageable/reversible. There was 1 grade 5 event on the 2/1 schedule (C1D3), of pulseless electrical activity and pulmonary hemorrhage. The MTDs on the 4/2 schedule were SU 25 mg and D 60 mg/m 2 . The MTDs on the 2/1 schedule were SU 37.5 mg and D 75 mg/m 2 ; PK analysis at this dose level is ongoing. Stable disease has been observed in 5 of 9 evaluable pts (56%) on the 4/2 schedule and 20 of 25 evaluable pts (80%) on the 2/1 schedule at the MTD. Conclusions: The combination of oral SU 37.5 mg/day on the 2/1 schedule with D 75 mg/m 2 IV q21d has a manageable safety profile in pts with advanced STs. PK and preliminary efficacy analyses are ongoing to support these dosing combinations for further study. [Table: see text] No significant financial relationships to disclose.
A fractionated schedule of oral vinorelbine (NVBo) with cisplatin (CDDP) concomitantly with radiotherapy (RT) after induction chemotherapy (CT) in locally advanced (LA) non-small cell lung cancer (NSCLC): Safety and efficacy results of a phase II trial
Authors: D. Lerouge, R. Gervais, E. Dansin, C. Dujon, C. Chouaid, A. Riviere, B. Precheur-Agulhon, V. Piolat, G. Zalcman, E. Lartigau
Journal: Journal of Clinical Oncology (2009)

7539 Background: NVB+CDDP as induction and concomitant regimen with RT is a recognized treatment in LA NSCLC (Vokes, J Clin Oncol. 2002). The oral formulation of NVB may simplify the administration and a new fractionated schedule may further improve the results during CT-RT. Methods: Non operable stage IIIA-IIIB NSCLC patients (pts) received an induction CT of 2 cycles of NVBiv 25 mg/m 2 + CDDP 80 mg/m 2 on D1 and NVBo 60mg/m 2 on D8 every 3 weeks. Non progressive pts received 2 additional cycles of fixed dose NVBo of 20 mg on D1, D3 and D5, + CDDP 80 mg/m 2 on D1 every 3 weeks, combined with a conformal RT at 66 Gy. Results: Between October 05 and May 08, 70 pts were enrolled (68 evaluable for the safety, 64 for response) : 28% stage IIIA, 72% IIIB; 44 % squamous, 30 % adenocarcinoma; 85% male; median age 61 years (range 41;73); median KPS 90%. After induction CT, OR was 42% (PR), Disease Control (DC) = 87%. 4 pts were down-staged and underwent surgery. After CT-RT completion, OR was 55% (CR = 7%), DC = 88%. Main Toxicities (G3–4, % of pts) were: neutropenia (19%), N/V (1%), radic pneumopathy (1%), anorexia (7%). Oesophagitis was recorded in 42% of pts with no G3–4 : G1 (26%), G2 (16%). Conclusions: This new schedule provides a disease control in 88% of pts with 55% OR. Given the optimal tolerance profile of this fractionated administration of NVBo+CDDP, 72% of pts could complete the planned treatment. Furthermore, NVBo taken at home at D3 and D5 reduces the organizational constraints linked to CT-RT. This new scheme offers a well tolerated and efficient therapeutic option in the treatment of non operable IIIA-IIIB NSCLC. Further follow-up is required in order to assess time to progression and survival. [Table: see text]