tbuckley/cabot-search huggingface dataset:
Abstract 19104: The Relationship of Parent Well-Being, Family Management, and Service Utilization in Families of Children With Hypoplastic Left Heart Syndrome From the Perspective of Mothers and Fathers
Authors: Ross T Ballantyne, Tamara Dorfman, Nicole Dahl, Laura Rogers, Joyce Magill-Evans, Andrew Mackie, Gwen Rempel
Journal: Circulation (2013)

Background: Given the prevelance of neurodevelopmental impairments in children with hypoplastic left heart syndrome (HLHS), and recommendations that they have early intervention, parents’ patterns of service utilization for their at-risk child warrants investigation. The purpose of this study was to (1) delineate parent, child, and family needs from the perspective of parents, and (2) identify the services and resources used and needed by parents to support themselves, their children, and their family. Method: Descriptive study employing the Family Management Measure (FaMM), Connor-Davison Resilience Scale (CD-RISC), Parenting Stress Index (PSI), Vineland Adaptive Behaviour Scales (VABS) and Education and Rehabilitation Services Questionnaire (ERSQ). Findings: Questionnaires were sent to 64 families. Thirty-four parents, 21 mothers and 13 fathers, from 22 families returned questionnaires ( 38% response rate). Mean age of the children was 4.81 years (range 13 months to 15 years). There was no significant difference between the resilience of mothers and fathers, with 5/32 (19%) scoring in the post-traumatic stress category. For parenting stress, 10 of 30 (33%) of parents scored in the clinically significant range. Ten of 24 (41%) parents fell into the problematic family management category. Half of the children on the Vineland had typical or above average mean scores. Four of the 22 children living with severe morbidities were receiving education and rehabilitation services. Children with mild to moderate morbidities, including inattention, learning and behavior difficulties, progressive hearing loss and sensory issues, were not receiving adequate services. Minimal community-based services for parents were reported. Conclusion: The presence of an impairment such as HLHS does not predict service needs or outcomes from a functional perspective. Rather, persistent comorbidities have distinct meaning for each child, parent, and family. Therefore, when considering intervention for both the child and the parent, it is important to consider parents’ perceptions the child’s limitations and community participation and how these perceptions influence their parenting processes, especially related to service utilization.
Phase 1 trial of metronomic cyclophosphamide (CTX), bevacizumab (BV) and imatinib (IM) in patients (pts) with advanced solid tumors
Authors: E. K. Bergsland, A. H. Ko, M. A. Tempero, K. Whittaker, T. Weber, L. Fong, J. W. Park, B. M. Yeh, D. Hanahan, A. P. Venook
Journal: Journal of Clinical Oncology (2008)

14620 Background: Low-dose chemotherapy without scheduled breaks (metronomic chemotherapy) is thought to be anti-angiogenic. Inhibitors of the VEGF and the PDGF signaling pathways may augment this effect. We initiated a prospective, phase I pharmacokinetic (PK) and biomarker study to assess the safety of a rationally designed combination anti-angiogenesis strategy consisting of metronomic CTX, BV (anti-VEGF antibody), and IM (PDGF-receptor inhibitor). Methods: Cycle length was 28 days. Doses: BV 5 mg/kg IV q 14 d, CTX 25–50 mg PO QD, IM 400–800 mg PO QD. DLT was defined as any treatment (tx)-related grade 4 hematologic or grade 3/4 non-hematologic event during cycle 1. Quantification of circulating tumor cells (CTC), endothelial cells (CEC, aEC) and endothelial progenitor cells (EPC) was performed. Parameters measured by CT perfusion were assessed. Results: 13 pts with metastatic colorectal cancer have been enrolled: M/ F= 7/6; ECOG PS 0/1= 8/5; median age=56 (range 33–68). All pts had received prior BV and had disease refractory to standard chemotherapy. Pts have received tx for a median of 56 days (range 28–252 days); 1 cycle (3 pts), 2 cycles (7 pts) and 7+ cycles (2 pts). Dose level 0 (DL 0) was expanded to 6 pts after 1/3 initial pts was removed from the study for a Gr 2 gastrointestinal fistula (after cycle 1). DL+1 and DL+2 had no DLT’s. 1 pt has been enrolled on DL+3. The MTD has not been reached. Tx has been well tolerated; there have been no tx-related Gr 3/4 toxicites. The most common tx-related AE’s have been Gr 1/2 nausea, vomiting, and rash. Two pts (DL 0, DL+1) demonstrated SD lasting > 6 months; 1 pt had a 19% decrease in target lesions by RECIST. Conclusions: The combination of metronomic CTX, IM, and BV can be safely administered. Class related side effects have been seen. Preliminary clinical activity has been observed in a heavily-pretreated patient population. Enrollment to this study continues, with CTX and IM PK to be performed at the MTD. Updated clinical and biomarker data will be presented. Dose Levels DL CTX (D1- 28) IM (D1–28) BV (D1,15) 0 25 mg PO QD 400 mg PO QD 5 mg/kg IV +1 50 mg PO QD 400 mg PO QD 5 mg/kg IV +2 50 mg PO QD 300 mg PO BID 5 mg/kg IV +3 50 mg PO QD 400 mg PO BID 5 mg/kg IV Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech, Genentech™ BioOncology, Johnson & Johnson, sanofi-aventis Genentech™ BioOncology, Johnson & Johnson Genentech™ BioOncology, Novartis
Poor quality animal studies cause clinical trials to follow false leads
Authors: Nigel Hawkes
Journal: BMJ (2015)

A lack of rigour in animal studies is damaging the quality of research and can send clinical trials up blind alleys, wasting time and money, an international study has found.1

The findings were echoed in a second, unconnected study from McGill University in Montreal, Canada, which showed that animal trials of the kidney cancer drug sunitinib (Sutent) overestimated its effect by 45%.2

Both teams concluded that improvements are needed in how preclinical studies in animals are planned, organised, and published. Malcolm Macleod, of the University of Edinburgh, UK, who was lead author of the first study, told a briefing at the Science Media Centre in London that these methods were no secret, as they are already used in clinical trials in humans: randomisation, blinding, sample size calculations, and declarations of interest, for example.

Macleod and colleagues1 used three …
Informed consent: Timely issues from the past. Factors motivating patients with advanced cancer to participate in phase II trials
Authors: C. G. Kardinal, J. B. Sanders, H. T. Cupper
Journal: Journal of Clinical Oncology (2009)

e20669 Background: The current regulatory burden is well intentioned, but hampers both the conduct and recruitment to clinical trials. What factors actually motivate patients to become research subjects? After “informed consent” is obtained, what is the subject's understanding of the study, and its risks and benefits? Methods: In 1973 data were collected on the factors motivating 50 consecutive patients with advanced cancer to participate in Phase II trials. The data had not been previously analyzed. Now, 35 years later, the data obtained seem surprisingly current. These patients were interviewed a few days after obtaining “informed consent”. The 60 minute interviews were semi-structured, and included the factors motivating participation, the purpose of the trial, potential side effects, and treatment options. Results: Patients seldom expressed a single reason for participation. The motivating factors fell into 5 categories. (1) Hope that the new treatment would help control their disease; expressed by all 50. (2) Avoidance of regret; i.e, if they declined they would regret not having participated (19 of 50). (3) Altruism was expressed by 29 of the 50. (4) Trust that a physician-investigator would not have suggested the trial unless he thought it might help (10 of 50). (5) Being trapped by a lack of therapeutic alternatives (14 of the 50). Potential risks and side effects were minimized or forgotten. Many developed a sense of commitment to a cause; their morale improved even if their disease did not. Conclusions: The factors motivating patients with advanced cancer to participate in Phase II trials are complex, but evolve primarily around their personal disease status rather than their understanding of the trial. Truly informed consent in this vulnerable patient population may not be possible. The ultimate responsibility for the protection of human subjects lies not with the IRB, but with the physician investigator. No significant financial relationships to disclose.
Laboratory automation in clinical bacteriology: what system to choose?
Authors: A. Croxatto, G. Prod'hom, F. Faverjon, Y. Rochais, G. Greub
Journal: Clinical Microbiology and Infection (2016)

Automation was introduced many years ago in several diagnostic disciplines such as chemistry, haematology and molecular biology. The first laboratory automation system for clinical bacteriology was released in 2006, and it rapidly proved its value by increasing productivity, allowing a continuous increase in sample volumes despite limited budgets and personnel shortages. Today, two major manufacturers, BD Kiestra and Copan, are commercializing partial or complete laboratory automation systems for bacteriology. The laboratory automation systems are rapidly evolving to provide improved hardware and software solutions to optimize laboratory efficiency. However, the complex parameters of the laboratory and automation systems must be considered to determine the best system for each given laboratory. We address several topics on laboratory automation that may help clinical bacteriologists to understand the particularities and operative modalities of the different systems. We present (a) a comparison of the engineering and technical features of the various elements composing the two different automated systems currently available, (b) the system workflows of partial and complete laboratory automation, which define the basis for laboratory reorganization required to optimize system efficiency, (c) the concept of digital imaging and telebacteriology, (d) the connectivity of laboratory automation to the laboratory information system, (e) the general advantages and disadvantages as well as the expected impacts provided by laboratory automation and (f) the laboratory data required to conduct a workflow assessment to determine the best configuration of an automated system for the laboratory activities and specificities.
Chromosome Changes in Hodgkin's Disease&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: G. S. F. Seif, A. I. Spriggs
Journal: JNCI Journal of the National Cancer Institute (1967)

Chromosomes were examined in lymph-node biopsies from 6 cases of classical Hodgkin's disease, 1 of paragranuloma, and 1 of a probably related lymphadenopathy. Direct preparations were used as well as 16- and 72-hour cultures. Stained imprint preparations were also studied to identify which types of cell were dividing. In 5 cases {including the paragranuloma) hypotetraploid cells were found, twice with long marker chromosomes. These apparently corresponded to the neoplastic reticulum cells. In all of them, seemingly normal diploid cells, probably dividing plasma cells, were also present. In 2, some diploid cells showed a possible deletion of the long arms of a 17–18 chromosome. In 2 cases of typical Hodgkin's disease, all the cells analyzed were diploid and hypodiploid. In the 1 atypical case, a single analyzed cell had 48 chromosomes, with missing as well as extra chromosomes. Lymph nodes showing reactive hyperplasia were used as controls, and these had only diploid and hypodiploid cells. Because of this and other series, it is concluded that the usual picture in classical Hodgkin's disease is of 2 dividing cell populations: neoplastic cells with abnormal chromosome sets that are generally hypotetraploid and normal diploid cells corresponding to the immune or inflammatory reaction.
Ultrastructural Observations on an Unidentified Cell Type Found in Epidermal Tumors of Flounders&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R E Brooks, G E McArn, S R Wellings
Journal: JNCI Journal of the National Cancer Institute (1969)

The ultrastructure of an unknown cell type found in skin tumors of flounders is illustrated and described. The unknown cell is characterized by membrane-bound, pleomorphic, cytoplasmic granules; large mitochondria with small, round cristae; and prominent nucleoli. This cell type appears in both the stromal and epidermal portions of the tumors. Some of these unknown cells have an extracellular cell coat relatively thick, about 500 A, on cells in the stroma, but, when present on cells in the epidermis, less than one-half that thickness. In the stroma, the unknown cells frequently occur in closely connected pairs and occasionally as linked triplets or quadruplets. The unknown cell is morphologically different from any cell found in normal fish epidermis or dermis. The possibility that this cell is an altered fish cell or a unicellular parasite of unknown type is discussed.
Pemetrexed in advanced non-small cell lung cancer: A randomized trial of 500 mg/m<sup>2</sup> vs 900 mg/m<sup>2</sup> in 588 patients who progressed after platinum-containing chemotherapy
Authors: M. Cullen, P. Zatloukal, S. Sörenson, S. Novello, J. R. Fischer, A. Joy, M. Zereu, P. Peterson, C. Visseren-Grul, N. Iscoe
Journal: Journal of Clinical Oncology (2007)

LBA7727 Introduction: The mild toxicity profile of pemetrexed (P), seen in a phase III trial of P 500 mg/m 2 vs docetaxel 75 mg/m 2 in vitamin-supplemented patients (pts), suggests higher doses of P can be given in pts with previously treated advanced non-small cell lung cancer (NSCLC) without significant toxicity. We conducted a phase III trial to determine if a higher dose of P (900 mg/m 2 ) could improve survival vs the standard P dose in pts with NSCLC. Methods: Pts with stage III/IV NSCLC, previously treated with platinum-based chemotherapy, were randomized to P 500 or 900 mg/m 2 iv q3week. After the second planned interim analysis, the Data Safety Monitoring Board recommended discontinuation of enrollment due to low probability of demonstrating a survival advantage and a greater incidence of some toxicities on the P 900 arm. Patients were allowed to continue treatment at the P 500 dose. Results: 588 randomized pts were evaluated for efficacy and 581 pts, who received =1 dose, for safety. Safety data for pts who transitioned from P 900 to P 500 were analyzed separately. The treatment arms were balanced regarding baseline characteristics and prior treatment. Both arms had: ∼67% males, median age 62 yrs, 87% pts with an ECOG PS of 0 or 1, and 77% pts with stage IV disease. Key results are shown in the table . There was no statistical difference between arms for any efficacy measure. In general, the incidence of adverse events (AEs) was comparable or numerically higher in the P 900 arm. Some AEs (all grades) reported a &gt;5% difference between the P 900 (N=240) and P 500 arms: fatigue (41.7% vs 32.8%), anemia (32.9% vs 22.1%), vomiting (20.0% vs 13.1%), stomatitis (17.9% vs 10.0%), diarrhea (15.4% vs 10.0%), and thrombocytopenia (11.3% vs 5.5%). Conclusion: P 900 offers no advantage over P 500 mg/m 2 as second-line therapy for pts with advanced NSCLC. Certain toxicities were somewhat more pronounced in the P 900 group. No significant financial relationships to disclose. [Table: see text]
BMA defends decision to end GPs’ responsibility for care home residents
Authors: Matthew Limb
Journal: BMJ (2016)

The BMA has denied looking to offload GPs’ responsibility for care home residents after a conference vote to seek separate contractual arrangements covering services for this group of patients.

Chaand Nagpaul, who chairs the BMA’s General Practitioners Committee, said that the decision by the conference of local medical committees, the bodies that represent GPs, showed that GPs were “overstretched” and that the current contract was resulting in a “piecemeal service.”

He said that GPs wanted to ensure that care home patients, …
Induction chemotherapy followed by alternating chemo-radiotherapy in advanced undifferentiated nasopharyngeal carcinoma (UNPC)
Authors: A. Ponzanelli, V. Vigo, A. Bacigalupo, M. Marcenaro, M. Benasso
Journal: Journal of Clinical Oncology (2006)

15508 Background: Concomitant chemo-radiotherapy is the standard treatment for advanced UNPC. Induction chemotherapy may improve the results further by enhancing both locoregional and distant control. Methods: Fifty patients with previously untreated, locoregionally advanced UNPC were initially treated with 3 courses of epidoxorubicin, 90 mg/mq, day 1 and cisplatin, 40 mg/mq, days 1 and 2, every 3 weeks. After a radiological and clinical response assessment patients underwent 3 courses of cisplatin, 20 mg/mq/day, days 1–4 and fluorouracil, 200 mg/mq/day, days 1–4, i.v. bolus, (weeks 1,4,7) alternated to 3 splits of radiation (week 2–3, 5–6, 8–9-10), with a standard fractionation, up to 70 Gy. Histology was WHO type 1 in 1 pt (2%), WHO type 2 in 10 pt (20%), WHO type 3 in 39 pts (78%). All patients had stage IV disease (UICC 1992). Results: All the patients are evaluable for toxicity and response. All but one received 3 cycles of induction chemotherapy. Toxicities from induction chemoyherapy were: 2% grade 3 or 4 mucositis, 22% grade 3 or 4 nausea/vomiting, 6% grade 3 or 4 haematological toxicity and one episode of febrile neutropenia. At the end of induction phase 12% of CRs, 84% of PRs and 4% of SD were recorded. All patients but two had the planned number of chemotherapy courses in the alternating phase and all but one received the planned radiation dose. Toxicities from alternating chemo-radiotherapy were: 28% grade 3 or 4 mucositis, 8% grade 3 or 4 nausea/vomiting, 24% grade 3 or 4 haematological toxicity with no episodes of febrile neutropenia. At the final response evaluation 86% of CRs and 14% of PRs were observed. At a median follow up of 39 months, 14% of patients had locoregional failure, 20% had distant failure and 2% both. The 4-year actuarial progression free survival and overall survival rates were 71% and 81%. Conclusions: Treatment of locoregionally advanced UNPC with induction chemotherapy followed by alternating chemo-radiotherapy is feasible and patients’ compliance is optimal. 4-year outcomes seems better than those reported with concomitant chemo-radiotherapy alone. No significant financial relationships to disclose.
Systemic Effects of Intravenous Polyriboinosinic-Polyribocytidylic Acid in Man 2
Authors: Cornelius J. Cornell, Kendall A. Smith, Gibbons G. Cornwell, Gregory P. Burke, O. Ross McIntyre
Journal: JNCI Journal of the National Cancer Institute (1976)

To investigate the systemic, clinical, and laboratory effects of iv polyriboinosinic-polyribocytidylic acid (I·poly C), 32 doses of I·poly C were administered to 22 patients. Doses between 1 and 10 mg/kg induced the formation of serum interferon (IF) and fever. Whereas a direct relationship was seen between the I·poly C dose and fever, serum IF levels were not significantly changed by increasing the dose of I·poly C over a log range from 1 to 10 mg/kg. Transient abnormalities were noted In liver function tests in 4 of 13 patients who received greater than 6.0 mg/kg. Other laboratory changes were confined to an increase in the absolute granulocyte count that paralleled fever development and abnormalities in coagulation parameters of 1 patient. In vitro lymphocyte DNA synthesis in response to mitogens was transiently impaired at times corresponding to serum IF appearance. These studies have established dose levels of I·poly C that can be safely administered to man with minimal toxicity and result in IF induction.
Coexisting childhood schizophrenia and myasthenia gravis treated successfully with neostigmine bromide
Authors: R C Schnackenberg, G Holmes
Journal: American Journal of Psychiatry (1977)

A 12-year-old boy who had suffered from severe schizophrenia for 8 years developed myasthenia gravis. Both disorders were treated simultaneously and successfully with neostigmine bromide. The authors suggest that these two disorders may in some cases be part of the same disease process and urge that physicians consider this possibility in patients with severe emotional problems and muscle weakness.
A pharmacological intervention with varenicline among a lung cancer LDCT screening trial: The MILD experience
Authors: Paolo Pozzi, Elena Munarini, Roberto Boffi, Ugo Pastorino
Journal: European Respiratory Journal (2012)

Introduction: Low dose CT screening (LDCT) for lung cancer may be a teachable moment for smoking cessation (SC),but no pharmacological intervention has been performed in LDCT trials.  Aim: A three-month Varenicline course in a group of patients (Pts) enrolled in the Milan Lung Detection Trial,with biochemical verification of the smoking status.  Matherials and Methods: 187 Pts received Varenicline;43% and 32% of them were allocated to 1 vs 2-year LDCT,while 25% to minimal SC advice and no LDCT (Ctrl).Lung function testings (PFTs),exhaled carbon monoxide (CO) and side effects were longitudinally recorded.Pts with a CO ≤6 ppm were considered abstinent.Descriptive statistic as well as parametric and non-parametric tests were performed.  Results: Pts were 61±5.2 years old,with a mean CO of 16.3±7.9 ppm,a smoking history of 22.2±21.9 pack/years,a Fagerstrom test of 7.5±2.2 points and a slight decrease in mean FEV1% (84.1±14.6).Global quit rates were 51.7%, 50.7% and 41.8% on month 1,3,6 respectively;quit rates were equal in LDCT subgroups but they were lower in the subgroup of Pts with FEV1%≥70  Conclusion: A pharmacological intervention within a LDCT trial can lead to rewarding percentages of SC. Mild function impairment poses a higher risk of continuative smoking, while being in an active LDCT arm may result in stronger smoking intensity over time.