tbuckley/cabot-search huggingface dataset:
A Primary Role for Nucleus Accumbens and Related Limbic Network in Vocal Tics
Authors: Kevin W. McCairn, Yuji Nagai, Yukiko Hori, Taihei Ninomiya, Erika Kikuchi, Ju-Young Lee, Tetsuya Suhara, Atsushi Iriki, Takafumi Minamimoto, Masahiko Takada, Masaki Isoda, Masayuki Matsumoto
Journal: Neuron (2016)
Development of core competencies in drug development in medical oncology: An unexplored field
Authors: I. Duran, L. L. Siu, A. Jimeno, D. Panisko, L. Seymour
Journal: Journal of Clinical Oncology (2008)

13516 Background: The field of drug development (DD) has emerged within medical oncology and many specialists have been trained in this discipline. However, no published document (outside of the clinical pharmacology literature) provides a structural framework from which a curriculum could be developed and no programs have formally defined how knowledge, skills and attitude acquisition of trainees might be evaluated. Methods: A questionnaire was developed and a modified Delphi technique used to look for consensus on the essential elements for a model of core competencies in DD. This survey was sent out to international medical oncologists and pharmaceutical-based leaders with expertise and teaching experience in DD. Through a five-point Likert scale (1=completely disagree; 5=completely agree), 137 items in 12 domains were assessed. For each item, two endpoints were defined: an “average score” which represents the mean rating by all respondents, and a “unanimity score” which represents the percentage of items within a domain rated ≥4 by all respondents. Results: Of 43 sent surveys, 31 were returned (response rate: 72%). Overall a remarkable amount of agreement was observed in most domains related to clinical trials methodology, principles of DD, ethics, pharmacokinetics, pharmacodynamics, statistics and patient care. The average score was ≥4 for 100% of items in these domains and the unanimity score >50%, indicating strong consensus on their incorporation into a DD curriculum. More heterogeneous responses were noted in the domains of practical skills acquisition, continuing medical education and manuscript/grant writing. For these, the average score was ≥4 for 75–99% of items and the unanimity score <50%. Interestingly, pharmacodynamic topics such as tissue procurement and functional imaging were in this group with only 78% of items scoring ≥4 and a unanimity score of 26%. Data management and regulatory/industry-related concepts scored lowest. Conclusions: This survey represents the first formal approach communicated in the literature attempting to identify core competencies in DD in medical oncology. Substantial agreement observed among respondents represents a clear opportunity to formalize a consensus document to be implemented in the teaching of this discipline. No significant financial relationships to disclose.
Mutagen Sensitivity (MS) may predict lung protection by amifostine for patients with locally advanced non-small cell lung cancer (NSCLC) treated by chemoradiotherapy
Authors: R. Komaki, M. R. Spitz, X. Wu, J. Y. Chang, P. K. Allen, M. Lika, F. V. Fossella, C. W. Stevens, Z. Liao, J. D. Cox
Journal: Journal of Clinical Oncology (2004)

7232 Background: Amifostine (AMF) has been shown to protect some normal tissues from acute effects of radiation therapy ± chemotherapy. We enrolled 62 pts in a randomized study investigating the efficacy of AMF: 31 had concurrent chemoradiation for NSCLC and 31 had the same treatment + AMF. AMF reduced the severity or frequency of esophagitis, pneumonitis and neutropenic fever. It was hypothesized that DNA repair capacity could predict outcome. Methods: Forty-six out of the 62 pts provided pretreatment blood for assessment of MS using a peripheral lymphocyte assay that infers DNA repair capacity from cellular damage remaining after in vitro mutagenic exposure and recovery. Bleomycin-induced chromosome breaks in 50 metaphases were counted and expressed as the mean number of breaks/cell. Pts with an average of >1 break/cell were deemed to exhibit the MS phenotype. Data analysis used Pearson's chi square and Kaplan-Meier survival function estimates with Strata 8.2 statistical software. The Log Rank test was used to assess the equality of survival function using a p-value of 0.05. Results: Twelve patients (10 AMF, 2 control) exhibited the MS phenotype. The remaining 34 pts (13 AMF, 21 control) were considered to have normal DNA repair. There were no significant differences in overall survival, disease specific survival, or local control by MS. Those with MS had shorter distant metastasis-free survival (DMFS) compared to nonsensitive pts (p=0.029). There were no differences in severe esophagitis or neutropenic fever by MS. Both MS pts from the control group developed severe lung fibrosis compared with 5 of 21 who did not have MS (p=0.025). The incidence of grade 3–4 lung fibrosis was 2/10 with AMF compared with 2/2 in the control group (p=0.025) with MS. Conclusions: MS was associated with shorter DMFS and more frequent Gr 3–4 lung fibrosis. AMF reduced the incidence of Gr 3–4 lung fibrosis. These data suggest that MS might help identify subgroups of pts who could derive benefit from AMF with respect to lung damage. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MedImmune
Shear-wave elastography in detection of residual breast cancer after neoadjuvant chemotherapy.
Authors: Su Hyun Lee, Jung Min Chang, Nariya Cho, Woo Kyung Moon
Journal: Journal of Clinical Oncology (2014)

102 Background: To evaluate the accuracy of shear-wave elastography (SWE) in detecting residual cancer after neoadjuvant chemotherapy. Methods: This retrospective study was approved by our institutional review board and the requirement for written informed consent was waived. From January 2012 to February 2013, 71 women with stage II-III invasive breast cancers who received neoadjuvant chemotherapy and were imaged with B-mode ultrasonography (US), SWE, and magnetic resonance (MR) imaging before surgery were included. Presence of residual cancer was evaluated and categorized according to the morphology on preoperative B-mode US and MR imaging. Quantitative elasticity values (maximum kPa) were acquired for primary lesions depicted on US. Pathological complete response (pCR) was defined as no residual invasive cancer cells. The quantitative SWE values were compared between the pCR and non-pCR group using independent samples t-test. The areas under the receiver operating characteristics curve (AUC), sensitivities, and specificities of B-mode US, MR, and SWE for detecting residual cancer were compared, with histopathologic examination as the reference standard. Results: Of the 71 women, 15 (21%) achieved pCR. The mean size of residual invasive cancers was 2.2 cm (range 0.1-6.4 cm).The maximum SWE value was significantly higher in the non-pCR group (mean, 122.9 kPa) than in the pCR group (30.6 kPa) (P &lt; 0.001). The AUC of SWE for detecting residual cancer (0.893) was higher than that of B-mode US (0.684) (P = 0.001) and comparable to that of MR (0.884) (P = 0.825). The optimal cut-off value, yielding the maximal sum of sensitivity and specificity, was 98.1 kPa, and the sensitivity and specificity of SWE at that cut-off value were 66% (37 of 56) and 100% (15 of 15). When SWE was added to B-mode US, the AUC value was significantly increased to 0.830 (P = 0.039). Conclusions: SWE was accurate in the detection of residual cancer after neoadjuvant chemotherapy. When SWE was combined with B-mode US, the accuracy was significantly improved.
Identifying clinically relevant prognostic subgroups in node-positive postmenopausal HR+ early breast cancer patients treated with endocrine therapy: A combined analysis of 2,485 patients from ABCSG-8 and ATAC using the PAM50 risk of recurrence (ROR) score and intrinsic subtype.
Authors: Michael Gnant, Mitchell Dowsett, Martin Filipits, Elena Lopez-Knowles, Richard Greil, Marija Balic, John W Cowens, Torsten O. Nielsen, Carl Shaper, Ivana Sestak, Christian Fesl, Jack M. Cuzick
Journal: Journal of Clinical Oncology (2013)

506 Background: Most postmenopausal women with node positive HR+ EBC receive adjuvant chemotherapy. We hypothesized that a molecular-based characterization of residual risk after endocrine therapy using the ROR score and IS may identify node-positive patient subgroups with limited long-term recurrence risk after endocrine therapy better than clinical-pathological risk assessment by clinical treatment score (CTS) alone. Methods: Long-term follow-up and tissue samples were obtained from 2,485 postmenopausal HR+ patients from the ABCSG-8 (N=1,478) and transATAC (N=1,007) trials. The PAM50 test was conducted on RNA extracted from paraffin blocks using the NanoString nCounter Analysis system. The ability of ROR, IS and ROR-defined risk groups (ROR-RG) to add prognostic information to CTS was assessed by the likelihood ratio test in a prospectively defined analysis plan. Results: Patients in the combined data set were grouped by the number of positive nodes into 1 (N1), 2 (N2), or 2 or 3 (N2-3),Baseline hazards for these subgroups were similar in the two trials. ROR score, IS and ROR-RG added statistically significant prognostic information (10-year distant recurrence risk) beyond CTS in all groups. In patients with one positive node, the absolute 10-year risk of distant recurrence was 6.6% [95% CI: 3.3%-12.8%] in the PAM-50-low risk group (40% of patients) and 8.4 % [5.3%-13.3%] in the Luminal A subgroup (69% of patients). Conclusions: The results of this combined analysis demonstrate that a significant proportion of N1 EBC patients have very limited long term recurrence risk and suggest the same for some N2 patients. The PAM50 ROR score, IS and ROR-RG reliably provide additional prognostic information beyond CTS and may be useful in deciding which women with node-positive HR+ EBC can be spared adjuvant chemotherapy. [Table: see text]
Is nutritional status correlated with quality of life measures in advanced colorectal cancer?
Authors: C. G. Lis, D. Gupta, C. A. Lammersfeld, P. G. Vashi, J. L. Burrows, S. L. Dahlk, J. F. Grutsch, S. Williams
Journal: Journal of Clinical Oncology (2005)

3728 Background: Malnutrition is a frequent complication in advanced colorectal cancer and is a significant cause of morbidity and mortality. While nutritional status has been hypothesized to have a positive impact on Quality of Life (QoL), little is known about the relationship between the two. We investigated if nutritional status is associated with QoL in advanced colorectal cancer. Methods: A case series of 58 stage III-IV colorectal cancer treated at Cancer Treatment Centers of America between 03/01 and 01/03. Nutritional status was evaluated using Subjective Global Assessment (SGA). QoL was evaluated using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC). EORTC has 5 functional scales, 9 symptom scales, and a global health scale. Possible scores range from 0 - 100. Higher scores in global and functional scales and lower scores in symptom scales indicate better QoL. Median QoL scores were compared across 2 classes of nutritional status using nonparametric t test owing to non-normal distribution of QoL scores. Results: 34 patients were identified well nourished and 24 malnourished by the SGA. Well-nourished patients had significantly better QoL scores on global, physical and role functions as compared to malnourished patients (Table 1). Interestingly, median role function score in well-nourished patients was 40 points > than that in malnourished patients, indicating “much better” QoL from patients’ perspective. Similarly, QoL on multiple symptom scales was significantly better in well-nourished patients. Conclusions: This study suggests that malnutrition is associated with poor QoL, as measured by EORTC in advanced colorectal cancer. Prospective studies are required to determine whether nutritional intervention can have any positive impact on QoL outcomes of these patients. Table 1. QoL stratified by nutritional status. No significant financial relationships to disclose.
Phase II study of preventive effect of topical menthol for chemotherapy-induced peripheral neurotoxicity.
Authors: Kumi Nakamura, Masato Nakamura, Toshihide Onikubo, Kazuya Uchibori, Katsunori Tauchi
Journal: Journal of Clinical Oncology (2015)

9610 Background: Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) is a major dose-limiting toxicity of many commonly used chemotherapeutic agents that not only negatively affects quality of life, but also can limit successful disease control in cancer care. Menthol is a compound derived from mint leaves that functions as an agonist of Transient Receptor Potential Melastatin-8 (TRPM-8). TRPM-8 is distributed in peripheral nerves and has been shown to be associated with cold hypersensitivity, noxious cold and sensory disturbance. It is also related to the occurrence of CIPN. We previously reported that applying topical menthol reduced existing CIPN in 75% of patients in a phase II study. As the next step, we conducted a phase II study about the preventive effect of menthol for CIPN. Methods: Patients who were to start regimens containing oxaliplatin (l-OHP) were included in this study. l-OHP is widely used for colorectal cancer (CRC), and is reported to cause grade 2+ CIPN (45-54% at the cumulative dose of 500mg/m2). Participants applied 1% topical menthol twice daily to their hands and feet from the start of l-OHP treatment. CIPN symptoms were assessed using the FACT&GOG-Ntx and Visual Analog Scale (VAS). The primary endpoint was the frequency of Grade 2{CIPN at the cumulative l-OHP dose of 500 mg/m2. Results: Thirty-two CRC patients who were to start regimens containing l-OHP were enrolled in this study. Twenty-two patients were in adjuvant setting and 10 were in metastatic setting.Treatment regimens were capecitabine and l-OHP (CapeOx) (n = 22), CapeOx plus bevacizumab (n = 9) and FOLFOX plus cetuximab (n = 1). Of the 32 registered patients, 8 terminated or changed their chemotherapy regimens before reaching a cumulative l-OHP dose of 500 mg/m2 and were excluded from analysis. The frequency of Grade 2{CIPN was 12.5% (95% CI: 2.7- 32.4%) at the cumulative l-OHP dose of 500 mg/m2. This was significantly lower than the expectation value (25%). The means of the FACT/GOG-Ntx score and the VAS scale were 3.6 (0-14) and 2.5 (0-8.8), respectively. There were no adverse events reported from menthol application. Conclusions: This phase II study showed preventive menthol application significantly reduced l-OHP-induced CIPN. Clinical trial information: UMIN000009655.
Bronchiolitis during the first year after birth in term and preterm infants
Authors: Evi Kosma, Maria Hammargren, Charlotte Palme Kilander
Journal: European Respiratory Journal (2014)

Objective: To study signs of impaired airway function prior to lower airway infection in preterm infants.

Design/Methods: 156 consecutively born infants, born at 27-33 weeks gestation, and 109 term infants were enrolled in a prospective study of lung and airway function. Lung function was studied using tidal breathing infant spirometry during quiet sleep at term.

The infants were assessed by the study nurse or doctor at every airway infection during the first year after birth and nasopharyngeal viral swabs were taken.

Results: Among infants born at 27-31 weeks, 9 % were hospitalized and 18 % were treated in ambulatory care due to bronchiolitis.

Among 32-33 weeks infants , 6,2 % needed hospitalization for bronchiolitis and 14 % had ambulatory care.Term infants had bronchiolitis in only 1,8 %: only 0,9 % in hospital.

Early bronchiolitis(during first 6 months) was caused by: 77% RSV, 23 % rhinovirus. Late bronchiolitis(after 6 months) was due to: RSV 43 % %, rhinovirus 33 % and others 24%.

In preterm infants who had early bronchiolitis,there was no difference in airway function before the bronchiolitis compared to preterms who did not have bronchiolitis.

Conclusions: Preterms who had bronchiolitis during the first six months after birth did not have impaired lung or airway function before the bronchiolitis. Preterm infants,who had RSV infection during first 6 months after birth, often had bronchiolitis compared to term infants, who mainly had upper airway symtoms.RSV was the main cause of bronchiolitis during the first 6 months, and RSV and also rhinovirus and to a lesser extent other viruses during 6-12 months after birth.

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Adolescent development
Authors: Deborah Christie, Russell Viner
Journal: BMJ (2005)

In the care of adolescent patients, all aspects of clinical medicine are played out against a background of rapid physical, psychological, and social developmental changes. These changes produce specific disease patterns, unusual presentations of symptoms, and above all, unique communication and management challenges. This can make working with adolescents difficult. However, with the right skills, practising medicine with young people can be rewarding and fruitful. These skills are needed by everyone who works with young people in the course of their work.

As a young person enters adolescence, their parents are still largely responsible for all aspects of their health. By the end of adolescence, health issues will be almost entirely the responsibility of the young person. The challenge is to maintain an effective clinical relationship while the health responsibilities transfer from the parents to the young person.​person.




Figure 1






Specialised clinical communication skills are needed to take an accurate history, bearing in mind new life domains not applicable to children (sex and drugs) and adding communication and engagement of the family to the standard adult consultation. Physical examinations of adolescents require consideration of privacy and personal integrity as well as requiring additional skills such as pubertal assessment. For effective treatment of illness in adolescence, doctors need to know about adolescent development if they are to manage adeptly issues of adherence (compliance), identity, consent and confidentiality, and relationships between young people and their families. Evidence from randomised controlled trials clearly shows that such skills can be developed and practised effectively in primary care.​care.



Table 1

The primary challenges of adolescence
Stealing sleep: is sport or society to blame?
Authors: Shona L Halson
Journal: British Journal of Sports Medicine (2015)

Sleep debt negatively impacts the daily lives of both athletes and the general population at large. Elite athletes sleep less and have poorer estimated sleep quality than non-athletes.1 With sleep being vital for psychological and physiological functioning, why do we neglect such a critical biological function? For athletes, is reduced sleep a function of the elite athletes’ unique lifestyle or is our modern lifestyle generally the primary contributing factor?

As sleep has an influence on nearly all molecular, cellular, physiological and neurological functions,2 it would seem that sleep should be one of the foundations of an athlete’s training programme. Sleep deprivation can influence athletic performance, cognition, reaction time, immune function and pain perception,3 but it appears that scientists have only recently started to give research in athletes sleep the attention it deserves. …
Errors in opioid dosing principles: A prospective survey
Authors: M. P. Davis, B. Estfan, W. Declan, P. Shaheen, S. B. Legrand, R. L. Lagman
Journal: Journal of Clinical Oncology (2004)

8059 Background: Pain in advanced cancer is complex; patients usually experience multiple pains, including intermittent pain. Proper opioid prescribing must consider the severity, quality and temporal patterns of pain to be successful. Opioid prescribing errors can be categorized into errors in strategy, errors in titration and errors in conversion or rotation. Such errors result in poorly controlled pain and/or opioid side effects. Methods: This prospective IRB approved survey evaluated opioid prescribing at an initial palliative service consultation. Principles of opioid dosing guidelines were derived from various sources (Agency for Health Care Policy and Research, European Association of Palliative Care, World Health Organization, American Pain Society). Deviations from guidelines were considered errors. Potential errors were categorized into 14 groups, 10 involved dosing strategy, 2 opioid conversion or rotation, 1 dose titration and 1 failure to use an adjuvant analgesic. Palliative attending palliative physicians and fellows assessed the current strategy for correctness in relationship to pain severity, temporal pattern and opioid side effects. More than one opioid dosing error could be recorded. Results: Between October 13 and December 12, 2003, 164 consecutive patients were evaluated; of which 80% had cancer. 95 patients had cancer pain: 66 (70%) had at least one error. In total 125 strategy or dosing errors were identified; 4 were due to inappropriate conversion or rotation, 12 due to failure to rotate and 98 were strategy errors. 11 had other non-categorized errors. The most common errors involved inadequate use of around-the-clock or continuous parenteral opioids for continuous pain (23), under treatment of opioid side-effects (19) or the use of multiple opioids (12). Conclusions: Most cancer patients with pain on opioids will have one or more opioid dosing errors or referral to a Palliative Medicine program. Most will involve failure to dose according to pain pattern or severity and failure to recognize and treat opioid side-effects. No significant financial relationships to disclose.
Induction Chemotherapy With Mitomycin, Epirubicin, Cisplatin, Fluorouracil, and Leucovorin Followed by Radiotherapy in the Treatment of Locoregionally Advanced Nasopharyngeal Carcinoma
Authors: Ruey-Long Hong, Lai-Lei Ting, Jenq-Yuh Ko, Mow-Ming Hsu, Tzung-Shiahn Sheen, Pei-Jen Lou, Chuan-Cheng Wang, Na-Na Chung, Louis Tak Lui
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Survival in advanced nasopharyngeal carcinoma (NPC) is compromised by distant metastasis. Because mitomycin is active against hypoxic and G0 cells, which may help to eradicate micrometastasis, we investigated the effect of mitomycin-containing cisplatin-based induction chemotherapy. PATIENTS AND METHODS: Recruited for this study were American Joint Committee on Cancer (AJCC) 1992 staging system stage IV NPC patients with the following adverse features: obvious intracranial invasion, supraclavicular or bilateral neck lymph node metastasis, large neck node (&gt; 6 cm), or elevated serum lactate dehydrogenase (LDH) level. Patients were given three cycles of chemotherapy before radiotherapy. The chemotherapy comprised a 3-week cycle of mitomycin, epirubicin, and cisplatin on day 1 and fluorouracil and leucovorin on day 8 (MEPFL). RESULTS: From January 1994 to December 1997, 111 patients were recruited. The median follow-up period was 43 months. The actuarial 5-year overall survival rate was 70% (95% confidence interval [CI], 60% to 80%; n = 111). For patients having completed radiotherapy (n = 100), the 5-year locoregional control rate was 70% (95% CI, 55% to 84%) and the distant metastasis–free rate was 81% (95% CI, 73% to 89%). The 5-year distant metastasis–free rate of N3a and N3b disease of AJCC 1997 staging system were 79% (95% CI, 62% to 95%) and 74% (95% CI, 60% to 89%), respectively. By Cox multivariate analysis, high pretreatment serum LDH level (P = .04) and neck nodal enlargement before radiotherapy (P = .001) were adverse prognostic factors of survival. CONCLUSION: The good 5-year survival of N3 disease supports the effectiveness of induction MEPFL in the primary treatment of advanced NPC. Further investigation to incorporate concurrent chemoradiotherapy is warranted.