tbuckley/cabot-search huggingface dataset:
Genetics of Autoimmune Thyroiditis in Type 1 Diabetes Reveals a Novel Association With <i>DPB1*</i>0201: Data From the Type 1 Diabetes Genetics Consortium
Authors: Heinrich Kahles, Pamela R. Fain, Peter Baker, George Eisenbarth, Klaus Badenhoop
Journal: Diabetes Care (2015)

BACKGROUND Autoimmune thyroiditis occurs in 10–25% of patients with type 1 diabetes (T1D). Most of these patients are also positive for thyroid peroxidase (TPO) antibodies. Thyroid dysfunction complicates T1D metabolic control and is a component of the autoimmune polyglandular syndrome (APS, type 2 or 3). Previous studies of isolated T1D and of T1D combined with other autoimmune disorders showed genetic susceptibility for alleles in HLA-DQB1 and -DRB1 and also CTLA4 and PTPN22. RESEARCH DESIGN AND METHODS We analyzed the Type 1 Diabetes Genetics Consortium Autoantibody Workshop data by differentiating those T1D probands with and without TPO antibodies or thyroid disease with respect to polymorphisms in HLA, CTLA4, INS, PTPN22, and VDR, taking into account the ethnic origin. Genotype and clinical/immunogenic phenotype data were analyzed by gene counting methods and logistic regression analysis. RESULTS The presence of TPO antibodies (25.2%) and thyroid disease (8.4%) was associated with older age, female sex, and presence of other autoantibodies (GAD65, ATPase, 21-OH) (all P &amp;lt; 0.001). The highest prevalence was in patients of Hispanic ancestry (31%) and the lowest in those of African ancestry (8%). In T1D non-Hispanic whites, HLA-DRB1*0101 is significantly (P &amp;lt; 0.0001) less frequent in TPO-positive than in TPO-negative individuals, whereas HLA-DRB1*0404, -DQB1*0301, and -DPB1*0201 are significantly (P &amp;lt; 0.0001) more frequent. Subjects with a high titer of TPO autoantibodies and with thyroid disease were associated with female sex and older age and negatively associated with DRB1*0401-DQB1*0302 (P &amp;lt; 0.0001). No significant differences were observed for an association of TPO positivity or thyroid disease with single nucleotide polymorphisms in the INS, CTLA4, or VDR loci, with nominal significance (P = 0.01) for PTPN22 R620W variant. CONCLUSIONS Thyroid autoimmunity is highly prevalent in T1D patients of non-Hispanic white, Asian, or Hispanic origin. The strongest disease risk is conferred by female sex and older age. This risk is modulated by HLA-DRB1 and HLA-DPB1 loci. The immunogenetic profile for T1D with thyroid autoimmunity may identify distinct pathways regulating polyglandular autoimmunity and disease.
Primary clinical use of sonodynamic therapy (SDT) for advanced breast cancer
Authors: X. J. Wang, D. Mitchell, T. J. Lewis
Journal: Journal of Clinical Oncology (2008)

12029 Background: There are increasing data showing that sonodynamic therapy (SDT), which refers to a synergistic effect of drugs and ultrasound, is a promising new modality for cancer treatment. Recently a new sonosensitizing agent has been developed by SonneMed, LLC. It is extremely sensitive to ultrasound. As with photodynamic sensitizers, it is specifically absorbed into tumor cells and produces singlet oxygen upon interaction with the right frequency and intensity of ultrasound. The singlet oxygen is able to create cellular necrosis. Our animal studies showed that SDT with SF1 inhibits growth of mouse S-180 sarcoma. Here we report initial clinical data using SDT with SF1 for advanced breast cancer. Methods: Three patients with metastasized pathologically proven breast carcinoma were studied. Their carcinoma failed to respond to conventional therapy and spread to the whole body. The SDT agent was provided through lingual absorption. After 24h, light and ultrasound was applied, irradiating the tumour area for 20 minutes daily for 4 days and repeated every two weeks. Results: Case 1 had breast carcinoma which spread to the whole body. She had surgery, chemo, RT, hormone, Herceptin, Zometa etc, but all failed. The tumor kept growing until she multiple acute symptoms. After 3 SDT treatments her symptom improved significantly and windpipe spile, gastric and urine catheter were all taken off. PET/CT scans showed a positive partial result (PR). Case 2 had left breast carcinoma with multi-organ metastases. After 2 treatments PET/CT scan showed very positive PR. PET/CT taken 28 months after treatment showed no signs of tumor in any cavity of the body. Case 3 had left breast carcinoma. All conventional treatments failed. Her carcinoma metastases broadly and her marrow function was very poor. After 2 cycle treatments PET/CT scan showed PR. Conclusions: Primary clinical data shows that SDT with SF1 is well tolerated and has a significant therapeutic effect for some patients with advanced breast cancer. Even a terminally ill patient can be treated safely and effectively. Sonodynamic therapy with SF1 has significant merit for further investigation. No significant financial relationships to disclose.
Utilisation of Markov-Monte Carlo modelling to determine treatment strategies in advanced non-small cell lung cancer
Authors: W. S. Liauw, R. Ward
Journal: Journal of Clinical Oncology (2004)

7125 Background: The selection of anti-cancer agents for phase III development is based on response rates (RR) determined in phase II trials despite the relationship between tumour response and survival being poorly understood. For example, meta-analysis of colorectal cancer chemotherapy trials demonstrates that substantial increases in RR result in small survival benefits. The role of RR as a surrogate endpoint is confounded by the development of cytostatic targeted therapies. The aim of this study was to develop a Markov-Monte Carlo model (MMCM) of survival in advanced non-small cell lung cancer (ANSCLC) in order to model hypothetical treatment scenarios. Methods: A systematic review was used to establish the current standard-of-care for ANSCLC and to derive assumptions for use in a decision tree modelling experiment. The baseline model assumed good performance status chemonaive subjects received 4 cycles of therapy with a conventional platinum-based doublet. Starting and transition probabilities were extrapolated from the ECOG 1594 trial and cycle length was set at 12 weeks. The MMCM was developed using Data 4.0 (Treeage Software) and all simulations employed 10,000 Monte Carlo iterations. Results: The baseline model produced survival outcomes identical to ECOG 1594. Different treatment scenarios superimposed on the baseline model included (1) concomitant therapy that doubles RR, (2) concomitant therapy that doubles RR followed by maintenance therapy that slows disease progression, and (3) progression delaying maintenance therapy alone. Doubling RR resulted in a small absolute survival gain of 1.7% at 2 years. The scenario of doubled RR and slowed progression produced the highest survival rate of 57.9% at 1 year and 27.1% at 2 years. Conclusions: The optimal therapeutic strategy is a combination of maximal tumour volume reduction and maintenance therapy to slow tumour progression. Markov-Monte Carlo modelling is a useful method for investigating the possible outcomes for new cancer therapeutics and facilitating clinical trial design. No significant financial relationships to disclose.
TCT-627 Identification of stenoses with high underlying coronary flow reserve from pressure-only measurements using baseline instant wave-free ratio (iFR) and hyperaemic fractional flow reserve (FFR)
Authors: Ricardo Petraco, Tim P van de Hoef, Sukhjinder S. Nijjer, Sayan Sen, M. Meuwissen, Rodney A. Foale, Iqbal S. Malik, Christopher Broyd, Nicolas Foin, Ghada Mikhail, Martijn A van Lavieren, Darrel P. Francis, Mauro Echavarria-Pinto, Javier Escaned, Alun D. Hughes, Jamil Mayet, Jan Piek, Justin E. Davies
Journal: Journal of the American College of Cardiology (2013)
Abstract 9454: Risk of Incident Hypertension in Relation to Long-term Exposure to Ambient Air Pollution in Ontario, Canada
Authors: Hong Chen, Ray Copes, Richard T Burnett, Jeff Kwong, Paul J Villeneuve, Mark S Goldberg, Robert D Brook, Aaron van Donkelaar, Michael Jerrett, Randall V Martin, Jeffrey R Brook
Journal: Circulation (2012)

Background - Laboratory studies suggest that exposure to fine particulate matter (2.5μm in diameter or less; PM2.5) can trigger a combination of changes in autonomic nervous system activity, systemic inflammation, and blood pressure which may in turn induce the development of hypertension. However, epidemiological evidence relating PM2.5 and hypertension is sparse. We thus conducted a population-based cohort study to determine whether long-term exposure to PM2.5 is associated with incident hypertension. Methods and Results - We assembled a cohort of 46,591 non-hypertensive adults from Ontario, Canada who responded to one of five population-based health surveys between 1996 and 2005 and were followed-up until December 31, 2010. Incident diagnoses of hypertension were ascertained from the Ontario Hypertension Database, a validated registry of persons diagnosed with hypertension in Ontario (sensitivity=73% and specificity=95%). Six-year average concentrations of PM2.5 at the subjects’ residences were derived from satellite observations. We used Cox proportional hazards models, adjusting for various individual and contextual risk factors such as body mass index, smoking, physical activity, and family income. We examined the presence of effect modification for selected comorbidities and sociodemographic characteristics. During the follow-up period from 1996 to 2010, we identified a total of 12,061 incident cases of hypertension. For every 10μg/m3 increase of PM2.5, the adjusted hazard ratio (HR) was 1.16 (95% confidence interval (CI): 1.09-1.24). The strongest evidence for an interaction between PM2.5 and hypertension was for congestive heart failure (CHF): HRs of 2.75 (95% CI: 1.26-5.97) and 1.15 (95% CI: 1.08-1.23) among subjects with and without CHF, respectively (interaction p=0.02). Conclusions - This study suggests that exposure to PM2.5 may be a contributing risk factor to the development of hypertension.
Abstract 17653: Improving Detection of Preclinical Organ Damage in Hypertension: Non-dipping Status versus Nocturnal Hypertension
Authors: Emmanuel Androulakis, Nikolaos Papageorgiou, Evaggelos Chatzistamatiou, George Hatzis, Costas Tsioufis, George Latsios, Andreas Synetos, Ioannis Kallikazaros, Christodoulos Stefanadis, Dimitris Tousoulis
Journal: Circulation (2014)

Introduction: The clinical relevance of nocturnal hypertension (NH) in comparison with non-dipping status has not been clarified yet regarding subclinical target organ damage.

Hypothesis: In the present study we aimed to elucidate whether nocturnal hypertension or dipping status reflects better organ damage and to explore potential underlying mechanisms.

Methods: The study population consisted of 319 newly diagnosed hypertensive patients. In all participants, several indices of preclinical organ damage were evaluated. Based on the nocturnal BP levels (systolic BP >120 mmHg and/or diastolic BP >70 mmHg) the study population was divided into two groups: nocturnal hypertensives (NH, n=161) and nocturnal normotensives (NN, n=158). Also, individuals with ≥ 10% difference in nocturnal systolic blood pressure (SBP) relative to daytime values were defined as dippers, while non-dippers were defined as <10% nocturnal decrease in SBP.

Results: Patients with NH were characterised by increased arterial pulse wave velocity (PWV) (9.1±1.7 vs 8.4±1.5 m/sec, p=0.0001) and marginally decreased flow mediated dilation values (5.1±3.4 vs 4.1±2.6, p=0.066). In addition, this group showed increased carotid intima-media thickness (0.77±0.18 vs 0.69±0.15 mm, p=0.016) compared to normotensive subjects, whereas no other significant differences were observed, regarding other vascular indices. Notably, they also exhibited higher values of LVMI (88.1±22.9 vs 82.8±16.6 gr/m2, p=0.043) and E/A (0.90±0.26 vs 0.88±0.43, p=0.030), respectively. On the contrary, non-dipping status was associated only with differences in PWV (9.26±0.2 vs 8.64±0.2 m/s, p=0.031,) and also in creatinine clearance values in the group of NH (95±3 vs 106±4, p=0.025).

Conclusions: The presence of NH is accompanied by subclinical atherosclerosis, as well as structural and functional abnormalities of the left ventricle, however without significant impairment of renal function. Therefore, NH should be preferably integrated with the risk of target organ damage rather than non-dipping status.
Books: La Maladie de Sachs
Authors: I. Bamforth
Journal: BMJ (1998)

Martin Winckler POL, Fr130, pp 474 ISBN 2867446031 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Evidence based medicine may be an inescapable term these days, for obvious reasons. Odd, though, that doctors have been slow to respond as advocates of their patients' interests as people, not just as bundles of symptoms, with what might be called, if the term were not a pleonasm, patient based medicine. It is a nice irony, particularly since some countries are still largely innocent of the concept, that one of the strongest pieces of patient based medicine to emerge recently is a French novel, La Maladie de Sachs . The author is a 42 year old former general practitioner who works as a clinical assistant in a Le Mans hospital. “In life,” he confided to a French magazine, “we don't suffer the way it is in medical books. Medical books are works of fiction—and bad fiction at that.” His novel has … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Australian doctors face two years in jail for reporting asylum seekers' health
Authors: M. Woodhead
Journal: BMJ (2015)

Doctors in Australia have vowed to fight a new law that threatens them with two years in jail if they speak out about abuse and poor conditions in detention centres for asylum seekers.

The new legislation has been enacted as part of the Australian government’s hardline “stop the boats” policy that transfers people arriving by boat in Australian waters to offshore detention centres on distant Pacific islands such as Nauru. Conditions in the immigration detention centres have been condemned as “appalling” by healthcare workers, who have reported unhygienic and overcrowded accommodation in tents, substandard medical care, sexual and physical abuse of children, and mental health problems among asylum seekers subject to indefinite detention.

The government’s own report conceded that conditions were harsh on the tropical islands, which have limited infrastructure and where detainees are at risk of diseases such as malaria.

The Royal Australasian College of Physicians last week called for an end to the …
The impact of anemia treatment visits on the patient and their caregiver
Authors: K. W. Tauer, L. Zhu, B. V. Fortner
Journal: Journal of Clinical Oncology (2004)

8114 Background: Anemia-related fatigue can decrease the quality of life in cancer patients (pts) receiving chemotherapy (ctx). Methods: This study used a cross-sectional survey design. Eligible pts had a diagnosis of cancer, were receiving ctx, and received either an erythropoietic agent or a colony-stimulating factor the month prior to the survey. The survey was administered by the study nurse as a semi-structured interview. Pt characteristics, impact of ctx-related anemia treatment on pt and caregiver time, pt activities affected by visits, and caregiver support activities were captured. Results: To date, data from 1960 pts at 72 outpatient oncology clinics were analyzed (mean age 62 years, SD:13years; 63% female). Most common tumor types were breast (28%) and lung (21%). Most common ctx dosing schedule was Q3W (37%). Most (75%) received an erythropoietic agent (39% darbepoetin alfa, 36% epoetin alfa). Almost all (95%) epoetin alfa pts received QW dosing whereas the majority (79%) of darbepoetin alfa pts received Q2W dosing. Of the 1428 pts reporting an anemia treatment visit, the mean time (SD) required was 2 hr 9 min (4 hr 26 min) for pts and 1 hr 10 min (1hr 40 min) for their caregivers. Pts reported having to cancel, alter or postpone paid time at work (23%), time with friends and family (61%), hobbies (50%) and vacation (51%) because of clinic visits. They reported needing help with transportation (83%), with coverage at work (17%), and with running errands (76%) because of clinic visits. Conclusions: Although clinic visits are frequently thought of as being of no consequence, these visits have a major impact on pts and their caregivers. Less frequent anemia-related visits should lead to reduced pt and caregiver burden and are likely to significantly improve their quality of life. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Inc.
Cost of follicular lymphoma (FL) in Medicare patients
Authors: M. Gleeson, R. Carolina, M. Danese, K. B. Knopf
Journal: Journal of Clinical Oncology (2008)

6634 Background: Over 10,000 cases of FL were diagnosed in 2007 in the United States. The direct medical costs attributable to FL are not clearly documented. Methods: We analyzed the cost of FL using SEER-Medicare data. Patients had FL (by histology) as their first primary cancer diagnosed between 1998–2002 with follow up through 2005. Patients had to have > 1 year of prior non-HMO Medicare coverage. Costs were taken from claims for inpatient, outpatient and physician services. Control comparisons were made both to the pre-diagnosis 12 month period and to a 5% sample of Medicare patients without a cancer diagnosis. Chemoimmunotherapy (CT) was classified based on agents used after diagnosis. Linear regression models were adjusted for age, co-morbidity score, diagnosis year, gender, and county of residence. Results: There were 2,053 patients who met the inclusion criteria. The median time from diagnosis to first CT was 159 days. The most common CT regimens included CHOP±R (32%) and rituximab alone (25%) and CVP±R (18%). The unadjusted mean monthly cost was similar compared to both control groups (>$3,000). This cost declined over time but did not reach the pre-diagnosis level. After adjustment the incremental cost of FL was $3,202/month for the first year compared to the 5% Medicare sample (p<0.05). Increasing age, male gender, and Black race were significantly associated with increased monthly costs (p<0.05). Conclusions: FL is associated with increased costs of care in the Medicare population, particularly in the first year after diagnosis where it is over $36,000 per patient. Mean monthly cost ($) relative to diagnosis date Health Service 12 Months Before 12 Months After 12–24 Months After 24–36 Months After Medicare 5% Sample Inpatient facility 230 2030 799 792 227 Provider 167 1507 732 1024 134 Outpatient facility 16 35 22 29 5 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech Genentech Genentech
Positive impact of FDG-PET on survival of esophageal cancer patients
Authors: C. P. Duong, R. J. Hicks, L. Weih, A. Thompson, E. Drummond, R. J. S. Thomas
Journal: Journal of Clinical Oncology (2004)

4055 Background: Compared with CT scan, positron emission tomography (FDG-PET) has been shown to be more accurate in the staging of esophageal cancer (EC). However, there is little published data on the impact of the PET findings on treatment decisions and outcomes. The aim of the study was to evaluate if better treatment selection & delivery, afforded by the more accurate staging that incorporated PET, leads to improved survival of EC patients. Methods: Prospective cohort study of 68 EC patients whose treatment planning was based on staging that incorporated PET findings. The control group was derived from a retrospective consecutive series of 111 EC patients undergoing treatment based only on conventional CT scan. Comparison of survival was analyzed using the Kaplan-Meier product limit method and Cox proportional hazards regression model. Results: There was no significant difference in patient demographics (age, gender) and tumour characteristics (histology, site of primary, stage) between the cases and controls. Treatment guidelines, chemoradiotherapy (CRT) regimen (5-fluouracil, cisplatin, and 50 Gy) and surgery performed (Ivor-Lewis oesophagectomy) were similar in both groups. Median follow up was 22 months (PET) and 19 months (control) respectively. The overall survival of PET-staged patients was superior to the control group, with improved estimated median survival in those receiving curative treatment (PET = 24 months, control = 18 months), as well as in patients undergoing palliation (PET = 11 months, control = 6 months). After adjusting for treatment intent, the hazard ratio for overall survival was 1.56 in favour of the PET cohort. For patients receiving CRT, both with and without surgery, survival was also significantly better in the PET-staged patients (p<0.001, hazard ratio of 2.24) when compared to the corresponding treatment arm in the control group. Conclusions: The use of FDG-PET for the staging of esophageal cancer facilitated better selection of patients for tailored treatment planning, leading to improved survival. No significant financial relationships to disclose.
A patient-level pooled analysis of the prognostic significance of baseline fatigue for overall survival (OS) among 3,915 patients participating in 43 North Central Cancer Treatment Group (NCCTG) and Mayo Clinic Cancer Center (MC) oncology clinical trials
Authors: J. A. Sloan, H. Liu, D. J. Sargent, D. Satele, P. L. Schaefer, M. Y. Halyard, A. Grothey, Y. I. Garces, P. D. Brown, C. L. Loprinzi, J. C. Buckner
Journal: Journal of Clinical Oncology (2009)

9599 Background: We have previously identified overall a single-item measure for baseline quality of life (QOL) as a strong prognostic factor for survival (Tan, ASCO 2008), and that fatigue was an important component of patient QOL (Sloan, 2007). To explore whether patient-reported fatigue was supplemental or redundant to the prognostic information of overall QOL, we performed a patient-level pooled analysis of 43 NCCTG and MCCC oncology clinical trials of the effect of baseline fatigue on OS. Methods: 3,915 patients participating in 43 trials provided data at baseline for fatigue on a single-item 0–100 point scale. OS was tested for association with clinically deficient fatigue (CDF, score 0–50, n=1,497) vs not clinically deficient fatigue (nCDF, score 51–100, n=2,418). Cox proportional hazards models adjusted for the effects of overall QOL, performance score, race, disease site, age and gender. Results: Baseline fatigue was a strong predictor of OS for the entire patient cohort (CDF vs. nCDF: 31.5 mos vs &gt;83.9 mos, p&lt;0.0001). The effect sizes were consistent across different disease sites (GI, esophageal, head and neck, prostate, lung, breast and others). After controlling for covariates, including performance status and overall QOL, baseline fatigue remained a strong prognostic factor in multivariate models (CDF vs. nCDF: HR=1.23, p=0.02). Conclusions: Fatigue is a strong prognostic factor for OS independent of overall QOL and PS in a wide variety of oncology patient populations. Single-item measures of overall QOL and fatigue can help to identify vulnerable subpopulations among cancer patients. No significant financial relationships to disclose.