tbuckley/cabot-search huggingface dataset:
Sex differences in the associations of obstructive sleep apnoea with epidemiological factors
Authors: Tianyi Huang, Brian M. Lin, Sarah C. Markt, Meir J. Stampfer, Francine Laden, Frank B. Hu, Shelley S. Tworoger, Susan Redline
Journal: European Respiratory Journal (2018)

Despite the well-known male predominance in the prevalence of obstructive sleep apnoea (OSA), sex differences in the associations between OSA and a comprehensive range of epidemiological factors remain less clear. We examined the prevalence of self-reported OSA in 143 326 females (age 48–93 years) from the Nurses' Health Study (NHS) and NHS-II and 22 896 males from the Health Professionals Follow-up Study (age 65–101 years) in 2012–2013. Multivariable logistic regression was used to estimate the sex-specific prevalence odds ratios (pOR) and 95% confidence intervals of OSA by demographic, anthropometric, lifestyle and comorbidity factors. The overall prevalence of self-reported OSA was 6.4% in females and 13.8% in males. After mutual adjustment, the associations of OSA with physical inactivity, hypertension and daytime sleepiness were stronger in females, whereas the associations with waist circumference and witnessed apnoea were stronger in males (p-heterogeneity &lt;0.01). There were qualitative sex differences in the associations with age (pOR per 5-year increment in females 0.95, 95% CI 0.94–0.96, and males 1.04, 1.01–1.08; p-heterogeneity &lt;0.0001) and marital status (pOR for married versus other in females 0.85, 95% CI 0.81–0.89, and males 1.11, 0.99–1.25; p-heterogeneity &lt;0.0001). Substantial sex differences exist in the associations with various factors, suggesting sex-specific mechanisms in OSA.
I have been shortlisted for a GP vocational training scheme post and would like some advice on preparation for the interview
Authors: Bill Irish
Journal: BMJ (2005)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
Effects of a Novel Compound (AL 721) on HTLV-III Infectivity in Vitro
Authors: Sarin Ps, Gallo Rc, Scheer Di, Crews F, Lippa As
Journal: New England Journal of Medicine (1985)

This letter reports the results of a study indicating that AL 721 a lipid compound with a demonstrated ability to extract cholesterol from cellular membranes inhibits human T-lymphotropic virus type III (HTLV-III) infection of human peripheral-blood lymphocytes or an immortalized helper T-cell line (H9).  When H9 cells were incubated with HTLV-III for 4 days reductions were detected in cell numbers and there were significant levels of reverse transciptase p15 and p24.  After H9 cells were infected with HTLV-III in the presence of AL 721 there was a reduction in viral infectivity.  The median dose for this effect was 100 mcg/ml of AL 721.  It is not clear whether the virucidal effects of AL 721 are due to its actions on the retroviral envelope or on the host cell membrane.  In preliminary clinical trials with elderly human subjects daily oral doses of AL 721 over a 6-week period restored diminished lymphocyte proliferative capacity and were well tolerated.  AL 721 is considered a promising new candidate for investigation in the treatment of acquired immunodeficiency syndrome (AIDS) especially since it does not produce the side effects that are associated with reverse transcriptase inhibitors.
Government is urged to improve performance management of consultants
Authors: Caroline White
Journal: BMJ (2013)

The Department of Health must tighten its performance management of consultants if the NHS is to avoid another “Mid Staffs,” warns a report from the parliamentary Committee on Public Accounts.1

The report, which calls for tough targets to be set for senior doctors to boost their productivity, has been published ahead of new contract negotiations on terms and conditions for consultants,2 after recommendations made by the Review Body on Doctors and Dentists’ Remuneration (DDRB) last December.34

The government now wants to change consultants’ pay structure to reflect the DDRB’s suggestions to link pay progression more closely to performance, introduce a new grade of consultant, and reconfigure national and local clinical excellence awards.

The committee’s report concludes that the current consultant contract does not provide value for …
GIANT CORONARY ARTERY ECTASIA AND ATHLETE'S HEART MIMICKING AN ACUTE CORONARY SYNDROME (ACS)
Authors: Vicente Jimenez Franco, Hernan Azpiri, Luis Manautou, Carlos Sanchez-Diaz, Felipe Valdes, José Gildardo Paredes-Vázquez
Journal: Journal of the American College of Cardiology (2018)
Dominant integration locus drives continuous diversification of plant immune receptors with exogenous domain fusions
Authors: Paul C. Bailey, Christian Schudoma, William Jackson, Erin Baggs, Gulay Dagdas, Wilfried Haerty, Matthew Moscou, Ksenia V. Krasileva
Journal: Genome biology (2018)

The plant immune system is innate and encoded in the germline. Using it efficiently, plants are capable of recognizing a diverse range of rapidly evolving pathogens. A recently described phenomenon shows that plant immune receptors are able to recognize pathogen effectors through the acquisition of exogenous protein domains from other plant genes.
The director of the International Institute of Child and Adolescent Mental Health
Authors: Imran Mushtaq, Hind Al-Khairulla
Journal: BMJ (2009)

Kedar Nath Dwivedi; visiting professor, London Metropolitan University; director, International Institute of Child and Adolescent Mental Health; formerly consultant child and adolescent psychiatrist, Northampton

My psychiatric training at Cambridge during the David Clarke era concentrated on group therapy. When I started as a consultant at Northampton, this background helped me to develop group therapy services, training courses, and publication of a book on group work with children and adolescents. We tried to cultivate an ethos where everyone (staff and users) is genuinely valued and empowered, as typical of group therapy. We also set up a family therapy clinic in which a small team of consultants from diverse backgrounds (for example, paediatrics, psychotherapy, marital therapy, and child psychiatry) brought their most difficult cases to the clinic. The unique approach to working together often led to a breakthrough in many hopeless situations. I looked forward to these weekly transformational events.

My training in public health also helped me to develop prevention and …
Coexistent Solid Malignancies in Pemphigus
Authors: Khalaf Kridin, Shira Zelber-Sagi, Doron Comaneshter, Arnon D. Cohen
Journal: JAMA Dermatology (2018)

The association of pemphigus vulgaris and pemphigus foliaceus with comorbid malignancies is yet to be firmly established.To estimate the association between pemphigus and a wide range of nonhematologic malignancies using one of the largest cohorts of patients with pemphigus to date.For this cross-sectional study, we used the computerized database of Clalit Health Services, the largest public health care provider organization in Israel insuring 4.4 million individuals in the settings of general community clinics, primary care and referral centers, and ambulatory and hospitalized health care. The study included 1985 patients with pemphigus and 9874 control patients and was conducted from January 2004 to December 2014.The prevalence of 17 different solid malignancies was compared between patients diagnosed with pemphigus and age-, sex-, and ethnicity-matched control patients; χ2 and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The association was examined following a sensitivity analysis that included only cases treated with long-term pemphigus-specific medications (corticosteroids, immunosuppressants, or rituximab), and following the adjustment for several confounding factors.Overall, the total sample included 11 859 eligible patients, of whom 1985 were patients with pemphigus (mean [SD] age at presentation, 72.1 [18.5] years; 1188 women [59.8%]). In patients with pemphigus compared with control patients, there was a greater prevalence of esophageal cancers (0.4% vs 0.1%; odds ratio [OR], 2.9; 95% CI, 1.1-7.4) and laryngeal cancers (0.6% vs 0.3%; OR, 2.0; 95% CI, 1.0-4.1). No significant associations between pemphigus and other solid malignancies were observed. Estimates were not altered significantly after controlling for comorbidities, health care overutilization, immunosuppressive therapy, and other malignancy-specific risk factors (ie, smoking and alcohol abuse in laryngeal cancer, gastroesophageal reflux disease in esophageal cancer).Significant associations were observed between pemphigus and solid malignancies of the larynx and the esophagus. Physicians treating patients with pemphigus should be aware of these findings. Further observational studies are warranted to establish this association in other cohorts.
Amelioration of Neurosensory Structure and Function in Animal and Cellular Models of a Congenital Blindness
Authors: Ji Yun Song, Puya Aravand, Sergei Nikonov, Lanfranco Leo, Arkady Lyubarsky, Jeannette L. Bennicelli, Jieyan Pan, Zhangyong Wei, Ivan Shpylchak, Pamela Herrera, Daniel J. Bennett, Nicoletta Commins, Albert M. Maguire, Jennifer Pham, Anneke I. den Hollander, Frans P.M. Cremers, Robert K. Koenekoop, Ronald Roepman, Patsy Nishina, Shangzhen Zhou, Wei Pan, Gui-shuang Ying, Tomas S. Aleman, Jimmy de Melo, Ilan McNamara, Junwei Sun, Jason Mills, Jean Bennett
Journal: Molecular Therapy (2018)

Most genetically distinct inherited retinal degenerations are primary photoreceptor degenerations. We selected a severe early onset form of Leber congenital amaurosis (LCA), caused by mutations in the gene LCA5, in order to test the efficacy of gene augmentation therapy for a ciliopathy. The LCA5-encoded protein, Lebercilin, is essential for the trafficking of proteins and vesicles to the photoreceptor outer segment. Using the AAV serotype AAV7m8 to deliver a human LCA5 cDNA into an Lca5 null mouse model of LCA5, we show partial rescue of retinal structure and visual function. Specifically, we observed restoration of rod-and-cone-driven electroretinograms in about 25% of injected eyes, restoration of pupillary light responses in the majority of treated eyes, an ∼20-fold decrease in target luminance necessary for visually guided behavior, and improved retinal architecture following gene transfer. Using LCA5 patient-derived iPSC-RPEs, we show that delivery of the LCA5 cDNA restores lebercilin protein and rescues cilia quantity. The results presented in this study support a path forward aiming to develop safety and efficacy trials for gene augmentation therapy in human subjects with LCA5 mutations. They also provide the framework for measuring the effects of intervention in ciliopathies and other severe, early-onset blinding conditions.
Pay has risen more for GPs than for hospital consultants, claims Department of Health
Authors: Helen Jaques
Journal: BMJ (2012)

General practitioners’ pay has increased by proportionally more since 2002 than salaries of hospital consultants, the Department of Health has claimed.

In its evidence on general medical practitioners for the Review Body on Doctors’ and Dentists’ Remuneration (DDRB),1 the department states that cash pay for GPs in England on the general medical services (GMS) contract rose by 46% between 2002-3 and 2009-10 (the last year for which figures are available) but increased by only 36.4% for consultants. 

In real terms, pay rose over this period by 24% for GPs and 16.1% for consultants. The department has estimated that …
Abstract P3-01-14: Nomogram predicting axillary lymph node metastases to skip intraoperative analysis of sentinel lymph nodes
Authors: JH Park, YW Ju, KE Kim, J Rhu, Y Kim, E Lee, H-B Lee, H-G Moon, D-Y Noh, W Han
Journal: Cancer Research (2018)

Abstract Background: According to the American College of Surgeons Oncology Group Z0011 trial, complete axillary lymph node dissection (ALND) did not affect survival of patients with clinical T1-T2 invasive breast cancer and one to two sentinel lymph nodes (SLNs) metastases treated with lumpectomy, adjuvant systemic therapy, and radiation therapy. A significant proportion of breast cancer patients may not require ALND, in whom intraoperative analysis of SLNs can be omitted reducing operation time and cost. The aim of this study was to develop a nomogram predicting three or more axillary lymph nodes (ALNs) metastases based on preoperative imaging and clinicopathological factors. Methods: The training set consisted of 1030 patients with clinical T1-T2 invasive breast cancer and clinically negative ALN who received surgery at Seoul National University Hospital (SNUH) between January 2010 and December 2013. Preoperative imaging techniques including ultrasonography (US), computed tomography (CT), positron emission tomography (PET), and clinicopathological features associated with three or more ALN metastases were evaluated by logistic regression analysis. A nomogram predicting three or more ALNs was developed with statistically significant factors. The validation set consisted of 781 independent patients who received surgery at SNUH between January 2014 and December 2015. Results: Of the 1030 patients, 89 (8.6%) had three or more ALN metastases. Multivariate analysis showed that three or more ALN metastases was independently associated with tumor size (cm) by US (p&amp;lt;0.001), suspicious ALNs findings in US (p&amp;lt;0.001), chest CT (p&amp;lt;0.001), and PET/CT (≥ 1.4 SUV, p&amp;lt;0.001). Established nomogram evaluating the probability of three or more ALNs metastases includes the above four associated factors. The areas under the receiver operating characteristic (ROC) curve of the nomogram were 0.866 (95% confidence interval [CI] 0.826-0.905) for the training set and 0.867 (95% CI: 0.801-0.932) for the validation set. With cutoff point of 142, false negative ratio is 3.6%, and 8.6% of patients were candidates for intraoperative SLN analysis. Conclusion: Patients with a strong possibility of three or more ALNs metastases can be identified using preoperative imaging methods including US, CT, and PET. The nomogram measuring this prospect may be valuable in skipping intraoperative analysis of SLNs with advantage of reduced operation time and cost. Citation Format: Park JH, Ju YW, Kim KE, Rhu J, Kim Y, Lee E, Lee H-B, Moon H-G, Noh D-Y, Han W. Nomogram predicting axillary lymph node metastases to skip intraoperative analysis of sentinel lymph nodes [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-14.
Chemotherapy choice in advanced pancreatic cancer: What patient and disease factors influence prescription patterns?
Authors: William Raskin, Helen Guo, Jaclyn Marie Beca, Wanrudee Isaranuwatchai, Lucy Qiao, Craig Earle, Scott R. Berry, James Joseph Biagi, Stephen Welch, Brandon Matthew Meyers, Nicole Mittmann, Natalie G. Coburn, Aliya Pardhan, Jessica Arias, Deborah Schwartz, Scott Gavura, Leta Marie Forbes, Robin McLeod, Erin Diane Kennedy, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2018)

327 Background: FOLFIRINOX (FFX), gemcitabine+nab-paclitaxel (GnP) and gemcitabine monotherapy (Gem)) are universally funded as first-line chemotherapy regimens for advanced pancreatic cancer (APC) in Ontario, Canada. However, there is scarce real-world data on factors that may influence choice of chemotherapy regimens in APC. Methods: Patients who received first-line chemotherapy for APC between April 2015-March 2016 in Ontario were identified from CCO’s New Drug Funding Program database and linked to the Ontario Cancer Registry and other provincial databases to ascertain baseline factors. Multinomial logistic regressions were used to examine the associations between the prescribed chemotherapy regimen and baseline factors. Results: 546 patients were identified, with a mean age of 65 and 43.6% female. 9.9% and 9.7% had received adjuvant gemcitabine and radiation treatment respectively. 17.6% had previous pancreatic resection. 68.3% had zero Charlson score and 30.6% had ECOG performance status (PS) of 0. 72.7% had metastatic disease. The majority of the patients received FFX (52.4%) compared to GnP (35.7%) and Gem (11.9%). Age and ECOG PS were strongly associated with choice of chemotherapy regimens. (See Table) Conclusions: In Ontario, increased patient age and worse ECOG PS are strongly associated with choice of Gem compared to GnP and FFX. Previous treatments and stage of disease also impact chemotherapy choice. Understanding how providers choose chemotherapy in APC aids in comprehending our practices. Odds ratio (OR) and p value from multinomial logistic regressions. [Table: see text]
Coronary Artery Calcium Scores and Atherosclerotic Cardiovascular Disease Risk Stratification in Smokers
Authors: Adam Leigh, John W. McEvoy, Parveen Garg, J. Jeffrey Carr, Veit Sandfort, Elizabeth C. Oelsner, Matthew Budoff, David Herrington, Joseph Yeboah
Journal: JACC. Cardiovascular imaging (2018)
High p95HER2/HER2 Ratio Associated With Poor Outcome in Trastuzumab-Treated HER2-Positive Metastatic Breast Cancer NCCTG N0337 and NCCTG 98-32-52 (Alliance)
Authors: Saranya Chumsri, Jeff Sperinde, Heshan Liu, Joseph Gligorov, Jean-Philippe Spano, Martine Antoine, Alvaro Moreno Aspitia, Winston Tan, John Winslow, Christos J. Petropoulos, Ahmed Chenna, Michael Bates, Jodi Marie Weidler, Weidong Huang, Amylou Dueck, Edith A. Perez
Journal: Clinical Cancer Research (2018)

Purpose: p95HER2 is a truncated form of HER2 that confers resistance to trastuzumab in vitro, but clinical results have been conflicting to date. Given that p95HER2 levels correlate with total HER2 expression levels, which confer better outcomes, we sought to evaluate the p95HER2/HER2 ratio in the North Central Cancer Treatment Group N0337 and N98-32-52 trials.Experimental Design: The HERmark assay and VeraTag technology (Monogram Biosciences) were used to measure total HER2 and p95HER2 expression levels in 91 patient samples.Results: In the multivariate model, increasing total HER2 level was significantly associated with longer (OS; HR, 0.33; P = 0.002) and decreasing p95HER2 level was significantly associated with longer OS (HR, 4.2; P = 0.01). Total HER2 expression level was significantly associated with longer progression-free survival (PFS) (HR, 0.57; P = 0.04), whereas p95HER2 level was not (HR, 1.7; P = 0.25). However, there was a positive association between p95HER2 and total HER2 expression levels (R2 = 0.48; P < 0.001). Consistent with our hypothesis, the ratio of p95HER2/HER2 was significantly associated with worsening PFS (HR, 1.7; P = 0.04) and OS (HR, 2.8; P = 0.002). Patients with the highest tertile of p95HER2/HER2 values had significantly less favorable PFS (HR, 1.8; P = 0.06) and OS (HR, 2.3; P = 0.02).Conclusions: A high p95HER2/HER2 ratio identified patients with metastatic breast cancer with poor outcomes on trastuzumab-based therapies. Further investigation of the p95HER2/HER2 ratio as a potential prognostic or predictive biomarker for HER2-targeted therapy is warranted. Clin Cancer Res; 24(13); 3053-8. ©2018 AACR.
Abstract P4-12-09: Molecular test for BRCA 1 and 2: Hereditary breast and ovarian cancer syndrome. Analysis of cost effectiveness of its implementation
Authors: MC Paez, MC Riggi, SJ Gogorza, F Petracchi
Journal: Cancer Research (2018)

Abstract Introduction Breast cancer is the leading cause of women cancer. Hereditary cause represents 5% -10% of cases. Molecular testing for BRCA1 and BRCA2 allows physicians to identify breast and ovarian cancer high risk women. Screening, diagnosis and treatment for high risk women differ from general population ones. As new drugs have been increasing health costs, the need of cost-effective strategies has raised. In Argentina, molecular tests are still very expensive and most health insurances do not cover it. Objectives To evaluate the long-term cost-effectiveness of germline BRCA1 and BRCA2 molecular testing in women with no personal history of cancer and &amp;gt;=10% mutation risk based on family history criteria, compared to no testing women. Methods We performed a decision-analytic model (decision tree) to compare the risks of breast and ovarian cancer, mortality rates, and costs and effects (life-years and QALYs) in women with and without molecular testing for BRCA1 and BRCA2. Carrier's probability undergoing risk-reducing surgeries was considered. This data has been analized in two private hospitals of Buenos Aires, Argentina. Results BRCA testing in all women with &amp;gt;=10% mutation risk based on family history criteria resulted cost-effective and even cost-saving in our country, with an incremental cost-effectiveness ratio of -$315.353/QALY and -$1.357.143/life-year. Our results demonstrate to be robust after sensitivity analyses varying the input parameters. Conclusion BRCA testing is cost-saving in our country probably because of prophylactic risk-reducing surgeries in BRCA carriers. This leads to a reduction of breast and ovarian cancer cases. Citation Format: Paez MC, Riggi MC, Gogorza SJ, Petracchi F. Molecular test for BRCA 1 and 2: Hereditary breast and ovarian cancer syndrome. Analysis of cost effectiveness of its implementation [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-12-09.
P031 In both rheumatoid and psoriatic arthritis naive CD4+ T lymphocytes are predisposed to differentiate towards TH17 cells and have characteristic cytokine profiles
Authors: E Baricza, N Marton, P Királyhidi, OT Kovács, IK Székely, E Lajkó, L Kohidai, B Rojkovich, É Barbara, EI Buzás, G Nagy
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> The Th17 helper T lymphocytes represent a subset of T cells that produce inflammatory cytokines. Increased Th17 cell differentiation has been observed in rheumatoid arthritis (RA) and in psoriatic arthritis (PsA). IL-17 induced inflammation promotes osteoclast differentiation which is contributes to the bone and join destruction in RA. In addition IL-17 and IL-22 are co-expressed by Th17 cells which redounds the psoriatic plaque formation in PsA. <h3>Objectives</h3> In this present work we studied Th17 cell differentiation in RA and PsA. <h3>Methods</h3> Blood samples from healthy donors, RA and PsA patients were collected. CD45RO<sup>-</sup> (naive) and CD45RO<sup>+</sup> (memory) T cells were isolated from PBMC by magnetic separation. Naive T cells were stimulated with anti-CD3, anti-CD28 and with goat anti-mouse IgG antibodies and treated with TGF<sub>β</sub>, IL-6, IL-1<sub>β</sub> and IL-23 cytokines and with anti-IL-4 antibody. IL-17A and IL-22 production were measured by ELISA, <i>RORC</i> and <i>TBX21</i> expression were analysed by qPCR and flow cytometry. CCR6, CCR4 and CXCR3 expression were determined by flow cytometry. Cell viability was monitored by impendance-based cell analyzer (CASY-TT). <h3>Results</h3> <i>RORC</i>, <i>TBX21</i>, CCR6 and CCR4 expression of memory T cells of healthy individuals (but not RA or PsA patients) were increased (p&lt;0.01; p&lt;0.001; p&lt;0.05; p&lt;0.05, respectively) compared to the naive cells. Cytokine-induced IL-17A production was different in both RA and PsA patients when compared to healthy donors (p=0.0000026 and p=0.0001047, respectively). By contrast, significant differences in IL-22 production were observed only between RA versus healthy or RA versus PsA patients (p=0.000006; p=0.0013454, respectively), but not between healthy donors versus PsA patients. <h3>Conclusions</h3> The naive CD4 T-lymphocytes are predisposed to differentiate to Th17 cells and the <i>in vitro</i> Th17-cell differentiation is profoundly altered in both RA and PsA. <h3>Disclosure of interest</h3> None declared