tbuckley/cabot-search huggingface dataset:
Glossopharyngeal breathing can allow a lung expansion greater than inspiratory capacity in muscular dystrophy
Authors: A. LoMauro, P. Banfi, M.G. D'Angelo, A. Aliverti
Journal: European Respiratory Journal (2019)

<b>In muscular dystrophy, glossopharyngeal breathing is effective in presence of severe dysphagia and diaphragmatic weakness: it recruits the lung above IC, reversing paradoxical respiratory abdominal motion with a presumably more homogeneously distributed pulmonary ventilation</b>http://bit.ly/2LyXDEL
Potential Clinical Error Arising From Use of HbA1c in Diabetes: Effects of the Glycation Gap
Authors: Ananth U Nayak, Baldev M Singh, Simon J Dunmore
Journal: Endocrine Reviews (2019)

The glycation gap (GGap) and the similar hemoglobin glycation index (HGI) define consistent differences between glycated hemoglobin and actual glycemia derived from fructosamine or mean blood glucose, respectively. Such a disparity may be found in a substantial proportion of people with diabetes, being >1 U of glycated HbA1c% or 7.2 mmol/mol in almost 40% of estimations. In this review we define these indices and explain how they can be calculated and that they are not spurious, being consistent in individuals over time. We evaluate the evidence that GGap and HGI are associated with variation in risk of complications and mortality and demonstrate the potential for clinical error in the unquestioning use of HbA1c. We explore the underlying etiology of the variation of HbA1c from mean glucose in blood plasma, including the potential role of enzymatic deglycation of hemoglobin by fructosamine-3-kinase. We conclude that measurement of GGap and HGI are important to diabetes clinicians and their patients in individualization of therapy and the avoidance of harm arising from consequent inappropriate assessment of glycemia and use of therapies.
Cognitive decline is related to high blood glucose levels in older Chinese adults with the ApoE ε3/ε3 genotype
Authors: Qi Qiu, Xiang Lin, Lin Sun, Min-jie Zhu, Tao Wang, Jing-hua Wang, Guan-jun Li, Shi-fu Xiao, Xia Li
Journal: Translational Neurodegeneration (2019)

Few studies have investigated the effects of blood glucose (BG) on cognitive function in community-dwelling elderly individuals carrying the apolipoprotein E (APOE) ε3 allele. To explore the effect of high BG levels on cognitive function in APOE ε3-carrying, non-demented, community-dwelling older adults, as compared to their counterparts carrying the APOE ε4 or APOE ε2 alleles. Within the China Longitudinal Ageing Study, we recruited 282 elderly adults without dementia. Data collected included demographic information; psychological measures; laboratory test results, including BG and plasma lipid levels; and APOE genotypes. We divided the participants into APOE ε2(ε2/ε2, ε2/ε3), ε3(ε3/ε3), and ε4(ε3/ε4, ε4/ε4) groups. Partial correlation analyses and multivariate linear regression analyses were utilized to compare the cognitive function and laboratory data between the APOE groups. White matter hyperintensity (WMH) was measured on magnetic resonance images in 77 participants. With adjustment for age, sex, education, and diabetes, higher BG in non-demented community-dwelling older adults was associated with cognitive decline in immediate memory and executive function. In the APOE ε3 group, elevated BG was associated with cognitive decline in immediate memory, executive function, and perceptual reasoning. In the APOE ε4 group, higher BG was also correlated with a decline in abstract reasoning. There was a trend for association between higher BG and more severe WMHs. Worse cognitive function was correlated withApoEε3/ε3 genotype carriers with higher BG in community-dwelling older adults.
Mitochondrial Dysfunction Leads to Cortical Under-Connectivity and Cognitive Impairment
Authors: Alejandra Fernandez, Daniel W. Meechan, Beverly A. Karpinski, Elizabeth M. Paronett, Corey A. Bryan, Hanna L. Rutz, Eric A. Radin, Noah Lubin, Erin R. Bonner, Anastas Popratiloff, Lawrence A. Rothblat, Thomas M. Maynard, Anthony-Samuel LaMantia
Journal: Neuron (2019)
QUALITY OF LIFE/AFTERCARE
Authors: K. Strobel, P. Simpson, P. Donohoue, S. Firat, S. Jogal, J.-S. Lai, J. Beaumont, S. Goldman, C. Huang, M. Barrera, A. Rokeach, K. Hancock, D. Cataudella, F. Schulte, J. Chung, U. Bartels, L. Janzen, L. Sung, D. Strother, J. Hukin, A. Downie, S. Zelcer, E. Atenafu, E. Schiavello, V. Biassoni, C. Meazza, M. Podda, M. Massimino, E. M. Wells, N. J. Ullrich, K. Seidel, W. Leisenring, C. Sklar, G. T. Armstrong, L. Diller, A. King, K. krull, J. P. Neglia, M. Stovall, K. Whelan, L. L. Robison, R. J. Packer, T. Remes, A. Harila-Saari, M. Suo-Palosaari, P. Lahteenmaki, P. Arikoski, P. Riikonen, H. Rantala, M. Ojaniemi, K. Bull, C. Kennedy, S. Bailey, D. Ellison, S. Clifford, B. Dembowska-Baginska, A. Brozyna, M. Drogosiewicz, M. Perek-Polnik, E. Swieszkowska, I. Filipek, M. Tarasinska, J. Korzeniewska, D. Perek, D. Salgado, S. Nunes, P. Pereira, S. Vinhais, S. Salih, S. Elsarrag, E. Prange, K. Contreas, P. Possin, S. Frierdich, J. Eickhoff, D. Puccetti, C. Huang, E. Ladas, C. Buck, N. Arbit, T. Gudrunardottir, B. Lannering, M. Remke, M. D. Taylor, E. M. Wells, R. F. Keating, R. J. Packer, S. Stapleton, J. Flanary, F. Hamblin, E. Amankwah, S. Ghazarian, C. T. Jagt, M. van de Wetering, A. Y. N. Schouten-van Meeteren, J.-S. Lai, C. Nowinski, W. Hartsell, J. H.-C. Chang, D. Cella, S. Goldman, U. Krishna, A. Nagrulkar, M. Takle, S. Kannan, T. Gupta, R. Jalali, L. Northman, M. Morris, S. Ross, D. Guo, C. Chordas, C. Liptak, B. Delaney, N. Ullrich, P. Manley, S. Avula, B. Pizer, C. C. Ong, S. Harave, C. Mallucci, R. Kumar, A. Margol, J. Finlay, G. Dhall, N. Robison, M. Krieger, E. Kiehna, T. Coates, M. Nelson, J. Grimm, A. Evans, M. B. Nelson, B. Britt, A. Margol, N. Robison, G. Dhall, J. Finlay, R. Cooksey, S. Wu, A. Gode, L. Klesse, J. Oden, G. Vega, L. Gargan, D. Bowers, J. R. Madden, E. Prince, P. Zeitler, N. K. Foreman, A. K. Liu
Journal: Neuro-Oncology (2014)
Abstract BL2: The Challenge of Doing Less
Authors: E Winer
Journal: Cancer Research (2019)

Abstract There are three groups of individuals with breast cancer who present distinct challenges from the standpoint of clinical care and research. First, there are individuals with breast cancer who develop disease that is refractory to all available therapies and ultimately lose their life to breast cancer. Second, there is a large group of women who do not have adequate access to high quality care or choose not to receive it. It is critical, if we are to eliminate mortality from breast cancer, that we bring effective treatment to these individuals. Finally, and importantly, there is a large group of individuals with breast cancer who are unlikely to die from breast cancer and in whom we need to consider minimizing toxic anti-cancer therapy. In recent years, a number of clinical trials have been conducted to reduce treatment intensity in breast surgery, radiation oncology, and medical oncology. These trials are often difficult to conduct. Both physicians and patients worry about leaving benefit on "the table", and hence many may be reluctant to participate. Many individuals are particularly risk averse when there is the potential for loss. In addition, statistical considerations can be challenging and often result in extremely large trials to demonstrate that there is significant loss of benefit when treatment is de-escalated. While the advantage of de-escalation is a reduction in toxicity, many physicians and patients underestimate the impact of side effects, both long- and short-term, on a patient. Examples of de-escalation trials will be reviewed and possible study designs will be discussed. Citation Format: Winer E. The Challenge of Doing Less [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr BL2.
Recruitment and Trial-Finding Apps—Time for Rules of the Road
Authors: Stephanie R Morain, Emily A Largent
Journal: JNCI Journal of the National Cancer Institute (2019)

The problem of insufficient recruitment to clinical oncology trials is well known. Some stakeholders view mobile apps as a solution with the potential to make recruitment more efficient, lower trial costs, support patient-centeredness, and accelerate treatment advances. Recruitment and trial-finding apps seek to disrupt the traditional approach to recruitment in several ways, including aggregating information about ongoing trials and presenting it in a user-friendly format, curating information to tailor search results to prospective participants' interests, facilitating direct contact between prospective participants and trial sites, and, in at least one case, analyzing individuals' tumor samples and medical records to provide tailored recommendations both for approved treatments and clinical trials. Although recruitment and trial-finding apps respond to a real need, they raise ethical concerns. Here, we outline six domains of ethical concern: review of recruitment materials, privacy and confidentiality, constrained choice and conflicts of interest, therapeutic misbranding, payment for accessing research-related information, and disruptions to care and research. We offer several suggestions and encourage additional dialogue to improve the ethical acceptability of these apps because, as third parties increasingly promise to revolutionize clinical trial recruitment by connecting patients and investigators via recruitment and trial-finding apps, we need some rules of the road.
Assessment of the Feasibility and Cost of Hepatitis C Elimination in Pakistan
Authors: Jagpreet Chhatwal, Qiushi Chen, Xiaojie Wang, Turgay Ayer, Yueran Zhuo, Naveed Z. Janjua, Fasiha Kanwal
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Chronic hepatitis C virus (HCV) infection is a global health problem. The World Health Assembly recently pledged to eliminate HCV by 2030. However, in Pakistan, a country with one of the highest prevalence rates, the feasibility and cost of HCV elimination are not known. <h3>Objectives</h3> To investigate whether and under what conditions HCV elimination is feasible in Pakistan and to estimate the cost of such elimination. <h3>Design, Setting, and Participants</h3> This decision analytical model study used a microsimulation model of the HCV epidemic in Pakistan from 2015 to 2030. Using Pakistan-specific variables, the model simulated the landscape of HCV in Pakistan and evaluated the minimum required screening and treatment rates needed to eliminate HCV in Pakistan. The study used simulated individuals chronically infected with HCV from 2015 to 2030. The analysis was performed in 2018. <h3>Interventions</h3> The status quo and 7 scenarios that can lead to HCV elimination in Pakistan by 2030, which were defined by different combinations of tests for screening, detection of viremia before treatment, and confirmation of treatment response. <h3>Main Outcomes and Measures</h3> Temporal trends in HCV infection prevalence, mortality, and disability-adjusted life-years and total cost of HCV infection care under the status quo and scenarios that can eliminate HCV by 2030. <h3>Results</h3> Under the status quo, from 2015 to 2030, 1.44 million people are projected to die of HCV infection; 48% of deaths would be among people younger than 50 years. To achieve HCV elimination in Pakistan, HCV testing would need to be scaled up to at least 25 million people to diagnose 900 000 persons and treatment to 700 000 people per year. Compared with the status quo, the elimination scenario would avert 323 000 liver-related deaths and 13.0 million HCV-associated disability-adjusted life-years from 2015 to 2030. The elimination scenario was associated with cost savings of $2.6 billion from 2018 to 2030 with use of a point-of-care test for population-wide antibody screening and detection of viremia and treatment response. <h3>Conclusions and Relevance</h3> Substantial scale-up of HCV testing and treatment may be essential to eliminate HCV infection in Pakistan, and such a strategy may be associated with cost savings in the near future. Although HCV elimination in Pakistan may be ambitious, strategic planning and strong support from the government may aid in its elimination.
Failure to evolve
Authors: Richard Scott Pye
Journal: BMJ (2010)

At his placement at a small Glaswegian health centre, a fellow student observed what is becoming an all too familiar consultation. The patient, a well looking young woman, had presented with a runny nose and light cough. “I’ll give you a course of antibiotics,” the general practitioner had said. “Come back if it hasn’t cleared up in a week or two.”

This story made me feel dismay: another unnecessary prescription of antibiotics, with another colony of bacteria evolving resistance to its effects. I wondered just how clued up medical professionals …
Placebo-Controlled Trial of an Oral BTK Inhibitor in Multiple Sclerosis
Authors: Xavier Montalban, Douglas L. Arnold, Martin S. Weber, Ivan Staikov, Karolina Piasecka-Stryczynska, Jonathan Willmer, Emily C. Martin, Fernando Dangond, Sana Syed, Jerry S. Wolinsky
Journal: New England Journal of Medicine (2019)

Bruton's tyrosine kinase (BTK) regulates the functions of B cells and myeloid cells that are implicated in the pathogenesis of multiple sclerosis. Evobrutinib is a selective oral BTK inhibitor that has been shown to inhibit B-cell activation both in vitro and in vivo.
We should value competency over empathy
Authors: Joseph O’Keeffe
Journal: BMJ (2015)

During a recent visit to my general practitioner, I had my blood taken by a medical student. He missed and, as his face paled from empathy to my pain, I leaked blood all over the table. Before he could take another stab at it, a stern faced but more competent nurse swooped in to finish the job.

Skim the bibles of modern medical practice, such as Tomorrow’s Doctors or Duties of a Doctor , and you will notice that empathy is regularly cited as a quality all doctors must have.1 Defined as emotional identification with patients, empathy features highly on the entrance criteria of medical schools—part of the general ebb and flow away from biomedical instruction and towards an integrated humanistic curriculum.2 If you don’t have empathy, you must at least …
Development and Evaluation of a New Frailty Index for Older Surgical Patients With Cancer
Authors: Armin Shahrokni, Amy Tin, Koshy Alexander, Saman Sarraf, Anoushka Afonso, Olga Filippova, Jennifer Harris, Robert J. Downey, Andrew J. Vickers, Beatriz Korc-Grodzicki
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Frailty based on the modified Frailty Index is associated with poor postoperative outcomes. However, the index requires high levels of personnel time and effort and often has missing data. <h3>Objective</h3> To evaluate the association of the Memorial Sloan Kettering–Frailty Index (MSK-FI) with established geriatric assessment (GA) and surgical outcomes. <h3>Design, Setting, and Participants</h3> This cohort study included prospectively evaluated patients with cancer 75 years and older who were referred to MSK Geriatrics Service clinics for preoperative evaluation before undergoing surgery requiring hospitalization between February 2015 and September 2017. Patients were comanaged by the Geriatrics Service and Surgery Service in the postoperative period. <h3>Exposures</h3> Impairments identified by GA and comorbid conditions retrieved from submitted<i>International Classification of Diseases, Ninth Revision </i>(<i>ICD-9</i>) and<i>ICD-10</i>codes within the first 48 hours of hospitalization. <h3>Main Outcomes and Measures</h3> The association of MSK-FI score (which included<i>ICD-9</i>and<i>ICD-10</i>codes) with GA impairments (based on clinical interview and examination as well as patient reports) was examined. The associations of MSK-FI score with short-term surgical outcomes (ie, frequency of complications, length of stay, 30-day surgical complications, 30-day intensive care unit admissions, and 30-day readmissions) and 1-year survival, estimated by Kaplan-Meier methods, were determined. <h3>Results</h3> In total, 1137 patients (median [interquartile range] age, 80 [77-84] years; 583 [51.2%] women) were included in the study. A higher MSK-FI score was associated with the number of GA impairments (ρ = 0.52; bootstrapped 95% CI, 0.47-0.56). Each 1-point increase in MSK-FI score was associated with longer length of stay (0.58 d; 95% CI, 0.22-0.95;<i>P</i> = .002) and higher odds of intensive care unit admission (odds ratio, 1.28; 95% CI, 1.04-1.58;<i>P</i> = .02). Median (interquartile range) follow-up among survivors was 12.1 (5.6-19.1) months. The MSK-FI score was associated with overall mortality; 12-month risk of death was 5% for a score of 0 and approximately 20% for scores of 4 and higher (nonlinear association,<i>P</i> = .005). <h3>Conclusions and Relevance</h3> In this study, the MSK-FI was associated with the previously validated GA and postoperative outcomes in older patients with cancer and may be a feasible tool for perioperative assessment of older surgical patients with cancer. Future studies should assess the association of MSK-FI score with postoperative care and outcomes of older, frail patients with cancer.
Validation of the <scp>REVEAL</scp> Prognostic Equation and Risk Score Calculator in Incident Systemic Sclerosis–Associated Pulmonary Arterial Hypertension
Authors: Christopher J. Mullin, Rubina M. Khair, Rachel L. Damico, Todd M. Kolb, Laura K. Hummers, Paul M. Hassoun, Virginia D. Steen, Stephen C. Mathai
Journal: Arthritis & Rheumatology (2019)

Objective A prognostic equation and risk score calculator derived from the Registry to Evaluate Early and Long‐term Pulmonary Arterial Hypertension Disease Management ( REVEAL ) are being used to predict 1‐year survival in patients with pulmonary arterial hypertension ( PAH ), but little is known about the performance of these REVEAL survival prediction tools in systemic sclerosis ( SS c)–associated PAH ( SS c‐ PAH ). Methods Prospectively gathered data from the Johns Hopkins Pulmonary Hypertension Program and Pulmonary Hypertension Assessment and Recognition of Outcome in Scleroderma Registries were used to evaluate the predictive accuracy of the REVEAL models for predicting the probability of 1‐year survival in patients with SS c‐ PAH . Model discrimination was assessed by comparison of the Harrell's C‐index, model fit was assessed using multivariable regression techniques, and model calibration was assessed by comparing predicted to observed survival estimates. Results The validation cohort consisted of 292 SS c‐ PAH patients with a 1‐year survival rate of 87.4%. The C‐index for predictive accuracy of the REVEAL prognostic equation (0.734, 95% confidence interval [95% CI ] 0.652–0.816) and for the risk score (0.743, 95% CI 0.663–0.823) demonstrated good discrimination, comparable to that in the model development cohort. The calibration slope was 0.707 (95% CI 0.400–1.014), indicating that the overall model fit was marginal ( P = 0.06). The magnitude of risk assigned to low distance on the 6‐minute walk test (6 MWD ) and elevated serum levels of brain natriuretic peptide ( BNP ) was lower in the validation cohort than was originally seen in the REVEAL derivation cohort. Model calibration was poor, particularly for the highest risk groups. Conclusion In predicting 1‐year survival in patients newly diagnosed as having SS c‐ PAH , the REVEAL prognostic equation and risk score provide very good discrimination but poor calibration. REVEAL prediction scores should be interpreted with caution in newly diagnosed SS c‐ PAH patients, particularly those with higher predicted risk of poor 1‐year survival resulting from a low 6 MWD or a high BNP serum level.
Abstract SY09-02: Can sitruin activation treat cancer
Authors: Leonard P. Guarente
Journal: Cancer Research (2010)

Abstract SIR2 and related genes are NAD-dependent deacetylases that slow aging in yeast, C. elegans, and Drosophila. In yeast and flies, SIR2 genes are also involved in the longevity conferred by dietary or calorie restriction (CR). The mammalian SIR2 homologs termed SIRT genes, or sirtuins, are involved in changes in stress resistance and metabolism and are known to be associated with CR. Critically, the CR diet in rodents not only extends life span, but also protects against many diseases of aging. In this talk, I will describe recent findings in the field regarding SIRT1 function in specific mammalian tissues in relation to murine disease models, with an emphasis on cancer. Our findings indicate that SIRT1 can influence many of the major diseases of aging, including metabolic diseases like diabetes, neurodegenerative diseases (Alzheimer's and Huntington's), cancer and osteoporosis. Therefore small molecules that alter the activity of SIRT1 (i.e. CR mimetic drugs) offer a new approach to prevent and possibly treat the major diseases of aging. Supported by NIA, The Glenn Foundation, and The AAF. Guarente consults for Sirtris/GSK Guarente, L. (2007). Sirtuins in aging and disease. CSH Symp. Quant. Biol. 72, 483-488. Guarente, L. (2008). Mitochondria - a nexus for aging, calorie restriction and sirtuins?. Cell 132, 171-175. Citation Format: Leonard P. Guarente. Can sitruin activation treat cancer [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SY09-02
Abstract P5-16-13: First results of the NOGGO-AWOGyn observational study: Skin and nipple sparing mastectomy and breast reconstruction with an implant and Epiflex®
Authors: J-U Blohmer, C Ankel, A Faridi, B Krause-Bergmann, C Neumann, K Schnuppe, L Beier, C Mau, H-J Strittmatter, C Gerber-Schäfer, L Bauer, S Paepke
Journal: Cancer Research (2019)

Abstract Acellular dermal matrices (ADM) were used to cover the implant to reduce implant rotations and to improve esthetic results. Current retrospective data on complication rates are heterogeneous. Prospective data are rare. Primary objective was to evaluate the explantation rate. 11 German sites, with experience in breast reconstruction using ADM, have been selected for participation in this study. Patients were enrolled according to predefined in- and exclusion criteria into two cohorts: group A - primary reconstruction and group B - secondary reconstruction after capsular contracture. After documentation of baseline characteristics and surgical parameters, endpoints such as rate of seroma, red breast syndrome, infection and explantation were assed at 1 day, 7 days, 1 month, 3, 6 and 12 months after surgery. In addition, patient- and surgeon-satisfaction were recorded. Data of 83 patients were analyzed (A: 50, B: 33). In 29 patients Epiflex was used bilaterally, so that it was used 112-times in total. The average age of the patient was 45.1 years (A: 41.5; B: 50.3), the average BMI was 22.2 (A: 22.3; B: 22.1). In total, 17.0 % seromas (A: 19.4 %; B: 12.5 %), 10.7 % red breast syndrome (A: 9.7 %; B: 12.5 %), 4.5 % infections (A: 6.9 %; B: 0 %) and 5.4 % explantations (A: 6.9 %; B: 2.5 %) were observed. During the average observation period of 8 month, the satisfaction of the patients and surgeons was high at all measured time points. On a scale from (1 - very satisfied to 6 - not satisfied) the satisfaction of patients and surgeons was 2.3 (A: 2.3; B:1.9) and 2.0 (A: 2.2; B: 1.8) respectively. Our data show, that both patients and surgeons are generally satisfied with the outcome of breast reconstruction using ADM. Complication rates were adequate and commonly lower in secondary reconstructions. Citation Format: Blohmer J-U, Ankel C, Faridi A, Krause-Bergmann B, Neumann C, Schnuppe K, Beier L, Mau C, Strittmatter H-J, Gerber-Schäfer C, Bauer L, Paepke S. First results of the NOGGO-AWOGyn observational study: Skin and nipple sparing mastectomy and breast reconstruction with an implant and Epiflex® [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-16-13.