tbuckley/cabot-search huggingface dataset:
Association of Prognostic Estimates With Burdensome Interventions in Nursing Home Residents With Advanced Dementia
Authors: Andrea J. Loizeau, Michele L. Shaffer, Daniel A. Habtemariam, Laura C. Hanson, Angelo E. Volandes, Susan L. Mitchell
Journal: JAMA Internal Medicine (2018)

Prognostication in advanced dementia is challenging but may influence care.To determine the accuracy of proxies' prognostic estimates for nursing home residents with advanced dementia, identify factors associated with those estimates, and examine the association between their estimates and use of burdensome interventions.Data were combined from 2 studies that prospectively followed 764 residents with advanced dementia and their proxies in Boston-area nursing homes for 12 months: (1) the Study of Pathogen Resistance and Exposure to Antimicrobials in Dementia, conducted from September 2009 to November 2012 (362 resident/proxy dyads; 35 facilities); and (2) the Educational Video to Improve nursing home Care in End-Stage Dementia, conducted from March 2013 to July 2017 (402 resident/proxy dyads; 62 facilities). Proxies were the residents' formally or informally designated medical decision makers.During quarterly telephone interviews, proxies stated whether they believed the resident would live less than 1 month, 1 to 6 months, 7 to 12 months, or more than 12 months. Prognostic estimates were compared with resident survival. Resident and proxy characteristics associated with proxy prognostic estimates were determined. The association between prognostic estimates and whether residents experienced any of the following was determined: hospital transfers, parenteral therapy, tube feeding, venipunctures, and bladder catheterizations.The residents' mean (SD) age was 86.6 (7.3) years; 631 (82.6%) were women and 133 (17.4%) were men. Of the 764 residents, 310 (40.6%) died later than 12 months. Proxies estimated survival with moderate accuracy (C statistic, 0.67). When proxies perceived the resident would die within 6 months, they were more likely to report being asked (183 [7.2%] of 2526) vs not being asked (126 [5.0%] of 2526) about goals of care by nursing home clinicians (adjusted odds ratio [AOR], 1.94; 95% CI, 1.50-2.52). Residents were less likely to experience burdensome interventions when the proxy prognostic estimate was less than 6 months (89 [4.4%] of 2031) vs greater than 6 months (1008 [49.6%] of 2031) (AOR, 0.46; 95% CI, 0.34-0.62).Proxies estimated the prognosis of nursing home residents with advanced dementia with moderate accuracy. Having been asked about their opinion about the goal of care was associated with the proxies' perception that the resident had less than 6 months to live and that perception was associated with a lower likelihood the resident experienced burdensome interventions.
AB0179 Bone mineral density measurements in obese patients
Authors: A Atalay, S Arslan, R Çeliker
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Obese patients are prone to develop many medical conditions, including musculoskeletal problems. Obesity seems to have a protective effect on bone explained by metabolic mechanisms. Further studies will lead to better understanding of the impact of the weight on bone mineral density (BMD) measurements. <h3>Objectives</h3> The aim of this study was to evaluate the relationship between obesity and lumbar and femoral BMD measurements. <h3>Methods</h3> The study population consisted of 71 female patients from our outpatient clinics. Clinical assessment and anthropometric measurements (height, weight, abdominal circumference, waist circumference, triceps skinfold thickness) were performed by the same physician. Body mass index (BMI) was calculated as kg/m<sup>2</sup> and cut-off points defined by World Health Organisation (WHO) were used to identify obesity. Cut-off values are as follows: 18.5–24.99: normal, 25.0–29.99 grade1 overweight, 30.0–39.99 grade 2 overweight, &gt; = 40.0 grade 3 overweight. Lumbar and femoral BMD measurements were obtained using dual energy X-ray absorptiometry (DEXA) (Hologic QDR 4500A). Subjects were divided into two groups: subjects with BMI &lt; = 29.9 and subjects &gt; 29.9, and statistical analysis were carried out accordingly. p &lt; 0.05 was considered to be statistically significant. <h3>Results</h3> The mean age of the subjects was 52.96 ± 10.87 years (range:25–78 years) and mean BMI was 31.40 ± 5.62 (range: 21.91–47.27). According to WHO criteria: 12 subjects (16.9%) were within the normal range, 16 subjects (22.5%) were grade 1 obese, 39 subjects (54.9%) grade 2 obese and 4 subjects (5.6%) grade 3 obese. BMD measurements in all areas examined (lumbar total, L1, L2, L3, L4, intertrochanteric, neck, trochanteric and femoral total) were correlated with anthropometric measurements. BMI was positively correlated with lumbar and femoral bone mineral density measurements in all regions evaluated. BMD measurements in all areas examined (lumbar total, L1, L2, L3, L4, intertrochanteric, neck, trochanteric and femoral total) were compared according to two groups (BMI &lt; = 29.9, BMI &gt; 29.9). In all areas there was a significant difference between the two groups in favour of the obese group. <h3>Conclusion</h3> In accordance with the previous studies, our study indicates the positive relationship between obesity and bone mineral density measurements. <h3>Reference</h3> World Health Organization. Physical status: <i>The use and interpretation of anthropometry. Report of a WHO expert committee</i>. Geneva: World Health Organization, 1995
Evaluation of the best cut-off point for Ki-67 and progesterone receptor as a prognostic factor in hormone receptor-positive (HR+) breast cancer.
Authors: Diego Hernán Enrico, Adrian Ricardo Hannois, Inés Bravo
Journal: Journal of Clinical Oncology (2018)

e12549 Background: Because in much of the world the analysis of intrinsic subtype of breast cancer are not available, surrogate approaches have been developed using Immunohistochemistry (IHC) measurement of estrogen receptor, progesterone receptor (PR), HER2 and Ki-67. Different cut-off points for Ki-67 and RP have been established mainly to differentiate the Luminal A and Luminal B subtypes by IHC, but without total international agreement. The aim of this study was to identify the best cut-off point for Ki-67 and PR expression to stratify the prognosis of patients with HR+ breast cancer. Methods: We retrospectively examined a mono-institutional cohort of 506 stage I-III breast cancer patients with ER+ and/or PR+ and HER2+/-, diagnosed between 1998 and 2016. Univariate Cox-regression analysis for disease-free survival (DFS) was performed using different Ki-67 and PR cut-off points and comparing the hazard ratios (HR). ROC curves were used to determine the accurate value with the best sensitivity and specificity to predict relapse. In order to estimate the association between Ki-67 and PR values with the other standard clinico-pathological variables, multivariable Cox proportional hazards regression model was used. Results: The univariate analysis of Ki-67, revealed that the cut-off point of 20% had the highest HR for DFS (HR 7.14; 95% CI, 3.87 to 13.16; p < 0.001). For PR this value was 30% (HR 5.30; 95% IC, 3,02 to 9.31; p < 0.001). ROC curve analysis showed that Ki-67 of 23.4% (AUC 0.72; p < 0.001) and PR of 32.5% (AUC 0.77; p < 0.001) had the best sensitivity and specificity to predict relapse. The multivariate analysis confirmed that these values were independently associated with DFS (Table). Conclusions: In our study, Ki-67 of 23.4% and PR of 32.5% were the most effective cut-off points to be used as independent prognostic factors in HR+ breast cancer patients. Multivariate analysis for DFS. Variables DFS HR (95% CI) p-value Grade (3 vs 2/1) 1.37 (0.73-2.57) 0.322 Tumor size ( > 2 cm vs ≤2 cm) 1.64 (0.71-3.81) 0.247 HER2 (+ vs -) 2.15 (1.02-4.54) 0.044 Node Status (+ vs -) 3.34 (1.59-6.99) 0.001 PR (≤32.5% vs > 32.5%) 2.89 (1.44-5.79) 0.003 Ki-67 ( > 23.4% vs ≤23.4%) 3.52 (1.66-7.49) 0.001
Ibrutinib as Treatment for Patients With Relapsed/Refractory Follicular Lymphoma: Results From the Open-Label, Multicenter, Phase II DAWN Study
Authors: Ajay K. Gopal, Stephen J. Schuster, Nathan H. Fowler, Judith Trotman, Georg Hess, Jing-Zhou Hou, Abdulraheem Yacoub, Michael Lill, Peter Martin, Umberto Vitolo, Andrew Spencer, John Radford, Wojciech Jurczak, James Morton, Dolores Caballero, Sanjay Deshpande, Gary J. Gartenberg, Shean-Sheng Wang, Rajendra N. Damle, Michael Schaffer, Sriram Balasubramanian, Jessica Vermeulen, Bruce D. Cheson, Gilles Salles
Journal: Journal of Clinical Oncology (2018)

Purpose The Bruton's tyrosine kinase inhibitor ibrutinib has demonstrated clinical activity in B-cell malignancies. The DAWN study assessed the efficacy and safety of single-agent ibrutinib in chemoimmunotherapy relapsed/refractory follicular lymphoma (FL) patients. Methods DAWN was an open-label, single-arm, phase II study of ibrutinib in patients with FL with two or more prior lines of therapy. Patients received ibrutinib 560 mg daily until progressive disease/unacceptable toxicity. The primary objective was independent review committee-assessed overall response rate (ORR; complete response plus partial response). Exploratory analyses of T-cell subsets in peripheral blood (baseline/cycle 3) and cytokines/chemokines (baseline/cycle 2) were performed for available samples. Results Between March 2013 and May 2016, 110 patients with a median of three prior lines of therapy were enrolled. At median follow-up of 27.7 months, ORR was 20.9% (95% CI, 13.7% to 29.7%, which did not meet the 18% lower-bound threshold for the primary end point). Twelve patients achieved a complete response (11%; 95% CI, 5.8% to 18.3%). Median duration of response was 19.4 months (range, 1 to ≥ 33 months), with a median progression-free survival of 4.6 months and a 30-month overall survival of 61% (95% CI, 0.51% to 0.70%). Lymphoma symptoms resolved in 67%. Seven of 32 patients who experienced initial radiologic progression responded upon continuing therapy (pseudoprogression). The most common adverse events were diarrhea, fatigue, cough, and muscle spasms; 48.2% of patients reported serious adverse events. In patients who experienced a response, regulatory T cells were downregulated at C3D1 ( P = .02), and Th1-promoting (antitumor) cytokines interferon-γ and interleukin-12 increased ( P ≤ .035). Conclusion With an ORR of 20.9%, ibrutinib failed to meet its primary efficacy end point in chemoimmunotherapy in patients with relapsed/refractory FL, although responses were durable and associated with a reduction in regulatory T cells and increases in proinflammatory cytokines.
Abstract 12421: Association Between Distance-to-index And Phenotype In Familial Hypercholesterolemia
Authors: Joost Besseling, Roeland Huijgen, Seth S Martin, Barbara A Hutten, John J Kastelein, Gerard K Hovingh
Journal: Circulation (2015)

Introduction: Familial hypercholesterolemia (FH) is a genetic disorder characterized by severely increased levels of low-density lipoprotein cholesterol (LDL-C) and premature cardiovascular disease (CVD). Early identification of patients is warranted, to initiate preventive therapy. Genetic cascade screening has been exploited during the last two decades in the Netherlands. However, since the cascade starts with an FH patient with high clinical suspicion, the FH phenotype might deflate in family members with FH who are identified in subsequent steps of cascade testing. We set out to test this hypothesis. Methods: We analyzed heterozygous FH patients identified by the genetic cascade screening program in the Netherlands from 1994 to 2014. A cascade starts with identification of a genetically proven FH patient (“index patient”) followed by testing in first degree relatives. If a mutation is found in one of them, their first degree relatives are tested as well, and so on. The association between exposure (i.e. distance to the index [1st, 2nd, 3rd or 4th or more degree family member]) and primary outcome (i.e., LDL-C level) was evaluated using linear regression models. Second, we tested whether increasing distance-to-index was associated with decreasing CVD risk by means of Cox proportional hazard models. In all regression analyses we adjusted for potential confounders and family relations. Results: A total of 64,171 persons participated in the screening program, of whom 26,176 had molecularly defined heterozygous FH. Of these, 4,531 (17%) were index patients. The distance-to-index could be determined in 13,392 (61%) of the remaining FH patients. Mean (± standard error) levels of LDL-C modestly decreased with increasing distance-to-index: 211 (56), 199 (54), 189 (52) and 178 (51) mg/dL in 1st, 2nd, 3rd and 4th or more, respectively (p-for-trend: 0.005). The adjusted hazard ratio of increasing distance-to-index for CVD was 0.92 (95% CI: 0.82 - 1.03). Conclusions: To our knowledge, this is the first study ever investigating the association between distance-to-index and the phenotype of a monogenetic disorder. The absence of a strong association between distance-to-index LDL-C or and CVD risk in FH lends support for genetic cascade testing.
The CHANCE study: A prospective, longitudinal study of chemotherapy and hormonal therapy induced hair changes and alopecia, skin aging and nail changes in women with non-metastatic breast cancer.
Authors: Mario E. Lacouture, Azael Freites-Martinez, Sujata Patil, Andrea Samuels, Jerry Shapiro, Kathryn Ciccolini, Oluwaseun Kukoyi, Shari Beth Goldfarb
Journal: Journal of Clinical Oncology (2018)

e12500 Background: Late effects such as persistent alopecia, skin aging, and nail dystrophy resulting from cytotoxic or endocrine agents used in early stages of breast cancer are poorly understood. The objective of the study is to describe the incidence, clinical pattern, severity and risk factors for permanent sequelae of adjuvant breast cancer therapies affecting the skin, hair, and nails, and evaluate their impact on patients quality of life (QoL). Methods: This is a single-center, prospective, longitudinal cohort study of non-metastatic breast cancer patients treated with cytotoxic chemotherapies and/or endocrine therapies. A total of 500 patients will be enrolled in each of 5 treatment cohorts, who will be followed for up to 3 years using standardized clinical images, objective skin hydration and elasticity measurements, and patient-reported outcome QoL questionnaires. Results: At data cutoff on 12/2017, 327 patients (65.4% of 500 patients), and 91 volunteers have been enrolled, and the study is ongoing. A total of 138 (42.2%) patients have been assessed at 6 months after chemotherapy completion (cohorts 1-3), or one year after the initiation of endocrine therapy (cohorts 4-5). Persistent scalp alopecia (pCIA) was identified in 23 patients (16.8%), most with grade 1 in severity (95.7%). Persistent madarosis (eyebrow/lash loss) was observed in 48 (35%), and hirsutism in 6 (4%). Facial skin aging was observed in 4 (3%) and persistent nail changes (including nail ridging, discoloration and onycholysis) were observed in 86 (78%). QoL questionnaires were completed at baseline and follow-up by 85 patients, and an overall worsening on QoL based on their hair condition was found (CADS questionnaire mean baseline; 1.18 vs follow-up; 1.30). Conclusions: Preliminary data from the CHANCE study shows that early-stage breast cancer patients may develop persistent scalp/eyebrow/lash alopecia and nail changes. Less frequently, hirsutism and skin aging were also observed. Despite the majority of these events being grade 1 in severity, a negative impact on QoL was revealed. Clinical trial information: NCT02530177.
The finding of casual sex partners on the internet, methamphetamine use for sexual pleasure, and incidence of HIV infection among men who have sex with men in Bangkok, Thailand: an observational cohort study
Authors: Phunlerd Piyaraj, Frits van Griensven, Timothy H Holtz, Philip A Mock, Anchalee Varangrat, Wipas Wimonsate, Warunee Thienkrua, Jaray Tongtoyai, Atitaya McNamara, Wannee Chonwattana, Kenrad E Nelson
Journal: The Lancet HIV (2018)
The FDA and the Next Wave of Drug Abuse — Proactive Pharmacovigilance
Authors: Douglas C. Throckmorton, Scott Gottlieb, Janet Woodcock
Journal: New England Journal of Medicine (2018)

The FDA and the Next Wave of Drug Abuse In responding to the opioid crisis, the FDA needs to recognize shifting trends in the addiction landscape. Taking a systematic approach to monitoring such trends should allow the agency to intervene promptly and appropriately to protect the public from associated risks.
Outcome in patients perceived as receiving excessive care across different ethical climates: a prospective study in 68 intensive care units in Europe and the USA
Authors: D. D. Benoit, H. I. Jensen, J. Malmgren, V. Metaxa, A. K. Reyners, M. Darmon, K. Rusinova, D. Talmor, A. P. Meert, L. Cancelliere, L. Zubek, P. Maia, A. Michalsen, S. Vanheule, E. J. O. Kompanje, J. Decruyenaere, S. Vandenberghe, S. Vansteelandt, B. Gadeyne, B. Van den Bulcke, E. Azoulay, R. D. Piers
Journal: Intensive Care Medicine (2018)

Whether the quality of the ethical climate in the intensive care unit (ICU) improves the identification of patients receiving excessive care and affects patient outcomes is unknown. In this prospective observational study, perceptions of excessive care (PECs) by clinicians working in 68 ICUs in Europe and the USA were collected daily during a 28-day period. The quality of the ethical climate in the ICUs was assessed via a validated questionnaire. We compared the combined endpoint (death, not at home or poor quality of life at 1 year) of patients with PECs and the time from PECs until written treatment-limitation decisions (TLDs) and death across the four climates defined via cluster analysis. Of the 4747 eligible clinicians, 2992 (63%) evaluated the ethical climate in their ICU. Of the 321 and 623 patients not admitted for monitoring only in ICUs with a good (n = 12, 18%) and poor (n = 24, 35%) climate, 36 (11%) and 74 (12%), respectively were identified with PECs by at least two clinicians. Of the 35 and 71 identified patients with an available combined endpoint, 100% (95% CI 90.0–1.00) and 85.9% (75.4–92.0) (P = 0.02) attained that endpoint. The risk of death (HR 1.88, 95% CI 1.20–2.92) or receiving a written TLD (HR 2.32, CI 1.11–4.85) in patients with PECs by at least two clinicians was higher in ICUs with a good climate than in those with a poor one. The differences between ICUs with an average climate, with (n = 12, 18%) or without (n = 20, 29%) nursing involvement at the end of life, and ICUs with a poor climate were less obvious but still in favour of the former. Enhancing the quality of the ethical climate in the ICU may improve both the identification of patients receiving excessive care and the decision-making process at the end of life.
David Oliver: Constant structural reorganisation won’t improve or transform healthcare
Authors: David Oliver
Journal: BMJ (2018)

NHS leaders and politicians seem to have an endless obsession with organisational restructuring. The King’s Fund has produced narrated animations of the NHS “organogram,”12 showing the bewilderingly complex accountabilities created by the 2012 Health and Social Care Act3 and subsequent new organisational forms and workarounds, such as integrated care systems emerging from NHS England’s Five Year Forward View .4

In May 2018 a report presented at a meeting of the boards of NHS Improvement and NHS England set out why and how the two bodies should work more closely.5 In the same week the health policy analyst Nick Timmins, in The World’s Biggest Quango ,6 reflected on how differently NHS England now operates from the …
Reply to Mark C. Kendall's Letter to the Editor re: Karl H. Pang, Ruth Groves, Suresh Venugopal, Aidan P. Noon, James W.F. Catto. Prospective Implementation of Enhanced Recovery After Surgery Protocols to Radical Cystectomy. Eur Urol 2018;73:363–71
Authors: Karl H. Pang, Ruth Groves, James W.F. Catto
Journal: European Urology (2018)
Increased liver stiffness in patients with severe sleep apnoea and metabolic comorbidities
Authors: Wojciech Trzepizur, Jérôme Boursier, Marc Le Vaillant, Pierre-Henri Ducluzeau, Séverine Dubois, Samir Henni, Pierre Abraham, Christophe Aubé, Paul Calès, Frédéric Gagnadoux
Journal: European Respiratory Journal (2018)

The goal of this study was to assess the relationship between the severity of obstructive sleep apnoea (OSA) and liver stiffness measurement (LSM), one of the most accurate noninvasive screening tools for liver fibrosis in nonalcoholic fatty liver disease.The study included 147 patients with at least one criterion for the metabolic syndrome, assessed by polysomnography for suspected OSA. LSM was performed using transient elastography (FibroScan). Significant liver disease and advanced liver fibrosis were defined as LSM ≥7.3 and ≥9.6 kPa, respectively.23 patients were excluded because of unreliable LSM. Among 124 patients, 34 (27.4%) had mild OSA, 38 (30.6%) had moderate OSA and 52 (42.0%) had severe OSA. LSM values were 7.3- <9.6 kPa in 18 (14.5%) patients and ≥9.6 kPa in 15 (12.1%) patients. A dose-response relationship was observed between OSA severity and LSM values (p=0.004). After adjustment for age, sex, metabolic syndrome and insulin resistance, severe OSA was associated with an increased risk of LSM ≥7.3 kPa (OR 7.17, 95% CI 2.51-20.50) and LSM ≥9.6 kPa (OR 4.73, 95% CI 1.25-17.88).In patients with metabolic comorbidities, severe OSA is independently associated with increased liver stiffness, which may predispose to a higher risk of significant liver disease and poorer prognosis.
Suppression of detyrosinated microtubules improves cardiomyocyte function in human heart failure
Authors: Christina Yingxian Chen, Matthew A. Caporizzo, Kenneth Bedi, Alexia Vite, Alexey I. Bogush, Patrick Robison, Julie G. Heffler, Alex K. Salomon, Neil A. Kelly, Apoorva Babu, Michael P. Morley, Kenneth B. Margulies, Benjamin L. Prosser
Journal: Nature Medicine (2018)
The Incidence of Tuberculosis in the United States Among Persons Infected with the Human Immunodeficiency Virus
Authors: N. Markowitz, Nellie Hansen, P. Hopewell, J. Glassroth, P. Kvale, B. Mangura, Timothy Wilcosky, J. Wallace, M. Rosen, L. Reichman
Journal: Annals of Internal Medicine (1997)
Obstetrics registrar gets nine month suspension for poor communication skills
Authors: Clare Dyer
Journal: BMJ (2018)

A locum registrar in obstetrics and gynaecology who internally examined a patient so roughly that she reported him to police has been suspended from the UK medical register for nine months.

Abdelkarim Mohamed failed to wear hospital identification or introduce himself to two patients before examining them on the same day in June 2016 at Northampton General Hospital.

Mohamed, who qualified in Sudan in 1977, did not attend his Manchester hearing and had last communicated briefly with the General Medical Council by email in 2016. The tribunal did not know his current whereabouts, although he was last known to be working in the Republic of Ireland.

Stephen Killen, chairing the tribunal, noted that “a common theme from the evidence given by each of the witnesses . . . was the issue of Dr Mohamed’s communication skills, or lack thereof.”

One colleague …
Letter by Löwe et al Regarding Article, “Low-Density Lipoprotein Cholesterol Lowering for the Primary Prevention of Cardiovascular Disease Among Men With Primary Elevations of Low-Density Lipoprotein Cholesterol Levels of 190 mg/dL or Above: Analyses From the WOSCOPS (West of Scotland Coronary Prevention Study) 5-Year Randomized Trial and 20-Year Observational Follow-Up”
Authors: Axel Lennart Löwe, Tinh-Hai Collet, Nicolas Rodondi
Journal: Circulation (2018)