tbuckley/cabot-search huggingface dataset:
Putting the data before the algorithm in big data addressing personalized healthcare
Authors: Eli M. Cahan, Tina Hernandez-Boussard, Sonoo Thadaney-Israni, Daniel L. Rubin
Journal: npj Digital Medicine (2019)

Abstract Technologies leveraging big data, including predictive algorithms and machine learning, are playing an increasingly important role in the delivery of healthcare. However, evidence indicates that such algorithms have the potential to worsen disparities currently intrinsic to the contemporary healthcare system, including racial biases. Blame for these deficiencies has often been placed on the algorithm—but the underlying training data bears greater responsibility for these errors, as biased outputs are inexorably produced by biased inputs. The utility, equity, and generalizability of predictive models depend on population-representative training data with robust feature sets. So while the conventional paradigm of big data is deductive in nature—clinical decision support—a future model harnesses the potential of big data for inductive reasoning. This may be conceptualized as clinical decision questioning, intended to liberate the human predictive process from preconceived lenses in data solicitation and/or interpretation. Efficacy, representativeness and generalizability are all heightened in this schema. Thus, the possible risks of biased big data arising from the inputs themselves must be acknowledged and addressed. Awareness of data deficiencies, structures for data inclusiveness, strategies for data sanitation, and mechanisms for data correction can help realize the potential of big data for a personalized medicine era. Applied deliberately, these considerations could help mitigate risks of perpetuation of health inequity amidst widespread adoption of novel applications of big data.
Therapeutic effect of gemcitabine on experimental tumors of the brain.
Authors: Viacheslav Chubenko, Aleksandr Nikolaevich Stukov, Olesya Belyaeva, Vladimir Bespalov, Fedor Vladimirovich Moiseenko, Valentina Lukyanchikova, Tatyana Semiglazova, Yaroslav Murazov, Sofia Vershinina
Journal: Journal of Clinical Oncology (2013)

e13005 Background: Gemcitabine has a very modest potency to penetrate blood-brain barrier (BBB). So far it's therapeutic activity in intracranial tumors is unknown. Methods: we explored the effect of gemcitabine (G) on overall survival in models of intracranial Ehrlich's tumor and lymphosarcoma LIO-1. As a comparison for the investigation group we've chosen drugs with different ability to penetrate into brain. We injected BCNU (50 mg/kg), cyclophosphamide (C) (150 mg/kg) and CDDP (9 mg/kg) intraperitoneally once 24 hours after transplantation. Results: The mean overall survival (OS) of mice in a selected model is 9,6+/-0,4 days. The injection of G resulted in substantial increase in OS up to 16,2 +/-0,4 (69%, p = 0,0000). In comparative groups administration of BCNU resulted in an increase in OS of 49% (the average OS 14,3+/-0,8, p = 0.000289), C - in 20% OS increase (11,5+/-0,4, p = 0.00272) and CDDP did not influence OS comparing with control group (10,2+0,4 days, p = 0.315). In other experiment mice with intracranial transplantated lymphosarcoma LIO-1 lived 15.4+1.3 days after single i.p. administration of G (25 mg/kg in 24 hours after transplantation) in comparison with 11.2+0.4 days in control group. The absolute increase of life expectancy was 37.5% (p = 0.013). In control group at 14 day after the transplantation all animals died whereas in G group only 3 mice out of 10 (30 %, g = 0.0003) died. Single i.p. administration of 25 mg/kg G on the 5th day after the intracranial transplantation of LIO-1, increased average OS of the animals from 10,9+ 0,4 days in control group to 13.5±0.5 days (increase in OS 24%, p = 0.0003). Conclusions: In our series of experiment we showed the potency of gemcitabine in treatment of various intracranial tumors. Until our work we can not find any data obtained on efficacy of gemcitabine in this tumor types.
Association of Mental Health Disorders With Health Care Utilization and Costs Among Adults With Chronic Disease
Authors: Barbora Sporinova, Braden Manns, Marcello Tonelli, Brenda Hemmelgarn, Frank MacMaster, Nicholas Mitchell, Flora Au, Zhihai Ma, Robert Weaver, Amity Quinn
Journal: JAMA Network Open (2019)

<h3>Importance</h3> A population-based study using validated algorithms to estimate the costs of treating people with chronic disease with and without mental health disorders is needed. <h3>Objective</h3> To determine the association of mental health disorders with health care costs among people with chronic diseases. <h3>Design, Setting, and Participants</h3> This population-based cohort study in the Canadian province of Alberta collected data from April 1, 2012, to March 31, 2015, among 991 445 adults 18 years and older with a chronic disease (ie, asthma, congestive heart failure, myocardial infarction, diabetes, epilepsy, hypertension, chronic pulmonary disease, or chronic kidney disease). Data analysis was conducted from October 2017 to August 2018. <h3>Exposures</h3> Mental health disorder (ie, depression, schizophrenia, alcohol use disorder, or drug use disorder). <h3>Main Outcomes and Measures</h3> Resource use, mean total unadjusted and adjusted 3-year health care costs, and mean total unadjusted 3-year costs for hospitalization and emergency department visits for ambulatory care–sensitive conditions. <h3>Results</h3> Among 991 445 participants, 156 296 (15.8%) had a mental health disorder. Those with no mental health disorder were older (mean [SD] age, 58.1 [17.6] years vs 55.4 [17.0] years;<i>P</i> &lt; .001) and less likely to be women (50.4% [95% CI, 50.3%-50.5%] vs 57.7% [95% CI, 57.4%-58.0%];<i>P</i> &lt; .001) than those with mental health disorders. For those with a mental health disorder, mean total 3-year adjusted costs were $38 250 (95% CI, $36 476-$39 935), and for those without a mental health disorder, mean total 3-year adjusted costs were $22 280 (95% CI, $21 780-$22 760). Having a mental health disorder was associated with significantly higher resource use, including hospitalization and emergency department visit rates, length of stay, and hospitalization for ambulatory care–sensitive conditions. Higher resource use by patients with mental health disorders was not associated with health care presentations owing to chronic diseases compared with patients without a mental health disorder (chronic disease hospitalization rate per 1000 patient days, 0.11 [95% CI, 0.11-0.12] vs 0.06 [95% CI, 0.06-0.06];<i>P</i> &lt; .001; overall hospitalization rate per 1000 patient days, 0.88 [95% CI, 0.87-0.88] vs 0.43 [95% CI, 0.43-0.43];<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> This study suggests that mental health disorders are associated with substantially higher resource utilization and health care costs among patients with chronic diseases. These findings have clinical and health policy implications.
Toxicity of adjuvant sequential chemo- and radiotherapy of high-risk endometrial carcinoma (HREC)—Results of a phase II multicenter feasibility NOGGO study
Authors: G. Koehler, J. Sehouli, H. Sommer, J. Blohmer, K. Bartz, A. Belau
Journal: Journal of Clinical Oncology (2007)

16074 Background: Isolated adjuvant radio- or chemotherapy (CHT) only reduces local or distant relapses in HREC without impact on overall-survival. Therefore a multicenter feasibility study on adjuvant sequential chemo- and radiotherapy of HREC was initiated in order to evaluate safety and toxicity. Planned number of patients was 40, if after 17 pts. no termination of therapy because of toxicity was necessary, study can be closed and a phase III-study can be initiated. The data on toxicity are presented. Methods: Eligibility criteria: adenocarcinomas G1/G2 stage IC or G3 stage IA-IC or all stages II and IIIA (histological), all tumours with more than 2 cm diameter in size or non endometrioid cancers stage IA-C, II and IIIA and all cases with vessel invasion. Surgery: abdominal hysterectomy with bilateral adnexectomy without lymphadenectomy or with pelvic and para-aortic lymphadenectomy and positive lymph nodes. Further: Karnofsky-Index &gt; 70, normal bone marrow, kidney, and liver function with laboratory tests not higher than 1.5 times of the normal local reference values. CHT: 175 mg/m 2 paclitaxel plus carboplatin AUC 5, q 3 weeks for 4 cycles beginning latest 6 weeks after surgery. Within 6 further weeks after CHT an external beam irradiation (total dose 50.4 Gy, 28 fractions with 1.8 GY/d) plus 3 intracavitary HDR-iridium-192- brachytherapy courses with 3 x 5 GY were performed. Results: To date 17 pts (mean 64.1 years) completed 68 cycles CHT and following radiotherapy. There was no termination of therapy. Grade III leucopenia was observed in 9 % with 2 pts. requiring prolongation of treatment interval. There were 3 and 1 % grade II anemia and thrombocytopenia respectively. Further grade II toxicity: alopecia 38, fatigue 12, nausea/emesis 3, sensory neuropathy 12 %. Administration of G-CSF (pegfilgrastim) and epoitin (darbepoetin) was necessary in 2 and 6 % of cycles. Conclusions: Adjuvant sequential chemo- and radiotherapy of HREC is feasible by safety and toxicity and a phase III study can be initiated. No significant financial relationships to disclose.
Ultrasound-based elastography: “hard” to implement in the pleural effusion work-up?
Authors: José M. Porcel
Journal: European Respiratory Journal (2019)

Thoracic ultrasound (TUS) has been incorporated as a routine bedside tool for the diagnosis of pleural diseases and the performance of safe pleural procedures [1]. It is generally accepted that TUS can provide valuable information on the possible malignant nature of a pleural effusion. Ultrasound appearances suggestive of malignancy include parietal or visceral pleural thickening of more than 1 cm, diaphragmatic thickness greater than 7 mm, pleural or diaphragmatic nodules and liver metastases, but the sonographic fluid characteristics themselves are nonspecific [2, 3]. These imaging criteria, also applicable to computed tomography [4], are highly specific and moderately sensitive when considered in combination. Accuracy data may be influenced by the overrepresentation of certain aetiologies, such as mesotheliomas (increases sensitivity) and tuberculosis (decreases specificity), in the study population. While conventional TUS reports morphological findings, ultrasound elastography provides stiffness information, which can also be potentially used for diagnostic purposes as the study by Jiang et al . [5] demonstrates in this issue of the European Respiratory Journal . Ultrasound elastography may have emerged as an adjunctive tool in combination with conventional ultrasound for pleural effusion differentiation <http://bit.ly/303bYg0>
Characterizing fatigue associated with sunitinib (SU) in patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: David Cella, Mellar P. Davis, Andrew G. Bushmakin, Joseph C Cappelleri, Elizabeth A Hahn, Beata Korytowsky, Helen Bhattacharyya, Rickard Sandin, Jennifer L Beaumont, Ewa Matczak, Robert John Motzer
Journal: Journal of Clinical Oncology (2012)

6092 Background: Fatigue is common in cancer pts and associated with use of tyrosine kinase inhibitors (TKIs) such as SU. Limited data exist on the time pattern of fatigue with TKI therapy. Methods: Data from treatment-naïve mRCC pts in SU arms of two clinical trials were analyzed retrospectively. Study 1; 375 pts were randomized to SU 50 mg/d on a 4 weeks-on-2-weeks-off schedule (Schedule 4/2), for up to 30 cycles. Study 2; pts were randomized to SU 50 mg/d Schedule 4/2 (Group 1; n=146) or 37.5 mg/d continuous daily dosing (CDD; Group 2; n=146). In both trials, fatigue was measured with the question to pts: “I feel fatigued” over the past week (5-point rating scale, not at all-very much), and with the provider-rated Common Terminology Criteria for Adverse Events (CTCAE). In addition to descriptive profiles, Study 1 used two modeling approaches; repeated measures model (M1), with time as a categorical predictor; and random intercept-slope model (M2), with time as a continuous predictor. Study 2 calculated mean absolute values of within-cycle rate of change (from one assessment to the next) through the first 6 treatment cycles. Results: In Study 1, representing fatigue across cycles, M1 showed that the initial increase in patient-reported fatigue was worst during Cycle 1; mean values at all subsequent cycles were numerically better. For CTCAE fatigue, M1 showed that all but one of the pair-wise comparisons of the cycle means were not significantly different. M2 showed that the overall trend for patient-reported fatigue and CTCAE fatigue was not statistically different from zero. In Study 2, the mean absolute rate of change for fatigue during 6 treatment cycles was greater for Group 1 (4/2) compared to Group 2 (CDD): 0.042 vs. 0.032, respectively; P=0.003, t-test. Conclusions: In Study 1, pts reported notable fatigue in Cycle 1, which improved or stabilized, thereafter. In Study 2, Schedule 4/2 was associated with more within-cycle fluctuation in fatigue. These findings illustrate how SU-associated fatigue occurs early in therapy and continues with more within-cycle fluctuation associated with 4/2 dosing. This may help patient-clinician communications and interventions that support maintaining effective therapy.
Abstract 12623: Complementary Role of Exercise Performance and Right Heart Metrics to the Validated MAGGIC score: Insights From a Network Analysis
Authors: Kegan J Moneghetti, Genevieve Giraldeau, Yukari Kobayashi, Miyuki Ariyama, David Boulate, Tatiana Kouznestsova, Ingela Schnittger, Matthew Wheeler, Joseph C Wu, Euan Ashley, Jonathan Myers, Francois Haddad
Journal: Circulation (2016)

Background: Risk stratification in heart failure can be completed with established risk scores. However, right heart metrics, deformation imaging and the cardiopulmonary response to exercise have not been routinely incorporated. We investigated the interaction and incremental prognostic value of novel echocardiographic metrics and exercise performance in a consecutive cohort of patients with dilated cardiomyopathy (DCM). Methods: The Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) score was applied to 208 ambulatory patients with DCM (age 47 ± 13 years) who had undergone echocardiography in conjunction with cardiopulmonary exercise testing. Patients were followed for the composite end point of death, heart transplant, left ventricular device implantation and hospitalization for acute heart failure. Partial correlation network analysis was used to assess interaction between variables. Cox proportional hazard models identified independent predictors of outcome. Results: Mean LVEF and LV GLS were 33 ± 13 % and -10.6 ± 4.4 % respectively. Among echocardiographic variables, LVEF and LV GLS and LV strain rate were strongly related (r = -0.89, and -0.86, respectively, p &lt; 0.01). Age, sex, BMI, LV GLS and RV GLS explained 56% of the variance in peak VO 2 . Over a median follow up of 5.3 years, 60 events occurred including 16 deaths. MAGGIC scores were normally distributed (Figure 1, left) and log rank testing showed significant differences in survival. Cox proportional hazards identified MAGGIC score (1.78 [1.27-2.50], p &lt;0.01), peak VO 2 (HR 0.40 [0.24-0.84], p&lt;0.01) and right atrial volume indexed (RAVI) (HR 1.10 [1.02-1.19], p = 0.01) as independently associated with outcome. In combination these variables were incremental in prognostic value compared to MAGGIC score alone ( x 2 = 65 vs 42, p &lt;0.01, Figure 1, right). Conclusion: In patients with DCM exercise performance and RAVI provide incremental prognostic value when combined with the validated MAGGIC score.
MMR vaccine: Johnson urges new impetus to increase uptake as UK loses measles-free status
Authors: Jacqui Wise
Journal: BMJ (2019)

The prime minister, Boris Johnson, has said that urgent action is needed to boost the number of children receiving the measles, mumps, and rubella (MMR) vaccine after the UK lost its measles-free status with the World Health Organization.

In the first quarter of 2019 some 231 cases of measles were confirmed in the UK. Many of these were acquired abroad, with some onward spread in under-vaccinated communities. The UK achieved measles-free status in 2016 after three years of limited spread due to high vaccination rates. However, a small but steady decline in MMR vaccine coverage has been measured in recent years.

Earlier this month WHO warned that, in the first six months of 2019, almost three times as many measles cases were reported globally as in the …
Subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors: phase 2 trial results
Authors: Amy D. Shapiro, Pantep Angchaisuksiri, Jan Astermark, Gary Benson, Giancarlo Castaman, Pratima Chowdary, Hermann Eichler, Victor Jiménez-Yuste, Kaan Kavakli, Tadashi Matsushita, Lone Hvitfeldt Poulsen, Allison P. Wheeler, Guy Young, Silva Zupancic-Salek, Johannes Oldenburg
Journal: Blood (2019)
Effects of intravenous (IV) iron supplementation on responses to every-3-week (Q3W) darbepoetin alfa (DA) by baseline hemoglobin in patients (pts) with chemotherapy-induced anemia (CIA)
Authors: T. Pinter, T. Mossman, T. Suto, J. Vansteenkiste
Journal: Journal of Clinical Oncology (2007)

9106 Background: Pts with CIA receiving erythropoiesis-stimulating agents (ESAs) may benefit from IV iron supplementation. This randomized, multicenter, open-label, 16-week, phase IIIb study evaluated the safety and efficacy of darbepoetin alfa in pts with CIA who also received IV iron versus oral iron/no iron. This exploratory analysis presents the clinical outcomes by subgroups based on baseline (BL) hemoglobin (Hb). Methods: Eligible pts were of legal age, had a non-myeloid malignancy, and had CIA (BL Hb &lt; 11g/dL). All pts received DA 500 mcg administered Q3W using the Aranesp (darbepoetin alfa) prefilled SureClick autoinjector. Patients were randomly allocated 1:1 to receive either DA plus 200 mg IV iron (200 mg Q3W with DA Q3W or two 100 mg doses within 3 weeks) or DA plus oral iron/no iron. Randomization was stratified by tumor type and BL Hb category (&lt; 10 or = 10 g/dL). The primary endpoint was the percentage of pts achieving a hematopoietic response (Hb = 12 g/dL or an increase = 2 g/dL). Results: A total of 396 pts were randomized and received = 1 dose of DA (IV iron arm = 200; oral iron/no iron arm = 196). Mean (SD) age was 61.0 (11.5) years; 61% (n = 240) were women; 28% (n = 111) had lung or gynecological tumors; and 45% (n = 178) had BL Hb &lt; 10 g/dL. Pt demographics were similar between arms. Clinical outcomes are shown in the table by BL Hb. Conclusions: DA 500 mcg Q3W with IV iron supplementation appeared to improve clinical outcomes in this study, especially in pts with BL Hb &lt; 10 g/dL; more pts achieved a hematopoietic response, fewer received transfusions, and more achieved the target Hb (= 11 g/dL) compared with those receiving oral iron/no iron. Also, in both treatment arms, pts with BL Hb = 10 g/dL demonstrated better clinical outcomes than pts with BL Hb &lt; 10 g/dL. Benefits associated with initiating ESA treatment on time, ie before pts Hb falls &lt; 10 g/dL, have been suggested previously (Lyman and Glaspy, Cancer 2006). [Table: see text] No significant financial relationships to disclose.
Antibody Responses to Cancer Antigens Identify Patients with a Poor Prognosis among HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma Patients
Authors: Simon Laban, Dominik S. Gangkofner, Dana Holzinger, Lea Schroeder, Stefan B. Eichmüller, Inka Zörnig, Dirk Jäger, Gunnar Wichmann, Andreas Dietz, Martina A. Broglie, Christel C. Herold-Mende, Gerhard Dyckhoff, Paolo Boscolo-Rizzo, Jasmin Ezić, Ralf Marienfeld, Peter Möller, Johann M. Kraus, Gunnar Völkel, Hans A. Kestler, Cornelia Brunner, Patrick J. Schuler, Marlene C. Wigand, Marie-Nicole Theodoraki, Johannes Doescher, Thomas K. Hoffmann, Michael Pawlita, Tim Waterboer, Julia Butt
Journal: Clinical Cancer Research (2019)

The identification of high-risk patients within human papillomavirus (HPV)-positive and -negative head and neck squamous cell carcinoma (HNSCC) is needed for improved treatment and surveillance strategies. In this study, we set out to discover antibody responses (AR) with prognostic impact in HNSCC stratified by HPV status.A fluorescent bead-based multiplex serology assay on 29 cancer antigens (16 cancer-testis antigens, 5 cancer-retina antigens, and 8 oncogenes) and 29 HPV antigens was performed in samples of 362 patients with HNSCC from five independent cohorts (153 HPV positive, 209 HPV negative). A multivariable Cox proportional hazard model with bootstrapping (M = 1000) was used for validation of prognostic antibody responses.Antibody response to any of the cancer antigens was found in 257 of 362 patients (71%). In HPV-negative patients, antibody responses to c-myc, MAGE-A1, -A4, and Rhodopsin E2 (combined as ARhigh risk) were significantly associated with shorter overall survival. In HPV-positive patients, antibody responses to IMP-1 were discovered as a negative prognostic factor. ARhigh risk (HR = 1.76) and antibody responses to IMP-1 (HR = 3.28) were confirmed as independent markers for a poor prognosis in a multivariable Cox proportional hazard model with bootstrapping (M = 1000).We identified antibody responses to cancer antigens that associate with a dismal prognosis in patients with HNSCC beyond HPV-positive status. ARhigh risk may be used to detect HPV-negative patients with an extraordinarily bad prognosis. Most importantly, antibody response to IMP-1 may serve as a marker for a subgroup of HPV-positive patients who present with a poor prognosis similar to that in HPV-negative patients.
Pension crisis: trusts take matters in their own hands
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Frustrated with government inaction, some NHS organisations have taken steps to shore up their workforce for the winter, reports Gareth Iacobucci Some NHS trusts are already taking action to tackle the NHS pensions crisis ahead of the government’s proposed solution, out of concern about the ongoing effects on their workforce, The BMJ has learnt. On 6 August, after months of lobbying by the BMA and employers, the government announced that it would consult on plans to allow doctors in England and Wales to control how much they pay into their pensions from April 2020, to avoid punitive tax charges that apply when the tax free allowance on the value of their pension is exceeded (box 1).1 Box 1 ### What we know about the proposed reforms so far #### What are the problems? Changes to pension tax rules introduced in 2016 meant that as earnings go up the amount of pension that can be saved without incurring tax goes down. Everyone pays tax on any growth of the deemed value of their pension above the tax free annual allowance of £40 000. The “taper” that was introduced meant that, for every £2 of “adjusted income” (all taxable income plus pension growth) above £150 000, the annual allowance is “tapered down” by £1, to a minimum of £10 000. In practice, most doctors with a taxable income of £160 000 to £170 000 face full tapering of their tax free allowance if they remain in the NHS pension. Some have received tax bills of £60 000 and have reduced their working hours or retired early as a result. The current lifetime allowance is £1.055m. Contributions rise with salary and range from 5% to 14.5%. Employers’ contributions range from 14.38% to 20.68%. #### What is the government consulting on? Giving senior clinicians flexibility to set the exact amount they put into their pension pots. For example, they could pay 30% contributions for a 30% accrual rate, or any other … RETURN TO TEXT