Miracle-dz/UniFAR-FTUs huggingface dataset:
Stromal gene signatures in large-B-cell lymphomas.

BACKGROUND The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear. METHODS We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group. RESULTS A multivariate model created from three gene-expression signatures--termed "germinal-center B-cell," "stromal-1," and "stromal-2"--predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infiltration. By contrast, the prognostically unfavorable stromal-2 signature reflected tumor blood-vessel density. CONCLUSIONS Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment.
Correlation between Pulmonary Artery Pressure Measured by Echocardiography and Right Heart Catheterization in Patients with Rheumatic Mitral Valve Stenosis (A Prospective Study)

Right heart catheterization (RHC) remains the gold standard for hemodynamic assessment of the right heart and pulmonary artery. However, this is an invasive tool, and noninvasive alternatives such as transthoracic echocardiography (TTE) are preferable. Nonetheless, the correlation between measurements by TTE and RHC are debated. In this study, we prospectively examined the correlation between systolic and mean pulmonary artery pressures (sPAP and mPAP) measured by RHC and TTE in patients with hemodynamically significant rheumatic mitral stenosis (MS).
An evaluation of interprofessional education for health and social care professionals : the teachers' views

There is accumulative evidence and successive government policy to suggest that the health and social care professions need to provide integrated services to the public. Interprofessional education is regarded as a solution to the problem and has developed from this demand. Educational initiatives of an interprofessional nature are now a regular occurrence. The role of the teacher in facilitating these programmes has been largely overlooked. The purpose of this thesis was to address this imbalance. The study adopted the illuminative evaluation paradigm to investigate the teachers' perceptions of interprofessional education and shared learning milieu. It took the form of three surveys. The first survey addressed the perceptions of the course leaders in centres for teacher education. The second survey involved new teachers, mentors and managers in colleges for nursing and midwifery education at that time. The third survey addressed interprofessional education from the perceptions of teachers of health and social care professions who were involved in IPE programmes in higher education. The central research question underlying the study was how do teachers view and implement IPE? Essential to this was the question are teachers prepared for their role in interprofessional education? Multiple methods were used to collect the data and both quantitative and qualitative methods were used in analysis. Non parametric statistics were applied to quantitative data. Computer assisted analysis was used for the qualitative data through a purpose built database using ACCESS software. The results showed that teachers or students did not have preparation for interprofessional education while the majority of teachers felt that they required it. The evidence suggested a lack of commitment at strategic level, and a lack of structuring and planning of resources to accommodate this type of education. Teachers were aware of the benefits interprofessional education could offer, but were sceptical as to the motives underlying it. In reality, interprofessional education was less than the proposed principles behind it.
DEA Applied to a Gauteng Sample of South African Public Hospitals

The ability of the South African government to provide antiretroviral medication to those in need will be determined by the ability of the public health services sector to efficiently provide that medication. If the delivery of other health services can be used as a guide, the goals of the anti-retroviral rollout will not be met. The research presented in this paper provides a preliminary analysis of the delivery of a few health care services by the public sector in Gauteng, South Africa. The data for the study was especially difficult to collect, suggesting the need for hospital level data information systems, as well as staff trained to analyse the information collected. The empirical results from the analysis suggest that services provided by small-scale medical facilities waste fewer resources, while medical centres offering more technical services, such as surgeries, also appear to deliver medical services more efficiently.
Depression and Unmet Needs for Assistance With Daily Activities Among Community-Dwelling Older Adults

Background and Objectives This study aims to investigate the impact of depressive symptoms on adverse consequences of unmet needs for assistance with daily activities among community-dwelling older adults. Research Design and Methods Data came from round 1 to 5 of the National Health and Aging Trends Study. Study sample consisted of 3,400 Medicare beneficiaries needing assistance with activities of daily living (ADL), instrumental activities of daily living (IADL), or mobility for any two consecutive years between 2011 and 2015. Study outcome was the number of self-reported adverse consequences of unmet needs for assistance with daily activities (e.g., went without eating, wet or soiled clothes). Mixed-effects negative binomial regression was used to estimate the association of lagged depressive symptoms and covariates in period t-1 and the number of adverse consequences of unmet needs in period t. Results The prevalence rates of adverse consequences of unmet needs were twice as high among older adults with elevated depressive symptoms as those without depression. After adjusting for covariates, prior wave depressive symptoms were associated with 1.24 times the rate of adverse consequences of unmet needs for assistance with ADL (Incidence Rate Ratio [IRR] = 1.24, 95% confidence interval [CI] = 1.09-1.41, p < .01) and IADL (IRR = 1.24, 95% CI = 1.06-1.44, p < .01), and 1.14 times the rate of adverse consequences of unmet needs for assistance with mobility (IRR = 1.14, 95% CI = 1.03-1.27, p < .05). Discussion and Implications Caring for older adults with mental health and long-term care needs calls for an integrated social and health services system.
Physician Champion Role in an Electronic Health Record Implementation, a Case History

The electronic health record (EHR) is an array of computer applications that is being touted as a key patient safety, quality and hospital efficiency initiative. Due to the complexity of the health care environment, the implementation of an EHR can be challenging especially if health care providers, in particular physicians, are not supportive of the process. Physicians play a key role in the provision of health care and should be involved in all phases of the implementation process. Variations of EHR acceptance have been widely documented highlighting the importance of a well-planned implementation process. Theoretical frameworks, such as Roger’s Science of Diffusion of Innovation, provide guidance on how process changes can be successfully incorporated into organizations and the physician champion role can be utilized as an extensive of the theory. To illustrate how an EHR implementation can employ the physician champion role to achieve widespread adoption, a case history of a 724 bed, private not for profit hospital will be presented. The rest of this paper will be organized as follows: In the first section a review of the history of the EHR; in the second section, a discussion of barriers to implementation; in the third section, an overview of the Science of Diffusion of Innovation; in the forth section, the presentation of the physician champion role; in the fifth section a recommendation for the physician role in an EHR implementation; and in the sixth section, the case history of an actual
Computational applications to hospital epidemiology

Healthcare associated infections are a considerable burden to the health care system. The affected patients have their prognosis worsened and demand more resources from hospitals. Furthermore, the bacteria causing these infections are becoming increasingly resistant to antibiotics while also becoming more deadly and contagious. Contributing with knowledge for stopping these infections is, therefore, important. This thesis reports on two projects centered on data collected at the University of Iowa Hospital and Clinics. The first project consisted in analyzing data collected by sensors that reported the location and hand washing behavior of health care workers. After extracting meaning from these radio signals, I studied two socially and epidemiologically relevant tasks: the inference of contact networks, which can be used to study the spread of infections in the hospital, and the study of associations between social pressure and hand washing, learning that effectively workers in proximity to others wash their hands more, but also that not all workers are as influential. In the second project, I developed a data mining method for analyzing medical records aimed at tackling the problems of class imbalance and high dimensionality, and applied it to predicting Clostridium Difficile infection. The learnt models performed better than the state of the art and even improved prediction as the onset of symptoms approached. The main contribution, however, was in the information discovered: certain events in certain orders increased the risk of developing the infection, suggesting that reversing these orders could improve prognosis.
Screening for epidermal growth factor receptor mutations in lung cancer.

BACKGROUND Activating mutations in the epidermal growth factor receptor gene (EGFR) confer hypersensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in patients with advanced non-small-cell lung cancer. We evaluated the feasibility of large-scale screening for EGFR mutations in such patients and analyzed the association between the mutations and the outcome of erlotinib treatment. METHODS From April 2005 through November 2008, lung cancers from 2105 patients in 129 institutions in Spain were screened for EGFR mutations. The analysis was performed in a central laboratory. Patients with tumors carrying EGFR mutations were eligible for erlotinib treatment. RESULTS EGFR mutations were found in 350 of 2105 patients (16.6%). Mutations were more frequent in women (69.7%), in patients who had never smoked (66.6%), and in those with adenocarcinomas (80.9%) (P<0.001 for all comparisons). The mutations were deletions in exon 19 (62.2%) and L858R (37.8%). Median progression-free survival and overall survival for 217 patients who received erlotinib were 14 months and 27 months, respectively. The adjusted hazard ratios for the duration of progression-free survival were 2.94 for men (P<0.001); 1.92 for the presence of the L858R mutation, as compared with a deletion in exon 19 (P=0.02); and 1.68 for the presence of the L858R mutation in paired serum DNA, as compared with the absence of the mutation (P=0.02). The most common adverse events were mild rashes and diarrhea; grade 3 cutaneous toxic effects were recorded in 16 patients (7.4%) and grade 3 diarrhea in 8 patients (3.7%). CONCLUSIONS Large-scale screening of patients with lung cancer for EGFR mutations is feasible and can have a role in decisions about treatment.
Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease.

BACKGROUND Deep-brain stimulation is the surgical procedure of choice for patients with advanced Parkinson's disease. The globus pallidus interna and the subthalamic nucleus are accepted targets for this procedure. We compared 24-month outcomes for patients who had undergone bilateral stimulation of the globus pallidus interna (pallidal stimulation) or subthalamic nucleus (subthalamic stimulation). METHODS At seven Veterans Affairs and six university hospitals, we randomly assigned 299 patients with idiopathic Parkinson's disease to undergo either pallidal stimulation (152 patients) or subthalamic stimulation (147 patients). The primary outcome was the change in motor function, as blindly assessed on the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III), while patients were receiving stimulation but not receiving antiparkinsonian medication. Secondary outcomes included self-reported function, quality of life, neurocognitive function, and adverse events. RESULTS Mean changes in the primary outcome did not differ significantly between the two study groups (P=0.50). There was also no significant difference in self-reported function. Patients undergoing subthalamic stimulation required a lower dose of dopaminergic agents than did those undergoing pallidal stimulation (P=0.02). One component of processing speed (visuomotor) declined more after subthalamic stimulation than after pallidal stimulation (P=0.03). The level of depression worsened after subthalamic stimulation and improved after pallidal stimulation (P=0.02). Serious adverse events occurred in 51% of patients undergoing pallidal stimulation and in 56% of those undergoing subthalamic stimulation, with no significant between-group differences at 24 months. CONCLUSIONS Patients with Parkinson's disease had similar improvement in motor function after either pallidal or subthalamic stimulation. Nonmotor factors may reasonably be included in the selection of surgical target for deep-brain stimulation. (ClinicalTrials.gov numbers, NCT00056563 and NCT01076452.)
Extended-release niacin or ezetimibe and carotid intima-media thickness.

BACKGROUND Treatment added to statin monotherapy to further modify the lipid profile may include combination therapy to either raise the high-density lipoprotein (HDL) cholesterol level or further lower the low-density lipoprotein (LDL) cholesterol level. METHODS We enrolled patients who had coronary heart disease or a coronary heart disease risk equivalent, who were receiving long-term statin therapy, and in whom an LDL cholesterol level under 100 mg per deciliter (2.6 mmol per liter) and an HDL cholesterol level under 50 mg per deciliter for men or 55 mg per deciliter for women (1.3 or 1.4 mmol per liter, respectively) had been achieved. The patients were randomly assigned to receive extended-release niacin (target dose, 2000 mg per day) or ezetimibe (10 mg per day). The primary end point was the between-group difference in the change from baseline in the mean common carotid intima-media thickness after 14 months. The trial was terminated early, on the basis of efficacy, according to a prespecified analysis conducted after 208 patients had completed the trial. RESULTS The mean HDL cholesterol level in the niacin group increased by 18.4% over the 14-month study period, to 50 mg per deciliter (P < 0.001), and the mean LDL cholesterol level in the ezetimibe group decreased by 19.2%, to 66 mg per deciliter (1.7 mmol per liter) (P < 0.001). Niacin therapy significantly reduced LDL cholesterol and triglyceride levels; ezetimibe reduced the HDL cholesterol and triglyceride levels. As compared with ezetimibe, niacin had greater efficacy regarding the change in mean carotid intima-media thickness over 14 months (P = 0.003), leading to significant reduction of both mean (P = 0.001) and maximal carotid intima-media thickness (P < or = 0.001 for all comparisons). Paradoxically, greater reductions in the LDL cholesterol level in association with ezetimibe were significantly associated with an increase in the carotid intima-media thickness (R = -0.31, P < 0.001). The incidence of major cardiovascular events was lower in the niacin group than in the ezetimibe group (1% vs. 5%, P = 0.04 by the chi-square test). CONCLUSIONS This comparative-effectiveness trial shows that the use of extended-release niacin causes a significant regression of carotid intima-media thickness when combined with a statin and that niacin is superior to ezetimibe. (ClinicalTrials.gov number, NCT00397657.)
Population trends in the incidence and outcomes of acute myocardial infarction.

BACKGROUND Few studies have characterized recent population trends in the incidence and outcomes of myocardial infarction. METHODS We identified patients 30 years of age or older in a large, diverse, community-based population who were hospitalized for incident myocardial infarction between 1999 and 2008. Age- and sex-adjusted incidence rates were calculated for myocardial infarction overall and separately for ST-segment elevation and non-ST-segment elevation myocardial infarction. Patient characteristics, outpatient medications, and cardiac biomarker levels during hospitalization were identified from health plan databases, and 30-day mortality was ascertained from administrative databases, state death data, and Social Security Administration files. RESULTS We identified 46,086 hospitalizations for myocardial infarctions during 18,691,131 person-years of follow-up from 1999 to 2008. The age- and sex-adjusted incidence of myocardial infarction increased from 274 cases per 100,000 person-years in 1999 to 287 cases per 100,000 person-years in 2000, and it decreased each year thereafter, to 208 cases per 100,000 person-years in 2008, representing a 24% relative decrease over the study period. The age- and sex-adjusted incidence of ST-segment elevation myocardial infarction decreased throughout the study period (from 133 cases per 100,000 person-years in 1999 to 50 cases per 100,000 person-years in 2008, P<0.001 for linear trend). Thirty-day mortality was significantly lower in 2008 than in 1999 (adjusted odds ratio, 0.76; 95% confidence interval, 0.65 to 0.89). CONCLUSIONS Within a large community-based population, the incidence of myocardial infarction decreased significantly after 2000, and the incidence of ST-segment elevation myocardial infarction decreased markedly after 1999. Reductions in short-term case fatality rates for myocardial infarction appear to be driven, in part, by a decrease in the incidence of ST-segment elevation myocardial infarction and a lower rate of death after non-ST-segment elevation myocardial infarction.
Patient-specific induced pluripotent stem-cell models for long-QT syndrome.

BACKGROUND Long-QT syndromes are heritable diseases associated with prolongation of the QT interval on an electrocardiogram and a high risk of sudden cardiac death due to ventricular tachyarrhythmia. In long-QT syndrome type 1, mutations occur in the KCNQ1 gene, which encodes the repolarizing potassium channel mediating the delayed rectifier I(Ks) current. METHODS We screened a family affected by long-QT syndrome type 1 and identified an autosomal dominant missense mutation (R190Q) in the KCNQ1 gene. We obtained dermal fibroblasts from two family members and two healthy controls and infected them with retroviral vectors encoding the human transcription factors OCT3/4, SOX2, KLF4, and c-MYC to generate pluripotent stem cells. With the use of a specific protocol, these cells were then directed to differentiate into cardiac myocytes. RESULTS Induced pluripotent stem cells maintained the disease genotype of long-QT syndrome type 1 and generated functional myocytes. Individual cells showed a “ventricular,” “atrial,” or “nodal” phenotype, as evidenced by the expression of cell-type–specific markers and as seen in recordings of the action potentials in single cells. The duration of the action potential was markedly prolonged in “ventricular” and “atrial” cells derived from patients with long-QT syndrome type 1, as compared with cells from control subjects. Further characterization of the role of the R190Q–KCNQ1 mutation in the pathogenesis of long-QT syndrome type 1 revealed a dominant negative trafficking defect associated with a 70 to 80% reduction in I(Ks) current and altered channel activation and deactivation properties. Moreover, we showed that myocytes derived from patients with long-QT syndrome type 1 had an increased susceptibility to catecholamine-induced tachyarrhythmia and that beta-blockade attenuated this phenotype. CONCLUSIONS We generated patient-specific pluripotent stem cells from members of a family affected by long-QT syndrome type 1 and induced them to differentiate into functional cardiac myocytes. The patient-derived cells recapitulated the electrophysiological features of the disorder. (Funded by the European Research Council and others.)
Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer.

BACKGROUND Primary debulking surgery before initiation of chemotherapy has been the standard of care for patients with advanced ovarian cancer. METHODS We randomly assigned patients with stage IIIC or IV epithelial ovarian carcinoma, fallopian-tube carcinoma, or primary peritoneal carcinoma to primary debulking surgery followed by platinum-based chemotherapy or to neoadjuvant platinum-based chemotherapy followed by debulking surgery (so-called interval debulking surgery). RESULTS Of the 670 patients randomly assigned to a study treatment, 632 (94.3%) were eligible and started the treatment. The majority of these patients had extensive stage IIIC or IV disease at primary debulking surgery (metastatic lesions that were larger than 5 cm in diameter in 74.5% of patients and larger than 10 cm in 61.6%). The largest residual tumor was 1 cm or less in diameter in 41.6% of patients after primary debulking and in 80.6% of patients after interval debulking. Postoperative rates of adverse effects and mortality tended to be higher after primary debulking than after interval debulking. The hazard ratio for death (intention-to-treat analysis) in the group assigned to neoadjuvant chemotherapy followed by interval debulking, as compared with the group assigned to primary debulking surgery followed by chemotherapy, was 0.98 (90% confidence interval [CI], 0.84 to 1.13; P=0.01 for noninferiority), and the hazard ratio for progressive disease was 1.01 (90% CI, 0.89 to 1.15). Complete resection of all macroscopic disease (at primary or interval surgery) was the strongest independent variable in predicting overall survival. CONCLUSIONS Neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary debulking surgery followed by chemotherapy as a treatment option for patients with bulky stage IIIC or IV ovarian carcinoma in this study. Complete resection of all macroscopic disease, whether performed as primary treatment or after neoadjuvant chemotherapy, remains the objective whenever cytoreductive surgery is performed. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003636.)