Background DCD liver grafts are known to be predisposed to primary nonfunction and ischemic cholangiopathy. Many DCD grafts are discarded because of older donor age or long warm ischemia times. Thus, it is critical to improve the quality of DCD liver grafts. Here, we have tested whether an enriched oxygen carrier added to the preservation solution can prolong graft survival and reduce biliary damage. Methods We assessed the ATP content decay of mouse liver grafts after cold ischemia, warm ischemia, and combined warm+cold ischemia. In addition, we used a rat model of liver transplantation to compare survival of DCD grafts preserved in high-oxygen solution (pre-oxygenated PFC+UW solution) vs. lower-oxygen solution (pre-oxygenated UW solution). Results ATP levels under UW preservation fall to less than 10% after 30 min of warm ischemia. Pre-oxygenated UW solution with PFC reached a significantly higher PaO2. After 45min of warm ischemia in oxygenated UW+PFC solution, grafts showed 63% higher levels of ATP (p=0.011). In addition, this was associated with better preservation of morphology when compared to grafts stored in standard UW solution. Animals that received DCD grafts preserved in higher oxygenation solution showed improved survival: 4 out of 6 animals survived long-term whereas all control group animals died within 24 hours. Conclusions The additional oxygen provided by PFC during static cold preservation of DCD livers can better sustain ATP levels, and thereby reduce the severity of ischemic tissue damage. PFC-based preservation solution extends the tolerance to warm ischemia, and may reduce the rate of ischemic cholangiopathy. Corresponding author: James F. Markmann MD, PhD, Transplant Center, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, USA, 02114, e-mail: jmarkmann@partners.org Authorship 1. Paulo N. Martins and James F. Markmann participated in research design, performance of the research and writing of the paper. 2. Timothy A. Berendsen, Heidi Yeh, Bote G. Bruinsma, Maria-Louisa Izamis, Sanna Op den Dries, Robert Porte, Martin L. Yarmush, and Korkut Uygun participated in performance of the research and writing of the paper. 3. Andrew R. Gillooly participated in writing of the paper. Disclosure The authors declare no conflicts of interest. Funding Departmental grant Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2B5BmYo
Τρίτη 13 Νοεμβρίου 2018
Asian Liver Transplant Network Clinical Guidelines on Immunosuppression in Liver Transplantation
Most management guidelines and much of the available clinical trial evidence for immunosuppressants in liver transplantation pertain to Western practice. While evidence from Western studies may not translate to Asian settings, there is a paucity of Asian randomized controlled trials of immunosuppression in liver recipients. Nonetheless, there are notable differences in the indications and procedures for liver transplantation between Western and Asian settings. The Asian Liver Transplant Network (ALTN) held its inaugural meeting in Singapore in November 2016 and aimed to provide an Asian perspective on aspects of immunosuppression following liver transplantation. Because of their importance to outcome following liver transplantation, the meeting focused on: (1) reducing the impact of renal toxicity, (2) hepatocellular carcinoma recurrence and (3) nonadherence with immunosuppressant therapy. Corresponding author: Poh Seng TAN, Division of Gastroenterology and Hepatology, National University Hospital, National University Health System, 1E Kent Ridge Road Tower Block, Level 10, Singapore 119228, DID (+65) 6772-4354; Fax (+65) 6775-1518, Email: poh_seng_tan@nuhs.edu.sg Authorship page Authorship P.S.T., M.D.M., and T.K. are co-first authors with equal contribution to writing the draft of the article. J.F., and K.L. are co-senior authors with equal contribution leading the project. All authors reviewed the draft, provided expertise for critical revisions, and approved the final version of the article. Disclosure P.S.T is a PI of a Novartis sponsored clinical trial (H2307). The other authors declare no conflict of interest. Funding The consensus meeting was supported by the educational grant provided by Novartis and Astellas. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2K1amfP
https://ift.tt/2K1amfP
The epidemiology of drug‐resistant epilepsy: A systematic review and meta‐analysis
Summary
Objective
The definition of drug‐resistant epilepsy (DRE) affects case identification and treatment, and impacts prevalence or incidence estimates and health burden estimation in epidemiology. The objective of this systematic review is to evaluate the consistency between definitions of DRE in the literature and the official definition in the International League Against Epilepsy (ILAE) guidelines, and to estimate the incidence, prevalence, and risk factors for DRE.
Methods
MEDLINE and EMBASE were searched for observational studies of DRE published between January 1980 and July 2015. The definitions of DRE in these studies were compared with the definition in the ILAE guidelines. Random‐effect model meta‐analyses were used to generate pooled estimates of prevalence or incidence and pooled odds ratios of the association with risk factors.
Results
Thirty‐five studies met inclusion criteria, including 13 080 epilepsy patients and 3941 patients with DRE. The definition of DRE varied widely across studies, with only 12% meeting the requirements of the ILAE definition. The pooled prevalence proportion of DRE among epilepsy patients was 0.30 (95% confidence interval [CI] 0.19‐0.42), and the pooled incidence proportion was 0.15 (95% CI 0.11‐0.19). Age at onset, symptomatic epilepsy, abnormal neuroimaging findings, abnormal electroencephalography results, history of mental retardation, neuropsychiatric disorders, febrile seizure, and status epilepticus increased risk for DRE.
Significance
There are limited high‐quality data available on DRE. Lack of consistency in definitions limits the ability to obtain robust estimates on the burden of DRE. More data based on the ILAE definition from well‐designed epidemiologic studies are needed to generate accurate and reliable results.
https://ift.tt/2OIM6zw
Formation of the oxidized flavor compounds at different heat treatment and changes in the oxidation stability of milk
Effects of heat treatment on the typical oxidized flavor compounds of heated milk were studied. It explicated the destruction of milk fat as the main flavor precursor. The changes in the natural antioxidant capacity and oxidation susceptibility of different heated milk were also determined.
Abstract
The oxidized flavor could affect the sensory acceptability of consumers. In this study, the oxidized flavor compound (OFC) in different heated milk was analyzed using the solid phase microextraction–gas chromatography–mass spectrometry (SPME–GC–MS). The concentration of OFC increased with increasing the intensity of heat treatment. The concentrations of heptanal, nonanal, 2‐heptanone, and 2‐nonanone in the heated milk samples were in the range of 1.88–5.51, 1.03–3.26, 6.89–88.04, and 1.46–12.78 μg/kg, respectively. The correlation coefficients between the OFC and the heat intensity were above 0.86. It was found that the intensity of heat treatment (below 80°C for 10 min) could not cause the significant changes in the distribution of fat globules. The contents of partial proteins in milk fat globule membrane gradually destructed with increasing the intensity of heat treatment. The DPPH˙ scavenging activity reduced by 23.15%, and the peroxide value (POV) increased by 37.23% as raw milk was heated at 90°C for 20 min. Values of thiobarbituric acid reactive substances (TBARS) had a tendency to increase as the heated time was operated for 20 min (p < 0.05). It indicated the heat treatment could change the oxidative environment of milk and influence the distribution of milk fat and the formation of oxidized flavor compounds.
https://ift.tt/2z994ep
Reference Intervals of Thyroid Hormones and Correlation of BMI with Thyroid Function in Healthy Zhuang Ethnic Pregnant Women
Ethnic differences in the level of thyroid hormones exist among individuals. The American Thyroid Association (ATA) recommends that an institution or region should establish a specific thyroid hormone reference value for each stage of pregnancy. To date, a limited number of studies have reported the level of thyroid hormones in Chinese minorities, and the exact relationship between BMI and thyroid function in pregnant women is ill. This study was performed to establish trimester-specific reference ranges of thyroid hormones in Zhuang ethnic pregnant women and explore the role of body mass index (BMI) on thyroid function. A total of 3324 Zhuang ethnic health pregnant women were recruited in this Zhuang population-based retrospective cross-sectional study. The values of thyroid stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were determined by automatic chemiluminescence immunoassay analyzer. Multivariate linear regression and binary logistic regression were constructed to evaluate the influence of BMI on the thyroid function. The established reference intervals for the serum thyroid hormones in three trimesters were as follows: TSH, 0.02–3.28, 0.03–3.22, and 0.08-3.71 mIU/L; FT4, 10.57–19.76, 10.05–19.23, and 8.96–17.75 pmol/L; FT3, 3.51–5.64, 3.42–5.42, and 2.93–5.03 pmol/L. These values were markedly lower than those provided by the manufacturers for nonpregnant adults which can potentially result in 6.10% to 19.73% misclassification in Zhuang pregnant women. Moreover, BMI was positively correlated with isolated hypothyroxinemia (OR=1.081, 95% CI=1.007–1.161), while the correlation between the BMI and subclinical hypothyroidism was not statistically significant (OR=0.991, 95% CI=0.917–1.072). This is the first study focusing on the reference ranges of thyroid hormones in Guangxi Zhuang ethnic pregnant women, which will improve the care of them in the diagnosis and treatment. We also found that high BMI was positively associated with the risk of isolated hypothyroxinemia.
https://ift.tt/2FgUXsS
Circulating MicroRNA-4739 May Be a Potential Biomarker of Critical Limb Ischemia in Patients with Diabetes
Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery disease, which is common but rarely diagnosed. Noninvasive biomarkers are urgently required to assist in the diagnosis of CLI. Accumulating evidence indicates that miRNAs play an important role in the development of various diseases. In this study, microarray profiling revealed 11 miRNAs with significantly altered expression in four T2DM patients with CLI compared with that in four sex- and age-matched T2DM patients without CLI. In independent cohorts, qRT-PCR validation confirmed the increased miRNA-4739 level in patients with CLI versus patients without CLI. miRNA-4739 levels increased with FPG and HbA1c (all P 0.05) and of miR-4739 (AUC 0.94 vs. 0.69, 95% CI -0.399 to -0.101, P
https://ift.tt/2qKnVat
Sero-prevalence and associated risk factors of Mycoplasma hyopneumoniae infection in Kailali and Kanchanpur District of Far Western, Nepal
Abstract
Respiratory diseases cause severe distress leading to serious effects on production characteristics of pigs. Mycoplasma hyopneumoniae (Mh) is one of the primary contributors of porcine respiratory disease complex (PRDC). A cross-sectional study was conducted to determine the sero-prevalence and associated risk factors of enzootic pneumonia (EP) caused by Mh in Kailali and Kanchanpur Districts of Nepal. The herd level information of the site was gathered using standardized questionnaire survey. A total of 184 porcine serum samples were collected randomly and tested by using competitive ELISA targeting anti-Mh antibodies. Of the total 184, 42 samples were tested positive resulting overall sero-prevalence of 22.83%. The husbandry practices, modern and semi-conventional, continuous and all-in all-out systems were found as the potential risk factors of EP in pigs. Significantly higher risk was observed in continuous production system (32%) as compared to all-in all-out (11.11%). Likewise, pen partitioning was also found to be associated with increased risk of the disease occurrence. Higher prevalence was observed in pigs in semisolid partition (34.95%) compared to solid partition (18.18%), improved breeds (27.46%) compared to local breeds (7.14%), and highest among growing age group (36.36%) than in the rest of the others. Thus, consideration of environmental and management factors for the prevention EP transmission in commercial pig farms is suggested.
https://ift.tt/2qMXl0u
Prognostic factors in neoadjuvant treatment followed by surgery in stage IIIA-N2 non-small cell lung cancer: a multi-institutional study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society)
Abstract
Purpose
To evaluate the prognostic factors associated with survival in patients treated with neoadjuvant treatment [chemoradiotherapy (CRT) or chemotherapy] followed by surgery (CRTS) in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC).
Methods
A retrospective study was conducted of 118 patients diagnosed with stage T1-T3N2M0 NSCLC and treated with CRTS at 14 hospitals in Spain between January 2005 and December 2014. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method and compared using the log-rank test. Cox regression analysis was performed.
Results
Surgery consisted of lobectomy (74.5% of cases), pneumectomy (17.8%), or bilobectomy (7.6%). Neoadjuvant treatment was CRT in 62 patients (52.5%) and chemotherapy alone in 56 patients (47.5%). Median follow-up was 42.5 months (5–128 months). 5-year OS and PFS were 51.1% and 49.4%, respectively. The following variables were independently associated with worse OS and PFS: pneumonectomy (vs. lobectomy); advanced pathologic T stage (pT3 vs. pT0–pT2); and presence of persistent N2 disease (vs. ypN0-1) in the surgical specimen.
Conclusions
In this sample of patients with stage IIIA-N2 NSCLC treated with CRTS, 5-year survival (both OS and PFS) was approximately 50%. After CRTS, the patients with the best prognosis were those whose primary tumour and/or mediastinal nodal metastases were downstaged after induction therapy and those who underwent lobectomy. These findings provide further support for neoadjuvant therapy followed by surgery in selected patients.
https://ift.tt/2T7NmQi
Investigating Potential Molecular Mechanisms of Carcinogenesis and Genes as Biomarkers for Prognosis of Gastric Cancer Based on Integrated Bioinformatics Analysis
Abstract
Gastric cancer, as the fifth most common malignancy worldwide, is a deadly disease afflicting nearly a million people. Researchers have devoted much to study the mechanisms of carcinogenesis and progression, but the exact information of tumor initiation and progression is remained largely unknown. Here, we hypothesized several differentially expressed genes and possible pathways by employing integrated bioinformatics analysis. We fully analyzed four gastric cancer-related microarray datasets to screen differentially expressed mRNAs (DEMs), miRNAs (DEMis) and lncRNAs (DELs). The functional enrichment analysis was deeply construed, PPI network and ceRNA regulatory network were constructed to investigate potential mechanisms of tumorigenesis and progression. Furthermore, survival analysis was performed to identify critical lncRNAs that may significantly affect pathogenesis of gastric cancer. QRT-PCR was applied to verify our result. We identified two hub subnetworks that may explain the progression, metastasis and poor prognosis of gastric cancer. Meanwhile, several potential significant lncRNAs were identified. In summary, we ascertained several significantly changed KEGG pathways in the tumor initiation and progression. We also hypothesized several lncRNAs that contribute to poor prognosis of gastric cancer via integrated bioinformatics, which deserve further investigation.
https://ift.tt/2RNuGUk
Patterns and predictors of end‐of‐life care in older patients with pancreatic cancer
Although hospice enrollment has increased among patients with PDAC, late enrollment still occurs in a substantial proportion of patients. In addition, patients receive high rates of aggressive end‐of‐life care. Further research is needed to determine effective ways of enhancing end‐of‐life care for patients with PDAC.
Abstract
Background
Little is known about end‐of‐life care among patients with pancreatic adenocarcinoma (PDAC). We used the Surveillance, Epidemiology, and End Results‐Medicare linked database to analyze patterns of hospice use and end‐of‐life treatment in patients with PDAC.
Methods
We included patients diagnosed with PDAC between 2000‐2011 and who had died by December 31, 2012. We assessed patterns of hospice use, chemotherapy receipt, and intensive care unit (ICU) admissions at end‐of‐life. We used multivariable logistic regression to investigate predictors of end‐of‐life care.
Results
In our cohort of 16 309 patients, 70.5% enrolled in hospice, of which 29.1% enrolled in the last 7 days of life. Use of hospice increased over time, from 61.6% in 2000 to 77.5% in 2012 (P‐value for trend <0.0001). Among the entire cohort, 6.4% received chemotherapy within the last 14 days of life and 13.1% were admitted to the ICU within the last 30 days of life. Late ICU admissions increased over time, while chemotherapy receipt at the end‐of‐life decreased. Patients who were older, female, with higher SES, or from the South or Midwest were more likely to enroll in hospice. Those who were younger or male were more likely to receive chemotherapy or have an ICU admission at the end‐of‐life.
Conclusion
Although hospice enrollment has increased among patients with PDAC, late enrollment still occurs in a substantial proportion of patients. While chemotherapy at the end‐of‐life has decreased slightly, ICU admissions at the end‐of‐life have continued to increase. Further research is needed to determine effective ways of enhancing end‐of‐life care for patients with PDAC.
https://ift.tt/2qJc4cC
Multiregional radiomics profiling from multiparametric MRI: Identifying an imaging predictor of IDH1 mutation status in glioblastoma
The radiomics model built with multiregional features from multiparametric magnetic resonance imaging (MRI) has the potential to preoperatively detect the isocitrate dehydrogenase 1 (IDH1) mutation status in glioblastoma (GBM) patients. The multiregional models built from all tumor subregions performed better than the single‐region models, while combining age with multiregional features achieved the best performance.
Abstract
Purpose
Isocitrate dehydrogenase 1 (IDH1) has been proven as a prognostic and predictive marker in glioblastoma (GBM) patients. The purpose was to preoperatively predict IDH mutation status in GBM using multiregional radiomics features from multiparametric magnetic resonance imaging (MRI).
Methods
In this retrospective multicenter study, 225 patients were included. A total of 1614 multiregional features were extracted from enhancement area, non‐enhancement area, necrosis, edema, tumor core, and whole tumor in multiparametric MRI. Three multiregional radiomics models were built from tumor core, whole tumor, and all regions using an all‐relevant feature selection and a random forest classification for predicting IDH1. Four single‐region models and a model combining all‐region features with clinical factors (age, sex, and Karnofsky performance status) were also built. All models were built from a training cohort (118 patients) and tested on an independent validation cohort (107 patients).
Results
Among the four single‐region radiomics models, the edema model achieved the best accuracy of 96% and the best F1‐score of 0.75 while the non‐enhancement model achieved the best area under the receiver operating characteristic curve (AUC) of 0.88 in the validation cohort. The overall performance of the tumor‐core model (accuracy 0.96, AUC 0.86 and F1‐score 0.75) and the whole‐tumor model (accuracy 0.96, AUC 0.88 and F1‐score 0.75) was slightly better than the single‐regional models. The 8‐feature all‐region radiomics model achieved an improved overall performance of an accuracy 96%, an AUC 0.90, and an F1‐score 0.78. Among all models, the model combining all‐region imaging features with age achieved the best performance of an accuracy 97%, an AUC 0.96, and an F1‐score 0.84.
Conclusions
The radiomics model built with multiregional features from multiparametric MRI has the potential to preoperatively detect the IDH1 mutation status in GBM patients. The multiregional model built with all‐region features performed better than the single‐region models, while combining age with all‐region features achieved the best performance.
https://ift.tt/2FiYOFX
Understanding the impact of delegated home visiting services accessed via general practice by community-dwelling patients: a realist review protocol
Introduction
In western countries, early visiting services (EVS) have been proposed as a recent intervention to reduce both general practitioner workload and hospital admissions among housebound individuals experiencing a healthcare need within the community. EVS involves the delegation of the patient home visits to other staff groups such as paramedics or nursing staff. However, the principles of organising this care are unknown and it remains unclear how different contexts, such as patient conditions and the processes of organising EVS influence care outcomes. A review has been designed to understand how EVS are enacted and, specifically, who benefits, why, how and when in order to provide further insight into the design and delivery of EVS.
Methods and analysisThe purpose of this review is to produce findings that provide explanations of how and why EVS contexts influence their associated outcomes. Evidence on EVS will be consolidated through realist review—a theory-driven approach to evidence synthesis. A realist approach is needed as EVS is a complex intervention. What EVS achieve is likely to vary for different individuals and contexts. We expect to synthesise a range of relevant data such as qualitative, quantitative and mixed-method research in the following stages: devising an initial programme theory, searching evidence, selecting appropriate documents, extracting data, synthesising and refining the programme theory.
Ethics and disseminationA formal ethics review is not required as this study is secondary research. Findings will be disseminated in a peer-reviewed journal, at national and international conferences and to relevant professional associations.
PROSPERO registration numberCRD42018096518.
https://ift.tt/2DFS0QU
Quality of life, loneliness and health-related characteristics among older people in Liaoning province, China: a cross-sectional study
Objectives
The aim of the study was to examine the relations among quality of life (QOL), loneliness and health-related characteristics in a sample of Chinese older people.
DesignCross-sectional study.
SettingCommunities in Dandong city, Liaoning province, China.
ParticipantsSample of 732 older people aged 60 and older who were living in Dandong, Liaoning province, China.
MethodsA questionnaire was administered to the participants face-to-face. The questionnaire contained four sections: demographic characteristics, health-related characteristics, the EQ-5D Scale and the UCLA Loneliness Scale. The t-test, F-test and multivariable linear regression analyses were performed to individually test associations between the demographic data, health-related characteristics, loneliness and QOL.
ResultsChronic diseases, loneliness, age and smoking status were negatively associated with QOL (p<0.05). Satisfaction with health services, income and physical activity were positively associated with QOL (p<0.05).
ConclusionsLoneliness, chronic diseases and health service satisfaction were important factors related to low QOL among older people in China. The findings indicate that reducing loneliness, managing chronic diseases and improving the health service may help to improve the QOL for older people.
https://ift.tt/2DBSfwx
Effect of beta-blocker therapy on clinical outcomes, safety, health-related quality of life and functional capacity in patients with chronic obstructive pulmonary disease (COPD): a protocol for a systematic literature review and meta-analysis with multiple treatment comparison
Introduction
Patients with chronic obstructive pulmonary disease (COPD) who have a clinical indication for beta-blocker therapy, are often not prescribed such medication, despite evidence suggesting that beta-blockers are not associated with adverse respiratory outcomes. The primary objective of this systematic review and meta-analysis is to examine the class effect of beta-blocker use in patients with COPD. We will focus on a broad range of endpoints including, clinical, safety, and patient-centric outcomes such as health related quality of life (HRQoL) and functional capacity. A secondary objective is to explore potential within-class variation in the effects of beta-blockers among patients with COPD, and rank individual agents according to their relative benefit(s).
Methods and analysisMEDLINE, Embase, The Cochrane Library and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases will be systematically searched, from inception to present, to identify randomised controlled trials (RCTs) and other prospective and interventional studies of beta-blocker use in patients with COPD which report on the outcomes of interest. Relative treatment effects with respect to mortality, COPD exacerbations, all-cause hospitalisation, lung function, HRQoL and exercise capacity will be summarised by meta-analysis. Individual treatments (agents) will be compared in a Bayesian network meta-analysis including RCT and observational data, if feasible.
Ethics and disseminationThe results of the study will be submitted for publication in a peer-reviewed journal. Only previously published aggregate data will be used for the purpose of this review.
PROSPERO registration numberCRD42018098983.
https://ift.tt/2RS5Y5n
Correction: Prevalence of diabetes, pre-diabetes and associated risk factors: second National Diabetes Survey of Pakistan (NDSP), 2016-2017
Basit A, Fawwad A, Qureshi H NDSP Members, et al. Prevalence of diabetes, pre-diabetes and associated risk factors: second National Diabetes Survey of Pakistan (NDSP), 2016–2017. BMJ Open 2018;8:e020961. doi: 10.1136/bmjopen-2017-020961.
The previous version of this manuscript contains incorrect versions of figures 2 and 3 in the published article. Figures 2 and 3 should appear as:
Figure 2: Age-stratified prevalence of diabetes among men and women with urban and rural distribution
Figure 3: Age-stratified prevalence of pre-diabetes among men and women with urban and rural distribution
The following related text should read as:
Urban women showed significantly higher prevalence of diabetes than rural women above the age of 40 years while in men this trend was seen in the age group of 60 years and above (p<0.05) (figure 2).
Relating to figure 3, the following text should read as:
Urban men showed significantly higher...
https://ift.tt/2DDrMic
Compliance with pathology testing guidelines in Australian general practice: protocol for a secondary analysis of electronic health record data
Introduction
In Australia, general practitioners usually are the first point of contact for patients with non-urgent medical conditions. Appropriate and efficient utilisation of pathology tests by general practitioners forms a key part of diagnosis and monitoring. However overutilisationand underutilisation of pathology tests have been reported across several tests and conditions, despite evidence-based guidelines outlining best practice in pathology testing. There are a limited number of studies evaluating the impact of these guidelines on pathology testing in general practice. The aim of our quantitative observational study is to define how pathology tests are used in general practice and investigate how test ordering practices align with evidence-based pathology guidelines.
Methods and analysisAccess to non-identifiable patient data will be obtained through electronic health records from general practices across three primary health networks in Victoria, Australia. Numbers and characteristics of patients, general practices, encounters, pathology tests and problems managed over time will be described. Overall rates of encounters and tests, alongside more detailed investigation between subcategories (encounter year, patient's age, gender, and location and general practice size), will also be undertaken. To evaluate how general practitioner test ordering coincides with evidence-based guidelines, five key candidate indicators will be investigated: full blood counts for patients on clozapine medication; international normalised ratio measurements for patients on warfarin medication; glycated haemoglobin testing for monitoring patients with diabetes; vitamin D testing; and thyroid function testing.
Ethics and disseminationEthics clearance to collect data from general practice facilities has been obtained by the data provider from the RACGP National Research and Evaluation Ethics Committee (NREEC 17–008). Approval for the research group to use these data has been obtained from Macquarie University (5201700872). This study is funded by the Australian Government Department of Health Quality Use of Pathology Program (Agreement ID: 4-2QFVW4M). Findings will be reported to the Department of Health and disseminated in peer-reviewed academic journals and presentations (national and international conferences, industry forums).
https://ift.tt/2RVq8vt
Is the Rule of Halves framework relevant for diabetes care in Copenhagen today? A register-based cross-sectional study
Objective
The study aimed at analysing whether the 'Rule of Halves' framework applies for diabetes care in the Danish healthcare system with high levels of accessibility and equity. The Rule of Halves states that only one-half of people with a particular chronic condition are diagnosed; one-half of those diagnosed get treatment, and one-half of treated achieve desired therapeutic goals.
DesignThe analysis is cross sectional based on available surveys, register data and clinical databases covering the adult population in Copenhagen. We analysed five levels of prevention and care including behavioural risk factors and biomarkers, prevalence of diagnosed and undiagnosed diabetes as well as how many received care according to guidelines and achieved relevant outcomes.
SettingThe study population is Copenhagen City with a population of 550 000 with 21 500 prevalent cases of diabetes. While the registers used cover the whole population, the surveys include 750 cases and the biobank data 365 cases.
Outcome measuresOutcome measures are for each level of analysis: the prevalence of high-risk individuals, prevalence of undiagnosed and diagnosed diabetes, proportion receiving treatment and proportion achieving quality and treatment targets.
ResultsWe found that the 'Rule of Halves' framework raises relevant questions on how diabetes care works in a specific population, but the actual proportions found in Copenhagen are far from halves. Our analyses showed that 74% are diagnosed and among those who are 90% are receiving care. 40%–60% have achieved target levels of treatment in terms of HbA1c level and lipid levels. 80% have received eye and foot examinations in the last 2 years. 11% have retinopathy and 25% have macrovascular complications.
ConclusionCopenhagen is doing much better than halves, when it comes to diagnosis and providing treatment, whereas the Rule of Halves still prevails when it comes to treatment targets. There is thus still room for improvement.
https://ift.tt/2RVq5jh
Correlates and aetiological factors associated with hedonic well-being among an ageing population of US men and women: secondary data analysis of a national survey
Objective
To understand the gender-specific factors that uniquely contribute to successful ageing in a US population of men and women, 57–85 years of age. This was achieved through the examination of the correlates of subjective well-being defined by health-related quality of life (HRQoL), across several biological and psychosocial determinants of health.
DesignCross-sectional study.
SettingThe National Social Life, Health and Ageing Project (NSHAP), 2010–2011 a representative sample of the US population.
Participants3377 adults aged 57–85 (1538 men, 1839 women) from the NSHAP.
Main outcome measuresThe biopsychosocial factors of biological/physiological function, symptom status, functional status, general health perceptions and HRQoL happiness.
MethodHRQoL was measured using the NSHAP wave 2 multistage, stratified area probability sample of US households (n=3377). Variable selection was guided by the Wilson and Cleary model (WCM) that classifies health outcomes at five main levels and characteristics.
ResultsOur findings indicate differences in biopsychosocial factors comprised in the WCM and their relative importance and unique impact on HRQoL by gender. Women reported significantly lower HRQoL than men (t=3.5, df=3366). The most significant contributors to HRQoL in women were mental health (B=0.31; 0.22, 0.39), loneliness (B=–0.26; –0.35, –0.17), urinary incontinence (B=–0.22; –0.40, –0.05) and support from spouse/partner (B=0.27; 0.10, 0.43) and family B=0.12; 0.03, 0.20). Men indicated mental health (B=0.21; 0.14, 0.29), physical health (B=0.17; 0.10, 0.23), functional difficulties (B=0.38; 0.10, 0.65), loneliness (B=–0.20; –0.26, –0.12), depression (B=–0.36; –0.58, –0.15) and support from friends (B=0.06; 0.10, 0.11) as significant contributors. Those with greater social support had better HRQoL (F=4.22, df=4). Lack of companionship and reliance on spouse/partner were significant HRQoL contributors in both groups.
ConclusionOur findings offer insight into ageing, gender and subjective well-being. The results provide an opportunity to identify biopsychosocial factors to inform interventions to support successful ageing.
https://ift.tt/2DDs8p2
Association between factors related to family planning/sexual and reproductive health and contraceptive use as well as consistent condom use among internal migrant population of reproductive ages in three cities in China, based on Heckprobit selection models
Objective
With the increased population mobility and the transition in population policy, scholars are quite concerned about family planning/sexual and reproductive health (SRH) and related factors among internal migrant population of reproductive age. Therefore, the proposed study was designed to explore the association between factors related to family planning/SRH and contraceptive use as well as consistent condom use among the above-described population in China.
DesignCross-sectional study.
SettingThree municipalities in China, namely Beijing, Shanghai and Chongqing.
ParticipantsAmong the 6545 participants, 2099, 2414 and 2031 subjects came from Beijing, Shanghai and Chongqing, respectively.
ResultsA total of 6545 eligible participants were included as the full sample, 6188 of whom who had intercourse in the last 3 months were selected as the subsample. Among the subsample, 80.88% (5005/6188) adopted any form of contraceptive methods and 49.14% (3041/6188) consistently used condom in the last three sexual intercourses. Meanwhile, the involved participants had a better mastery of knowledge on SRH than on contraception (p<0.0001). The results of the Heckprobit models revealed that the factors associated with both contraceptive use and consistent condom use were relationship with the first intercourse partner, communication frequency with spouse/sexual partners on sex, actual number of children and knowledge on SRH, while knowledge on contraception and age at first intercourse were associated with contraceptive use and consistent condom use, respectively (p<0.05).
ConclusionsIn the current study, we revealed a high-level contraceptive prevalence, a relatively low-level consistent condom use and a poor mastery of knowledge on contraception and SRH. The Heckprobit selection model specified the existence of selection bias, providing evidence on the association between the factors on family planning/SRH and contraceptive use as well as consistent condom use, respectively. Our findings indicated that health institutions should offer appropriate technology and high-quality family planning/SRH services for the internal migrant population in China.
https://ift.tt/2DDv4BV
Socioeconomic differences in experiences with treatment of coronary heart disease: a qualitative study from the perspective of elderly patients
Objectives
This qualitative study aims to analyse socioeconomic differences in patients' experiences along the treatment pathway for coronary heart disease (CHD).
DesignA longitudinal qualitative study using in-depth semistructured interviews to explore patients' experiences with treatment was conducted. We analysed the transcripts of the records according to qualitative content analysis and identified differences between patients with lower and higher socioeconomic status (SES) by comparing and contrasting the narratives.
SettingThe University Hospital in Halle (Saale), Germany.
Participants41 elderly patients (aged 59–80 years) who suffered from CHD.
ResultsFrom various patient's experiences along the pathway of care which were found to differ according to SES we derived three major themes: (1) information: patients with higher SES had greater knowledge about treatment and could use medical records as sources of information; (2) illness perception: patients with lower SES focused on improving symptoms and survival, while patients with higher SES focused on physical performance and disease management; and (3) perceived role in healthcare: patients with lower SES tended to delegate responsibility to healthcare professionals.
ConclusionsDifferences in the patient's knowledge about treatment, their perceived role in healthcare and illness perception can be the factors and mechanisms that contribute to explain socioeconomic inequalities in the treatment of CHD. These factors should be considered in quantitative studies to better understand the disparities in treatment and mortality. We suggest that improving patient–physician communication and patient knowledge can change the patient's understanding of CHD and their perceived role in healthcare and reduce inequalities in CHD treatment.
Trial registration numberhttps://ift.tt/2RVpVbF
Retrospective analysis of alcohol testing in trauma team activation patients at a Canadian tertiary trauma centre
Objectives
Although alcohol screening is an essential requirement of level I trauma centre accreditation, actual rates of compliance with mandatory alcohol testing in trauma patients are seldom reported. Our objective was to determine the prevalence of blood alcohol concentration (BAC) testing in patients requiring trauma team activation (TTA) for whom blood alcohol testing was mandatory, and to elucidate patient-level, injury-level and system-level factors associated with BAC testing.
DesignRetrospective cohort study.
SettingTertiary trauma centre in Halifax, Canada.
Participants2306 trauma patients who required activation of the trauma team.
Primary outcome measureThe primary outcome was the rate of BAC testing among TTA patients. Trends in BAC testing over time and across patient and injury characteristics were described. Multivariable logistic regression examined patient-level, injury-level and system-level factors associated with testing.
ResultsOverall, 61% of TTA patients received BAC testing despite existence of a mandatory testing protocol. Rates of BAC testing rose steadily over the study period from 33% in 2000 to 85% in 2010. Testing varied considerably across patient-level, injury-level and system-level characteristics. Key factors associated with testing were male gender, younger age, lower Injury Severity Score, scene Glasgow Coma Scale score <9, direct transport to hospital and presentation between midnight and 09:00 hours, or on the weekend.
ConclusionsAt this tertiary trauma centre with a policy of empirical alcohol testing for TTA patients, BAC testing rates varied significantly over the 11-year study period and distinct factors were associated with alcohol testing in TTA patients.
https://ift.tt/2DAn057
The Anti-malarial Drug Artesunate Blocks Wnt/β-catenin Pat hway and Inhibits Growth, Migration and Invasion of Uveal Melanoma Cells
Background: Uveal melanoma is the most common primary intraocular malignancy in adults. So far, there have been no effective targeted therapeutic agents in patients with uveal melanoma. Artesunate is a semi-synthetic derivative of artemisinin extracted from traditional Chinese medicine Artemisia annua L for treatment of severe and multidrug-resistant malaria. Besides its antimalarial activity, artesunate is identified as an anti-cancer drug due to the inhibition of Wnt/β- catenin pathway in multiple types of cancer. However, the effect of artesunate on uveal melanoma remains unknown.
Objective: We evaluated the anti-tumor effects of artesunate on uveal melanoma cells, and analyzed in terms of Wnt/β-catenin pathway, cell growth, cell death, cell migration, invasion and cancer stemlike cells (CSCs) properties.
Methods: Primary (92.1, Mel270) and metastatic (Omm1 and Omm2.3) uveal melanoma cells were used. Immunofluorescence staining, dual luciferase reporter assay, Western blotting, MTS, soft agar cloning technique, Annexin V/PI analyses, wound healing scratch assay, in vitro transwell migration and invasion assays, aldehyde dehydrogenase (ALDH) analyses and melanosphere formation assay et al. were carried out.
Results: Artesunate suppressed the phosphorylation of GSK3β at S9, and lowered the protein level of β-catenin and its downstream targets (c-Myc, cyclin D1). Artesunate potently inhibited cell viability and colony formation ability. Treatment with artesunate significantly induced apoptosis. In addition, artesunate significantly reduced the migration and invasion of uveal melanoma cells, impaired the traits of CSCs in vitro.
Conclusion: Artesunate may be a potential interest for the therapy of uveal melanoma.
https://ift.tt/2OHHHNy
Noxa: Role in Cancer Pathogenesis and Treatment
The B-cell lymphoma 2 (Bcl-2) family proteins play an important role in regulating apoptosis, or programmed cell death, in response to several extracellular and intracellular signals. These proteins are either pro-apoptotic or anti-apoptotic. The pro-apoptotic Noxa is a Bcl-2 family protein that belongs to a subclass of BH3-only proteins. Noxa induces apoptosis via p53-dependent and/or p53-independent mechanisms. While Noxa may play a limited role in apoptosis, it is a crucial player that interacts with several proteins in the apoptosis pathway, highlighting its importance in the pathogenesis and treatment of certain cancers. In this review, we will elucidate the mechanisms by which Noxa regulates apoptosis and review the roles of chemotherapeutic drugs in relation to Noxa.
https://ift.tt/2z3ZdXa
Molecular Mechanisms of Resistance in Testicular Germ Cell Tumors - clinical Implications
Testicular germ cell tumors (TGCTs) represent the most common malignancy in men aged 15-35. Due to these tumors' biological and clinical characteristics, they can serve as an appropriate system for studying molecular mechanisms associated with cisplatin-based treatment resistance. This review describes treatment resistance from clinical and molecular viewpoints. Cisplatin resistance is determined by various biological mechanisms, including the modulation of the DNA repair capacity of cancer cells, alterations to apoptotic cell death pathways, deregulation of gene expression pathways, epigenetic alterations and insufficient DNA binding. Moreover, this review describes TGCTs as a model system that enables the study of the cellular features of cancer stem cells in metastatic process and describes experimental models that can be used to study treatment resistance in TGCTs. All of the abovementioned aspects may help to elucidate the molecular mechanisms underlying cisplatin resistance and may help to identify promising new therapeutic targets.
https://ift.tt/2OIiG4S
Role of MicroRNAs in Treatment Response in Prostate Cancer
Prostate cancer (PCa) is the most common non-skin cancer in men worldwide, resulting in significant mortality and morbidity. Depending on the grade and stage of the cancer, patients may be given radiation therapy, hormonal therapy, or chemotherapy. However, more than half of these patients develop resistance to treatment, leading to disease progression and metastases, often with lethal consequences. MicroRNAs (miRNAs) are short, non-coding RNAs, which regulate numerous physiological as well as pathological processes, including cancer. miRNAs mediate their regulatory effect predominately by binding to the 3′-untranslated region (UTR) of their target mRNAs. In this review, we will describe the mechanisms by which miRNAs mediate resistance to radiation and drug therapy (i.e. hormone therapy and chemotherapy) in PCa, including control of apoptosis, cell growth and proliferation, autophagy, epithelial-to-mesenchymal transition (EMT), invasion and metastasis, and cancer stem cells (CSCs). Furthermore, we will discuss the utility of circulating miRNAs isolated from different body fluids of prostate cancer patients as non-invasive biomarkers of cancer detection, disease progression, and therapy response. Finally, we will shortlist the candidate miRNAs, which may have a role in drug and radioresistance, that could potentially be used as predictive biomarkers of treatment response.
https://ift.tt/2zc0mvT
PRDM14: A Potential Target for Cancer Therapy
PRDM14 belongs to the PR domain-containing (PRDM) family. Although a precise understanding focused on the function of PRDM14 to maintain stemness and pluripotency in embryonic stem cells via epigenetic mechanisms, growing experimental evidence has been linked PRDM14 to human cancers. In adults, PRDM14 has low expression in human tissues. Aberrant PRDM14 expression is connected with various malignant histological types and solid cancers, where PRDM14 can act as a driver of oncogenic processes. Overexpression of RPDM14 enhanced cancer cells growth and reduced cancer cells sensitive to chemotherapeutic agents. Reducing the expression of PRDM14 in cancer cells can enhance the therapeutic sensitivity of drugs to cancer cells, suggesting that aberrant PRDM14 may have a carcinogenic characteristic in tumor therapy and as a new molecular target. This review summarizes the structure and oncogenic properties of PRDM14 in different malignancies and suggests that PRDM14 may be a potential therapeutic molecular target for tumor treatment.
https://ift.tt/2OIKtSy
Targeting FGFR with BGJ398 in Breast Cancer: Effect on Tumor Growth and Metastasis
Background: Endocrine resistance and metastatic dissemination comprise major clinical challenges for breast cancer treatment. The fibroblast growth factor receptor family (FGFR) consists of four tyrosine kinase transmembrane receptors, involved in key biological processes. Genomic alterations in FGFR have been identified in advanced breast cancer and thus, FGFR are an attractive therapeutic target. However, the efficacy of FGFR inhibitors on in vivo tumor growth is still controversial.
Objective: The purpose of this study was to evaluate the role of FGFR in tumor growth and breast cancer progression.
Methods: Cell proliferation was assessed by 3H-thymidine uptake and cell counting in primary cultures of endocrine resistant mammary carcinomas and a human cell line, respectively. Tumor transplants and cell injections were used to determine in vivo growth and spontaneous metastasis. FGFR1-3 and αSMA expression were evaluated on primary tumors by immunohistochemistry.
Results: Antiprogestin resistant murine transplants and a human xenograft express high levels of total FGFR1-3. In vitro treatment with the FGFR inhibitor, BGJ398, impaired cell proliferation of resistant variants versus vehicle. In vivo, versus control, BGJ398 treatment decreased one out of four resistant tumors, however all tumors showed a decreased epithelial/stromal ratio. Finally, in a model of hormone resistant mammary cancer that spontaneously metastasizes to the lung, BGJ398 decreased the number of mice with lung metastasis.
Conclusion: FGFR inhibitors are promising tools that require further investigation to identify sensitive tumors. These studies suggest that targeting FGFR combined with other targeted therapies will be useful to impair breast cancer progression.
https://ift.tt/2z6gXkz
Anticancer Properties of Essential Oils: An Overview
Background: Essential oils are complex mixtures of low molecular weight compounds extracted from plants. Their main constituents are terpenes and phenylpropanoids, which are responsible for their biological and pharmaceutical properties, such as insecticidal, parasiticidal, antimicrobial, antioxidant, anti-inflammatory, analgesic, antinociceptive, anticarcinogenic, and antitumor properties. Cancer is a complex genetic disease considered as a serious public health problem worldwide, accounting for more than 8 million deaths annually.
Objective: The activities of prevention and treatment of different types of cancer and the medicinal potential of essential oils are addressed in this review.
Conclusion: Several studies have demonstrated anti-carcinogenic and antitumor activity for many essential oils obtained from various plant species. They may be used as a substitution to or in addition to conventional anti-cancer therapy. Although many studies report possible mechanisms of action for essential oils compounds, more studies are necessary in order to apply them safely and appropriately in cancer therapy.
https://ift.tt/2OIiFOm
Complete intracorporeal defect closure using unidirectional barbed suture in laparoscopic incisional hernia repair: Preliminary experience with short‐term follow‐up
Abstract
Introduction
Surgical techniques to close defects in laparoscopic incisional hernia repair vary across the literature. We herein demonstrate our original and standardized surgical technique for laparoscopic incisional hernia repair with complete intracorporeal defect closure using barbed suture.
Materials and Surgical Technique
Complete intracorporeal defect closures were indicated for defects less than or equal to 6 cm in transverse diameter. We performed a defect closure with a running suture using barbed suture in a caudal to cranial direction, with tissue bites and inter‐suture spacing of 1 cm each. The hernial sac was incorporated into the suturing to reduce possible dead space. After the procedure, intraperitoneal onlay mesh was placed. Seven patients underwent this procedure. The median total operative time was 188 min, and the median time specifically for defect closure was 25 min. There was no seroma, mesh bulge, persisting pain, or hernia recurrence at follow‐up.
Discussion
Our proposed technique is simple and can be safely performed with good short‐term outcomes.
https://ift.tt/2DDCOE3
Autologous Chondrocyte Implantation with Chondrosphere for Treating Articular Cartilage Defects in the Knee: An Evidence Review Group Perspective of a NICE Single Technology Appraisal
Abstract
Chondrosphere (Spherox) is a form of autologous chondrocyte implantation (ACI). It is licensed for repair of symptomatic articular cartilage defects of the femoral condyle and the patella of the knee with defect sizes up to 10 cm2 in adults. In a single technology appraisal (STA) [TA508] undertaken by the National Institute of Health and Care Excellence (NICE), Warwick Evidence was the Evidence Review Group (ERG) invited to independently review the evidence submitted by the manufacturer, Co.Don. The clinical effectiveness data came from their COWISI randomised controlled trial (RCT), which compared Chondrosphere with microfracture (MF). The timing of this appraisal was unfortunate given that MF was no longer the most relevant comparator because NICE had contemporaneously published guidance approving ACI in place of MF. Moreover, the COWISI RCT enrolled mostly patients with small defect sizes. Evidence of clinical effectiveness for Chondrosphere used in people with larger defect size came from another RCT, which compared three doses of Chondrosphere and that by design could not provide evidence comparing Chondrosphere to any other forms of ACI. To estimate the relative clinical performance of Chondrosphere versus other ACI, Co.Don conducted an indirect treatment comparison by network meta-analyses (NMA). The NMA was flawed in that the distribution of population characteristics that are effect modifiers greatly differed across the treatment comparisons of the network. The ERG questioned both the appropriateness of the NMA and the validity of the resulting estimates. Co.Don estimated the cost-effectiveness of Chondrosphere using a lifetime Markov model with all patients receiving the first repair during the first cycle of the model then moving into one of three health states: success, no further repair (NFR), or a second repair, if necessary. Subsequent to the first cycle, those who were a success either remained a success or moved to second repair. All those in NFR remained in NFR. The cost-effectiveness of Chondrosphere compared to other ACI forms relied on the clinical effectiveness estimates of success and failure rates obtained from the company's indirect comparisons, the validity of which the ERG questioned. The company revised cost-effectiveness estimates for Chondrosphere versus MF and for Chondrosphere versus matrix-applied characterised autologous cultured chondrocyte implant (MACI) were £4360 and around £18,000 per quality-adjusted life year gained, respectively. NICE recommended ACI using Chondrosphere for treating symptomatic articular cartilage defects of the femoral condyle and patella of the knee in adults only if certain requirements were met.
https://ift.tt/2PtboH6
Arsenic Trioxide for Treating Acute Promyelocytic Leukaemia: An Evidence Review Group Perspective of a NICE Single Technology Appraisal
Abstract
The National Institute for Health and Care Excellence (NICE) invited Teva, the company manufacturing arsenic trioxide (ATO; tradename Trisenox®), to submit evidence for the clinical and cost effectiveness of ATO for untreated and relapsed or refractory acute promyelocytic leukaemia (APL). Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Maastricht University Medical Center, was commissioned as the independent Evidence Review Group (ERG). This paper presents a summary of the company submission (CS), the ERG's critical review of the clinical and cost effectiveness evidence in the CS, key methodological considerations and the development of the NICE guidance by the Appraisal Committee (AC). The CS presented three randomized controlled trials (RCTs). Two of these were trials in newly diagnosed APL (APL0406 and AML17) and the third trial was in patients with relapsed APL. Results from APL0406 showed that more people having AATO [ATO plus all-trans retinoic acid (ATRA)] were alive at 50 months compared with people having AIDA (ATRA in combination with idarubicin) (99% vs. 93%; p = 0.007). There was also a statistically significant lower cumulative incidence of relapse with AATO compared with AIDA at 50 months (2% vs. 14%; p = 0.001). At 4 years, results from AML17 showed a significant difference in event-free survival (91% vs. 70%; p = 0.002) favouring AATO but not in overall survival (93% vs. 89%; p = 0.250). The only trial presented for relapsed/refractory patients compared AATO with ATO, which was not a relevant comparison according to the NICE scope. The AC concluded that AATO was effective for untreated APL while for relapsed or refractory APL the effectiveness of ATO was considered uncertain and the long-term safety remains unexplored. In the CS base-case, AATO was less expensive (£31,088 saved) and more effective (2.546 quality-adjusted life-years (QALYs) gained) than AIDA and thus the dominating strategy for newly diagnosed low- to intermediate-risk APL. However, the ERG's critical assessment highlighted a number of concerns, including deviations from the NICE reference case and a lack of detailed description and justification of parameters and assumptions related to (the extrapolation of) treatment effectiveness. However, it was reassuring that AATO for untreated APL remained dominant in the ERG base-case, and that the worst-case scenario produced by the ERG resulted in an incremental cost-effectiveness ratio (ICER) of £21,622. The AC concluded that although there was uncertainty in the model, it could recommend ATO for both untreated and relapsed or refractory APL.
https://ift.tt/2Prmrkg
The Transcriptional Regulator Hbx1 Affects the Expression of Thousands of Genes in the Aflatoxin-Producing Fungus Aspergillus flavus
In filamentous fungi, homeobox proteins are conserved transcriptional regulators described to control conidiogenesis and fruiting body formation. Eight homeobox (hbx) genes are found in the genome of the aflatoxin-producing ascomycete, Aspergillus flavus. While loss-of-function of seven of the eight genes had little to no effect on fungal growth and development, disruption of hbx1, resulted in aconidial colonies and lack of sclerotial production. Furthermore, the hbx1 mutant was unable to produce aflatoxins B and B2, cyclopiazonic acid and aflatrem. In the present study, hbx1 transcriptome analysis revealed that hbx1 has a broad effect on A. flavus gene expression, and the effect of hbx1 increases overtime, impacting more than five thousand protein-coding genes. Among the affected genes, those in the category of secondary metabolism (SM), followed by that of cellular transport, were the most affected. Specifically, regarding the effect of hbx1 on SM, we found that genes in 44 SM gene clusters where upregulated while 49 were downregulated in the absence of hbx1, including genes in the SM clusters responsible for the synthesis of asparasone, piperazine and aflavarin, all known to be associated with sclerotia. In addition, our study revealed that hbx1 affects the expression of other transcription factor genes involved in development, including the conidiation central regulatory pathway and flb genes.
https://ift.tt/2FlKZqi
A collaborative analysis of individual participant data from 19 prospective studies assesses circulating vitamin D and prostate cancer risk
Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between pre-diagnostic concentrations of 25-hydroxyvitamin D (25(OH)D) and 1,25(OH)2D and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided individual participant data on circulating 25(OH)D and 1,25(OH)2D for up to 13,462 men with incident prostate cancer and 20,261 control participants. Odds ratios (OR) for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest versus lowest study-specific fifth was 1.22, 95% CI 1.13-1.31; P trend<0.001). However, this association varied by disease aggressiveness (Pheterogeneity=0.014); higher circulating 25(OH)D was associated with a higher risk of non-aggressive disease (OR per 80 percentile increase=1.24, 1.13-1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78-1.15). 1,25(OH)2D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of non-aggressive prostate cancer may be influenced by detection bias.
https://ift.tt/2RN0by2
miR-146a controls immune response in the melanoma microenvironment
Micro-RNAs (miR) are small non-coding RNAs that regulate gene expression, post-transcription, and manipulate immune responses in different types of cancer. In this study, we identify miR-146a as a negative regulator of immune activation, comparable to immune checkpoint molecules. miR-146a levels were increased in melanoma microenvironmental tissue, and miR-146a-/- mice survived longer and developed less metastases in comparison to wild type melanoma-bearing mice. T cells isolated from miR-146a-/- mice revealed higher expression levels of the miR-146a target gene Stat1 and the Stat1-regulated cytokine Interferon-γ (IFN-γ). Neutralization of IFN-γ in miR-146a-/- mice decreased survival and increased melanoma metastasis patterns to those of wild-type mice. In vitro, IFN-γ reduced melanoma cell migration, cell cycle activity, and basal metabolic rate. Conversely, IFN-γ also increased PD-L1 levels on the melanoma cells, which may counterbalance some of the beneficial effects increasing immune escape in vivo. Combined treatment with a miR-146a antagomiR and anti-PD-1 resulted in improved survival over isotype-control or anti-PD-1 treatment alone. In summary, these data show that miR-146a plays a central role within the STAT1/IFN-γ axis in the melanoma microenvironment, affecting melanoma migration, proliferation, and mitochondrial fitness as well as PD-L1 levels. Additionally, combined inhibition of PD-1 and miR-146a could be a novel strategy to enhance anti-tumor immune response elicited by checkpoint therapy.
https://ift.tt/2DD2JeT
Aberrant activation of {beta}-catenin signaling drives glioma tumorigenesis via USP1-mediated stabilization of EZH2
Aberrant activation of β-catenin signaling is a critical driver for tumorigenesis, but the mechanism underlying this activation is not completely understood. In this study, we demonstrate a critical role of β-catenin signaling in stabilization of Enhancer of Zeste Homolog 2 (EZH2) and control of EZH2-mediated gene repression in oncogenesis. β-catenin/TCF4 activated transcription of the deubiquitinase USP1, which then interacted with and deubiquitinated EZH2 directly. USP1-mediated stabilization of EZH2 promoted its recruitment to the promoters of CDKN1B, RUNX3, and HOXA5, resulting in enhanced enrichment of histone H3K27me3 and repression of target gene expression. In human glioma specimens, expression levels of nuclear β-catenin, USP1, and EZH2 correlated with one another. Depletion of β-catenin/USP1/EZH2 repressed glioma cell proliferation in vitro and tumor formation in vivo. Our findings indicate that a β-catenin-USP1-EZH2 axis orchestrates the interplay between dysregulated β-catenin signaling and EZH2-mediated gene epigenetic silencing during glioma tumorigenesis.
https://ift.tt/2RS16x7
Looking back and moving forward: Evaluating and advancing translation from animal models to human studies of early life stress and DNA methylation
Abstract
Advances in epigenetic methodologies have deepened theoretical explanations of mechanisms linking early life stress (ELS) and disease outcomes and suggest promising targets for intervention. To date, however, human studies have not capitalized on the richness of diverse animal models to derive and systematically evaluate specific and testable hypotheses. To promote cross‐species dialog and scientific advance, here we provide a classification scheme to systematically evaluate the match between characteristics of human and animal studies of ELS and DNA methylation. Three preclinical models were selected that are highly cited, and that differ in the nature and severity of the ELS manipulation as well as in the affected epigenetic loci (the licking and grooming, maternal separation, and caregiver maltreatment models). We evaluated the degree to which human studies matched these preclinical models with respect to the timing of ELS and of DNA methylation assessment, as well as the type of ELS, whether sex differences were explicitly examined, the tissue sampled, and the targeted loci. Results revealed <50% match (range of 8–83%) between preclinical models and human work on these variables. Immediate and longer‐term suggestions to improve translational specificity are offered, with the goal of accelerating scientific advance.
https://ift.tt/2OKzqbs
Comparative safety and effectiveness of direct oral anticoagulants in patients with atrial fibrillation in clinical practice in Scotland
Abstract
Aims
To compare the clinical effectiveness and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) in routine clinical practice.
Methods
Retrospective cohort study using linked administrative data. The study population (n=14,577) included patients with a diagnosis of AF (confirmed in hospital) who initiated DOAC treatment in Scotland between August 2011 and December 2015. Multivariate Cox proportional hazard models were used to estimate hazard ratios of thromboembolic events, mortality, and bleeding events.
Results
No differences between the DOACs were observed in the risks of stroke, systemic embolism, or cardiovascular death. In contrast, the risk of myocardial infarction was higher among apixaban patients in comparison to rivaroxaban (1.67 [1.02 – 2.71]), and all‐cause mortality was higher among rivaroxaban patients in contrast to both apixaban (1.22 [1.01 – 1.47]) and dabigatran (1.55 [1.16 – 2.05]); rivaroxaban patients also had a higher risk of pulmonary embolism than apixaban patients (5.27 [1.79 – 15.53]). The risk of other major bleeds was higher among rivaroxaban patients compared to apixaban (1.50 [1.10 – 2.03]) and dabigatran (1.58 [1.01 – 2.48]); the risks of gastro‐intestinal bleeds and overall bleeding were higher among rivaroxaban patients than among apixaban patients (1.48 [1.01 – 2.16] and 1.52[1.21 – 1.92], respectively).
Conclusions
All DOACs were similarly effective in preventing strokes and systemic embolisms, while patients being treated with rivaroxaban exhibited the highest bleeding risks. Observed differences in the risks of all‐cause mortality, myocardial infarction, and pulmonary embolism warrant further research.
https://ift.tt/2FlwZgj
Effectiveness and safety of 110 or 150 mg dabigatran versus vitamin K antagonists in non‐valvular atrial fibrillation.
Abstract
Background
We compared the 1‐year safety and effectiveness of dabigatran 110 mg (D110) or 150 mg (D150) to vitamin K antagonists (VKA) in patients with non‐valvular atrial fibrillation (NVAF),
Methods
New user cohort study of patients dispensed D110 or D150 vs. VKA in 2013 for NVAF, followed 1 year in the French Système National des Données de Santé (SNDS, 66 million persons). D110 and D150 users were matched 1:1 with VKA users on sex, age, date of first drug dispensing, and high‐dimensional propensity score (hdPS). Hazard ratios (HR [95% confidence intervals]) for stroke and systemic embolism (SSE), major bleeding (MB), and death were computed using Cox proportional hazards or Fine and Gray models during exposure.
Results
In 14,442 matched D110 and VKA patients, mean age 79, 49% male, 91% with CHA2DS2‐VASc ≥2 and 8% with HAS‐BLED >3, incidence rates of SSE were 1.9% and 2.6% person‐years (HR 0.69 [0.56‐0.84]), MB 1.8% and 2.9% (0.62 [0.51‐0.76]), death 7.2% and 8.6% (0.84 [0.76‐0.94]). In 8,389 matched D150 and VKA patients, mean age 67, 67% male, 65% with CHA2DS2‐VASC ≥ 2; < 5% HAS‐BLED > 3, incidence rates were for SSE 1.4% and 1.9% (0.76 [0.56‐1.04]), MB 0.6 % and 1.9% (0.30 [0.20‐0.46]), death 1.6% and 3.6% (0.46 [0.35‐0.59]). Numbers needed to treat to observe one fewer death were 78 for D110, 88 for D150
Conclusion
In real life D110 and D150 were at least as effective and safer than VKA.
https://ift.tt/2qMtd5u
Prognostic value of RANKL/OPG serum levels and disseminated tumor cells in non-metastatic breast cancer
Background: We assessed serum concentrations of the receptor activator of nuclear factor kappa-B ligand (RANKL) and its decoy receptor osteoprotegerin (OPG), two proteins implicated in the development and progression of breast cancer (BC), in 509 patients with primary, non-metastatic BC. Then the results were evaluated with regards to the occurrence of bone metastases, the presence of disseminated tumor cells (DTC) in the bone marrow, survival and risk of developing metastatic disease. Patients and Methods: Before surgery, two bone marrow aspirates were analyzed for DTC using density centrifugation followed by immunocytochemistry (pan-cytokeratin antibody A45-B/B3). RANKL and OPG levels in the serum were measured by ELISA. Results: RANKL levels were significantly lower in women >60 years (p<0.0001) and RANKL/OPG ratios higher in lymph node-positive patients (p<0.05). High OPG serum levels were associated with a higher risk of death from BC (HR 1.94 95%CI 1.23-3.07; p=0.005) and OPG was an independent prognostic marker for BC specific survival (multivariate analyses, p=0.035). RANKL levels were 33% higher (p<0.0001) in DTCpos patients (41%) whereas high levels were associated with a significantly better BC specific survival in DTCneg patients as compared to low levels (HR 0.524; 95%CI 0.30-0.95; p=0.04). RANKL serum levels were significantly increased in patients who developed bone metastases (p=0.01) and patients within the highest quartile of RANKL had a significantly increased risk of developing bone metastases compared to those in the lowest (HR 4.62, 95%CI 1.49-14.34, p=0.03). Conclusion: These findings warrant further investigation as they provide a rationale for novel diagnostic or therapeutic approaches.
https://ift.tt/2qL9OSv
Phase 1 Study of AMG 337, a Highly Selective Small-Molecule MET Inhibitor, in Patients With Advanced Solid Tumors
Purpose: This first-in-human, open-label phase 1 study evaluated AMG 337, an oral, highly selective small-molecule inhibitor of MET in advanced solid tumors. Experimental Design: Patients enrolled into dose-escalation cohorts received AMG 337 up to 400 mg once daily (QD) or up to 250 mg twice daily (BID), following a modified 3+3+3 design. Dose expansion was conducted in MET-amplified patients at the maximum tolerated dose (MTD). Primary endpoints included assessment of adverse events (AEs), establishment of the MTD, and pharmacokinetics; clinical response was a secondary endpoint. Results: The safety analysis set included 111 patients who received ≥1 dose of AMG 337. Thirteen patients had ≥1 AE qualifying as dose-limiting toxicity. The MTD was determined to be 300 mg QD; the MTD for BID dosing was not reached. Most frequent treatment-related AEs were headache (63%) and nausea (31%). Grade ≥3 treatment-related AEs occurred in 23 patients (21%), most commonly headache (n=6) and fatigue (n=5). Maximum plasma concentration occurred at 3.0 hours following 300-mg QD dosing, indicating AMG 337 absorption soon after treatment. Objective response rate was 9.9% (11/111; 95% CI, 5.1%-17.0%) in all patients and 29.6% (8/27; 95% CI, 13.8%-50.2%) in MET-amplified patients; median (range) duration of response was 202 (51-1430+) days in all patients and 197 (64-1430+) days in MET-amplified patients. Conclusions: Oral AMG 337 was tolerated with manageable toxicities, with an MTD and recommended phase 2 dose of 300 mg QD. The promising response rate observed in patients with heavily pretreated MET-amplified tumors warrants further investigation.
https://ift.tt/2Fnap6S
Preventing Lck activation in CAR T cells confers Treg resistance but requires 4-1BB signaling for them to persist and treat solid tumors in non-lymphodepleted hosts
Purpose: CAR T cells have shown promise against solid tumors, but their efficacy has been limited, due in part, to immunosuppression by CD4+FoxP3+ regulatory T cells (Tregs). Although lymphodepletion is commonly used to deplete Tregs, these regimens are non-specific, toxic, and provide only a narrow window before Tregs repopulate hosts. Importantly, CARs have also been shown to inadvertently potentiate Tregs by providing a source of IL-2 for Treg consumption. We explored whether disruption of the IL-2 axis would confer efficacy against solid tumors without the need for lymphodepletion. Experimental Design: We developed second- (CD28z) and third- (CD28-4-1BBz) generation CARs targeting EGFRvIII. To eliminate secretion of IL-2, two amino acid substitutions were introduced in the PYAP Lck binding-motif of the CD28 domain (DCD28). We evaluated CARs against B16 melanomas expressing EGFRvIII. Results: CD28z CARs failed to engraft in vivo. Although 4-1BB addition improved expansion, CD28-4-1BBz CARs required lymphodepletion to treat solid tumors. CARs deficient in Lck signaling, however, significantly retarded tumor growth without a need for lymphodepletion and this was dependent on inclusion of 4-1BB. To evaluate CAR vulnerability to Tregs, we lymphodepleted mice and transferred CARs alone or with purified Tregs. Co-transfer with Tregs abrogated the efficacy of CD28-4-1BBz CARs, whereas the efficacy of DCD28-4-1BBz CARs remained unperturbed. Conclusions:In the absence of lymphodepletion, CARs targeting solid tumors are hindered by Treg immunosuppression and poor persistence. Here, CARs were modified to circumvent Treg suppression and to simultaneously improve in vivo engraftment. Modified CARs treated solid tumors without a need for lymphodepletion.
https://ift.tt/2qMeOWK
Rare, pathogenic germline variants in Fanconi Anemia genes increase risk for squamous lung cancer
Purpose: Lung cancer is the leading cause of cancer deaths worldwide, with substantial better prognosis in early stage as opposed to late state disease. Identifying genetic factors for lung squamous carcinoma (SqCC) risk will enable their use in risk stratification, and personalized intensive surveillance, early detection, and prevention strategies for high-risk individuals. Experimental Design: We analyzed whole-exome sequencing datasets of 318 cases and 814 controls (discovery cohort) and then validated our findings in an independent cohort of 444 patients and 3,479 controls (validation cohort), all of European descent, totaling a combined cohort of 765 cases and 4,344 controls. We focused on rare pathogenic variants found in the ClinVar database and used penalized logistic regression to identify genes in which such variants are enriched in cases. All statistical tests were two-sided. Results: We observed an overall enrichment of rare, deleterious germline variants in Fanconi Anemia genes in cases with SqCC (joint analysis OR=3.08, p=1.4e-09, 95% confidence interval [CI]=2.2-4.3). Consistent with previous studies, BRCA2 in particular exhibited an increased overall burden of rare, deleterious variants (joint OR=3.2, p=8.7e-08, 95% CI=2.1-4.7). More importantly, rare deleterious germline variants were enriched in Fanconi Anemia genes even without the BRCA2 rs11571833 variant that is strongly enriched in lung SqCC cases (joint OR=2.76, p=7.0e-04, 95% CI=1.6-4.7). Conclusions: These findings can be used towards the development of a genetic diagnostic test in the clinic to identify SqCC high-risk individuals, who can benefit from personalized programs, improving prognosis.
https://ift.tt/2FlHEri
A phase Ib dose-escalation and expansion study of the oral MEK inhibitor pimasertib and PI3K/MTOR inhibitor voxtalisib in patients with advanced solid tumours
A phase Ib dose-escalation and expansion study of the oral MEK inhibitor pimasertib and PI3K/MTOR inhibitor voxtalisib in patients with advanced solid tumours
A phase Ib dose-escalation and expansion study of the oral MEK inhibitor pimasertib and PI3K/MTOR inhibitor voxtalisib in patients with advanced solid tumours, Published online: 14 November 2018; doi:10.1038/s41416-018-0322-4
A phase Ib dose-escalation and expansion study of the oral MEK inhibitor pimasertib and PI3K/MTOR inhibitor voxtalisib in patients with advanced solid tumourshttps://ift.tt/2Q1tvDw
Fibroblast growth factor 21 as a circulating biomarker at various stages of colorectal carcinogenesis
Fibroblast growth factor 21 as a circulating biomarker at various stages of colorectal carcinogenesis
Fibroblast growth factor 21 as a circulating biomarker at various stages of colorectal carcinogenesis, Published online: 14 November 2018; doi:10.1038/s41416-018-0280-x
Fibroblast growth factor 21 as a circulating biomarker at various stages of colorectal carcinogenesishttps://ift.tt/2DnW9rI
Long-term treatment with the PARP inhibitor niraparib does not increase the mutation load in cell line models and tumour xenografts
Long-term treatment with the PARP inhibitor niraparib does not increase the mutation load in cell line models and tumour xenografts
Long-term treatment with the PARP inhibitor niraparib does not increase the mutation load in cell line models and tumour xenografts, Published online: 14 November 2018; doi:10.1038/s41416-018-0312-6
Long-term treatment with the PARP inhibitor niraparib does not increase the mutation load in cell line models and tumour xenograftshttps://ift.tt/2PTWgSK
North American population-based validation of the National Comprehensive Cancer Network Practice Guideline Recommendations for locoregional lymph node and bone imaging in prostate cancer patients
North American population-based validation of the National Comprehensive Cancer Network Practice Guideline Recommendations for locoregional lymph node and bone imaging in prostate cancer patients
North American population-based validation of the National Comprehensive Cancer Network Practice Guideline Recommendations for locoregional lymph node and bone imaging in prostate cancer patients, Published online: 14 November 2018; doi:10.1038/s41416-018-0323-3
North American population-based validation of the National Comprehensive Cancer Network Practice Guideline Recommendations for locoregional lymph node and bone imaging in prostate cancer patientshttps://ift.tt/2DkOfQ8
Effect of home-based specialised palliative care and dyadic psychological intervention on caregiver anxiety and depression: a randomised controlled trial
Effect of home-based specialised palliative care and dyadic psychological intervention on caregiver anxiety and depression: a randomised controlled trial
Effect of home-based specialised palliative care and dyadic psychological intervention on caregiver anxiety and depression: a randomised controlled trial, Published online: 14 November 2018; doi:10.1038/s41416-018-0193-8
Effect of home-based specialised palliative care and dyadic psychological intervention on caregiver anxiety and depression: a randomised controlled trialhttps://ift.tt/2PTb5VL
Prognostic impact of CDX2 in stage II colon cancer: results from two nationwide cohorts
Prognostic impact of CDX2 in stage II colon cancer: results from two nationwide cohorts
Prognostic impact of CDX2 in stage II colon cancer: results from two nationwide cohorts, Published online: 14 November 2018; doi:10.1038/s41416-018-0285-5
Prognostic impact of CDX2 in stage II colon cancer: results from two nationwide cohortshttps://ift.tt/2Dk0ts5
Using Quick Response Codes to Increase Students' Participation in Case-Based Learning Courses
The purpose of this study was to use Quick Response codes to increase engagement in a case-based learning course. A quasi-experiment was conducted, and 103 students enrolled in a pharmacology course participated. The students were divided into high-, medium-, and low-scoring groups, based on their previous semester grades in the pharmacology course. A Chinese-version questionnaire of the Nursing Students' Attitude Toward Quick Response Codes in Case-Based Learning Scale was used. The major findings were as follows: (1) Most participants held positive attitudes toward the use of Quick Response codes in case-based learning courses. It was suggested that participants perceived the use of Quick Response codes to be easy and useful in learning activities. They also demonstrated positive attitudes toward the Quick Response codes and expressed their intention to use this application in the future. (2) After applying Quick Response codes in classroom teaching, students performed better in asking questions and discussions than they did before. The performance of the medium-level students improved significantly.https://ift.tt/2QH24Mo
A Mobile Application for Patients With Heart Failure: Theory- and Evidence-Based Design and Testing
Self-care is vital for the successful management of heart failure. Mobile health can enable patients with heart failure to perform effective self-care. This article describes the theory-guided development and beta testing of a mobile application intervention to support self-care and increase symptom awareness in community-dwelling patients with heart failure. Ten participants entered physiologic data, answered qualitative questions about symptoms, and reviewed heart failure education within the HF App daily. Two validated instruments, the Self-care of Heart Failure Index and Heart Failure Somatic Awareness Scale, were administered both before and after the intervention, and results were compared using t tests. Results indicated that there were clinically significant changes from preintervention to postintervention in self-care scores in each subscale, with a statistically significant difference in the confidence subscale scores (P = .037). However, there were no statistically significant differences between preintervention and postintervention symptom awareness scores. These results indicate that incorporating mobile applications that comprise symptom monitoring, reminders, education, and the ability to track trends in physiologic data is most useful to assist individuals with heart failure to perform effective self-care.https://ift.tt/2QHGqYw
Using Clinical Decision Support to Improve Referral Rates in Severe Symptomatic Aortic Stenosis: A Quality Improvement Initiative
Clinical decision support systems are used to ensure compliance with guidelines and can assist providers in improving quality of care. This quality improvement initiative was designed to evaluate the use of a clinical decision support system to improve specialist referral rate for patients with severe aortic stenosis. A clinical decision support system for cardiology and primary care providers was implemented to improve diagnosis of severe aortic stenosis. The ordering provider received an electronic medical record in-basket alert providing feedback and recommendations for referral to specialist for evaluation. The echocardiogram data were evaluated for change in specialist referral rate. Before clinical decision support system implementation, the referral rate was 72% for a 3-month period. All providers ordering echocardiograms received clinical decision support system notification if patient results met criteria based on valve severity (aortic valve areahttps://ift.tt/2PrfEXO
Nurse Attitudes Related to Accepting Electronic Health Records and Bedside Documentation
No abstract availablehttps://ift.tt/2QGw8b5
Development and Evaluation of “Chronic Illness Care Smartphone Apps” on Nursing Students’ Knowledge, Self-efficacy, and Learning Experience
This study developed smartphone-based virtual experiential nursing applications to care for patients with chronic illness, especially patients with hypertension and diabetes, and evaluated the effect of the applications on nursing students' knowledge, self-efficacy, and learning experiences. Applications using gamification elements were developed according to the steps of assessment, design, development, implementation, and evaluation. Knowledge and self-efficacy were assessed via questionnaires, while learning experiences were assessed via six focus group interviews after the applications were used for 1 week. Quantitative data were analyzed using descriptive analysis, χ2 test, Fisher's exact test, t test for the homogeneity of participants (experimental, 49; control, 43), an independent t test, and a paired t test for effectiveness in each group. Qualitative data were analyzed using qualitative thematic analysis. Knowledge on hypertension (t = 4.41, Phttps://ift.tt/2QNtobO
Factors Affecting Consumer Acceptance of an Online Health Information Portal Among Young Internet Users
Despite the proliferation of health and nursing informatics applications in the past decade, factors influencing consumer acceptance of the applications are not well understood. This study was conducted to investigate factors affecting acceptance of a consumer-used nursing informatics application (ie, online health information portal) within the framework of the Technology Acceptance Model. A cross-sectional study was conducted in which 201 Chinese young adults were invited to participate in usability testing with a typical health information portal and to complete a self-report questionnaire measuring the model's constructs and five hypothesized variables drawn from consumer and portal characteristics. Hierarchical regression analyses were used to test research hypotheses. Fifteen of the 22 research hypotheses were supported. Perceived ease of use and perceived usefulness predicted satisfaction and behavioral intention, respectively, over and above the portal and consumer characteristics examined in the study. All portal and consumer characteristics had significant, although varied, impacts on the original model constructs. This study demonstrated that an adapted Technology Acceptance Model, extended with portal and consumer characteristics, provides an effective means to understand consumer acceptance of health portals. The findings hold important implications for design and implementation strategies to increase the likelihood of acceptance of consumer-used nursing informatics applications.https://ift.tt/2PqgHYb
Perioperative Mortality in Cancer Esophagus—a Case Control Study at a High-Volume Regional Cancer Center in South India
Abstract
Surgery for esophageal cancers carries high rates of morbidity and mortality despite improvements in perioperative care especially with increasingly safe anesthesia and postoperative ICU care. A case control study was conducted on 713 patients operated for esophageal cancer over a period of 8 years (2009–2016). Multiple preoperative, intraoperative, and postoperative clinical and laboratory parameters were compared between patients who succumbed to the surgery, i.e., 30-day mortality, and those who did not. Of the preoperative parameters, age > 58.5 years (p = 0.01), history of dysphagia with significant weight loss (p = 0.028), diabetes (p = 0.002), ischemic cardiac disease (p = 0.0001), low FEV1 < 69.5% (p = 0.036), preoperative length of hospital stay > 6.94 days (p = 0.001), involvement of gastroesophageal junction (p = 0.04), and ASA score > 2 (p = 0.002) were significantly associated with perioperative mortality. Intraoperatively, blood loss (p = 0.003), intraoperative (p = 0.015) and postoperative (p = 0.0001) blood transfusion, splenectomy (p = 0.0001), and excessive intraoperative intravenous fluids (p = 0.003) were associated with mortality. Decreased postoperative day 1 serum albumin level < 2.38 mg/dl (p = 0.0001), increased ICU stay > 7.32 days (SD+/- = 6.28, p = 0.03), number of positive lymph nodes > 2.97 (SD+/- = 4.19, p = 0.013), conduit necrosis (p = 0.0001), recurrent laryngeal nerve palsy (p = 0.013), pulmonary venous thromboembolism (p = 0.0001), multiple organ dysfunction syndrome (p = 0.0001), LRTI (p = 0.0001), arrhythmia (p = 0.005), sepsis (p = 0.0001), and ARDS (p = 0.0001) were the postoperative complications that were significantly associated with mortality. Comprehensive patient care involving preoperative optimization, improved surgical skills, rigorous intraoperative fluid management, and dedicated intensive care units will continue to play a major role in further minimizing mortality and morbidity associated with esophageal cancer surgeries.
https://ift.tt/2QNrnfK
AHA: Icosapent Ethyl Cuts CV Risk From Elevated Triglycerides
TUESDAY, Nov. 13, 2018 -- Icosapent ethyl is associated with a reduced risk for ischemic events among patients with elevated triglyceride levels despite taking statins, according to a study published online Nov. 10 in the New England Journal of...
https://ift.tt/2PtQKa4
AHA: Cardiogenic Shock Ups Mortality in Takotsubo Syndrome
TUESDAY, Nov. 13, 2018 -- For patients with takotsubo syndrome (TTS), those with cardiogenic shock (CS) have an increased risk for mortality, according to a research letter published online Nov. 10 in Circulation to coincide with the annual meeting...
https://ift.tt/2Ps0QYP
Online Tool Helps Patients With Advance Care Planning
TUESDAY, Nov. 13, 2018 -- The patient-facing PREPARE advance care planning program plus an easy-to-read advance directive significantly increases documentation of advance care planning and patient-reported engagement, according to a study published...
https://ift.tt/2QGso9x
USPSTF Recommends Screening Adults for Unhealthy Alcohol Use
TUESDAY, Nov. 13, 2018 -- The U.S. Preventive Services Task Force (USPSTF) recommends that primary care clinicians screen all adults, including pregnant women, for unhealthy alcohol use and provide brief behavioral counseling to reduce unhealthy...
https://ift.tt/2QBd4uF
Access to In-Home Support Soon to Be Available for Seniors
TUESDAY, Nov. 13, 2018 -- In-home services such as help with household chores and caregiver respite will be available to seniors with private Medicare Advantage plans in more than 20 states next year. A health-related reason is needed to qualify,...
https://ift.tt/2PoFmfA
Hypoxia-mediated mitochondria apoptosis inhibition induces temozolomide treatment resistance through miR-26a/Bad/Bax axis
Hypoxia-mediated mitochondria apoptosis inhibition induces temozolomide treatment resistance through miR-26a/Bad/Bax axis
Hypoxia-mediated mitochondria apoptosis inhibition induces temozolomide treatment resistance through miR-26a/Bad/Bax axis, Published online: 13 November 2018; doi:10.1038/s41419-018-1176-7
Hypoxia-mediated mitochondria apoptosis inhibition induces temozolomide treatment resistance through miR-26a/Bad/Bax axishttps://ift.tt/2B5xeI3
TGFβ1 signaling sustains aryl hydrocarbon receptor (AHR) expression and restrains the pathogenic potential of TH17 cells by an AHR-independent mechanism
TGFβ1 signaling sustains aryl hydrocarbon receptor (AHR) expression and restrains the pathogenic potential of TH17 cells by an AHR-independent mechanism
TGFβ1 signaling sustains aryl hydrocarbon receptor (AHR) expression and restrains the pathogenic potential of T<sub>H</sub>17 cells by an AHR-independent mechanism, Published online: 13 November 2018; doi:10.1038/s41419-018-1107-7
TGFβ1 signaling sustains aryl hydrocarbon receptor (AHR) expression and restrains the pathogenic potential of TH17 cells by an AHR-independent mechanismhttps://ift.tt/2K3SKj6
Ribosomal protein S27-like regulates autophagy via the β-TrCP-DEPTOR-mTORC1 axis
Ribosomal protein S27-like regulates autophagy via the β-TrCP-DEPTOR-mTORC1 axis
Ribosomal protein S27-like regulates autophagy via the β-TrCP-DEPTOR-mTORC1 axis, Published online: 13 November 2018; doi:10.1038/s41419-018-1168-7
Ribosomal protein S27-like regulates autophagy via the β-TrCP-DEPTOR-mTORC1 axishttps://ift.tt/2B58jEk
Nitric oxide triggers the assembly of “type II” stress granules linked to decreased cell viability
Nitric oxide triggers the assembly of "type II" stress granules linked to decreased cell viability
Nitric oxide triggers the assembly of "type II" stress granules linked to decreased cell viability, Published online: 13 November 2018; doi:10.1038/s41419-018-1173-x
Nitric oxide triggers the assembly of "type II" stress granules linked to decreased cell viabilityhttps://ift.tt/2K3SIYw
Renal tubular epithelial cells: the neglected mediator of tubulointerstitial fibrosis after injury
Renal tubular epithelial cells: the neglected mediator of tubulointerstitial fibrosis after injury
Renal tubular epithelial cells: the neglected mediator of tubulointerstitial fibrosis after injury, Published online: 13 November 2018; doi:10.1038/s41419-018-1157-x
Renal tubular epithelial cells: the neglected mediator of tubulointerstitial fibrosis after injuryhttps://ift.tt/2B5Rj0S
Correction: Guanylate-binding protein 2 regulates Drp1-mediated mitochondrial fission to suppress breast cancer cell invasion
Correction: Guanylate-binding protein 2 regulates Drp1-mediated mitochondrial fission to suppress breast cancer cell invasion
Correction: Guanylate-binding protein 2 regulates Drp1-mediated mitochondrial fission to suppress breast cancer cell invasion, Published online: 13 November 2018; doi:10.1038/s41419-018-1133-5
Correction: Guanylate-binding protein 2 regulates Drp1-mediated mitochondrial fission to suppress breast cancer cell invasionhttps://ift.tt/2K3SG2Q
The influence of prostatic Cutibacterium acnes infection on serum levels of IL6 and CXCL8 in prostate cancer patients
Abstract
Background
Chronic prostatic inflammation, caused by Cutibacterium acnes (C. acnes), has been proposed to influence the risk of prostate cancer development. In vitro studies have demonstrated the capacity of C. acnes to induce secretion of Interleukin 6 (IL6) and C-X-C motif chemokine ligand 8 (CXCL8) by prostate epithelial cells. Both these inflammatory mediators have been implicated in prostate cancer pathophysiology. In this cohort study, we aimed to investigate the influence of prostatic C. acnes on serum levels of IL6 and CXCL8.
Methods
We recruited 99 prostate cancer patients who underwent radical prostatectomy at Örebro University Hospital. The cultivation of pre-operatively obtained prostate biopsies identified C. acnes in 60 of the 99 patients. Levels of IL6 and CXCL8 in pre-operative serum samples were analyzed using ELISA, and concentrations were compared between prostate cancer patients with and without prostatic C. acnes infection using standard statistical methods.
Results
No statistical differences were observed in serum levels of IL6 and CXCL8 between subjects with and without prostatic C. acnes infection.
Conclusions
Our results indicate that prostatic C. acnes infection may give rise to low-grade inflammation with little effect on systemic levels of IL6 and CXCL8.
https://ift.tt/2QAIwcC
Multifocal Visual Evoked Potentials and Contrast Sensitivity Correlate with Ganglion Cell-Inner Plexiform Layer Thickness in Multiple Sclerosis
Neurodegeneration is an important component of the pathological process in multiple sclerosis (MS), a chronic disease of the central nervous system (CNS). The anterior visual pathway, a small compartment within the CNS, is a prominent site of demyelination and neurodegenerative damage and serves as a good model in MS (Pisa et al., 2017, Toosy et al., 2017). It is well known that within the first 3 to 6 months following acute optic neuritis (ON), significant axonal and neuronal loss occurs (Costello et al., 2008, Syc et al., 2012), resulting in permanent visual dysfunction.
https://ift.tt/2zUkt1o
IMRT and image-guided adapted brachytherapy for cervix cancer
IMRT and 3D image-guided adapted brachytherapy (3D-IGABT) is increasingly used for definitive cervical cancer treatment. We compared patterns of failure and survival to patients treated with 2D external beam radiation and brachytherapy, with all patients receiving a pre-treatment PET and all surviving patients having 5 years minimum follow up. IMRT and 3D-IGABT was associated with higher survival and reduced late bowel and bladder toxicities.
https://ift.tt/2qIwgeO
SABR in high risk prostate cancer: outcomes from two prospective clinical trials with and without elective nodal irradiation
There is limited data on SABR with ENI in high-risk PCa. This study compares two phase II SABR trials with and without ENI in high-risk PCa. Trial1 prescribed 40Gy/5 to prostate and 30G/5 to SVs, while trial2 prescribed 40Gy/5 to prostate and 25Gy/5 to pelvis and SVs. Biochemical control rates were comparable to other RT modalities, and ENI was led to a significant improvement in 4yPSARR without an increase in late toxicity.
https://ift.tt/2FisAdK
Early changes in cardiovascular biomarkers with contemporary thoracic radiation therapy for breast cancer, lung cancer and lymphoma
We characterized the early changes in cardiovascular biomarkers with contemporary thoracic radiation therapy (RT) and evaluated their associations with radiation dose volume metrics including mean heart dose (MHD), V5 and V30.
https://ift.tt/2FisByk
The Anatomy of Concussion and Chronic Traumatic Encephalopathy–A Comprehensive Review
Concussion is defined as a complex pathophysiological process that affects the brain as a result of traumatic biomechanical forces. Repeated unrecovered concussions can result in chronic brain injury syndrome which is referred to in the literature today as chronic traumatic encephalopathy." There is an exponential increase in public and political interest in this condition in the recent times resulting in a significant investment in research to improve the current understanding of the disease, ways to decrease its incidence and determine its prognosis.
Broadly the research involves three main disciplines of medicine including neuropathology, neuroradiology and biological markers. Although progress has been made, to date there is no definite pathological, radiological or neurobiological marker which has shown consistent promise to make the diagnosis and prognosticate the disease. Possible reasons are multiple such as inconsistencies in the methods studies have used, different time periods in which the tests were conducted, the small numbers of subjects included in the studies, and inconsistencies in the definitions of concussion or mild TBI. Herein, we present a comprehensive review of the current literature on this topic. PET scans with radioactive ligands such as T807 as an imaging biomarker, and neurofilament light (NfL) and Ubiquitin C‐terminal Hydrolase (UCH‐L1) as serum biomarkers have shown some promise lately in diagnosing concussion and CTE and also determining their prognosis.
This article is protected by copyright. All rights reserved.
https://ift.tt/2PrCoXP
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
